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BACKGROUND AND OBJECTIVE: While some patients with metastatic renal cell carcinoma (mRCC) may experience an indolent disease progression and could benefit from deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), the evidence on its oncological efficacy and safety are still not well-established. We aimed to provide an overview of the available evidence on oncological outcomes of patients with mRCC undergoing deferred ST. METHODS: A systematic review of the literature was conducted in August 2024 using the PubMed, Scopus, and Embase databases to identify prospective and retrospective studies evaluating AS or deferred ST for patients with mRCC (PROSPERO ID: CRD42024579021). The co-primary outcomes were ST-free survival (ST-FS) and overall survival (OS). A random-effects model was used for quantitative analysis. KEY FINDINGS AND LIMITATIONS: We identified 15 eligible studies including 2,912 patients. Of these, 4 were prospective (n = 589 patients) and 11 were retrospective (n = 2,323 patients). The estimated 1-, 2-, 3-, 4-, and 5-year ST-FS rates (n = 1,070) were 74%, 54%, 49%, 43%, and 37%, respectively. The estimated 1-, 2-, 3-, 4-, and 5-year OS rates (n = 2,872) were 96%, 89%, 80%, 71%, and 69%, respectively. Key limitations at a study-level included selection bias, unmeasured confounding, and variability across deferred ST/AS protocols, including the indications for metastasis-directed therapy. Moreover, most studies used tyrosine kinase inhibitors as ST. The proportion of patients receiving MDT, including metastasectomy or stereotactic body radiation therapy, ranged from 14 to 100%. CONCLUSIONS AND CLINICAL IMPLICATIONS: Deferring ST by AS or MDT was associated with favorable oncological outcomes in carefully-selected patients with mRCC, highlighting the potential value of this approach in the contemporary multidisciplinary management of mRCC. Considering the limitations of available evidence and the lack of data on the oncological efficacy and safety of deferred ST for mRCC in the immune-oncology era, our review calls for further research in this field.

DOI： 10.1016/j.urolonc.2025.11.008

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

ABSTRACT

Objectives

Nocturnal enuresis is common in early childhood. While daytime bladder control typically precedes nighttime continence, the temporal relationship between early daytime bladder control and subsequent bedwetting remains unclear. We investigated whether daytime bladder control status at age 2.5 years—as indicated by diaper use—is associated with bedwetting at age 4.5 years in a Japanese nationwide cohort.

Methods

We analyzed data from the Japanese Longitudinal Survey of Newborns in the 21st Century (2010 cohort). Daytime bladder control was assessed at age 2.5 years through caregiver‐reported diaper use, and bedwetting frequency at age 4.5 years through parental questionnaires. Modified Poisson regression estimated risk ratios (RRs), adjusting for birth‐related factors, socioeconomic status, daycare attendance, and developmental milestones.

Results

Among 32 168 children, 26 651 (82.8%) still used diapers at 2.5 years. Bedwetting prevalence at 4.5 years was 42.2%: 34.5% in children who achieved daytime bladder control at 2.5 years versus 43.9% in those still using diapers. After multivariable adjustment, incomplete daytime bladder control at 2.5 years was associated with higher bedwetting risk (adjusted RR 1.25; 95% CI, 1.20–1.31). Multinomial regression revealed dose–response relationships: odds ratios 1.41 (95% CI, 1.30–1.52) for “sometimes” and 1.58 (95% CI, 1.42–1.77) for “often” bedwetting.

Conclusions

Daytime bladder control status at 2.5 years was associated with a 25% increased bedwetting risk at 4.5 years. This association likely reflects individual differences in bladder control maturation rather than causal effects. While daytime bladder control may serve as a developmental marker, its validity as an intervention target remains unestablished.

