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Objectives: To clarify disease behavior and oncological outcomes as well as the need for ureteroscopy (URS) implementation in patients with clinically suspected upper tract carcinoma in situ (UT-CIS). Patients and Methods: In this multi-institutional study, we retrospectively analyzed patients who met three criteria for clinically suspected UT-CIS between 2008 and 2018: positive high-grade cytology from the upper tract, absence of a solid upper tract lesion on imaging, and negative bladder biopsy. Patients who underwent URS were compared with those who did not. Kaplan-Meier curve was used to assess the natural history of treated UT-CIS and the prognostic impact of URS. Results: In total, 48 patients with clinically suspected UT-CIS were analyzed, of whom 27 (57%) had a previous history of urothelial carcinoma. Of 28 (58%) patients who underwent URS, pathologically confirmed UT-CIS and UT-non-CIS were detected in 7 (25%) and 6 (21%), respectively. As initial treatment, 23 (48%) patients received upper tract bacillus Calmette-Guérin, while 21 (44%) underwent radical nephroureterectomy (RNU). During a median follow-up of 44.8 months, the most common site that suffered recurrence and progression was the bladder (40% and 17%), followed by the affected (15% and 6%) and contralateral (8% and 4%) upper tract, respectively. Three-year overall, cancer-specific, upper tract-specific, progression-free (PFS), and recurrence-free survival estimates were 88.2%, 94.8%, 100%, 80.8%, and 52.4%, respectively. Survival outcomes were comparable regardless of URS implementation, with the exception of PFS. However, URS implementation resulted in an earlier transition to surgical intervention in 11% and avoided unnecessary RNU in 11%. Conclusions: UT-CIS is a pan-urothelial disease and frequently shows metachronous recurrence and progression in any part of the urinary tract, necessitating long-term, meticulous follow-up. Despite the lack of a statistical difference between patients with and without URS, we found that a non-negligible number of patients benefited from URS implementation.

DOI： 10.1177/08927790251374291

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Background/Objectives: Limited research exists on risk factors for urinary tract infections (UTIs) in kidney transplant recipients, particularly in high-risk groups such as ABO-incompatible or donor-specific antibody (DSA)-positive cases. Early UTIs, especially within the first month post-transplant, impact on acute rejection and long-term graft outcomes, highlighting the need for risk factor identification and management. Methods: Among 157 living donor kidney transplant cases performed at our institution between 2009 and 2024, 128 patients were included after excluding cases with >72 h of perioperative prophylactic antibiotics or urological complications. UTI was defined as the presence of pyuria and a positive urine culture, accompanied by clinical symptoms requiring antibiotic treatment, occurring within one month post-transplantation. Results: The median onset of UTI was postoperative day 8 (interquartile range, IQR: 6.8-9.3). No subsequent acute rejection episodes were observed. The median serum creatinine at 1 month postoperatively was 1.3 mg/dL (IQR: 1.1-1.7), and this was not significantly different from those who did not develop UTI. In univariate analysis, low or high BMI (<20 or >25), longer dialysis duration (>2.5 years), desensitization therapy (plasmapheresis + rituximab), elevated preoperative neutrophil-to-lymphocyte ratio (NLR) (≥3), and longer warm ischemic time (WIT) (≥7.8 min) were significantly associated with an increased infection risk of UTI (p = 0.010, 0.036, 0.028, 0.015, and 0.038, respectively). Multivariate analyses revealed that abnormal BMI, longer dialysis duration, desensitization therapy, and longer WIT were independent risk factors for UTI (p = 0.012, 0.031, 0.008, and 0.033, respectively). The incidence of UTI increased with the number of risk factors: 0% (0/16) for zero, 10% (5/48) for one, 31% (16/51) for two, 45% (5/11) for three, and 100% (2/2) for four risk factors. Conclusions: Desensitization therapy, BMI, dialysis duration, and WIT were identified as independent risk factors for perioperative UTI. In patients with risk factors, additional preventive strategies should be considered, with extended antibiotic prophylaxis being one potential option.

DOI： 10.3390/jcm14176102

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BACKGROUND: Although the long-term survival of kidney transplant recipients has significantly improved, malignant neoplasms remain one of the leading causes of death in this population. The recipients face a 1.8-fold increased risk of developing malignant neoplasms compared with the general population. This risk increases with time after transplantation. Tacrolimus (TAC) is preferred over cyclosporine A (CyA) in terms of efficacy against organ rejection, but evidence on the risk of malignant neoplasms is lacking. We aimed to describe the incidence and types of malignant neoplasms in kidney transplant recipients and evaluate the association between malignant neoplasms development and the type of prescribed CNI. METHODS: This retrospective cohort study was conducted using the Japanese National Database of Health Insurance Claims, including data covering 99% of kidney transplant patients in Japan. Patients who underwent kidney transplantation and were prescribed TAC or CyA between April and June 2011 were included. The primary outcome included the incidence of malignant neoplasms, and secondary outcomes included overall survival and graft survival. RESULTS: A total of 7,590 patients were included, with 11.0% developing malignant neoplasms during the follow-up period. The most common malignant neoplasms were in the digestive organs and urinary tract. No statistically significant difference in malignant neoplasms incidence was observed between TAC and CyA users (hazards ratio: 0.97, 95% CI: 0.84 to 1.12; estimated average treatment effect: -24.05, 95% CI: -184.90 to 136.80). The patient and graft survival rates were also comparable between the groups. CONCLUSIONS: This large study suggests that TAC is not associated with an increased risk of malignant neoplasms compared to CyA in the late post-transplant period. CLINICAL TRIAL NUMBER: Not applicable.

DOI： 10.1186/s12882-025-04405-8

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Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23-4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39-5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.

DOI： 10.1038/s41598-025-08767-9

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OBJECTIVE: Venous thromboembolism (VTE) is one of the serious complications after robot-assisted radical cystectomy (RARC). This study aims to investigate the optimal duration of VTE prophylaxis and the predictive value of D-dimer measurement on the early detection of VTE. METHODS: Retrospectively, we evaluated 86 RARC patients from July 2020 to September 2023. Thromboprophylaxis was modified two times (July 2020-; no-enoxaparin administration, June 2021-; enoxaparin for one week postoperatively, December 2022-; for two weeks), and patients were divided into three groups according to the duration. For early detection of VTE, D-dimer was measured postoperatively over time. In cases of D-dimer exceeding 10 μg/mL, contrast-enhanced CT was performed. The incidence of VTE was analyzed, and multivariate analysis was performed to identify the predictive factors. RESULTS: Of the 40 patients who experienced postoperative D-dimer levels > 10 μg/mL, 37 underwent CT or ultrasound. VTE was observed in 10/26 cases (38%) in the no-enoxaparin group, 8/36 cases (22%) in the one-week group, and 1/24 cases (4%) in the two-week group, with a significant difference in incidence between the no-enoxaparin and 2-week groups (p = 0.005). Symptomatic VTE was observed in only one case in the no-enoxaparin group. Multivariate analyses of VTE predictive factors showed significant differences in D-dimer levels ≥ 12 on postoperative day 1 (OR = 14.2, 95% CI 2.47-81.1, p = 0.003) and enoxaparin administration for two weeks (OR = 0.10, 95% CI 0.01-0.96, p = 0.046). CONCLUSION: Chemoprophylaxis for 2 weeks significantly reduces the risk of VTE after RARC. In addition, routine measurement of D-dimer enables early detection of asymptomatic VTE, helping to prevent the development of symptomatic VTE.

DOI： 10.1111/iju.70066

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DOI： 10.1093/jjco/hyaf025

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DOI： 10.1245/s10434-025-17017-1

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BACKGROUND/AIM: This study investigated the correlation between body mass index (BMI, kg/m2) and clinical outcomes in patients with advanced renal cell carcinoma (RCC) treated with ipilimumab and nivolumab. PATIENTS AND METHODS: A total of 113 patients with advanced RCC, treated with first-line ipilimumab and nivolumab were analyzed. Patients were divided into two groups based on their BMI at treatment initiation: the high BMI (BMI ≥25) and the low BMI group (BMI <25). The objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and duration of response (DOR) were analyzed to compare the two groups. RESULTS: Patient characteristics for the high BMI (n=30) and the low BMI (n=83) were as follows: median age at treatment initiation (70 years for both groups), percentage of male patients (77% vs. 82%), International Metastatic RCC Database Consortium (IMDC) poor-risk category (23% vs. 33%), the presence of liver metastasis (7% vs. 8%). The ORR was 53% (16/30) in the high BMI and 37% (29/77) in the low BMI (p=0.01). The median OS was not estimated in the high BMI and 33 months in the low BMI (p=0.049). Multivariable analysis identified IMDC poor-risk status with a hazard ratio (HR) of 2.31 and the presence of liver metastasis with an HR of 4.83 as independent factors affecting OS. CONCLUSION: A higher ORR for the combination of ipilimumab and nivolumab was observed in patients with high BMI compared to those with low BMI. IMDC poor risk and the presence of liver metastasis significantly influenced the prognosis of patients with advanced RCC treated with the combination.

DOI： 10.21873/anticanres.17635

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Background: Urinary tract infection (UTI) is predominantly caused by uropathogenic Escherichia coli (UPEC). Previous studies have reported that the fimbriae of UPEC are involved in virulence and antimicrobial resistance. We aimed to analyze the fimbrial gene profiles of UPEC and investigate the specificity of these expressions in symptomatic UTI, urinary device use, and levofloxacin (LVFX) resistance/extended-spectrum beta-lactamase (ESBL) production. Methods: A total of 120 UPEC strains were isolated by urine culture between 2019 and 2023 at our institution. They were subjected to an antimicrobial susceptibility test and polymerase chain reaction (PCR) to identify 14 fimbrial genes and their association with clinical outcomes or antimicrobial resistance. Results: The prevalence of the papG2 gene was significantly higher in the symptomatic UTI group by multivariate analyses (OR 5.850, 95% CI 1.390-24.70, p = 0.016). The prevalence of the c2395 gene tended to be lower in the symptomatic UTI group with urinary devices (all p < 0.05). In LVFX-resistant UPEC strains from both the asymptomatic bacteriuria (ABU) and the symptomatic UTI group, the expression of the papEF, papG3, c2395, and yadN genes tended to be lower (all p < 0.05). Conclusion: The fimbrial genes of UPEC are associated with virulence and LVFX resistance, suggesting that even UPEC with fewer motility factors may be more likely to ascend the urinary tract in the presence of the urinary devices. These findings may enhance not only the understanding of the virulence of UPEC but also the management of UTI.

DOI： 10.3390/antibiotics14050468

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Size-related changes in reproductive potential are essential for understanding population dynamics and life history strategies; however, the mechanisms driving variation between individuals and sexes remain unclear. Using a diet-switch experiment and carbon and nitrogen stable isotope ratios (SIRs) as quantitative indicators, we investigated how large (parents) and small (offspring) spawning male and female Japanese anchovies (Engraulis japonicus) allocate energy to reproduction. Large individuals of both sexes exhibited higher energy investment in gamete production than small individuals, reflecting a trade-off between growth and reproduction. The turnover rates of SIRs after a diet switch suggest that anchovies predominantly rely on income breeding. However, significant differences in turnover rates between large and small individuals indicate that large fish can also utilize facultative capital resources for gamete production. Notably, males exhibited slower isotopic turnover than females, partly due to the influence of sperm storage. These findings demonstrate that spawning individuals display temporal diversity in resource use for reproduction, with large individuals showing greater flexibility in energy allocation strategies. This study advances our understanding of size- and sex-dependent resource allocation in Japanese anchovy and contributes to a broader understanding of reproductive strategies in small pelagic fishes.

DOI： 10.1038/s41598-025-99911-y

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BACKGROUND: Immune checkpoint inhibitors (ICI) and chemotherapy, including antibody-drug conjugates, are widely used for the treatment of patients with advanced unresectable or metastatic urothelial carcinoma (UC). The majority of elderly patients receive concomitant medications to address various comorbidities. We aimed to evaluate the impact of concomitant medications on oncological outcomes in patients with advanced unresectable or metastatic UC treated with systemic therapy. MATERIAL & METHODS: In August 2024, three datasets were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic UC. The review protocol was registered in PROSPERO (CRD42024547335). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis depending on the heterogeneity. RESULTS: We identified 16 eligible studies (3 prospective and 13 retrospective) comprising 4,816 patients. Most reported concomitant medications included proton pump inhibitors (PPIs), antibiotics, steroids, and opioids. The use of concomitant PPIs, antibiotics, steroids or opioids during ICI therapy was associated with worsened OS (PPIs: HR: 1.43, 95% CI: 1.31-1.57, p < 0.001; antibiotics: HR: 1.2, 95% CI: 1.04-1.38, p = 0.01; steroids: HR: 1.45, 95% CI: 1.25-1.67, p < 0.001; and opioids: HR: 1.74, 95% CI: 1.46-2.07, p < 0.001). Concomitant use of antibiotics during chemotherapy did not impact OS (HR: 1.01, 95% CI: 0.67-1.51). CONCLUSIONS: When treating advanced unresectable or metastatic UC with ICI therapy, we need to pay attention to concomitant medications, such as PPIs and antibiotics to avoid reducing the efficacy of ICI therapy. The mechanism of action of these drugs on ICI efficacy requires further examination.

DOI： 10.1186/s12894-025-01754-2

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

DOI： 10.18926/AMO/68646

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Despite currently used intravesical therapies in non-muscle-invasive bladder cancer (NMIBC), the rate of intravesical recurrence remains very high. We aimed to evaluate the effectiveness of adding nonintravesical interventions to standard intravesical therapies to prevent intravesical recurrence. In April 2024, 3 databases were queried for prospective studies evaluating nonintravesical interventions in addition to standard intravesical therapies for NMIBC (CRD42024490988). The primary outcome was intravesical recurrence-free survival (iRFS). Standard pairwise meta-analyses were performed using hazard ratios (HR) and 95% confidence intervals (95% CI) with a random-effects model. We identified 18 eligible studies (14 RCTs and 4 prospective trials) comprising 4,593 NMIBC patients, which investigated pharmacological interventions (eg, selenium, vitamins, Lactobacillus casei, celecoxib, metformin, mistletoe lectin) and lifestyle modifications (diet). The addition of Lactobacillus casei significantly improved iRFS (HR: 0.50; 95% CI: 0.34-0.73; P < .001). A high western diet pattern significantly worsened iRFS (HR:1.48, 95%CI:1.06-2.06, P = .03). The other nonintravesical interventions were not associated with iRFS. Our comprehensive review of the published literature highlights the need for further research into the efficacy of nonvesical interventions for NMIBC. While Lactobacillus was shown to improve iRFS in 2 RCTs, additional high-quality randomized studies are required to evaluate the effectiveness of other interventions.

DOI： 10.1016/j.clgc.2025.102306

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OBJECTIVE: This study aimed to perform a systematic review and meta-analysis of stretched, erect, and flaccid penis length as well as circumference according to geographic WHO regions. METHODS: PubMed, Embase, Scopus, and Cochrane Library were searched for articles published until February 2024. Studies in which a healthcare professional evaluated the penis size were considered eligible. After assessing the risk of bias, a systematic review and meta-analyses were performed according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement, and the outcomes were grouped based on the WHO regions. RESULTS: A total of 33 studies comprising 36 883 patients were included. The risk of bias in the included studies was moderate/low. A comprehensive systematic review was done and meta-analyses performed for flaccid length [n = 28 201, mean (SE) 9.22 (0.24) cm], stretched length [n = 20 814, mean (SE) 12.84 (0.32) cm], erect length [n = 5669, mean (SE) 13.84 (0.94) cm], flaccid circumference [n = 30 117, mean (SE) 9.10 (0.12) cm], and erect circumference [n = 5168, mean (SE) 11.91 (0.18) cm]. The mean length of the stretched penis was largest in Americans [14.47 (0.90) cm]. The mean length of the flaccid penis was the largest in the Americas [10.98 (0.064) cm]. The mean flaccid penile circumference was largest in Americans [n = 29 714, mean (SE) 10.00 (0.04) cm]. CONCLUSIONS: Penis sizes vary across WHO regions, suggesting the need to adjust standards according to geography to better understand councilmen and their partners. These data provide a framework for discussing body image expectations and therapeutic strategies in this sensitive and emotional subject matter.

DOI： 10.5152/tud.2025.24038

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Language：Japanese  

With the advancement of modern ureteroscopes and laser technology, kidney-sparing surgery(KSS)has an expanding role for patients with upper tract urothelial carcinoma(UTUC), although radical nephroureterectomy remains the gold standard. Patients with UTUC are generally elderly and often have major medical comorbidities. As such, KSS is recommended for patients with imperative indications, such as bilateral disease, renal insufficiency, or a solitary kidney, while maintaining renal function, resulting in the avoidance of potential long-term cardiovascular morbidity and hemodialysis. In addition, KSS is also advocated for low-risk patients(elective indication)based on the risk stratifications recommended by each guideline. The big issue of risk stratifications is their narrow indications at the cost of providing accuracy, but the current elective indications have been updated and expanded year by year. KSS includes endoscopic management through antegrade or retrograde access to the upper tract and segmental ureterectomy. Thulium: YAG laser in combination with Ho: YAG laser is recently used for KSS due to the advantages of its shallow penetration depth in tissue, with a reduced risk of upper urinary tract perforation. The concern regarding KSS is a high recurrence rate. Adjuvant intracavitary instillation to the upper tract has the potential to reduce the risk of recurrence. The phase Ⅲ trial assessing a mitomycin-containing reverse thermal gel (JelmytoTM)revealed the promising result despite their use not being approved in Japan. Therefore, KSS is assumed to have an increasing demand for patients with UTUC in our aged society and is expected to be widely utilized nationwide.

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Recent phase 3 randomized controlled trials (RCTs) demonstrate the promising impact of immune checkpoint inhibitor (ICI)-based combination therapies on locally advanced or metastatic urothelial carcinoma (UC). However, comparative data on the efficacy and toxicity of different ICI-based combinations are lacking. This study aims to compare the efficacy of first-line ICI-based combination therapies for locally advanced or metastatic UC using phase 3 RCT data. In November 2023, three databases were searched for RCTs evaluating oncological outcomes in patients with locally advanced or metastatic UC who were treated with first-line ICI-based combination therapies. Network meta-analysis (NMA) was conducted to compare outcomes, including overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), complete response rates (CRRs), and treatment-related adverse events (TRAEs). Subgroup analyses were based on PD-L1 status and cisplatin eligibility. The NMA included five RCTs. Enfortumab vedotin (EV) + pembrolizumab ranked the highest for improving OS (100%), PFS (100%), ORR (96%), and CRR (96%), followed by nivolumab + chemotherapy. EV + pembrolizumab combination superiority held across PD-L1 status and cisplatin eligibility. In patients who are cisplatin-eligible, EV + pembrolizumab significantly improved OS (HR: 0.68, 95%CI 0.47-0.99) and PFS (HR: 0.67, 95%CI 0.49-0.92) compared to nivolumab + chemotherapy. Durvalumab + tremelimumab was the safest combination for severe TRAEs, and EV + pembrolizumab ranked second. Our analyses support EV + pembrolizumab combination as a first-line treatment for locally advanced or metastatic UC. Thus, EV + pembrolizumab may become a guideline-changing standard treatment.

DOI： 10.1007/s00262-024-03910-3

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CONTEXT: Adjuvant immune checkpoint inhibitors (ICIs) have recently emerged as guideline-recommended treatments of high-risk muscle-invasive urothelial carcinoma (MIUC). However, there is limited evidence regarding the optimal candidates and the differential efficacy of adjuvant ICI regimens. OBJECTIVE: To synthesize and compare the efficacy and safety of adjuvant ICIs for high-risk MIUC using updated data from phase III randomized controlled trials. EVIDENCE ACQUISITION: In April 2024, three databases were searched for eligible randomized controlled trials that evaluated oncologic outcomes in patients with MIUC treated with adjuvant ICIs. Pairwise meta-analysis (MA) and network meta-analyses were performed to compare the hazard ratios of oncological outcomes, including disease-free survival (DFS), overall survival (OS), and adverse events. Subgroup analyses were conducted on the basis of predefined clinicopathological features. EVIDENCE SYNTHESIS: Three randomized controlled trials that assessed the efficacy of adjuvant nivolumab, pembrolizumab, and atezolizumab were included in the MAs and network meta-analyses groups. Pairwise MAs showed that treatment with adjuvant ICIs significantly improved DFS [hazards ratio: 0.77, 95% confidence interval (CI): 0.66-0.90] as well as OS (hazards ratio: 0.87, 95% CI 0.76-1.00) in patients with MIUC compared with in the placebo/observation group. The DFS benefit was prominent in patients who underwent neoadjuvant chemotherapy (P = 0.041) and in those with bladder cancer (P = 0.013) but did not differ across programmed death-ligand 1 and lymph node status. Adjuvant ICI therapy was associated with increased risk of any (OR: 2.98, 95% CI 2.06-4.33) and severe adverse events (OR: 1.78, 95% CI 1.49-2.13). The treatment rankings revealed that pembrolizumab for DFS (84%) and nivolumab for OS (93%) had the highest likelihood of improving survival. CONCLUSIONS: Our analyses demonstrated the DFS and OS benefits of adjuvant ICIs for high-risk MIUC. Furthermore, patients with bladder cancer who underwent neoadjuvant chemotherapy appeared to be the optimal candidates for adjuvant ICIs regarding prolonged DFS. Adjuvant ICIs are the standard of care for high-risk MIUC, and differential clinical behaviors and efficacy will enrich clinical decision-making.

DOI： 10.1007/s11523-024-01114-4

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BACKGROUND/AIM: This study assessed the accuracy of preoperative contrast-enhanced computed tomography (CECT) scans in staging small-sized, locally advanced (cT3a) renal cell carcinoma (RCC) and identified predictors of pathological downstaging following surgery. PATIENTS AND METHODS: Seventy-six patients who underwent radical nephrectomy for cT3aN0M0 RCC with tumors ≤7 cm were analyzed. Preoperative CECT evaluated features such as venous, peritumoral, or renal sinus fat, and urinary tract invasion, predictive values, and concordance index between radiological and pathological findings were calculated for these categories. The study also examined the impact of clinicopathologic factors on downstaging. RESULTS: Of 76 patients with cT3 RCC, 37% were down-staged to pT1. Down-staged cases had a higher proportion of male patients and non-clear cell carcinoma (86% vs. 58%, 32% vs. 6%; p=0.02, p=0.007, respectively). Multiple cT3a factors were less common in down-staged cases (4% vs. 23%, p=0.04). Non-clear cell carcinoma was significantly associated with downstaging compared to clear cell carcinoma (75% vs. 30%, p=0.006). Multivariate analysis confirmed non-clear cell carcinoma as an independent predictor (odds ratio=8.2, p=0.01). For venous invasion, CECT sensitivity and positive predictive value were high (73.5% and 83.3%, respectively) and the degree of agreement was substantial (κ=0.62). CONCLUSION: The accuracy of preoperative CECT was acceptable for detecting venous invasion. The downstaging to pT1 occurred in 37% of cT3a RCC cases in the final pathology, with non-clear cell carcinoma being a significant predictor.

DOI： 10.21873/invivo.14077

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CONTEXT: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs. EVIDENCE ACQUISITION: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs). EVIDENCE SYNTHESIS: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo. CONCLUSIONS: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings.

DOI： 10.1177/23523735251335122

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For small renal tumors, nephron-preserving treatment, including partial nephrectomy or ablation therapy, is recommended. According to major guidelines, ablation therapies are advised for patients who are deemed not suitable to undergo surgery due to an advanced age or the presence of comorbidities. However, compared with surgery, ablation therapy can result in superior safety and functional outcomes. The present review discusses the factors affecting decision-making as regards treatment options for small renal tumors. When determining an appropriate treatment option, tumor locations, as well as the condition and preferences of the patient, are considered. Scoring systems, such as the RENAL Nephrometry Score can assist in guiding treatment decisions. However, surgery may be the preferred approach for tumors near major vessels and collecting systems. For endophytic tumors, partial nephrectomy can be challenging due to the difficulty in visualizing intra-parenchymal tumors during the procedure, whereas ablation therapies may be inferior to partial nephrectomy. Although treatment selection for small renal tumors can be affected by tumor location, partial nephrectomy remains the gold standard for numerous cases.

DOI： 10.3892/mi.2025.247

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OBJECTIVE: To examine whether antimicrobial prophylaxis based on screening rectal cultures using selective media prevented acute bacterial prostatitis following transrectal prostate biopsy (TRPB). METHODS: In this multicenter, randomized controlled trial, we enrolled 403 patients undergoing TRPB with low risks of infectious complications. Patients were randomized into a cultured group (CG) or no cultured group (NCG). In the CG, patients with positive culture results for fluoroquinolone (FQ)-resistant or extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) used piperacillin/tazobactam as prophylaxis, and those with negative culture results and in the NCG used levofloxacin. The primary endpoint was the incidence of acute prostatitis after TRPB. The secondary endpoint was the accuracy of the selective media. RESULTS: Of 373 patients (CG, 187; NCG, 186), 67 were positive, and 120 were negative for rectal culture in the CG. The overall incidence of prostatitis after TRPB was 1.1% (n=4). The incidences in the CG and the NCG were 1.6% (n=3, all negative-culture cases) and 0.5% (n=1), respectively, without significant difference (P=0.3). No prostatitis occurred in the positive-culture group. The sensitivity and specificity of the levofloxacin-insusceptible selective media were 98.1% and 94.7%, respectively. CONCLUSION: Screening with selective media before TRPB in patients with low infectious risks may provide additive value to preventing post-biopsy prostatitis. Piperacillin/tazobactam can be considered when FQ-resistant or ESBL-producing E. coli is detected.

DOI： 10.1016/j.urology.2024.12.018

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Although partial nephrectomy (PN) is preferred over radical nephrectomy (RN) for preserving renal function in patients with cT1 renal cancer, its impact on cardiovascular events (CVe) remains controversial. This study aimed to compare PN and RN in regard to the occurrence of CVe, including cerebrovascular events and exacerbation of hypertension (HT). We retrospectively analyzed 418 consecutive patients who underwent PN or RN for cT1 renal cancer. Propensity score-matching analysis was used to adjust for imbalances between patients who underwent PN and RN, leaving 102 patients in each group. The 5-year probability of cumulative CVe incidence was 6% in the PN group and 12% in the RN group (p=0.03), with a median follow-up of 73.5 months. The statistical significance was retained after propensity score matching for patients without preoperative proteinuria (p=0.03). For all CVe including cerebrovascular events and exacerbation of HT analyzed, PN provided a lower probability of occurrence than RN in patients with small renal cancers.

DOI： 10.18926/AMO/67868

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OBJECTIVES: This study aimed to compare the clinical outcomes of robot-assisted partial nephrectomy (RAPN) and image-guided percutaneous cryoablation (IG-PCA) for clinical T1 renal cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective analysis of 679 patients with clinical T1 renal cell carcinoma treated with RAPN or IG-PCA between 2012 and 2021. Propensity scores were calculated via logistic analysis to adjust for imbalances in baseline characteristics. We compared oncological and functional outcomes between the 2 treatment groups. RESULTS: Following the matching process, 108 patients were included in each group. No patient in the RAPN group developed local recurrence. In the IG-PCA group, three patients experienced local tumor progression. The patients underwent salvage thermal ablations by the secondary technique; 2 underwent IG-PCA and 1 underwent microwave ablation, resulting in a local control rate of 100%. The Kaplan-Meier analysis showed no statistically significant differences between the groups in terms of 5-year recurrence-free survival, metastasis-free survival, and overall survival (log-rank test; P = 0.11, P = 0.64, and P = 0.17, respectively). No significant differences were observed in the 2 treatments in major and overall complication rates (P = 0.75 and P = 0.82, respectively). Both groups showed similar rates of less than 10% estimated glomerular filtration rate decline at 12 months post-treatment and 5-year renal function preservation rates (P = 0.88 and P = 0.38, respectively). CONCLUSIONS: IG-PCA demonstrated oncological outcomes comparable to those of RAPN. RAPN addressed the disadvantages of conventional procedures and allowed for safety outcomes comparable to IG-PCA.

DOI： 10.1016/j.urolonc.2024.09.012

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Although immune checkpoint inhibitors (ICI) and/or tyrosine kinase inhibitors (TKI) are the standard treatment of advanced unresectable or metastatic renal cell carcinoma (RCC), the impact of concomitant medications remains unclear. We aimed to evaluate the impact of concomitant medications on survival outcomes in patients treated with systemic therapy for advanced unresectable or metastatic RCC. In August 2024, PubMed, Scopus, and Web of Science were queried for studies evaluating concomitant medications in patients with advanced unresectable or metastatic RCC (PROSPERO: CRD42024573252). The primary outcome was overall survival (OS). A fixed- or random-effects model was used for meta-analysis according to heterogeneity. We identified 22 eligible studies (5 prospective and 17 retrospective) comprising 16,072 patients. Concomitant medications included proton pump inhibitors (PPI) (n = 3959), antibiotics (n = 571), statins (n = 5466), renin-angiotensin system inhibitors (RASi) (n = 6615), and beta-blockers (n = 1964). Both concomitant PPI and antibiotics were significantly associated with worse OS in patients treated with ICI (PPI: HR: 1.22, P = .01, and antibiotics: HR: 2.09, P < .001). Concomitant statins, RASi, or beta-blocker were significantly associated with improved OS in patients treated with TKI (statins: HR: 0.81, P = .03, RASi: HR: 0.63, P < .001, beta-blocker: HR: 0.69, P < .001, respectively). In patients treated with ICI, RASi was significantly associated with improved OS (HR: 0.64, P = .02). Concomitant use of antibiotics or PPI with ICI can reduce its oncologic efficacy. Conversely, concomitant statins, RASi, or beta-blockers can enhance the oncologic efficacy of TKI. When initiating systemic therapy for metastatic RCC, it may be important for clinicians to assess baseline co-medications and recognize their possible positive or negative effects.

DOI： 10.1016/j.clgc.2024.102237

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BACKGROUND AND OBJECTIVE: While active surveillance (AS) is an alternative to surgical interventions in patients with small renal masses (SRMs), evidence regarding its oncological efficacy is still debated. We aimed to evaluate oncological outcomes for patients with SRMs who underwent AS in comparison to surgical interventions. METHODS: In April 2024, PubMed, Scopus, and Web of Science were queried for comparative studies evaluating AS in patients with SRMs (PROSPERO: CRD42024530299). The primary outcomes were overall (OS) and cancer-specific survival (CSS). A random-effects model was used for quantitative analysis. KEY FINDINGS AND LIMITATIONS: We identified eight eligible studies (three prospective, four retrospective, and one study based on Surveillance, Epidemiology and End Results [SEER] data) involving 4947 patients. Pooling of data with the SEER data set revealed significantly higher OS rates for patients receiving surgical interventions (hazard ratio [HR] 0.73; p = 0.007), especially partial nephrectomy (PN; HR 0.62; p < 0.001). However, in a sensitivity analysis excluding the SEER data set there was no significant difference in OS between AS and surgical interventions overall (HR 0.84; p = 0.3), but the PN subgroup had longer OS than the AS group (HR 0.6; p = 0.002). Only the study based on the SEER data set showed a significant difference in CSS. The main limitations include selection bias in retrospective studies, and classification of interventions in the SEER database study. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients treated with AS had similar OS to those who underwent surgery or ablation, although caution is needed in interpreting the data owing to the potential for selection bias and variability in AS protocols. Our review reinforces the need for personalized shared decision-making to identify patients with SRMs who are most likely to benefit from AS. PATIENT SUMMARY: For well-selected patients with a small kidney mass suspicious for cancer, active surveillance seems to be a safe alternative to surgery, with similar overall survival. However, the evidence is still limited and more studies are needed to help in identifying the best candidates for active surveillance.

DOI： 10.1016/j.euo.2024.10.008

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OBJECTIVES: The advancement of laparoscopic surgery has allowed surgeons to see finer anatomical structures during surgery. As a result, several issues have arisen regarding Gerota fascia that cannot be explained by previous interpretations, such as its various forms observed during surgery. To address these issues, we histologically examined the structure of Gerota fascia. METHODS: Specimens for study were prepared from kidneys with Gerota fascia from four cadavers, and the structure was studied histologically. Its thickness and collagen fiber area ratios were measured using ImageJ and compared to those of the epimysium of the rectus abdominis muscle. RESULTS: Connective tissue that appeared to be Gerota fascia was observed in 26 specimens. Histologically, the basic structure of Gerota fascia was a sandwich-like structure with a thin layer of thick, long collagen fibers in the central layer, and small granular collagen fibers scattered at the edges. However, not all areas observed had a similar structure; eight specimens were composed only of small granular collagen fibers. The average thickness of the Gerota fascia was 466 μm, and the area ratio of collagen was 27.1%. In contrast, the epimysium was much thicker than Gerota fascia, and its collagen fibers were much thicker and denser. CONCLUSIONS: Gerota fascia, unlike the epimysium, was a very thin and fragile layer of collagen fibers, and its structure was diverse. This explains why Gerota fascia was observed in various states during surgery. It is important for surgeons to understand the properties of Gerota fascia and to treat it appropriately.

DOI： 10.1111/iju.15596

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Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.

DOI： 10.1016/j.urolonc.2024.09.014

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DOI： 10.1007/s00345-024-05195-8

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BACKGROUND: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy(RNU) pathology. METHODS: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. RESULTS: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p=0.007). Downgrading was comparable across all tumor locations. On multivariable analyses, middle ureteral location was significantly associated with a low probability of grade concordance (OR 0.59; 95%CI, 0.35-1.00; p =0.049) and an increased risk of upgrading (OR 2.80; 95%CI, 1.20-6.52; p =0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. CONCLUSIONS: Middle ureteral tumors diagnosed to be low-grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counselling and shared decision making regarding the choice of kidney sparing vs RNU.

DOI： 10.1089/end.2024.0335

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OBJECTIVE: To investigate the influence of statins on the survival outcomes of patients with non-muscle-invasive bladder cancer (NMIBC) treated with adjuvant intravesical bacille Calmette-Guérin (BCG) immunotherapy. PATIENTS AND METHODS: A retrospective cohort of consecutive patients with NMIBC who received intravesical BCG therapy from 2001 to 2020 and statins prescription were identified. Overall survival (OS), cancer-specific survival (CSS), recurrence-free survival (RFS), and progression-free survival (PFS) were analysed between the Statins Group vs No-Statins Group using Kaplan-Meier method and multivariable Cox regression. RESULTS: A total of 2602 patients with NMIBC who received intravesical BCG were identified. The median follow-up was 11.0 years. On Kaplan-Meier analysis, the Statins Group had significant better OS (P < 0.001), CSS (P < 0.001), and PFS (P < 0.001). Subgroup analysis indicated statins treatment started before BCG treatment had better CSS (P = 0.02) and PFS (P < 0.01). Upon multivariable Cox regression analysis, the 'statins before BCG' group was an independent protective factor for OS (hazard ratio [HR] 0.607, 95% confidence interval [CI] 0.514-0.716), and CSS (HR 0.571, 95% CI 0.376-0.868), but not RFS (HR 0.885, 95% CI 0.736-1.065), and PFS (HR 0.689, 95% CI 0.469-1.013). CONCLUSIONS: Statins treatment appears to offer protective effects on OS and CSS for patients with NMIBC receiving adjuvant intravesical BCG.

DOI： 10.1111/bju.16493

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Language：Japanese   Publisher：(一社)日本性科学会  

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BACKGROUND: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. METHODS: We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. RESULTS: Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). CONCLUSIONS: There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.