DOI： 10.1111/iju.70288

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DOI： 10.1038/s41598-025-26777-5

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DOI： 10.1111/iju.70207

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BACKGROUND: Despite durable benefits of ipilimumab and nivolumab in metastatic renal cell carcinoma (mRCC), early progressive disease (PD), defined as disease progression within 3 months, occurs, and its predictors remain unclear. We aimed to investigate the clinical factors associated with early PD in patients with mRCC treated with this regimen. METHODS: A retrospective analysis of a multi-institutional database identified 193 patients with mRCC treated with ipilimumab plus nivolumab. Logistic regression analyses assessed associations between clinical factors and early PD. RESULTS: During a median follow-up of 17 months, patients had median overall (OS) and progression-free survival (PFS) of 35 and 14 months, respectively. Objective response and PD rates were 49.9% and 24.9%, respectively. Patients with early PD had significantly worse OS than those with non-early PD (10 vs. 42 months; P = 0.0002). Multivariate analyses identified bone metastasis and performance status (PS) as independent indicators of early PD (P = 0.03 and 0.01, respectively). Early PD rates varied by metastatic site (lung, 19.3%; bone, 31.2%; brain, 10%; and liver, 30%). Patients with clear-cell RCC had a median OS of 48 months and PFS of 22 months. The identified variables of early PD were consistent across all patient populations evaluated. CONCLUSIONS: Bone metastasis and PS predict early PD in patients with mRCC treated with ipilimumab plus nivolumab, with antitumor effect of the regimen varying by metastatic site. Clarifying the characteristics of early PD may guide clinical decision-making in treatment selection.

DOI： 10.1007/s10147-025-02878-z

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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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INTRODUCTION: Immunotherapy treatments, such as intravesical Bacillus Calmette-Guérin (BCG) for non-muscle invasive bladder cancer (NMIBC) and systemic immune checkpoint inhibitors (ICIs) for all stages are central to the management of urothelial carcinoma (UC). Biomarkers that are prognostic or predictive and that help in monitoring these therapies are needed to guide and improve efficacy and tolerability. In this review, we evaluated the current landscape of urinary biomarkers for predicting response to immunotherapy (BCG and ICIs) in UC patients and their potential to guide personalized treatment strategies. AREAS COVERED: This narrative review summarizes current evidence on urinary biomarkers for predicting responses to BCG and ICIs therapies in UC, based on a comprehensive search of PubMed literature. EXPERT OPINION: Urinary biomarkers show significant potential for transforming UC immunotherapy by facilitating personalized treatment. Despite promising initial data for various analytes, large-scale validation and standardization must be addressed. We still need better, faster, easier, cheaper, reliable and valid urine-based biomarkers. Future research should focus on multiplex panels to enhance patient stratification and improve therapeutic outcomes and follow-up.

DOI： 10.1080/14737159.2025.2573459

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PURPOSE: Despite 4-6 cycles of first-line chemotherapy being recommended before the initiation of avelumab maintenance treatment, a non-negligible number of patients received <4 cycles of first-line chemotherapy due to adverse events or pre-existing comorbidities. We assessed the prognostic impact of the number of first-line chemotherapy cycles in patients with metastatic urothelial carcinoma (mUC) treated with avelumab maintenance. METHODS: In this multi-institutional study, data were collected from patients with mUC who received avelumab maintenance treatment following first-line chemotherapy. Patients were divided into those who received <4 cycles versus ≥4 cycles of first-line chemotherapy. Kaplan-Meier curves and Cox regression analysis were used to assess the association of chemotherapy cycle numbers with overall survival (OS) and cancer-specific survival (CSS). RESULTS: Of 91 patients included in this analysis, 17 (19%) underwent <4 cycles of chemotherapy. Patients with <4 cycles of first-line chemotherapy were less likely to receive carboplatin-containing chemotherapy compared with their counterparts (6% versus 39%). On multivariable Cox regression analyses adjusted for the effects of confounding factors, receiving <4 cycles of chemotherapy was significantly associated with worse OS and CSS (HR 2.85; P = .006 and HR 3.18; P = .005, respectively), which was confirmed by subgroup analysis focusing on patients with 1-6 cycles of chemotherapy. Cisplatin-based chemotherapy use was associated with better OS over carboplatin-based chemotherapy (HR 0.41; P = .033). CONCLUSIONS: An inadequate number of first-line chemotherapy cycles was associated with poor survival outcomes. Four or more cycles of first-line platinum-based chemotherapy may be beneficial to ensure the efficacy of avelumab maintenance treatment in patients with mUC.