DOI： 10.1093/jjco/hyae108

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CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

DOI： 10.1007/s00345-024-05185-w

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Language：Japanese   Publisher：(一社)日本性機能学会  

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Language：Japanese   Publisher：(一社)日本性機能学会  

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Language：Japanese   Publisher：(一社)日本性機能学会  

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PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

DOI： 10.1016/j.urolonc.2024.06.013

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Language：Japanese   Publisher：(一社)腎癌研究会  

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

J-GLOBAL

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

J-GLOBAL

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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BACKGROUND: To prevent infectious complications after transrectal ultrasound-guided prostate biopsy (TRUS-PB), some studies have investigated the efficacy of rectal disinfection using povidone-iodine (PI) and antibiotic prophylaxis (AP). OBJECTIVE: To summarize available data and compare the efficacy of rectal disinfection using PI with non-PI methods prior to TRUS-PB. EVIDENCE ACQUISITION: Three databases were queried through November 2023 for randomized controlled trials (RCTs) analyzing patients who underwent TRUS-PB. We compared the effectiveness of rectal disinfection between PI groups and non-PI groups with or without AP. The primary outcomes of interest were the rates of overall infectious complications, fever, and sepsis. Subgroups analyses were conducted to assess the differential outcomes in patients using fluoroquinolone groups compared to those using other antibiotics groups. EVIDENCE SYNTHESIS: We included ten RCTs in the meta-analyses. The overall rates of infectious complications were significantly lower when rectal disinfection with PI was performed (RR 0.56, 95% CI 0.42-0.74, p < 0.001). Compared to AP monotherapy, the combination of AP and PI was associated with significantly lower risk of infectious complications (RR 0.54, 95% CI 0.40-0.73, p < 0.001) and fever (RR 0.47, 95% CI 0.30-0.75, p = 0.001), but not with sepsis (RR 0.49, 95% CI 0.23-1.04, p = 0.06). The use of fluoroquinolone antibiotics was associated with a lower risk of infectious complications and fever compared to non-FQ antibiotics. CONCLUSION: Rectal disinfection with PI significantly reduces the rates of infectious complications and fever in patients undergoing TRUS-PB. However, this approach does not show a significant impact on reducing the rate of sepsis following the procedure.

DOI： 10.1007/s00345-024-04941-2

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CONTEXT: It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression. OBJECTIVE: To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP). EVIDENCE ACQUISITION: Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT). EVIDENCE SYNTHESIS: Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract. CONCLUSIONS: In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting. PATIENT SUMMARY: Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.

DOI： 10.1016/j.euo.2024.03.007

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BACKGROUND: Transgender individuals undergo the gender-affirming hormone therapy (GAHT) to achieve physical changes consistent with their gender identity. Few studies are available on the long-term safety and efficacy of GAHT. OBJECTIVES: To investigate the long-term physical effects and the safety of the testosterone therapy for trans men and to assess the impact of differential hormone dose. MATERIALS AND METHODS: Trans men who initiated GAHT between May 2000 and December 2021 were included in this retrospective analysis. Physical findings (body mass index, body fat percentage (BFP), lean body mass (LBM), and grip strength), blood testing results (hemoglobin, hematocrit, uric acid, creatinine, total cholesterol, triglycerides, and total testosterone), and menstrual cessation were recorded. We assessed the effects of testosterone on body composition changes and laboratory parameters, comparing a low-dose group (≤ 62.5 mg/wk) to a high-dose group (> 62.5 mg/wk). RESULTS: Of 291 participants, 188 patients (64.6%) were in the low-dose group and 103 (35.4%) in the high-dose group. Cumulative menstrual cessation rates up to 12 months were not significantly different between groups. Both groups showed a decrease in BFP and an increase in LBM during the first year of therapy, followed by a slight increase in both over the long term. The high-dose group exhibited greater LBM gains during the first year. Higher hormone doses and lower initial LBM values were associated with LBM increases at 3 and 6 months (3 mo, P = 0.006, P < 0.001; 6 mo, P = 0.015, P < 0.001). There were no long-term, dose-dependent side effects such as polycythemia or dyslipidemia. CONCLUSION: Long-term GAHT for trans men is safe and effective. Low-dose testosterone administration is sufficient to increase LBM in trans men. Higher testosterone doses can lead to an earlier increase in muscle mass.

DOI： 10.1111/andr.13640

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

INTRODUCTION: Concomitant medications can affect the efficacy of immune checkpoint inhibitors. The association between histamine-2 receptor antagonists (H2RAs), major antacids similar to proton pump inhibitors (PPIs), and the efficacy of pembrolizumab for metastatic urothelial carcinoma (mUC) treatment has been poorly evaluated. We evaluated the impact of PPIs and H2RAs on oncological outcomes in mUC patients treated with pembrolizumab. PATIENTS AND METHODS: This retrospective multicenter study included patients with mUC treated with pembrolizumab. Patients prescribed PPIs or H2RAs within 30 days before and after the initial administration were extracted. The overall survival (OS), cancer-specific survival (CSS), progression-free survival (PFS), and objective response rates (ORR) were assessed. Kaplan-Meier survival curve analysis and multivariable Cox proportional hazard models were employed to assess the association between PPIs or H2RAs and survival outcomes. RESULTS: Overall, 404 patients were eligible for this study; 121 patients (29.9%) used PPIs, and 34 (8.4%) used H2RAs. Kaplan-Meier analysis showed significantly worse OS, CSS, and PFS in patients using PPIs compared to no PPIs (P = .010, .018, and .012, respectively). In multivariable analyses, the use of PPIs was a significant prognostic factor for worse OS (HR = 1.42, 95% CI 1.08-1.87, P = .011), CSS (HR = 1.45, 95% CI 1.09-1.93, P = .011), and PFS (HR = 1.35, 95% CI 1.05-1.73, P = .020). PPIs were not associated with ORRs. The use of H2RAs was not associated with survival or ORRs. CONCLUSION: PPIs were significantly associated with worse survival of patients with mUC treated with pembrolizumab, and H2RAs could be an alternative during administration. Both the oncological and gastrointestinal implications should be carefully considered when switching these antacids.

DOI： 10.1016/j.clgc.2024.102097

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Language：Japanese   Publisher：(一社)日本生殖医学会  

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This review presents the latest insights on robot-assisted kidney autotransplantation (RAKAT). RAKAT is a minimally invasive surgical procedure and represents a promising alternative to conventional laparoscopic nephrectomy followed by open kidney transplantation for the treatment of various complex urological and vascular conditions. RAKAT can be performed either extracorporeally or intracorporeally. Additionally, a single-port approach can be performed through one small incision without the need to reposition the patient. Of 86 patients undergoing RAKAT, 8 (9.3%) developed postoperative > Grade 2 Clavien-Dindo (CD) complications. Although the feasibility of RAKAT was established in 2014, the long-term efficacy and safety along with outcomes of this surgical approach are still being evaluated, and additional studies are needed. With improvements in the technology of RAKAT and as surgeons gain more experience, RAKAT should become increasingly used and further refined, thereby leading to improved surgical outcomes and improved patients' quality of life.

DOI： 10.1111/iju.15426

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OBJECTIVE: We aimed to develop and validate a preoperative nomogram that predicts low-grade, non-muscle invasive upper urinary tract urothelial carcinoma (LG-NMI UTUC), thereby aiding in the accurate selection of endoscopic management (EM) candidates. METHODS: This was a retrospective study that included 454 patients who underwent radical surgery (Cohort 1 and Cohort 2), and 26 patients who received EM (Cohort 3). Utilizing a multivariate logistic regression model, a nomogram predicting LG-NMI UTUC was developed based on data from Cohort 1. The nomogram's accuracy was compared with conventional European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) models. External validation was performed using Cohort 2 data, and the nomogram's prognostic value was evaluated via disease progression metrics in Cohort 3. RESULTS: In Cohort 1, multivariate analyses highlighted the absence of invasive disease on imaging (odds ratio [OR] 7.04; p = 0.011), absence of hydronephrosis (OR 2.06; p = 0.027), papillary architecture (OR 24.9; p < 0.001), and lack of high-grade urine cytology (OR 0.22; p < 0.001) as independent predictive factors for LG-NMI disease. The nomogram outperformed the two conventional models in predictive accuracy (0.869 vs. 0.759-0.821) and exhibited a higher net benefit in decision curve analysis. The model's clinical efficacy was corroborated in Cohort 2. Moreover, the nomogram stratified disease progression-free survival rates in Cohort 3. CONCLUSION: Our nomogram ( https://kmur.shinyapps.io/UTUC_URS/ ) accurately predicts LG-NMI UTUC, thereby identifying suitable candidates for EM. Additionally, the model serves as a useful tool for prognostic stratification in patients undergoing EM.

DOI： 10.1245/s10434-023-14514-z

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DOI： 10.1245/s10434-023-14635-5

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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Immune checkpoint inhibitor (ICI)-based combination therapies are the recommended first-line treatment for metastatic renal cell carcinoma (mRCC). However, no head-to-head phase-3 randomized controlled trials (RCTs) have compared the efficacy of different ICI-based combination therapies. Here, we compared the efficacy of various first-line ICI-based combination therapies in patients with mRCC using updated survival data from phase-3 RCTs. Three databases were searched in June 2023 for RCTs that analyzed oncologic outcomes in mRCC patients treated with ICI-based combination therapies as first-line treatment. A network meta-analysis compared outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and complete response (CR) rate. Subgroup analyses were based on the International mRCC Database Consortium risk classification. The treatment ranking analysis of the entire cohort showed that nivolumab + cabozantinib (81%) had the highest likelihood of improving OS, followed by nivolumab + ipilimumab (75%); pembrolizumab + lenvatinib had the highest likelihood of improving PFS (99%), ORR (97%), and CR (86%). These results remained valid even when the analysis was limited to patients with intermediate/poor risk, except that nivolumab + ipilimumab had the highest likelihood of achieving CR (100%). Further, OS benefits of ICI doublets were not inferior to those of ICI + tyrosine kinase inhibitor combinations. Recommendation of combination therapies with ICIs and/or tyrosine kinase inhibitors based on survival benefits and patient pretreatment risk classification will help advance personalized medicine for mRCC.

DOI： 10.1007/s00262-023-03621-1

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BACKGROUND/AIM: Patients with advanced renal cell carcinoma (aRCC) treated with immune-oncology (IO) drugs may need to discontinue the treatment when severe immune-related adverse events (irAE) occur; however, the impact of discontinuation on survival remains unknown. PATIENTS AND METHODS: This is a retrospective multicenter analysis using a database of 183 aRCC patients treated with first-line IO drugs combination. The patients were divided into two groups according to the necessity of discontinuation due to irAEs. The primary endpoint was overall survival (OS). Cox proportional hazard models determined the predictive factors on OS. RESULTS: Among a total of 135 patients who experienced irAE, 38 patients had to discontinue and 52 continued the treatment while treating irAE. When compared to patients who were able to continue treatment, discontinuation was associated with significantly higher rates of IO-IO doublet use, severe irAE (grade ≥3), steroid use, and the occurrence of immune-related pneumonitis (p=0.03, p<0.001, p<0.001, and p=0.02, respectively). The objective response rates were comparable between the two groups (discontinuation 55.6% vs. no discontinuation 56.0%, p=0.7). On univariate analysis, patients who discontinued had a significantly worse OS when compared to those who continued treatment (p=0.02). On the contrary, on multivariate analysis treatment discontinuation was not associated with poor OS (HR=1.1, p=0.9). CONCLUSION: Treatment discontinuation due to irAE was not associated with poor prognosis in aRCC patients treated with ICI-based combination therapy. Treatment discontinuation may be a reasonable treatment option for well-selected patients, specifically for those who experienced good treatment responses.

DOI： 10.21873/anticanres.16822

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Boron neutron capture therapy (BNCT) is a treatment method that focuses on improving the cure rate of patients with cancer who are difficult to treat using traditional clinical methods. By utilizing the high neutron absorption cross-section of boron, material rich in boron inside tumor cells can absorb neutrons and release high-energy ions, thereby destroying tumor cells. Owing to the short range of alpha particles, this method can precisely target tumor cells while minimizing the inflicted damage to the surrounding normal tissues, making it a potentially advantageous method for treating tumors. Globally, institutions have progressed in registered clinical trials of BNCT for multiple body parts. This review summarized the current achievements in registered clinical trials, Investigator-initiated clinical trials, aimed to integrate the latest clinical research literature on BNCT and to shed light on future study directions.

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Language：Japanese   Publisher：(NPO)日本血管外科学会  

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One-third of renal cell carcinomas (RCCs) without metastases develop metastatic disease after extirpative surgery for the primary tumors. The majority of metastatic RCC cases, along with treated primary lesions, involve limited lesions termed "oligo-recurrent" disease. The role of metastasis-directed therapy (MDT), including stereotactic body radiation therapy (SBRT) and metastasectomy, in the treatment of oligo-recurrent RCC has evolved. Although the surgical resection of all lesions alone can have a curative intent, SBRT is a valuable treatment option, especially for patients concurrently receiving systemic therapy. Contemporary immune checkpoint inhibitor (ICI) combination therapies remain central to the management of metastatic RCC. However, one objective of MDT is to delay the initiation of systemic therapies, thereby sparing patients from potentially unnecessary burdens. Undertaking MDT for cases showing progression under systemic therapies, known as "oligo-progression", can be complex in considering the treatment approach. Its efficacy may be diminished compared to patients with stable disease. SBRT combined with ICI can be a promising treatment for these cases because radiation therapy has been shown to affect the tumor microenvironment and areas beyond the irradiated sites. This may enhance the efficacy of ICIs, although their efficacy has only been demonstrated in clinical trials.

DOI： 10.3390/cancers15245873

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

PURPOSE: Radiological tumor burden has been reported to be prognostic in many malignancies in the immunotherapy era, yet whether it is prognostic in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab remains uninvestigated. We sought to assess the predictive and prognostic value of radiological tumor burden in patients with mUC. METHODS: We performed a retrospective analysis of 308 patients with mUC treated with pembrolizumab. Radiological tumor burden was represented by baseline tumor size (BTS) and baseline tumor number (BTN). Optimal cut-off value of BTS was determined as 50 mm using the Youden index (small BTS: n = 194, large BTS: n = 114). Overall (OS), cancer-specific (CSS), progression-free survival (PFS), and objective response rate (ORR) were compared. Non-linear associations between BTS and OS and CSS were evaluated using restricted cubic splines. RESULTS: Patients with large BTS were less likely to have undergone the surgical resection of the primary tumor (P = 0.01), and more likely to have liver metastasis (P < 0.001) and more metastatic lesions (P < 0.001). On multivariable analyses controlling for the effects of confounders (resection of primary tumor, metastatic site, number of metastases and lactate dehydrogenase level), large BTS and high BTN were independently associated with worse OS (HR 1.52; P = 0.015, and HR 1.69; P = 0.018, respectively) and CSS (HR 1.59; P = 0.01, and HR 1.66; P = 0.031, respectively), but not PFS. Restricted cubic splines revealed BTS was correlated with OS and CSS in linear relationships. Additionally, large BTS was significantly predictive of lower ORR and complete response rate on univariable analyses (P = 0.041 and P = 0.032, respectively), but its association disappeared on multivariable analyses. CONCLUSION: Radiological tumor burden has independent prognostic value with a linear relationship in pembrolizumab-treated patients with mUC and might help drive the earlier introduction of second-line pembrolizumab and/or switching to subsequent therapies.

DOI： 10.1016/j.urolonc.2023.11.009

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Language：Japanese   Publisher：GID(性同一性障害)学会  

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PURPOSE: This study aimed to investigate the effectiveness of the Geriatric Nutritional Risk Index (GNRI) in predicting the efficacy of first-line immune checkpoint inhibitor (ICI) combination therapy for metastatic or unresectable renal cell carcinoma (RCC) and associated patient prognosis. METHODS: A retrospective study was conducted using data from 19 institutions. The GNRI was calculated using body mass index and serum albumin level, and patients were classified into two groups using the GNRI values, with 98 set as the cutoff point. RESULTS: In all, 119 patients with clear cell RCC who received first-line drug therapy with ICIs were analyzed. Patients with GNRI ≥ 98 had significantly better overall survival (OS) (p = 0.008) and cancer-specific survival (CSS) (p = 0.001) rates than those with GNRI < 98; however, progression-free survival (PFS) did not differ significantly. Inverse probability of treatment weighting analysis showed that low GNRI scores were significantly associated with poor OS (p = 0.004) and CSS (p = 0.015). Multivariate analysis showed that the Karnofsky performance status (KPS) score was a better predictor of prognosis (OS; HR 5.17, p < 0.001, CSS; HR 4.82, p = 0.003) than GNRI (OS; HR 0.36, p = 0.066, CSS; HR 0.35, p = 0.072). In a subgroup analysis of patients with a good KPS and GNRI ≥ 98 vs < 98, the 2-year OS rates were 91.4% vs 66.9% (p = 0.068), 2-year CSS rates were 91.4% vs 70.1% (p = 0.073), and PFS rates were 39.7% vs 21.4 (p = 0.27), respectively. CONCLUSION: The prognostic efficiency of GNRI was inferior to that of the KPS score at the initiation of the first-line ICI combination therapy for clear cell RCC.

DOI： 10.1007/s12672-023-00816-x

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Adjuvant immune checkpoint inhibitor therapies have radically altered the treatment landscape for renal cell carcinoma and urothelial carcinoma. However, studies have reported negative data regarding adjuvant immune checkpoint inhibitor therapies. Thus, this study aimed to assess the role of adjuvant immune checkpoint inhibitor therapy for both renal cell carcinoma and urothelial carcinoma. A systematic review and network meta-analysis were conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases were searched for articles published as of February 2023. Studies were deemed eligible if they evaluated disease-free survival in patients with renal cell carcinoma and urothelial carcinoma receiving adjuvant immune checkpoint inhibitor therapy. Five studies met the inclusion criteria. In a network meta-analysis, pembrolizumab was shown to be the most effective regimen for patients with renal cell carcinoma, whereas nivolumab was found to be the most effective regimen for patients with urothelial carcinoma. Additionally, these results were consistently observed in a sub-analysis of the T stage. The present analysis provides findings that support the usefulness of adjuvant nivolumab therapy in urothelial carcinoma and adjuvant pembrolizumab therapy in renal cell carcinoma, in agreement with the currently available guidelines. However, the caveat is that the randomized controlled trials included in this analysis differed in important respects despite being similar in study design. Therefore, with these differences in mind, care needs to be taken when selecting patients for these immune checkpoint inhibitor therapies to maximize their benefits.

DOI： 10.1111/iju.15319

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BACKGROUND: Japanese men receiving apalutamide often experience skin-adverse events (AEs), possibly requiring treatment interruption or dose reduction. However, concerns have arisen regarding the impact of these adjustments on the efficacy of apalutamide. Our study evaluated the efficacy, safety, and persistence of apalutamide in men with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: We retrospectively reviewed the medical records of 108 men with mCSPC from 14 Japanese institutions. The primary outcomes were the efficacy of apalutamide: prostate-specific antigen (PSA) response (50%, 90% and < 0.2 decline) and progression to castration-resistant prostate cancer (CRPC). The secondary outcomes were the skin-AE and compliance of apalutamide. RESULTS: PSA50%, PSA90% and PSA < 0.2 declines were observed in 89.8, 84.3 and 65.7%, and the median time to CRPC progression was not reached. PSA < 0.2 decline and an initial full dose of apalutamide were significantly associated with a longer time to CRPC. The most common AE was skin-AE (50.9%), and there was no association between the occurrence of skin-AE and the time to CRPC (P = 0.72). The median apalutamide persistence was 29 months, which was longer in the initial full dose recipients than in the reduced dose recipients. The dosage is reduced in about 60% of patients within the first year of treatment in the initial full dose recipients. CONCLUSIONS: Our findings indicate the effectiveness of apalutamide in Japanese men with mCSPC, despite a substantial portion requiring dose reduction within a year among the initial full dose recipients.

DOI： 10.1093/jjco/hyad143

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Language：English   Publisher：(一社)日本癌治療学会  

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Language：English   Publisher：(一社)日本癌学会  

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Language：Japanese   Publisher：日本女性骨盤底医学会  

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Language：Japanese   Publisher：日本女性骨盤底医学会  

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Language：Japanese   Publisher：(公社)日本化学療法学会  

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DOI： 10.1111/iju.15221

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publisher：(一社)日本泌尿器科学会総会事務局  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Spandidos Publications  

Intravesical immunotherapy using bacillus Calmette-Guérin (BCG) is recommended for patients with intermediate- to high-risk non-muscle invasive bladder cancer. Bladder tuberculosis (TB) is a rare complication of BCG therapy. The present study describes the case of a 73-year-old man who underwent intravesical BCG therapy for urothelial carcinoma in situ of the bladder. Red patches around the resection scar were first detected 1 year and 5 months after BCG treatment; these findings gradually spread to encompass more of the bladder wall. Transurethral biopsy revealed a benign lesion, but the patient developed bilateral hydronephrosis and mild voiding dysfunction. The patient was eventually diagnosed with bladder TB by mycobacterial urine culture and TB-specific polymerase chain reaction (PCR). The patient was given multidrug therapy (isoniazid, rifampicin and ethambutol) and their bladder TB was completely cured; however, their voiding dysfunction and bilateral hydronephrosis did not fully improve. Bladder TB can occur long after intravesical BCG administration and cystoscopy findings consistent with inflammation can be the key to suspecting this condition. Acid-fast examination and PCR testing of a urine sample are necessary for early diagnosis.

DOI： 10.3892/mco.2022.2603

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OBJECTIVES: Technical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated. METHODS: Patients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low-grade on URS biopsy) versus same grade (high-grade on URS biopsy) for high-grade UTUC tumors on radical nephroureterectomy (RNU) specimens. RESULTS: This study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy-based low- and high-grade tumors, respectively. Median follow-up was 27.3 months. Patients with high-grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high-grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10-2.75; p = 0.018), cancer-specific (HR 1.94; 95% CI, 1.07-3.52; p = 0.03), and recurrence-free survival (HR 1.80; 95% CI, 1.13-2.87; p = 0.013). In subgroup analyses of patients with pT2-T4 and/or positive LN, its significant association retained. Furthermore, high-grade biopsy in clinically non-muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low-grade biopsy. CONCLUSIONS: High tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low-grade UTUC that becomes upgraded to high-grade might carry a better prognosis than high-grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high-grade on RNU.

DOI： 10.1111/iju.15061

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PURPOSE: To assess the prognostic value of sex for non-muscle-invasive/muscle-invasive bladder urothelial carcinoma (NMIBC/MIBC) treated with radical surgery. METHODS: The PubMed, Web of Science, and Scopus databases were searched in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Studies were deemed eligible if they involved the comparison of the overall, cancer-specific, progression, and recurrence-free survival of patients with NMIBC/MIBC. Formal sex-stratified meta-analyses of these outcomes were performed. RESULTS: Thirty-one studies, which included 32,525 patients with NMIBC, and 63 studies, which included 85,132 patients with MIBC, were eligible for review and meta-analysis. Female sex was associated with worse cancer-specific survival (pooled hazard ratio [HR], 1.21; 95% confidence interval [CI], 1.11-1.31) and overall survival (pooled HR, 1.02; 95% CI, 1.00-1.05) in patients with MIBC. In contrast, however, sex was not associated with cancer-specific survival (pooled HR, 1.01; 95% CI, 0.70-1.46), progression-free survival (pooled HR, 1.04; 95% CI, 0.88-1.24), and recurrence-free survival (pooled HR, 1.06; 95% CI, 0.98-1.16) in patients with NMIBC. CONCLUSIONS: Sex is associated with an increased risk of worse survival outcomes in patients with MIBC but not in those with NMIBC. Given the genetic and social differences between sexes, sex may represent a key factor in the clinical decision-making process.

DOI： 10.1007/s00345-022-04116-x

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BACKGROUND: Apalutamide-associated skin adverse events are more common in the Japanese than in the global population. However, limited clinical data have hampered further understanding. This real-world study investigated the clinical characteristics of skin adverse events in patients with advanced prostate cancer. METHODS: We retrospectively reviewed 119 patient records from 16 institutions in Japan. Skin adverse events were graded according to the Common Terminology Criteria for Adverse Events (v5.0). The incidence and characteristics of skin adverse events (along with the clinical risk factors for their incidence, worsening, and recurrence) were evaluated. RESULTS: Fifty-five patients (46.2%) experienced skin adverse events. The median times to the incidence and remission of skin adverse events were 62 and 30 days, respectively. Grade 3 skin adverse events were observed in 15 patients (12.6%). The median time from the first incidence to apalutamide interruption was significantly longer in patients with progression to grade 3 skin adverse events than in those without such a progression (8 vs. 0 days, p = 0.005). Skin adverse events were observed in 45.2% of patients who resumed apalutamide treatment (median treatment interruption time: 31.5 days). Sixteen patients (13.4%) permanently discontinued apalutamide due to skin adverse events. No significant clinical risk factors for the incidence, worsening and recurrence of apalutamide-associated skin adverse events were observed. CONCLUSIONS: Nearly half of the Japanese patients in this study experienced skin adverse events following apalutamide administration. The time to apalutamide discontinuation after the incidence of skin adverse events was positively correlated with the worsening of these events.

DOI： 10.1007/s10147-022-02183-z

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INTRODUCTION: Although upper tract urothelial carcinoma (UTUC) is more common in the elderly, outcomes of neoadjuvant chemotherapy (NAC) in this population have never been explored. The objective of the study was to assess the impact of NAC on pathologic response and oncological outcomes stratified by age. PATIENTS AND METHODS: This multicenter study included 164 patients treated with NAC and radical nephroureterectomy (RNU) for clinically non-metastatic, high-risk UTUC. The cohort was stratified into two groups according to median age. Patients received either cisplatin-based or non-cisplatin-based chemotherapies. Pathologic responses were defined as pathologic objective response (pOR; ≤ ypT1N0) and pathologic complete response (pCR; ypT0N0). Univariable and multivariable logistic and Cox regression analyses were performed to identify predictors for pathologic response and survival outcomes. RESULTS: The cohorts' median age was 68 years with the elderly group (> 68 years) comprising 74 patients. Neoadjuvant chemotherapy included methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) in 66 (40%), gemcitabine cisplatin (GC) in 66 (40%) and non-cisplatin chemotherapy in 32 patients (20%). Younger patients received more often MVAC (50% vs. 28%) while elderly received more GC (34% vs. 47%) or non-cisplatin chemotherapy (16% vs. 24%) (P = .02). Overall, pOR and pCR were similar across age groups (52% vs. 47%; P = .5 and 10% vs. 8%; P = .7). While GC and non-cisplatin chemotherapy showed a lower pCR of 5% and 3%, respectively, MVAC revealed a pCR of 17% (P = .03) and was independently associated with a higher pCR (OR 4.31; P = .03). Kaplan-Meier analysis showed no difference in recurrence-free and cancer-specific survival, whereas a lower rate was seen in overall survival for the elderly. CONCLUSION: Elderly patients with high-risk UTUC eligible for cisplatin-based NAC prior to RNU may benefit from this multimodal therapy equally as their younger counterparts. Cisplatin-ineligible patients undergoing non-cisplatin-based NAC appeared to have lower response rates and should be considered for immediate RNU.

DOI： 10.1016/j.clgc.2022.01.004

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Aim: We aimed to assess the prognostic value of pretreatment hematological biomarkers in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (ICIs). Methods: PubMed, Web of Science and Scopus databases were searched for articles according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Results: Fifteen studies comprising 1530 patients were eligible for meta-analysis. High levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein and lactate dehydrogenase were significantly associated with worse progression-free survival. High NLR and PLR were significantly associated with worse overall survival. Conclusion: High pretreatment NLR and PLR appear to be hematological prognostic factors of progression and overall mortality in mRCC patients treated with ICIs. These findings might help in the design of correlative biomarker studies to guide the clinical decision-making in the immune checkpoint inhibitor era.

DOI： 10.2217/imt-2021-0207

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DOI： 10.1245/s10434-022-11742-7

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Background: Radical cystectomy (RC) is indicated in primary or secondary muscle-invasive bladder cancer (primMIBC, secMIBC) and in primary or recurrent high- or very high-risk non-muscle-invasive bladder cancer (primHR-NMIBC, recHR-NMIBC). The optimal timing for RC along the disease spectrum of nonmetastatic urothelial carcinoma remains unclear. Objective: To compare outcomes after RC between patients with primHR-NMIBC, recHR-NMIBC, primMIBC, and secMIBC. Design setting and participants: This retrospective, multicenter study included patients with clinically nonmetastatic bladder cancer (BC) treated with RC. Outcome measurements and statistical analysis: We assessed oncological outcomes for patients who underwent RC according to the natural history of their BC. primHR-NMIBC and primMIBC were defined as no prior history of BC, and recHR-NMIBC and secMIBC as previously treated NMIBC that recurred or progressed to MIBC, respectively. Log-rank analysis was used to compare survival outcomes, and univariable and multivariable Cox and logistic regression analyses were used to identify predictors for survival. Results and limitations: Among the 908 patients included, 211 (23%) had primHR-NMIBC, 125 (14%) had recHR-NMIBC, 404 (44%) had primMIBC, and 168 (19%) had secMIBC. Lymph node involvement and pathological upstaging were more frequent in the secMIBC group than in the other groups (p < 0.001). The median follow-up was 37 mo. The 5-year recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were 77.9%, 83.2%, and 72.7% in primHR-NMIBC, 60.0%, 59%, and 48.9% in recHR-NMIBC, 60.9%, 64.5%, and 54.8% in primMIBC, and 41.3%, 46.5%, and 39% in secMIBC, respectively, with statistically significant differences across all survival outcomes except between recHR-NMIBC and primMIBC. On multivariable Cox regression, recHR-NMIBC was independently associated with shorter RFS (hazard ratio [HR] 1.64; p = 0.03), CSS (HR 1.79; p = 0.01), and OS (HR 1.45; p = 0.03), and secMIBC was associated with shorter CSS (HR 1.77; p = 0.01) and OS (HR 1.57; p = 0.006). Limitations include the biases inherent to the retrospective study design. Conclusions: Patients with recHR-NMIBC and primHR-MIBC had similar survival outcomes, while those with sec-MIBC had the worst outcomes. Therefore, early radical intervention may be indicated in selected patients, and potentially neoadjuvant systemic therapies in some patients with recHR-NMIBC. Patient summary: We compared cancer outcomes in different bladder cancer scenarios in a large, multinational series of patients who underwent removal of the bladder with curative intent. We found that patients who experienced recurrence of non-muscle-invasive bladder cancer (NMIBC) had similar survival outcomes to those with initial muscle-invasive bladder cancer (MIBC), while patients who experienced progression of NMIBC to MIBC had the worst outcomes. Selected patients with non-muscle-invasive disease may benefit from early radical surgery or from perioperative chemotherapy or immunotherapy.

DOI： 10.1016/j.euros.2022.02.011

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OBJECTIVES: Insulin-like growth factor-I and its binding proteins are involved in cancer development, progression, and metastasis. In urothelial carcinoma, the impact of this pathway is still poorly investigated. The present large cohort study aimed to evaluate the association of preoperative circulating levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 on outcomes after radical cystectomy. METHODS: A retrospective cohort study of the plasma specimens from 1036 consecutive urothelial carcinoma patients who were treated with radical cystectomy. The primary and secondary outcomes were adverse histopathological features and survival outcomes. Binominal logistic regression and multivariable Cox regression analyses were performed to assess the association of plasma levels of insulin-like growth factor-I, insulin-like growth factor-I binding protein-2 and -3 with outcomes. RESULTS: On multivariable analysis adjusting for the effects of preoperative variables, lower insulin-like growth factor-I binding protein-2 levels were associated with an increased risk of lymph node metastasis and (any non-organ confined disease) any non-organ confined disease. Insulin-like growth factor-I binding protein-3 levels were also inversely independently associated with lymph node metastasis. Receiver operating characteristic curve analysis showed that the addition of insulin-like growth factor-I binding proteins biomarkers to a reference model significantly improved the discriminating ability for the prediction of lymph node metastasis (+10.0%, P < 0.001). On multivariable Cox regression models, lower levels of both insulin-like growth factor-I binding protein-2 and -3 plasma levels were associated with recurrence-free survival, cancer-specific survival, and overall survival. insulin-like growth factor-I binding protein-2 and -3 levels and improved the discrimination of a standard reference model for the prediction of recurrence-free survival, cancer-specific survival, and overall survival (+4.9%, 4.9%, 2.3%, respectively). CONCLUSIONS: Preoperative insulin-like growth factor-I binding protein-2 and -3 are significantly associated with features of biologically and clinically aggressive urothelial carcinoma. These biomarkers improved prognostic urothelial carcinoma models.

DOI： 10.1111/iju.14869

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Background and Objective: Identifying evidence-based and measurable quality-of-care indicators is crucial for optimal management of patients requiring radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC). RC with urinary diversion and lymphadenectomy is the standard treatment for patients with MIBC. Preoperatively, neoadjuvant chemotherapy (NAC) with cisplatin-based combinations improves survival outcomes and is the recommended standard of care for eligible patients. Intraoperatively, lymph node dissection (LND) by, at least, following a standard pelvic lymph node template improves overall- and recurrence-free survival and allows for accurate tumour staging. Avoiding positive soft tissue surgical margins (STSM) should be a main target intraoperatively since they are almost universally associated with mortality. Implementing enhanced recovery after surgery (ERAS) programs can reduce lengths of hospital stay (LOS) and postoperative complication rates without increasing readmission rates after RC. Moreover, several studies have shown that smoking negatively affects local and systemic treatment outcomes in bladder cancer (BC) patients. Therefore, smoking cessation counselling for smokers should be an essential part of bladder cancer management regardless of the disease state. Methods: We performed a comprehensive, non-systematic review of the latest literature to define indicators representing the best evidence available for optimal care of MIBC patients treated with RC. Key Content and Findings: In this review, we propose five major quality indicators that are easily implementable for optimized management of MIBC patients treated with RC, including: usage of cisplatin-based NAC in eligible patients, ensurance of negative STSM, performance of (at least) a standard pelvic template LND, implementation of ERAS strategies, and professional smoking cessation counselling. Conclusions: Optimal management of MIBC needs to be framed by evidence-based, reproducible, and measurable quality indicators that will allow for guidance and comparative effectiveness assessment of clinical practices; adherence to them is likely to improve patients' prognoses by a tensible margin. For the treatment of MIBC patients with RC, we identified five essential quality indicators. Keywords: Assessment; bladder cancer (BC); muscle-invasive bladder cancer (MIBC); cystectomy; radical cystectomy (RC); quality.

DOI： 10.21037/tcr-21-1116

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PURPOSE: This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP). METHODS: We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term (<6 months) or long-term (≥6 months) neoadjuvant ADT before RP. RESULTS: Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93-1.51, p = 0.17), metastasis (OR 0.73, 95% CI, 0.45-1.19, p = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43-1.21, p = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39-0.80, p = 0.001, and OR 1.48, 95% CI 1.10-1.99, p = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00-3.93). CONCLUSION: Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.

DOI： 10.1080/21681805.2022.2034941

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BACKGROUND: Angiogenesis-related marker vascular cell adhesion molecule-1 (VCAM-1) has been shown to be elevated in urothelial carcinoma of the bladder (UCB), but its predictive/prognostic role has not been determined. Thus, this study aimed to investigate the predictive/prognostic role of VCAM-1 for patients who have UCB treated with radical cystectomy (RC). METHODS: The study enrolled 1036 patients with clinically non-metastatic advanced UCB who underwent RC, and plasma VCAM-1 was evaluated preoperatively. The correlation of plasma VCAM-1 with pathologic and survival outcomes was assessed using binominal logistic regression and multivariable Cox regression analyses. Discrimination was assessed using the area under the curve and concordance indices. The clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS: Preoperative VCAM-1 was significantly elevated in patients with adverse pathologic features. Higher VCAM-1 levels were independently associated with increased risk of lymph-node-metastasis (LNM), ≥pT3 disease, and non-organ-confined disease (NOCD (p < 0.001 for each). Preoperative plasma VCAM-1 was independently associated with recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) in pre- and postoperative multivariable models. Adding VCAM-1 to these predictive models improved their discriminatory ability to predict all outcomes by a significant margin. In the DCA, VCAM-1 addition to the reference models for prediction of LNM, NOCD, RFS, and CSS resulted in relevant improvement. CONCLUSIONS: Elevated plasma VCAM-1 was associated with biologically and clinically aggressive UCB disease features. After validation, preoperative VCAM-1 may serve as a biomarker to help identify patients likely to benefit from intensified/multimodal therapy. In addition, VCAM-1 improved the discriminatory power of predictive/prognostic models and can be used to refine personalized clinical decision-making.