DOI： 10.1093/jjco/hyaf163

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BACKGROUND AND OBJECTIVE: Transperineal ultrasound-guided prostate biopsy is the recommended approach in guidelines, while transrectal ultrasound-guided prostate biopsy (TRUS-PB) is still widely used to diagnose prostate cancer (PCa); however, it is associated with a significant rate of infectious complications. We aimed to assess the efficacy of targeted prophylactic antibiotics (TPAs), based on rectal swabs, in reducing the incidence of infectious complications after TRUS-PB compared with empiric prophylactic antibiotics. METHODS: PubMed, Web of Science, and Scopus were queried in December 2024 for randomized controlled trials (RCTs) comparing infectious complications between patients who received TPAs based on rectal swab culture before TRUS-PB and those who received empiric prophylactic antibiotics before TRUS-PB (PROSPERO: CRD42024523794). The primary outcomes were the incidence rates of febrile urinary tract infection (fUTI) and sepsis. KEY FINDINGS AND LIMITATIONS: Overall, nine RCTs (n = 3002) were included in our analyses. The incidence of fUTI was approximately half as high in patients who received TPAs as in those who received empiric prophylactic antibiotics (n = 3002, 2.7% vs 5.2%, risk ratio [RR]: 0.54, 95% confidence interval [CI]: 0.36-0.81, p = 0.003). Based on these pooled incidence rates, the number of patients needed to treat to prevent fUTI after TRUS-PB was 40; however, there was no statistically significant difference in the incidence of sepsis between patients receiving TPAs and those who received empiric antibiotic prophylaxis (n = 2735, 1.3% vs 1.8%, RR: 0.74, 95% CI: 0.31-1.75, p = 0.4). CONCLUSIONS AND CLINICAL IMPLICATIONS: TPAs based on rectal swab culture significantly reduces the incidence of fUTI in patients who undergo TRUS-PB for PCa diagnosis compared with that in patients who receive empiric prophylactic antibiotics; however, there is insufficient evidence to assess its effect on the risk of sepsis. We recommend, based on the clinically relevant reduction in the incidence of fUTI, performing rectal swab-based TPAs in patients undergoing TRUS-PB. PATIENT SUMMARY: We reviewed infections occurring after transrectal prostate biopsy in over 3000 patients. The use of antibiotics chosen based on a simple rectal swab decreased the rate of postbiopsy fever and urinary tract infections by half compared with the use of standard antibiotics. More research is needed to understand whether this approach also prevents the rare but serious complication of sepsis.

DOI： 10.1016/j.euros.2025.08.007

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

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BACKGROUND: Testosterone replacement therapy is commonly used in transgender men for masculinization. One of the most common adverse effects of testosterone replacement therapy is androgenetic alopecia. In Japan, finasteride is approved exclusively for cisgender men and is not indicated for transgender men. The aim of this clinical trial was to evaluate the safety and efficacy of finasteride in transgender men with androgenetic alopecia. CASE PRESENTATION: This study included three transgender men (assigned female at birth, identifying as male), aged 44, 43, and 29 years. All participants were of Asian ethnicity. A clinical trial was conducted from October 2021 to December 2023. Transgender men aged 20-60 years who had not undergone hysterectomy, were undergoing testosterone replacement therapy, and who had been diagnosed with stage ≥ II androgenetic alopecia on the basis of the Norwood-Hamilton scale were recruited. The participants initiated treatment with 0.2 mg of finasteride per day for 3 months (phase 1). If no adverse events above grade 2 occurred, the dose was increased to 1.0 mg per day for an additional 3 months (phase 2). The primary endpoints were the incidence of treatment-related adverse events at 1 week, 1 month, and 3 months, as well as the rate of participants continuing treatment at 3 months. None of the patients experienced serious adverse events at 3 months, and all the patients extended their treatment to a total of 6 months. Improvements of at least one stage on the N-H scale were observed, but two participants experienced resumption of menstruation. CONCLUSION: Finasteride appears to be a safe and effective treatment for androgenetic alopecia in transgender men undergoing testosterone replacement therapy. However, its potential for reducing some of the effects of testosterone replacement therapy warrants further investigation. TRIAL REGISTRATION: jRCT, jRCTs061210040, registered 7 October 2021, https://jrct.mhlw.go.jp/latest-detail/jRCTs061210040 .