DOI： 10.1245/s10434-022-11575-4

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BACKGROUND: Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. We aimed to assess the role of ICI-combination therapy based on CN status. METHODS: Multiple databases were searched for articles published until June 2021. Studies comparing overall and/or progression-free survival (OS/PFS) in mRCC patients treated with ICI combination-therapy were deemed eligible. RESULTS: Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59-0.77/HR, 0.57; 95% CI, 0.44-0.74, respectively; both P < 0.001), and in those who had not (HR, 0.69; 95% CI, 0.57-0.85/HR, 0.63; 95% CI, 0.52-0.77, respectively; both P < 0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy's treatment effect did not differ substantially with or without CN. In network meta-analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN. CONCLUSION: The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. As each ICI combination regimen varied widely in its effect in patients undergoing and not undergoing CN, CN may contribute to better treatment decision-making for ICI-combination therapy recipients.

DOI： 10.1016/j.intimp.2022.108720

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CONTEXT: Platinum-based combination chemotherapy is the standard treatment for advanced or metastatic urothelial carcinoma (AMUC). However, data comparing the efficacy of different platinum agents are limited. OBJECTIVE: This review aimed to assess the efficacy of carboplatin as a first-line treatment for AMUC using phase 3 randomized trial data. EVIDENCE ACQUISITION: Multiple databases were searched for articles published until August 2021. Studies that compared overall survival (OS), complete response (CR), and objective response rates (ORRs) in chemotherapy-eligible patients with AMUC were deemed eligible. EVIDENCE SYNTHESIS: Four studies were included. Compared with immune checkpoint inhibitor (ICI) monotherapy, neither cisplatin- nor carboplatin-based chemotherapy was associated with significant OS (hazard ratio [HR]: 0.97, 95% confidence interval [CI]: 0.85-1.11, p = 0.64 and HR: 0.90, 95% CI: 0.78-1.04, p = 0.16, respectively) and CR (odds ratio [OR]: 1.16, 95% CI: 0.70-1.92, p = 0.57 and OR: 0.89, 95% CI: 0.52-1.53, p = 0.67, respectively benefits, while both were associated with a favorable ORR (OR: 0.54, 95% CI: 0.40-0.74, p < 0.001 and OR: 0.58, 95% CI: 0.42-0.80, p < 0.001, respectively). A network meta-analysis (NMA)-based indirect comparison between carboplatin and cisplatin revealed that while cisplatin was slightly better than carboplatin in terms of OS, CR, and ORR, no significant difference was noted. CONCLUSIONS: Cisplatin- and carboplatin-based chemotherapies offer similar OS/CR benefits to ICI monotherapy and elicit a greater ORR than ICI monotherapy. Moreover, our NMA demonstrated that both cisplatin- and carboplatin-based chemotherapy have a similar efficacy in terms of OS, CR, and ORR. Given that carboplatin-based chemotherapy is shown to be more effective in contemporary series than in historical controls, it is strongly recommended that carboplatin be re-examined for its value in the era of ICIs and beyond. PATIENT SUMMARY: Cisplatin- as well as carboplatin-based chemotherapy is as effective as immune checkpoint inhibitors in terms of survival and eliciting a positive response. It is currently believed that cisplatin provides greater benefits than carboplatin; this requires re-evaluation.

DOI： 10.1016/j.euf.2022.02.007

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Language：Japanese   Publisher：(一社)日本臨床腎移植学会  

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PURPOSE: The HGF/MET pathway is involved in cell motility, angiogenesis, proliferation, and cancer invasion. We assessed the clinical utility of plasma HGF level as a prognostic biomarker in patients with MIBC. METHODS: We retrospectively analyzed 565 patients with MIBC who underwent radical cystectomy. Logistic regression and Cox regression models were used, and predictive accuracies were estimated using the area under the curve and concordance index. To estimate the clinical utility of HGF, DCA and MCID were applied. RESULTS: Plasma HGF level was significantly higher in patients with advanced pathologic stage and LN metastasis (p = 0.01 and p < 0.001, respectively). Higher HGF levels were associated with an increased risk of harboring LN metastasis and non-organ-confined disease (OR1.21, 95%CI 1.12-1.32, p < 0.001, and OR1.35, 95%CI 1.23-1.48, p < 0.001, respectively) on multivariable analyses; the addition of HGF improved the predictive accuracies of a standard preoperative model (+ 7%, p < 0.001 and + 8%, p < 0.001, respectively). According to the DCA and MCID, half of the patients had a net benefit by including HGF, but the absolute magnitude remained limited. In pre- and postoperative predictive models, a higher HGF level was significant prognosticator of worse RFS, OS, and CSS; in the preoperative model, the addition of HGF improved accuracies by 6% and 5% for RFS and CSS, respectively. CONCLUSION: Preoperative HGF identified MIBC patients who harbored features of clinically and biologically aggressive disease. Plasma HGF could serve, as part of a panel, as a biomarker to aid in preoperative treatment planning regarding intensity of treatment in patients with clinical MIBC.

DOI： 10.1007/s00432-021-03887-x

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Elevated preoperative plasma level of endoglin has been associated with worse oncologic outcomes in various malignancies. The present large-scale study aimed to determine the predictive and prognostic values of preoperative endoglin with regard to clinicopathologic and survival outcomes in patients treated with radical cystectomy (RC) for nonmetastatic urothelial carcinoma of the bladder (UCB). We prospectively collected preoperative blood samples from 1036 consecutive patients treated with RC for UCB. Logistic and Cox regression analyses were undertaken to assess the correlation of endoglin levels with pathologic and survival outcomes, respectively. The AUC and C-index were used to assess the discrimination. Patients with adverse pathologic features had significantly higher median preoperative endoglin plasma levels than their counterparts. Higher preoperative endoglin level was independently associated with an increased risk for lymph node metastasis, ≥pT3 disease, and nonorgan confined disease (NOCD; all p < 0.001). Plasma endoglin level was also independently associated with cancer-specific and overall survival in both pre- and postoperative models (all p < 0.05), as well as with recurrence-free survival (RFS) in the preoperative model (p < 0.001). The addition of endoglin to the preoperative standard model improved its discrimination for prediction of lymph node metastasis, ≥pT3 disease, NOCD, and RFS (differential increases in C-indices: 10%, 5%, 5.8%, and 4%, respectively). Preoperative plasma endoglin is associated with features of biologically and clinically aggressive UCB as well as survival outcomes. Therefore, it seems to hold the potential of identifying UCB patients who may benefit from intensified therapy in addition to RC such as extended lymphadenectomy or/and preoperative systemic therapy.

DOI： 10.1002/mc.23355

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Language：Japanese   Publisher：(一社)西日本泌尿器科学会  

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Laparoscopic fenestration of a postrenal transplant lymphocele is associated with a risk of renal hilar vessel and ureteral injury. Consequently, determination of the incision line is difficult. We describe a case of a 73-year-old man with postrenal transplant lymphocele who underwent a laparoscopic fenestration. We report a surgical video containing a new technique of laparoscopic fenestration using a fluorescent ureteral catheter in combination with a flexible ureteroscope. The combination of a fluorescent ureteral catheter and flexible ureteroscope during surgery enabled us to determine the incision line safely and accurately. Intraoperative real-time visualization of the lymphocele and ureter using a fluorescent ureteral catheter and a flexible ureteroscope is safer than conventional methods for laparoscopic fenestration. To the best of our knowledge, this is the first report of this novel technique.

DOI： 10.1155/2022/9948425

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Objective: To present an update of the available literature on external beam radiation therapy (EBRT) with or without brachytherapy (BT) compared to radical prostatectomy (RP) for patients with high-risk localised prostate cancer (PCa). Methods: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes in patients with high-risk PCa who received EBRT with or without BT compared to RP as the first-line therapy with curative intent. We queried PubMed and Web of Science database in January 2021. Moreover, we used random or fixed-effects meta-analytical models in the presence or absence of heterogeneity per the I2 statistic, respectively. We performed six meta-analyses for overall survival (OS) and cancer-specific survival (CSS). Results: A total of 27 studies were selected with 23 studies being eligible for both OS and CSS. EBRT alone had a significantly worse OS and CSS compared to RP (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.16-1.65; and HR 1.55, 95% CI 1.25-1.93). However, there was no difference in OS (HR 1.1, 95% CI 0.76-1.34) and CSS (HR 0.69, 95% CI 0.45-1.06) between EBRT plus BT compared to RP. Conclusion: While cancer control affected by EBRT alone seems inferior to RP in patients with high-risk PCa, BT additive to EBRT was not different from RP. These data support the need for BT in addition to EBRT as part of multimodal RT for high-risk PCa.Abbreviations: ADT: androgen-deprivation therapy; BT: brachytherapy; CSS: cancer-specific survival; HR: hazard ratio; MFS, metastatic-free survival; MOOSE: Meta-analyses of Observational Studies in Epidemiology; OR: odds ratio; OS: overall survival; PCa: prostate cancer; RR: relative risk; RP: radical prostatectomy; RCT: randomised controlled trials; (EB)RT: (external beam) radiation therapy.

DOI： 10.1080/2090598X.2022.2026010

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Intraoperative physiologic changes related to the steep Trendelenburg position have been investigated with the widespread adoption of robot-assisted pelvic surgery (RAPS). However, the impact of the steep Trendelenburg position on postoperative complications remains unclear. We conducted a meta-analysis to compare RAPS to laparoscopic/open pelvic surgery with regards to the rates of venous thromboembolism (VTE), cardiac, and cerebrovascular complications. Meta-regression was performed to evaluate the influence of confounding risk factors. Ten randomized controlled trials (RCTs) and 47 non-randomized controlled studies (NRSs), with a total of 380,125 patients, were included. Although RAPS was associated with a decreased risk of VTE and cardiac complications compared to laparoscopic/open pelvic surgery in NRSs [risk ratio (RR), 0.59; 95% CI 0.51-0.72, p < 0.001 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively], these differences were not confirmed in RCTs (RR 0.92; 95% CI 0.52-1.62, p = 0.77 and RR 0.93; 95% CI 0.58-1.50, p = 0.78, respectively). In subgroup analyses of laparoscopic surgery, there was no significant difference in the risk of VTE and cardiac complications in both RCTs and NRSs. In the meta-regression, none of the risk factors were found to be associated with heterogeneity. Furthermore, no significant difference was observed in cerebrovascular complications between RAPS and laparoscopic/open pelvic surgery. Our meta-analysis suggests that the steep Trendelenburg position does not seem to affect postoperative complications and, therefore, can be considered safe with regard to the risk of VTE, cardiac, and cerebrovascular complications. However, proper individualized preventive measures should still be implemented during all surgeries including RAPS to warrant patient safety.

DOI： 10.1007/s11701-021-01361-x

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OBJECTIVE: To determine the oncologic and toxicity outcomes of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) compared to adjuvant chemotherapy in patients treated with radical surgery for urothelial carcinoma (UC). METHODS: We used the Bayesian approach in the network meta-analysis of different therapy regimens compared to observation or placebo. RESULTS: Nine studies comprised of 2,444 patients met the eligibility criteria. In bladder UC, chemotherapy, atezolizumab, and nivolumab did not improve disease progression compared to observation/placebo. In upper tract UC (UTUC), chemotherapy was significantly associated with a lower likelihood of disease progression compared to observation/placebo, while atezolizumab and nivolumab were not. Based on the analysis of the treatment ranking, adjuvant chemotherapy appeared as the best treatment approach in both bladder UC and UTUC. The risk of adverse events with ICIs was comparable to that of observation/placebo. CONCLUSION: Our analysis suggests a superior oncologic benefit to adjuvant chemotherapy over ICIs in patients treated with radical surgery for both bladder UC and UTUC.

DOI： 10.1016/j.critrevonc.2021.103570

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PURPOSE: We assessed the prognostic value of systemic immune-inflammation index (SII) to refine risk stratification of the heterogeneous spectrum of patients with non-muscle-invasive bladder cancer (NMIBC) METHODS: In this multi-institutional cohort, preoperative blood-based SII was retrospectively assessed in 1117 patients with NMIBC who underwent transurethral resection of bladder (TURB) between 1996 and 2007. The optimal cut-off value of SII was determined as 580 using the best Youden index. Cox regression analyses were performed. The concordance index (C-index) and decision curve analysis (DCA) were used to assess the discrimination of the predictive models. RESULTS: Overall, 309 (28%) patients had high SII. On multivariable analyses, high SII was significantly associated with worse PFS (hazard ratio [HR] 1.84; 95% confidence interval [CI] 1.23-2.77; P = 0.003) and CSS (HR 2.53; 95% CI 1.42-4.48; P = 0.001). Subgroup analyses, according to the European Association of Urology guidelines, demonstrated the main prognostic impact of high SII, with regards to PFS (HR 3.39; 95%CI 1.57-7.31; P = 0.002) and CSS (HR 4.93; 95% CI 1.70-14.3; P = 0.005), in patients with intermediate-risk group; addition of SII to the standard predictive model improved its discrimination ability both on C-index (6% and 12%, respectively) and DCA. In exploratory intergroup analyses of patients with intermediate-risk, the improved discrimination ability was retained the prediction of PFS and CSS. CONCLUSION: Preoperative SII seems to identify NMIBC patients who have a worse disease and prognosis. Such easily available and cheap standard biomarkers may help refine the decision-making process regarding adjuvant treatment in patients with intermediate-risk NMIBC.

DOI： 10.1007/s00345-021-03740-3

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We aimed to conduct a systematic review and meta-analysis assessing the incidence and risk factors of urethral recurrence (UR) as well as summarizing data on survival outcomes in patients with UR after radical cystectomy (RC) for bladder cancer. The MEDLINE and EMBASE databases were searched in February 2021 for studies of patients with UR after RC. Incidence and risk factors of UR were the primary endpoints. The secondary endpoint was survival outcomes in patients who experienced UR. Twenty-one studies, comprising 9,435 patients, were included in the quantitative synthesis. Orthotopic neobladder (ONB) diversion was associated with a decreased probability of UR compared to non-ONB (pooled OR: 0.44, 95% CI: 0.31-0.61, P < 0.001) and male patients had a significantly higher risk of UR compared to female patients (pooled OR: 3.16, 95% CI: 1.83-5.47, P < 0.001). Among risk factors, prostatic urethral or prostatic stromal involvement (pooled HR: 5.44, 95% CI: 3.58-8.26, P < 0.001; pooled HR: 5.90, 95% CI: 1.82-19.17, P = 0.003, respectively) and tumor multifocality (pooled HR: 2.97, 95% CI: 2.05-4.29, P < 0.001) were associated with worse urethral recurrence-free survival. Neither tumor stage (P = 0.63) nor CIS (P = 0.72) were associated with worse urethral recurrence-free survival. Patients with UR had a 5-year CSS that varied from 47% to 63% and an OS - from 40% to 74%; UR did not appear to be related to worse survival outcomes. Male patients treated with non-ONB diversion as well as patients with prostatic involvement and tumor multifocality seem to be at the highest risk of UR after RC. Risk-adjusted standardized surveillance protocols should be developed into clinical practice after RC.

DOI： 10.1016/j.urolonc.2021.06.009

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Optimal neoadjuvant hormone therapy (NHT) for reducing prostate cancer (PC) patients' prostate volume pre-brachytherapy is controversial. We evaluated the differential impact of neoadjuvant gonadotropin-releasing hormone (GnRH) antagonist versus agonist on post-brachytherapy testosterone recovery in 112 patients treated pre-brachytherapy with NHT (GnRH antagonist, n=32; GnRH agonists, n=80) (Jan. 2007-June 2019). We assessed the effects of patient characteristics and a GnRH analogue on testosterone recovery with logistic regression and a propensity score analysis (PSA). There was no significant difference in the rate of testosterone recovery to normal levels (> 300 ng/dL) between the GnRH antagonist and agonists (p=0.07). The GnRH agonists induced a significantly more rapid testosterone recovery rate at 3 months post-brachytherapy versus the GnRH antagonist (p<0.0001); there was no difference in testosterone recovery at 12 months between the GnRH antagonist/agonists (p=0.8). In the multivariate analysis, no actor was associated with testosterone recovery. In the PSA, older age and higher body mass index (BMI) were significantly associated with longer testosterone recovery. Post-brachytherapy testosterone recovery was quicker with the neoadjuvant GnRH agonists than the antagonist, and the testosterone recovery rate was significantly associated with older age and higher BMI. Long-term follow-ups are needed to determine any differential effects of GnRH analogues on the quality of life of brachytherapy-treated PC patients.

DOI： 10.18926/AMO/62810

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J-GLOBAL

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Language：Japanese   Publisher：(一社)日本泌尿器科学会総会事務局  

J-GLOBAL

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PURPOSE: To investigate the predictive and prognostic value of the preoperative systemic immune-inflammation index (SII) in patients undergoing radical cystectomy (RC) for clinically non-metastatic urothelial cancer of the bladder (UCB). METHODS: Overall, 4,335 patients were included, and the cohort was stratified in two groups according to SII using an optimal cut-off determined by the Youden index. Uni- and multivariable logistic and Cox regression analyses were performed, and the discriminatory ability by adding SII to a reference model based on available clinicopathologic variables was assessed by area under receiver operating characteristics curves (AUC) and concordance-indices. The additional clinical net-benefit was assessed using decision curve analysis (DCA). RESULTS: High SII was observed in 1879 (43%) patients. On multivariable preoperative logistic regression, high SII was associated with lymph node involvement (LNI; P = 0.004), pT3/4 disease (P <0.001), and non-organ confined disease (NOCD; P <0.001) with improvement of AUCs for predicting LNI (P = 0.01) and pT3/4 disease (P = 0.01). On multivariable Cox regression including preoperative available clinicopathologic values, high SII was associated with recurrence-free survival (P = 0.028), cancer-specific survival (P = 0.005), and overall survival (P = 0.006), without improvement of concordance-indices. On DCAs, the inclusion of SII did not meaningfully improve the net-benefit for clinical decision-making in all models. CONCLUSION: High preoperative SII is independently associated with pathologic features of aggressive disease and worse survival outcomes. However, it did not improve the discriminatory margin of a prediction model beyond established clinicopathologic features and failed to add clinical benefit for decision making. The implementation of SII as a part of a panel of biomarkers in future studies might improve decision-making.

DOI： 10.1016/j.urolonc.2021.10.006

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Introduction: It has been hypothesized that transurethral en bloc (TUEB) of bladder tumor offers benefits over conventional transurethral resection of bladder tumor (cTURBT). This study aimed to compare disease outcomes of TUEB and cTURBT with focus on the different energy sources. Methods: A systematic search was performed using PubMed and Web of Science databases in June 2021. Studies that compared the pathological (detrusor muscle presence), oncological (recurrence rates) efficacy, and safety (serious adverse events [SAEs]) of TUEB and cTURBT were included. Random- and fixed-effects meta-analytic models and Bayesian approach in the network meta-analysis was used. Results: Seven randomized clinical trials (RCTs) and seven non-RCTs (NRCT), with a total of 2092 patients. The pooled 3- and 12-month recurrence risk ratios (RR) of five and four NRCTs were 0.46 (95% CI 0.29-0.73) and 0.56 (95% CI 0.33-0.96), respectively. The pooled 3- and 12-month recurrence RRs of four and seven RCTs were 0.57 (95% CI 0.25-1.27) and 0.89 (95% CI 0.69-1.15), respectively. The pooled RR for SAEs such as prolonged hematuria and bladder perforation of seven RCTs was 0.16 (95% CI 0.06-0.41) in benefit of TUEB. Seven RCTs (n = 1077) met our eligibility criteria for network meta-analysis. There was no difference in 12-month recurrence rates between hybridknife, laser, and bipolar TUEB compared with cTURBT. Contrary, laser TUEB was significantly associated with lower SAEs compared with cTURBT. Surface under the cumulative ranking curve ranking analyses showed with high certainty that laser TUEB was the best treatment option to access all endpoints. Conclusion: While NRCTs suggested a recurrence-free benefit to TUEB compared with cTURBT, RCTs failed to confirm this. Conversely, SAEs were consistently and clinically significantly better for TUEB. Network meta-analyses suggested laser TUEB has the best performance compared with other energy sources. These early findings need to be confirmed and expanded upon.

DOI： 10.1089/end.2021.0688

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Pembrolizumab is the standard for the first and second lines in treating metastatic urothelial carcinoma (UC). This systematic review and meta-analysis aimed to assess the value of pretreatment clinical characteristics and hematologic biomarkers for prognosticating response to pembrolizumab in patients with metastatic UC. PUBMED®, Web of Science™, and Scopus® databases were searched for articles published before May 2021 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they evaluated overall survival (OS) in patients with metastatic urothelial carcinoma treated with pembrolizumab and pretreatment clinical characteristics or laboratory examination. Overall, 13 studies comprising 1311 patients were eligible for the meta-analysis. Several pretreatment patients' demographics and hematologic biomarkers were significantly associated with worse OS as follows: Eastern Cooperative Oncology Group Performance Status (ECOG-PS) ≥ 2 (Pooled hazard ratio [HR]: 3.24, 95% confidence interval [CI] 2.57-4.09), presence of visceral metastasis (Pooled HR: 1.84, 95% CI 1.42-2.38), presence of liver metastasis (Pooled HR: 4.23, 95% CI 2.18-8.20), higher neutrophil-lymphocyte ratio (NLR) (Pooled HR: 1.29, 95% CI 1.07-1.55) and, higher c-reactive protein (CRP) (Pooled HR: 2.49, 95% CI 1.52-4.07). Metastatic UC patients with poor PS, liver metastasis, higher pretreatment NLR and/or CRP have a worse survival despite pembrolizumab treatment. These findings might help to guide the prognostic tools for clinical decision-making; however, they should be interpreted carefully, owing to limitations regarding the retrospective nature of primary data.

DOI： 10.1007/s10147-021-02061-0

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PURPOSE: To evaluate the predictive and prognostic value of the Systemic Immune-inflammation Index (SII) in a large cohort of patients treated with radical prostatectomy (RP) for clinically non-metastatic prostate cancer (PCa). METHODS: We retrospectively analyzed our multicenter database comprising 6,039 consecutive patients. The optimal preoperative SII cut-off value was assessed with the Youden index calculated on a time-dependent receiver operating characteristic (ROC) curve. Logistic regression and Cox regression analyses were used to investigate the association of SII with pathologic features and biochemical recurrence (BCR), respectively. The discriminatory ability of the models was evaluated by calculating the concordance-indices (C-Index). The clinical benefit of the implementation of SII in clinical decision making was assessed using decision curve analysis (DCA). RESULTS: Patients with high preoperative SII (≥ 620) were more likely to have adverse clinicopathologic features. On multivariable logistic regression analysis, high preoperative SII was independently associated with extracapsular extension (odds ratio [OR] 1.16, P = 0.041), non-organ confined disease (OR 1.18, P = 0.022), and upgrading at RP (OR 1.23, P < 0.001). We built two Cox regression models including preoperative and postoperative variables. In the preoperative multivariable model, high preoperative SII was associated with BCR (hazard ratio [HR] 1.34, 95% CI 1.15-1.55, P < 0.001). In the postoperative multivariable model, SII was not associated with BCR (P = 0.078). The addition of SII to established models did not improve their discriminatory ability nor did it increase the clinical net benefit on DCA. CONCLUSION: In men treated with RP for clinically nonmetastatic PCa, high preoperative SII was statistically associated with an increased risk of adverse pathologic features at RP as well as BCR. However, it did not improve the predictive accuracy and clinical value beyond that obtained by current predictive and prognostic models. SII together with a panel of complementary biomarkers is praised to help guide decision-making in clinically nonmetastatic PCa.

DOI： 10.1016/j.urolonc.2021.05.002

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PURPOSE: Tyrosine kinase inhibitors (TKIs) have been widely used in the management of patients with metastatic renal cell carcinoma (RCC). However, the use of systemic therapies in the adjuvant setting of localized and locally advanced RCC has shown conflicting results across the literature. Therefore, we aimed to conduct an updated systematic review and meta-analysis comparing the efficacy and safety of TKIs in the adjuvant setting for patients with localized and locally advanced RCC. MATERIALS AND METHODS: The MEDLINE and EMBASE databases were searched in December 2020 to identify phase III randomized controlled trials of patients receiving adjuvant therapies with TKI for RCC. Disease-free survival (DFS) and overall survival (OS) were the primary endpoints. The secondary endpoints included treatment-related adverse events (TRAEs) of high and any grade. RESULTS: Five trials (S-TRAC, ASSURE, PROTECT, ATLAS, and SORCE) were included in our meta-analysis comprising 6,531 patients. The forest plot revealed that TKI therapy was associated with a significantly longer DFS compared to placebo (pooled HR: 0.88, 95% CI: 0.81-0.96, P= 0.004). The Cochrane's Q test (P = 0.51) and I2 test (I2 = 0%) revealed no significant heterogeneity. Adjuvant TKI was not associated with improved OS compared to placebo (pooled HR: 0.93, 95% CI: 0.83-1.04, P= 0.23). The Cochrane's Q test (P = 0.74) and I2 test (I2 = 0%) revealed no significant heterogeneity. The forest plot revealed that TKI therapy, compared to placebo, was associated with higher rates of high grade TRAEs (OR: 5.20, 95% CI: 4.10-6.59, P< 0.00001) as well as any grade TRAEs (OR: 3.85, 95% CI: 1.22-12.17, P= 0.02). The Cochrane's Q tests (P < 0.0001 and P < 0.00001, respectively) and I2 tests (I2 = 79% and I2 = 90%, respectively) revealed significant heterogeneity. CONCLUSIONS: The findings of our analyses suggest an improved DFS in patients with localized and locally advanced RCC receiving adjuvant TKI as compared to placebo; however, this did not translate into any significant OS benefit. Additionally, TKI therapy led to significant toxicity. Adjuvant TKI does not seem to offer a satisfactory risk and/orbenefit balance for all patients. Select patients with very poor prognosis may be considered in a shared decision-making process with the patient. With the successful arrival of immune-based therapies in RCC, these may allow a more favorable risk/benefit profile.

DOI： 10.1016/j.urolonc.2021.07.022

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PURPOSE: We sought to validate the association of plasma levels of urokinase-type plasminogen activator (uPA), its soluble receptor (SuPAR) and its inhibitor (PAI-one) with oncologic outcomes in a large cohort of patients treated with radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). MATERIALS AND METHODS: We collected preoperative blood samples from 1,036 consecutive patients treated with RC for UCB. Plasma specimens were assessed for levels of uPA, SuPAR and PAI-one. Retrospective logistic and Cox regression analyses were performed to assess their correlation with clinical outcomes. The additional clinical net benefit provided by the biomarkers was evaluated using decision curve analysis. RESULTS: Preoperative plasma uPA, SuPAR and PAI-one levels were significantly elevated in patients harboring adverse pathological features. Higher levels of all biomarkers were independently associated with an increased risk of lymph node metastasis; uPA levels were also independently associated with ≥pT3 disease. Preoperative uPA and SuPAR were independently associated with recurrence-free and cancer-specific survival. The addition of these biomarkers to standard pre-treatment and post-treatment models improved the discriminatory power for prediction of lymph node metastasis, ≥pT3 disease, and recurrence-free and cancer-specific survival by a prognostically significant margin. CONCLUSIONS: We confirmed that elevated preoperative plasma levels of uPA, SuPAR and PAI-one are associated with features of aggressive disease and worse survival outcomes in patients treated with RC for UCB. These biomarkers hold potential in identifying patients who are likely to benefit from intensified/multimodal therapy. They also demonstrated the ability to improve the discriminatory power of predictive/prognostic models, thus refining personalized clinical decision-making.

DOI： 10.1097/JU.0000000000001936

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PURPOSE: To summarize the available evidence on the survival and pathologic outcomes after deferred radical prostatectomy (RP) in men with intermediate- and high-risk prostate cancer (PCa). METHODS: The PubMed database and Web of Science were searched in November 2020 according to the PRISMA statement. Studies were deemed eligible if they reported the survival and pathologic outcomes of patients treated with deferred RP for intermediate- and high-risk PCa compared to the control group including those patients treated with RP without delay. RESULTS: Overall, nineteen studies met our eligibility criteria. We found a significant heterogeneity across the studies in terms of definitions for delay and outcomes, as well as in patients' baseline clinicopathologic features. According to the currently available literature, deferred RP does not seem to affect oncological survival outcomes, such as prostate cancer-specific mortality and metastasis-free survival, in patients with intermediate- or high-risk PCa. However, the impact of deferred RP on biochemical recurrence rates remains controversial. There is no clear association of deferring RP with any of the features of aggressive disease such as pathologic upgrading, upstaging, positive surgical margins, extracapsular extension, seminal vesicle invasion, and lymph node invasion. Deferred RP was not associated with the need for secondary treatments. CONCLUSIONS: Owing to the different definitions of a delayed RP, it is hard to make a consensus regarding the safe delay time. However, the current data suggest that deferring RP in patients with intermediate- and high-risk PCa for at least around 3 months is generally safe, as it does not lead to adverse pathologic outcomes, biochemical recurrence, the need for secondary therapy, or worse oncological survival outcomes.

DOI： 10.1007/s00345-021-03703-8

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Language：English   Publisher：(一社)西日本泌尿器科学会  

J-GLOBAL

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Language：English   Publisher：(一社)西日本泌尿器科学会  

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

J-GLOBAL

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INTRODUCTION: This study aimed to determine the prognostic value of a panel of SIR-biomarkers, relative to standard clinicopathological variables, to improve mRCC patient selection for cytoreductive nephrectomy (CN). MATERIAL AND METHODS: A panel of preoperative SIR-biomarkers, including the albumin-globulin ratio (AGR), De Ritis ratio (DRR), and systemic immune-inflammation index (SII), was assessed in 613 patients treated with CN for mRCC. Patients were randomly divided into training and testing cohorts (65/35%). A machine learning-based variable selection approach (LASSO regression) was used for the fitting of the most informative, yet parsimonious multivariable models with respect to prognosis of cancer-specific survival (CSS). The discriminatory ability of the model was quantified using the C-index. After validation and calibration of the model, a nomogram was created, and decision curve analysis (DCA) was used to evaluate the clinical net benefit. RESULTS: SIR-biomarkers were selected by the machine-learning process to be of high discriminatory power during the fitting of the model. Low AGR remained significantly associated with CSS in both training (HR 1.40, 95% CI 1.07-1.82, p = 0.01) and testing (HR 1.78, 95% CI 1.26-2.51, p = 0.01) cohorts. High levels of SII (HR 1.51, 95% CI 1.10-2.08, p = 0.01) and DRR (HR 1.41, 95% CI 1.01-1.96, p = 0.04) were associated with CSS only in the testing cohort. The exclusion of the SIR-biomarkers for the prognosis of CSS did not result in a significant decrease in C-index (- 0.9%) for the training cohort, while the exclusion of SIR-biomarkers led to a reduction in C-index in the testing cohort (- 5.8%). However, SIR-biomarkers only marginally increased the discriminatory ability of the respective model in comparison to the standard model. CONCLUSION: Despite the high discriminatory ability during the fitting of the model with machine-learning approach, the panel of readily available blood-based SIR-biomarkers failed to add a clinical benefit beyond the standard model.

DOI： 10.1007/s00345-021-03844-w

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INTRODUCTION: This study aimed to evaluate the concordance in tumor stage and grade between ureteroscopic (URS) biopsy and radical nephroureterectomy (RNU) in patients with upper tract urothelial carcinoma (UTUC). PATIENTS AND METHODS: Records of 1,214 UTUC patients who had undergone URS biopsy followed by RNU were included. Univariable and multivariable logistic regression analyses were performed to identify factors contributing to the pathological upstaging. RESULTS: The concordance between URS biopsy-based clinical and RNU pathological staging was 34.5%. Clinical understaging occurred in 59.5% patients. Upstaging to muscle-invasive disease occurred in 240 (41.7%) of 575 patients diagnosed with ≤cT1 disease. Of those diagnosed with muscle-invasive disease on final pathology, 89.6% had been clinically diagnosed with ≤cT1 disease. In the univariable analyses, computed tomography urography (CTU)-based invasion, ureter location, hydronephrosis, high-grade cytology, high-grade biopsy, sessile architecture, age, and women sex were significantly associated with pathological upstaging (P < .05). In the multivariable analyses, CTU-based invasion and hydronephrosis remained associated with pathological upstaging (P < .05). URS biopsy-based clinical and pathological gradings were concordant in 634 (54.2%) patients. Clinical undergrading occurred in 496 (42.4%) patients. CONCLUSIONS: Clinical understaging/undergrading and upstaging to muscle-invasive disease occurred in a high proportion of UTUC patients undergoing RNU. Despite the inherent selection bias, these data underline the challenges of accurate UTUC staging and grading. In daily clinical practice, URS biopsy and CTU offer the most accurate preoperative information albeit with limited predictive value when used alone. These findings should be considered when utilizing preoperative, risk-adapted strategies.

DOI： 10.1016/j.clgc.2021.10.002

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PURPOSE: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP). MATERIALS AND METHODS: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker. RESULTS: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1). CONCLUSIONS: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance.

DOI： 10.1007/s00345-021-03715-4

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PURPOSE: This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients. METHODS: We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval. RESULTS: From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG. CONCLUSIONS: We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.

DOI： 10.1016/j.urolonc.2021.02.029

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CONTEXT: The choice of the most efficacious drug for patients with idiopathic overactive bladder (IOAB) remains challenging. OBJECTIVE: The aim of this network meta-analysis was to determine the most efficacious oral antimuscarinic or β-adrenoceptor agonist accounting for adverse events for the management of IOAB. EVIDENCE ACQUISITION: A comprehensive electronic search was done in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and Ovid for studies in any language in February 2021 considering the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. We included all randomized controlled trials assessing oral antimuscarinics or β-adrenoceptor agonists for the treatment of IOAB. We determined the effect of specific bothersome symptoms separately. EVIDENCE SYNTHESIS: Fifty-four articles were included in our analysis. The most efficacious agents considering the evaluated outcomes were oxybutynin 15 mg/d in reducing incontinence episodes, imidafenacin 0.5 mg/d together with solifenacin 10 and 5 mg/d in reducing micturition episodes, fesoterodine 4 and 8 mg/d as well as solifenacin 10 mg/d in reducing urgency episodes, imidafenacin 0.5 mg/d and solifenacin 10 mg/d in reducing urgency urinary incontinence episodes, and solifenacin 10 mg/d, vibegron 50 mg/d, and fesoterodine 8 mg/d in improving the voided volume. Gastrointestinal problems, especially due to antimuscarinic agents, were the most prevalent adverse events. CONCLUSIONS: Taken together, there is only minimal difference between the efficacy of oral antimuscarinics and that of β-adrenoceptor agonists. Although finding the best medication for all is impossible, finding the best treatment for every individual patient can be done by considering the efficacy of a medicine for the most bothersome symptom(s) in balance with drug-specific adverse events. PATIENT SUMMARY: This study aimed to find the most efficient oral medication to treat overactive bladder, taking into consideration the adverse events. Based on our study, there is a minimal difference in the efficacy between the two major drug classes used to treat overactive bladder. Gastrointestinal problems were the most common adverse events in medical treatment of overactive bladder. Selection of the best treatment is possible through shared decision-making between the doctor and the patient based on the patient's most bothersome symptom. We provide a framework for physicians to facilitate shared decision-making with each individual patient.

DOI： 10.1016/j.euf.2021.08.011

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PURPOSE: To investigate the prognostic role of the preoperative systemic immune-inflammation index (SII) in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed our multi-institutional database to identify 2492 patients. SII was calculated as platelet count × neutrophil/lymphocyte count and evaluated at a cutoff of 485. Logistic regression analyses were performed to investigate the association of SII with muscle-invasive and non-organ-confined (NOC) disease. Cox regression analyses were performed to investigate the association of SII with recurrence-free, cancer-specific, and overall survival (RFS/CSS/OS). RESULTS: Overall, 986 (41.6%) patients had an SII > 485. On univariable logistic regression analyses, SII > 485 was associated with a higher risk of muscle-invasive (P = 0.004) and NOC (P = 0.03) disease at RNU. On multivariable logistic regression, SII remained independently associated with muscle-invasive disease (P = 0.01). On univariable Cox regression analyses, SII > 485 was associated with shorter RFS (P = 0.002), CSS (P = 0.002) and OS (P = 0.004). On multivariable Cox regression analyses SII remained independently associated with survival outcomes (all P < 0.05). Addition of SII to the multivariable models improved their discrimination of the models for predicting muscle-invasive disease (P = 0.02). However, all area under the curve and C-indexes increased by < 0.02 and it did not improve net benefit on decision curve analysis. CONCLUSIONS: Preoperative altered SII is significantly associated with higher pathologic stages and worse survival outcomes in patients treated with RNU for UTUC. However, the SII appears to have relatively limited incremental additive value in clinical use. Further study of SII in prognosticating UTUC is warranted before routine use in clinical algorithms.

DOI： 10.1007/s00262-021-02884-w

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OBJECTIVE: To assess whether single immediate intravesical chemotherapy (SIIC) adds value to bladder tumour management in combination with novel optical techniques: enhanced transurethral resection of bladder tumour (TURBT). METHODS: A systematic search was performed using the PubMed and Web of Science databases in September 2020 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) extension statement for network meta-analyses. Studies that compared recurrence rates among intervention groups (TURBT with photodynamic diagnosis [PDD] ± SIIC, narrow-band imaging [NBI] ± SIIC, or white-light cystoscopy [WLC] + SIIC) and a control group (TURBT with WLC alone) were included. We used the Bayesian approach in the network meta-analysis. RESULTS: Twenty-two studies (n = 4519) met our eligibility criteria. Out of six different interventions including three different optical techniques, compared to WLC alone, blue-light cystoscopy (BLC) plus SIIC (odds ratio [OR] 0.349, 95% credible interval [CrI] 0.196-0.601) and BLC alone (OR 0.668, 95% CrI 0.459-0.931) were associated with a significantly lower likelihood of 12-month recurrence rate. In the sensitivity analysis, out of eight different interventions compared to WLC alone, PDD by 5-aminolevulinic acid plus SIIC (OR 0.327, 95% CrI 0.159-0.646) and by hexaminolevulinic acid plus SIIC (OR 0.376, 95% CrI 0.172-0.783) were both associated with a significantly lower likelihood of 12-month recurrence rate. NBI with and without SIIC was not associated with a significantly lower likelihood of 12-month recurrence rate (OR 0.385, 95% CrI 0.105-1.29 and OR 0.653, 95% CrI 0.343-1.15). CONCLUSION: Blue-light cystoscopy during TURBT with concomitant SIIC seems to yield superior recurrence outcomes in patients with non-muscle-invasive bladder cancer. The use of PDD was able to reduce the 12-month recurrence rate; moreover, concomitant SIIC increased this risk benefit by a 32% additional reduction in odds ratio. Although using PDD could reduce the recurrence rate, SIIC remains necessary. Moreover, ranking analysis showed that both PDD and NBI, plus SIIC, were better than these techniques alone.

DOI： 10.1111/bju.15383

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This systematic review and meta-analysis aimed to assess and compare the perioperative and oncological outcomes of intracorporeal (ICUD) and extracorporeal (ECUD) urinary diversion following robot-assisted radical cystectomy (RARC). A systematic literature search of articles was performed in PubMed®, Web of Science®, and Scopus® databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. We included studies that compared patients who underwent RARC with ICUD to those with ECUD. Twelve studies including 3067 patients met the eligibility criteria. There were no significant differences between ICUD and ECUD in overall and major complications, regardless of the period (short-term [≤ 30 days] or mid-term [> 30 days]). Subgroup analyses demonstrated that ICUD performed by high-volume centers exhibited a significantly reduced risk of major complications (short-term: OR 0.57, 95% CI 0.37-0.86, p = 0.008, mid-term: OR 0.66, 95% CI 0.46-0.94, p = 0.02). Patients who underwent ICUD had lower estimated blood loss (MD -102.3 ml, 95% CI - 132.8 to - 71.8, p < 0.00001), less likely to receive blood transfusion rates (OR 0.36, 95% CI 0.20-0.62, p = 0.00003); and these findings were consistent in subgroup analyses by low-volume centers (MD-121.6 ml, 95% CI - 160.9 to - 82.3, p < 0.00001 and OR 0.36, 95% CI 0.20-0.62, p = 0.00003, respectively). ICUD had a higher lymph node yield (MD 3.68, 95% CI 0.80-6.56, p = 0.01). Patients receiving ICUD provided comparable complications, superior perioperative outcomes, and similar oncological outcomes compared with ECUD. Centralization of patients may contribute to a reduction of postoperative complications, while maintaining the advantages.

DOI： 10.1007/s10147-021-01972-2

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BACKGROUND: The programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) pathway is important in metastatic renal cell carcinoma (mRCC). However, some dissimilarities between anti-PD-1 and anti-PD-L1 inhibitors have emerged. We aimed to assess differences between anti-PD-1 and anti-PD-L1 combination immunotherapies as first-line treatments in mRCC patients. METHODS: Multiple databases (PubMed, Web of Science, and Scopus) were searched for articles published until March 2021. Studies were eligible if they compared overall survival (OS), progression-free survival (PFS), objective response rates (ORR), complete response rates (CRR), and adverse events. RESULTS: Five studies met the eligibility criteria. PD-1 combination therapy was associated with significantly better OS and PFS and higher ORR and CRR than sunitinib (hazard ratio [HR]: 0.60, 95% confidence interval [CI]: 0.40-0.89; HR: 0.52, 95% CI: 0.37-0.75; odds ratio [OR]: 3.20, 95% CI: 2.18-4.68; and OR: 3.05, 95% CI: 2.13-4.37, respectively; P < 0.001). For all oncological outcomes, anti-PD-1 agents were superior to anti-PD-L1 agents based on HR and OR (OS: HR = 0.88, PFS: HR = 0.76, ORR: OR = 1.85, and CRR: OR = 2.24). Conversely, anti-PD-L1 agents were superior to anti-PD-1 agents in their safety profiles. In network meta-analyses, pembrolizumab plus lenvatinib seemed the worst tolerated anti-PD-1 combination therapy. CONCLUSIONS: Our analysis indicates the superior oncologic benefits of first-line anti-PD-1 combination therapies over anti-PD-L1 combination therapies in mRCC patients. This biological difference is of vital importance for clinical treatment decision making and the design of future rational combination therapy trials in mRCC.

DOI： 10.1016/j.ctrv.2021.102242

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BACKGROUND: The aim of this study is to compare the perioperative outcomes and learning curves between intracorporeal and extracorporeal urinary diversion at our medium-sized institution. METHODS: Between January 2018 and September 2020, a single surgeon at our institution performed 46 consecutive robot-assisted radical cystectomies with ileal conduit. We compared the perioperative outcomes between patients who underwent intracorporeal versus extracorporeal urinary diversion. We also investigated learning curves for the first and last 10 patients in each group. RESULTS: The extracorporeal group had shorter overall operative time (P = 0.003) and urinary diversion time (P < 0.0001) than the intracorporeal group. The intracorporeal group had shorter length of hospital stay (P = 0.02). There was no difference in complication and readmission rates. The extracorporeal group demonstrated no difference between the first and last 10 patients for overall operative time or time for cystectomy, lymph node dissection, or urinary diversion. However, the intracorporeal group had shorter urinary diversion time for the last 10 patients compared with the first 10 patients. The first 10 patients in the extracorporeal group had shorter overall operative time than the first 10 in the intracorporeal group, but there was no difference for the last 10 patients. CONCLUSIONS: Intracorporeal urinary diversion requires longer overall operative time than extracorporeal diversion for the first 10 patients, due to longer urinary diversion time. However, there is no difference in overall operative time for the last 10 patients. The benefit of intracorporeal over extracorporeal urinary diversion was not confirmed at our medium-sized institution.

DOI： 10.1007/s10147-021-01957-1

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BACKGROUND: Elevated preoperative plasma levels of the angiogenesis-related marker VEGF have been associated with worse oncological outcomes in various malignancies. OBJECTIVE: To investigate the predictive/prognostic role of VEGF in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). DESIGN, SETTING, AND PARTICIPANTS: VEGF plasma levels were measured preoperatively in 1036 patients with UCB who underwent RC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The correlation between plasma VEGF levels and pathological and survival outcomes was assessed using logistic regression and Cox regression analyses. Discrimination was assessed using the concordance index (C index). The clinical net benefit was evaluated using decision curve analysis (DCA). RESULTS AND LIMITATIONS: Patients with higher pretreatment plasma VEGF levels had poorer recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) according to log-rank tests (all p < 0.001). Higher VEGF levels were not independently associated with higher risk of lymph node metastasis, ≥pT3 disease, or non-organ-confined disease (all p > 0.05). Preoperative plasma VEGF levels were independently associated with RFS, CSS, and OS in preoperative and postoperative multivariable models. However, in all cases the C index increased by <0.02 and there was no improvement in net benefit on DCA. A limitation is that none of the patients received current elements of standard of care such as neoadjuvant chemotherapy. CONCLUSIONS: Elevated plasma VEGF levels were associated with features of biologically and clinically aggressive disease such as worse survival outcomes among patients with UCB treated with RC. However, VEGF appears to have relatively limited incremental additive value in clinical use. Further study of VEGF for UCB prognostication is warranted before routine use in clinical algorithms. PATIENT SUMMARY: Currently available models for predicting outcomes in bladder cancer are less than optimal. A protein called vascular endothelial growth factor (VEGF), which is a marker of the formation of blood vessels (angiogenesis), may have a role in predicting survival outcomes in bladder cancer. TAKE HOME MESSAGE: Elevated plasma VEGF levels are associated with worse survival outcomes for patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy. VEGF could be used as a part of a biomarker panel to enhance tools currently used for risk stratification for patients with UCB.

DOI： 10.1016/j.euf.2021.08.006

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PURPOSE: To examine the effect of lymph node dissection on the outcomes of patients who underwent salvage radical prostatectomy (SRP). MATERIAL AND METHODS: We retrospectively reviewed data from radiation-recurrent patients with prostate cancer (PCa) who underwent SRP from 2000-2016. None of the patients had clinical lymph node involvement before SRP. The effect of the number of removed lymph nodes (RLNs) and the number of positive lymph nodes (PLNs) on biochemical recurrence (BCR)-free survival, metastases free survival, and overall survival (OS) was tested in multivariable Cox regression analyses. RESULTS: About 334 patients underwent SRP and pelvic lymph node dissection (PLND). Lymph node involvement was associated with increased risk of BCR (p < .001), metastasis (p < .001), and overall mortality (p = .006). In a multivariable Cox regression analysis, an increased number of RLNs significantly lowered the risk of BCR (hazard ratio [HR] 0.96, p = .01). In patients with positive lymph nodes, a higher number of RLNs and a lower number of PLNs were associated with improved freedom from BCR (HR 0.89, p = .001 and HR 1.34, p = .008, respectively). At a median follow-up of 23.9 months (interquartile range, 4.7-37.7), neither the number of RLNs nor the number of PLNs were associated with OS (p = .69 and p = .34, respectively). CONCLUSION: Pathologic lymph node involvement increased the risk of BCR, metastasis and overall mortality in radiation-recurrent PCa patients undergoing SRP. The risk of BCR decreased steadily with a higher number of RLNs during SRP. Further research is needed to support this conclusion and develop a precise therapeutic adjuvant strategy based on the number of RLNs and PLNs.

DOI： 10.1002/pros.24173

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INTRODUCTION: The management of non-metastatic castration-resistant prostate cancer (nmCRPC) has undergone a paradigm shift with the development of androgen receptor axis-targeted (ARAT) agents. The updated results with final overall survival (OS) data of the phase III PROSPER, SPARTAN, and ARAMIS trials have recently been reported. Therefore, we performed an updated meta-analysis and network meta-analysis to indirectly compare the efficacy and safety of currently available treatments. EVIDENCE ACQUISITION: Multiple databases were searched for articles published before January 2021. Studies that compared OS and adverse events (AEs) in patients with nmCRPC were considered eligible. EVIDENCE SYNTHESIS: Three studies (n=4,117) met our eligibility criteria. Formal network meta-analyses were conducted. ARAT agent is associated with significantly longer OS compared to placebo (pooled hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.65-0.83, P<0.001), with similar results shown for patients with both N1 and N0 disease (pooled HR 0.61 and pooled HR 0.76, respectively). In the network meta-analysis, apalutamide, darolutamide, and enzalutamide were more effective than placebo, with similar efficacies in terms of OS. For AEs (including any AEs, grade 3 or grade 4 AEs, grade 5 AEs, serious AEs, and AEs leading to treatment discontinuation), darolutamide was shown to be likely well tolerated. Quality-of-life was preserved in treatment arms irrespective of the drug. CONCLUSIONS: All three ARAT agents are efficacious options for the treatment of nmCRPC, whereas darolutamide appears to have the most favorable tolerability profile. These findings may facilitate individualized treatment strategies and inform future direct comparative trials.

DOI： 10.23736/S2724-6051.21.04431-1

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CONTEXT: Degarelix is associated with high rates of injection site reaction. The US Food and Drug Administration approved relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, for the treatment of advanced prostate cancer patients. OBJECTIVE: This systematic review and network meta-analysis aimed to compare the efficacy and safety of relugolix versus degarelix. EVIDENCE ACQUISITION: A systematic search was performed using major web databases for studies published before January 30, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) extension statement for a network meta-analysis. Studies that compared the efficacy (12-mo castration rate with testosterone ≤50 ng/dl) and safety (adverse events [AEs]) of relugolix or degarelix and of the control group (GnRH agonists) were included. We used the Bayesian approach in the network meta-analysis. EVIDENCE SYNTHESIS: Four studies (n = 2059) met our eligibility criteria. The main efficacy analysis was conducted for two different treatments (relugolix and all doses of degarelix vs GnRH agonists); relugolix (risk ratio [RR] 1.09, 95% credible interval [CrI]: 0.95-1.23) and degarelix (RR 0.98, 95% CrI: 0.91-1.06) were not associated with different 12-mo castration rates. In the subgroup analysis, degarelix 480 mg was significantly associated with a lower castration rate (RR 0.46, 95% CrI: 0.07-0.92). In all efficacy ranking analyses, relugolix achieved the best rank. The safety analyses showed that relugolix (RR 0.99, 95% CrI: 0.6-1.6 and RR 0.72, 95% CrI: 0.4-1.3, respectively) and degarelix (RR 1.1, 95% CrI: 0.75-1.35 and RR 1.05, 95% CrI: 0.42-2.6, respectively) were not associated with either all AE or serious AE rates. In the ranking analyses, degarelix achieved the worst rank of all AEs and the best rank of serious AEs. Relugolix (RR 0.44, 95% CrI: 0.16-1.2) and degarelix (RR 0.74, 95% CrI: 0.37-1.52) were not associated with different cardiovascular event (CVE) rates; both were associated with lower CVE rates than GnRH agonists in the ranking analyses. CONCLUSIONS: We found that the efficacy and safety of relugolix are comparable with those of degarelix, albeit with no injection site reaction. Such data should be interpreted with caution until large-scale direct comparison studies with a longer follow-up are available. PATIENT SUMMARY: We found that relugolix, an oral gonadotropin-releasing hormone (GnRH) antagonist, has comparable efficacy and safety with degarelix, a parenteral GnRH antagonist, for the treatment of advanced prostate cancer patients.

DOI： 10.1016/j.euo.2021.07.002

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BACKGROUND: Although detection of microscopic hematuria is a well-known diagnostic method for urolithiasis, its ability to predict urolithiasis treatment outcomes in adults is unknown. OBJECTIVE: To evaluate the role of microscopic hematuria in conservative treatment of ureteral calculus. DESIGN, SETTING, AND PARTICIPANTS: This cohort study involved 482 patients who were diagnosed with a single uncomplicated ureteral calculus (≤10 mm) using computed tomography and underwent conservative therapy at two Japanese community hospitals between 2013 and 2018. Patients were divided into three groups according to the severity of microscopic hematuria (no, ≤4; mild to moderate, 5-99; and severe, ≥100 red blood cells per high-power field) and as determined during the first emergency department or urologic outpatient clinic visit. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A multivariate logistic regression analysis was performed to estimate the odds ratio for successful conservative therapy at 28 d after the diagnosis. Statistical significance was set at p < 0.05. RESULTS AND LIMITATIONS: Of the 482 patients, 81 (16.8%), 209 (43.4%), and 192 (39.8%) had no, mild to moderate, and severe microscopic hematuria, respectively. After adjustments for six relevant confounders, severe microscopic hematuria showed a significant association with successful conservative therapy at 28 d (adjusted odds ratio, 1.91; 95% confidence interval, 1.02-3.57; p = 0.043), whereas mild to moderate microscopic hematuria did not (adjusted odds ratio, 1.05; 95% confidence interval, 0.57-1.93; p = 0.872) when compared with no microscopic hematuria. CONCLUSIONS: Severe microscopic hematuria was significantly associated with successful conservative therapy for single uncomplicated ureteral calculus. PATIENT SUMMARY: Microscopic hematuria might have predictive value for conservative treatment of a single uncomplicated ureteral calculus. Using the presence or absence of blood in urine and other predictive factors, clinicians may lead patients with a single uncomplicated ureteral calculus to successful conservative therapy.

DOI： 10.1016/j.euf.2020.04.004

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CONTEXT: The question of the ability of frozen section analysis (FSA) to accurately detect malignant pathology intraoperatively has been discussed for many decades. OBJECTIVE: We aimed to conduct a systematic review and meta-analysis assessing the diagnostic estimates of FSA of the urethral and ureteral margins in patients treated with radical cystectomy (RC) for bladder cancer (BCa). EVIDENCE ACQUISITION: The MEDLINE and EMBASE databases were searched in February 2021 for studies analyzing the association between FSA and the final urethral and ureteral margin status in patients treated with RC for BCa. The primary endpoint was the value of pathologic detection of urethral and ureteral malignant involvement with FSA during RC compared with the final margin status. We included studies that provided true positive, true negative, false positive, and false negative values for FSA, which allowed us to calculate the diagnostic estimates. EVIDENCE SYNTHESIS: Fourteen studies, comprising 8208 patients, were included in the quantitative synthesis. Forest plots revealed that the pooled sensitivity and specificity for FSA of urethral margins during RC were 0.83 (95% confidence interval [CI] 0.38-0.97) and 0.95 (95% CI 0.91-0.97), respectively. While for the FSA of ureteral margins, the pooled sensitivity and specificity were 0.77 (95% CI 0.67-0.84) and 0.97 (95% CI 0.95-0.98), respectively. Calculated diagnostic odds ratios indicated high FSA effectiveness, and patients with a positive urethral or ureteral margin at final pathology are over 100 times more likely to have positive FSA than patients without margin involvement at final pathology. Area under the curves of 96.6% and 96.7% were reached for FSA detection of urethral and ureteral tumor involvement, respectively. CONCLUSIONS: Intraoperative FSA demonstrated high diagnostic performance in detecting both urethral and ureteral malignant involvement at the time of RC for BCa. FSA of both urethral and ureteral margins during RC is accurate enough to be of great value in the routine management of BCa patients treated with RC. While its specificity was great to guide intraoperative decision-making, its sensitivity remains suboptimal yet. PATIENT SUMMARY: We believe that the frozen section analysis of both urethral and ureteral margins during radical cystectomy should be considered more often in urologic practice, until quality of life-based cost-effectiveness studies can identify patients within each institution who are unlikely to benefit from it.

DOI： 10.1016/j.euf.2021.05.010

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BACKGROUND: To investigate the predictive and prognostic value of the preoperative modified Glasgow Prognostic Score (mGPS) in patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). METHODS: We conducted a retrospective analysis of an established multicenter database consisting of 4,335 patients who were treated with RC +/- adjuvant chemotherapy for UCB between 1979 and 2012. The mGPS of each patient was calculated on the basis of preoperative serum C-reactive protein and albumin. Uni- and multivariable logistic and Cox regression analyses were performed. The discriminatory ability of the models was assessed by calculating the area under receiver operating characteristics curves (AUC) and concordance-indices (C-Index). The additional clinical net-benefit was assessed using the decision curve analysis (DCA). RESULTS: A mGPS of 0, 1, and 2 was observed in 3,158 (72.8%), 1,020 (23.5%), and 157 (3.6%) patients, respectively. On multivariable logistic regression analyses, mGPS of 1 or 2 were associated with an increased risk of pT3/4 disease at RC (OR 1.25, p=0.004 and OR 2.58, p<0.001, respectively) and/or lymph node metastasis (OR 1.7, p<0.001 and OR 3.9, p<0.001, respectively). Addition of the mGPS to a predictive model based on preoperatively available variables improved its accuracy for prediction of lymph node metastasis (change of AUC +3.7%, p<0.001). On multivariable Cox regression analyses, mGPS of 1 or 2 remained associated with worse recurrence-free survival (HR 1.14, p=0.03 and HR 1.89 p<0.001, respectively), cancer-specific survival (HR 1.16, p=0.032 and HR 2.1, p<0.001, respectively) and overall survival (HR 1.5, p=0.007 and HR 1.92 p<0.001, respectively) compared to mGPS of 0. The additional discriminatory ability of the mGPS for prognosis of survival outcomes in separate models that included either established pre- or postoperative variables did not improve the C-Index by a prognostically relevant degree (change of C-Index <2% for all models). On DCA, the inclusion of the mGPS did not meaningfully improve the net-benefit for clinical decision-making regarding survival outcomes. CONCLUSIONS: We confirmed that an elevated mGPS is an independent risk factor for non-organ confined disease and poor survival outcomes in patients with UCB undergoing RC. However, the mGPS showed little value in improving the discriminatory ability of predictive and prognostic models that relied on either pre- or postoperative clinicopathological variables. The discriminatory ability of this biomarker in the age of immunotherapy warrants further evaluation.

DOI： 10.23736/S2724-6051.21.04216-6

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BACKGROUND: Among various clinicopathologic factors used to identify low-risk upper tract urothelial carcinoma (UTUC), tumor grade and stage are of utmost importance. The clinical value added by inclusion of other risk factors remains unproven. OBJECTIVE: To assess the performance of a tumor grade- and stage-based (GS) model to identify patients with UTUC for whom kidney-sparing surgery (KSS) could be attempted. DESIGN, SETTING, AND PARTICIPANTS: In this international study, we reviewed the medical records of 1240 patients with UTUC who underwent radical nephroureterectomy. Complete data needed for risk stratification according to the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) guidelines were available for 560 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Univariable and multivariable logistic regression analyses were performed to determine if risk factors were associated with the presence of localized UTUC. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the GS, EAU, and NCCN models in predicting pathologic stage were calculated. RESULTS AND LIMITATIONS: Overall, 198 patients (35%) had clinically low-grade, noninvasive tumors, and 283 (51%) had ≤pT1disease. On multivariable analyses, none of the EAU and NCCN risk factors were associated with the presence of non-muscle-invasive UTUC among patients with low-grade and low-stage UTUC. The GS model exhibited the highest accuracy, sensitivity, and negative predictive value among all three models. According to the GS, EAU, and NCCN models, the proportion of patients eligible for KSS was 35%, 6%, and 4%, respectively. Decision curve analysis revealed that the net benefit of the three models was similar within the clinically reasonable range of probability thresholds. CONCLUSIONS: The GS model showed favorable predictive accuracy and identified a greater number of KSS-eligible patients than the EAU and NCCN models. A decision-making algorithm that weighs the benefits of avoiding unnecessary kidney loss against the risk of undertreatment in case of advanced carcinoma is necessary for individualized treatment for UTUC patients. PATIENT SUMMARY: We assessed the ability of three models to predict low-grade, low-stage disease in patients with cancer of the upper urinary tract. No risk factors other than grade assessed on biopsy and stage assessed from scans were associated with better prediction of localized cancer. A model based on grade and stage may help to identify patients who could benefit from kidney-sparing treatment of their cancer.

DOI： 10.1016/j.euf.2021.05.002

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BACKGROUND: The advantages of photodynamic diagnostic technology using 5-aminolevulinic acid (ALA-PDD) have been established. The aim of this prospective cohort study was to evaluate the usefulness of ALA-PDD to diagnose upper tract urothelial carcinoma (UT-UC) using the Olympus VISERA ELITE video system. METHODS: We carried out a prospective, interventional, non-randomized, non-contrast and open label cohort pilot study that involved patients who underwent ureterorenoscopy (URS) to detect UT-UC. 5-aminolevulinic acid hydrochloride was orally administered before URS. The observational results and pathological diagnosis with ALA-PDD and traditional white light methods were compared, and the proportion of positive subjects and specimens were calculated. RESULTS: A total of 20 patients were enrolled and one patient who had multiple bladder tumors did not undergo URS. Fifteen of 19 patients were pathologically diagnosed with UT-UC and of these 11 (73.3%) were ALA-PDD positive. Fourteen of 19 patients were ALA-PDD positive and of these 11 were pathologically diagnosed with UC. For the 92 biopsy specimens that were malignant or benign, the sensitivity for both traditional white light observation and ALA-PDD was the same at 62.5%, whereas the specificities were 73.1% and 67.3%, respectively. Of the 38 specimens that were randomly biopsied without any abnormality under examination by both white light and ALA-PDD, 11 specimens (28.9%) from 5 patients were diagnosed with high grade UC. In contrast, four specimens from 4 patients, which were negative in traditional white light observation but positive in ALA-PDD, were diagnosed with carcinoma in situ (CIS). CONCLUSIONS: Our results suggest that ALA-PDD using VISERA ELITE is not sufficiently applicable for UT-UC. Nevertheless, it might be better particularly for CIS than white light and superior results would be obtained using VISERA ELITE II video system. TRIAL REGISTRATION: The present clinical study was approved by the Okayama University Institutional Review Board prior to study initiation (Application no.: RIN 1803-002) and was registered with the UMIN Clinical Trials Registry (UMIN-CTR), Japan (Accession no.: UMIN000031205).

DOI： 10.1186/s12894-021-00819-2

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CONTEXT: Patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC) may pose a clinical dilemma without an agreed evidence-based decision tree for personalized treatment. OBJECTIVE: To perform a systematic review and network meta-analysis (NMA) to summarize available evidence on the oncologic outcomes of intravesical therapy in patients with intermediate-risk NMIBC. EVIDENCE ACQUISITION: The MEDLINE, EMBASE, and ClinicalTrials.gov databases were searched in October 2020 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Studies were deemed eligible if they reported on oncologic outcomes in patients with intermediate-risk NMIBC treated with transurethral resection of bladder tumor with and without intravesical chemotherapy or bacillus Calmette-Guérin (BCG) immunotherapy. EVIDENCE SYNTHESIS: Twelve studies were included in a qualitative synthesis (systematic review); three were deemed eligible for a quantitative synthesis (NMA). An NMA of five different regimens was conducted for the association of treatment with the 5-yr recurrence risk. Chemotherapy with maintenance was associated with a lower likelihood of 5-yr recurrence than chemotherapy without maintenance (odds ratio [OR] 0.51, 95% credible interval [CI] 0.26-1.03). Immunotherapy, regardless of whether a full- or reduced-dose regimen, was not associated with a significantly lower likelihood of 5-yr recurrence when compared with chemotherapy without maintenance (OR 0.90, 95% CI 0.39-2.11 vs OR 0.93, 95% CI 0.40-2.19). Analysis of the treatment ranking revealed that chemotherapy with maintenance had the lowest 5-yr recurrence risk (P score 0.9666). CONCLUSIONS: Our analysis indicates that chemotherapy with a maintenance regimen confers a superior oncologic benefit in terms of 5-yr recurrence risk compared to chemotherapy without maintenance in patients with intermediate-risk NMIBC. Regardless of the dose regimen, immunotherapy with BCG does not appear to be superior to chemotherapy in patients with intermediate-risk NMIBC in term of disease recurrence. However, owing to the lack of comparative studies, there is an unmet need for well-designed, large-scale trials to validate our findings and generate robust evidence on disease recurrence and progression. PATIENT SUMMARY: A maintenance schedule of chemotherapy reduces the rate of long-term recurrence of bladder cancer that has not invaded the bladder muscle. Chemotherapy inserted directly into the bladder and immunotherapy without maintenance schedules seem to have limited benefit in preventing cancer recurrence.

DOI： 10.1016/j.euf.2021.03.016

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OBJECTIVES: To determine the predictive and prognostic value of a panel of systemic inflammatory response (SIR) biomarkers relative to established clinicopathological variables in order to improve patient selection and facilitate more efficient delivery of peri-operative systemic therapy. MATERIALS AND METHODS: The preoperative serum levels of a panel of SIR biomarkers, including albumin-globulin ratio, neutrophil-lymphocyte ratio, De Ritis ratio, monocyte-lymphocyte ratio and modified Glasgow prognostic score were assessed in 4199 patients treated with radical cystectomy for clinically non-metastatic urothelial carcinoma of the bladder. Patients were randomly divided into a training and a testing cohort. A machine-learning-based variable selection approach (least absolute shrinkage and selection operator regression) was used for the fitting of several multivariable predictive and prognostic models. The outcomes of interest included prediction of upstaging to carcinoma invading bladder muscle (MIBC), lymph node involvement, pT3/4 disease, cancer-specific survival (CSS) and recurrence-free survival (RFS). The discriminatory ability of each model was either quantified by area under the receiver-operating curves or by the C-index. After validation and calibration of each model, a nomogram was created and decision-curve analysis was used to evaluate the clinical net benefit. RESULTS: For all outcome variables, at least one SIR biomarker was selected by the machine-learning process to be of high discriminative power during the fitting of the models. In the testing cohort, model performance evaluation for preoperative prediction of lymph node metastasis, ≥pT3 disease and upstaging to MIBC showed a 200-fold bootstrap-corrected area under the curve of 67.3%, 73% and 65.8%, respectively. For postoperative prognosis of CSS and RFS, a 200-fold bootstrap corrected C-index of 73.3% and 72.2%, respectively, was found. However, even the most predictive combinations of SIR biomarkers only marginally increased the discriminative ability of the respective model in comparison to established clinicopathological variables. CONCLUSION: While our machine-learning approach for fitting of the models with the highest discriminative ability incorporated several previously validated SIR biomarkers, these failed to improve the discriminative ability of the models to a clinically meaningful degree. While the prognostic and predictive value of such cheap and readily available biomarkers warrants further evaluation in the age of immunotherapy, additional novel biomarkers are still needed to improve risk stratification.

DOI： 10.1111/bju.15379

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PURPOSE: The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS: Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION: We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.

DOI： 10.1016/j.urolonc.2020.12.019

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Language：Japanese   Publisher：西日本泌尿器科学会  

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Purpose: The Plasminogen Activation System (PAS) plays a role in tumor growth, invasion and metastasis and has been associated with oncological outcomes in urinary bladder carcinoma (UBC). The use of the different components of this system as molecular markers could improve our understanding of the heterogeneous behavior of UBC and might enable earlier disease detection, individual risk stratification, more accurate outcome prediction and be a rationale for new targeted therapies. Methods: A comprehensive literature search including relevant articles up to October 2020 was performed using the MEDLINE/PubMed database. Results: The components of the PAS axis are involved in tumor progression through their signaling processes during angiogenesis, cell migration, metastasis and adhesion. The body of evidence shows an association of PAS component overexpression with adverse pathological features and clinical outcome in UBC. Overexpressed PAS components correlate with a higher pathological tumor grade and advanced tumor stage. In non-muscle-invasive bladder cancer (NMIBC), the PAS components were associated with disease outcome while in muscle-invasive bladder cancer (MIBC), it was associated with disease outcome and pathological features. Possible therapeutic approaches in the PAS for the treatment of UBC have only been sparsely investigated in in vitro and in vivo studies. Intravesical plasminogen activator inhibitor 1 (PAI-1) instillation in animal models yielded interesting results and warrant further exploration in Phase II studies. Conclusion: The overexpression of PAS components in UBC tumor tissue is associated with adverse pathological features and worse oncological outcomes. These findings are mainly based on preclinical studies and retrospective series, which requires further prospective studies to translate the PAS into clinically useful biomarkers and therapeutic targets.

DOI： 10.2147/OTT.S242248

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INTRODUCTION: While several recent studies investigated the influence of statins on survival outcomes in prostate cancer (PCa) patients on androgen deprivation therapy (ADT), definitive conclusions are still missing. The present systematic review and meta-analysis aimed to develop an overarching framework for the association of statins use and survival outcomes in PCa patients who receive ADT. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes for statin compared to non-statin users in PCa patients who received ADT. We searched PubMed and Web of Science for studies published before March 1, 2021. We used the random effect model in the presence of heterogeneity and the fixed-effects model in the absence of heterogeneity per the I 2 statistic. We did two meta-analyses; the primary meta-analysis was accomplished for articles reporting cancer-specific survival (CSS) as an outcome. A secondary meta-analysis was completed for articles reporting overall survival (OS) as an outcome. RESULTS: Ten studies were eligible for inclusion. Nine studies included in the first meta-analysis comprising 136,285 patients showed no statistically significant difference in CSS (HR 0.77; 95% CI 0.49-1.21) between statin users and non-users in PCa patients who received ADT. In four studies included in the second meta-analysis comprising 95,032 patients, statin users had a significantly better OS compared to non-users (HR 0.67; 95% CI 0.62-0.73). CONCLUSIONS: Although the combination of statins and ADT in PCa patients significantly improves OS, it seems not to be through an effect on cancer-specific factors.

DOI： 10.5173/ceju.2021.0260

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Language：Japanese   Publisher：腎移植・血管外科研究会  

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We report a 47-year-old Japanese female with 10 previous treatments for multiple bilateral renal cell carcinoma (RCC) associated with von Hippel-Lindau disease. The 14-mm right lower pole renal tumor was in contact with the right ureter. Laparoscopic cryoablation was performed to protect the ureter wrapped with gauze. Computed tomography (CT) monitoring was used to confirm the precise ≥ 6 mm ice-ball margin. There was no local progression at 6-months post-surgery. The serum creatinine has been stable. This is apparently the first report of combined laparoscopic and CT monitoring of an ice-ball formation and its margin during cryoablation for RCC.

DOI： 10.18926/AMO/60806

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Language：Japanese   Publisher：The West Japan Urological Association  

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01004&link_issn=&doc_id=20200514090018&doc_link_id=%2Fer9niuro%2F2020%2F008201%2F018%2F0106-0110%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fer9niuro%2F2020%2F008201%2F018%2F0106-0110%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese   Publisher：(一社)日本泌尿器内視鏡・ロボティクス学会  

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Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal, malignancy-related respiratory complication; we herein report a PTTM case induced by metastatic prostate cancer. An 81-year-old Japanese man developed dyspnea. High-resolution computed tomography (HRCT) revealed ground-glass opacities spread across bilateral lung fields. Pulmonary microvascular aspiration cytology detected prostate cancer cells. As PTTM was highly suspected, docetaxel chemotherapy was performed immediately. His respiratory condition and HRCT findings improved temporarily, but he died approx. 6 weeks after admission. Autopsy showed fibrocellular intimal proliferation of small pulmonary arterioles, which confirmed the diagnosis of PTTM induced by prostate cancer. As in the present case, it is often difficult to confirm the presence of not only tumor embolization but also fibrocellular intimal proliferation before the patient's death.

DOI： 10.18926/AMO/56078

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Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jac/dkw424

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Language：Japanese   Publisher：Japanese Urological Association  

DOI： 10.5980/jpnjurol.107.239

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Language：Japanese  

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Language：Japanese   Publishing type：Book review, literature introduction, etc.   Publisher：The West Japan Urological Association  

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DOI： 10.11302/jsejje.27.395

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DOI： 10.11213/tonyobyo.53.845

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Language：Japanese   Publisher：(一社)日本腹部救急医学会  

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