DOI： 10.1186/s13256-025-05562-y

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Clinical improvement in pigmentation is frequently observed after kidney transplantation. However, the underlying molecular and histological mechanisms remain unclear. We conducted a study to quantify the skin color change using a handheld reflected light colorimeter and to investigate protein expression changes in the skin before and after kidney transplantation. Paired skin biopsies were obtained from three patients who underwent kidney transplantation before and one month after transplantation. Protein expression was analyzed using iTRAQ-based quantitative proteomics. Differentially expressed proteins were identified and visualized using hierarchical clustering and volcano plots. Histopathological evaluation included hematoxylin and eosin (H&E), Masson's trichrome, and immunohistochemical (IHC) staining for keratin (KRT) 7, KRT19, and MelanA. Skin pigmentation of the arms, ankles, and abdomen had significant L-value improvement after kidney transplantation. Proteomic profiling identified 2148 proteins, with six proteins showing significant differential expression after transplantation. Among them, KRT7, KRT19, and prostaglandin D2 synthase (PTGDS) were significantly downregulated, potentially reflecting reduced epithelial stress and systemic inflammation. H&E and Masson's trichrome staining revealed a post-transplantation reduction in dermal pigmentation and collagen content. IHC showed decreased KRT7, KRT19, and MelanA expression after transplantation. Our results suggest that targeting KRT or prostaglandin pathways may offer new treatments for ESRD-related skin symptoms.

DOI： 10.1038/s41598-025-18391-2

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DOI： 10.1111/iju.70116

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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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DOI： 10.3390/jcm14176102

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BACKGROUND/AIM: Immune-related adverse events (irAEs) are associated with improved clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immuno-oncology therapy. However, various irAEs occur during such therapy. In this study, we analyzed the association between irAEs and prognosis of patients with mRCC treated with nivolumab and ipilimumab. PATIENTS AND METHODS: We retrospectively collected data from 193 patients with mRCC who were treated with nivolumab and ipilimumab as first-line treatment between September 2018 and February 2023 at multiple institutions. We performed Cox proportional hazards analysis for progression-free (PFS) and overall (OS) survival to identify specific irAEs associated with prognosis. RESULTS: Among the 153 eligible patients (median age=68 years; range=27-86 years, the median PFS was 7.8 months (95% confidence interval=6.0-12.5 months), and the median OS was 34.0 months (95% confidence interval=23.9 months - not reached). The most common irAEs were endocrine disorder (28.8%), rash (18.3%), pulmonary disorder (10.5%), and liver dysfunction (9.8%). In the multivariate analysis, endocrine disorder-related irAEs were identified as prognostic factors for significantly better PFS and OS. Additionally, rash-related irAEs were significant prognostic factors, specifically for better OS (p<0.05). CONCLUSION: Both rash and endocrine disorder-related irAEs were predictors of survival outcomes in patients with mRCC treated with nivolumab and ipilimumab. Optimal management of these irAEs is essential for improving prognosis.

DOI： 10.21873/anticanres.17696

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

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

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Background

No direct cost comparison has been conducted between percutaneous cryoablation (PCA) and robot-assisted partial nephrectomy (RAPN) for clinical T1a renal cell carcinoma (RCC) in Japan. This study aimed to compare their costs.

Methods

We retrospectively analyzed data from 212 PCAs (including 155 with transcatheter arterial embolization) and 119 RAPN cases performed between December 2017 and May 2022.

Results

PCA patients were older with higher American Society of Anesthesiologists scores, Charlson Comorbidity Index, and history of previous RCC treatment, cardiovascular disease, and antithrombotic drug use than RAPN patients. PCA was associated with a significantly shorter procedure time and hospitalization duration with fewer major complications than those associated with RAPN. While PCA incurred a slightly lower total cost (1,123,000 vs. 1,155,000 yen), it had a significantly higher procedural cost (739,000 vs. 693,000 yen) and markedly worse total (− 93,000 vs. 249,000 yen) and procedural income-expenditure balance (− 189,000 vs. 231,000 yen) than those of RAPN. After statistical adjustment, PCA demonstrated significantly higher total (difference: 114,000 yen) and procedural costs (difference: 72,000 yen), alongside significantly worse total (difference: − 358,000 yen) and procedural income-expenditure balances (difference: − 439,000 yen). The incremental cost-effectiveness ratio was more favorable for PCA than for RAPN.

Conclusion

For high- risk patients, PCA demonstrated a safer option with shorter hospitalization duration than those of RAPN. Although PCA was more cost-effective, its higher procedural cost and unfavorable income-expenditure balance require careful evaluation, especially for large tumors that require three or more needles.

DOI： 10.1007/s10147-025-02783-5

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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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DOI： 10.1245/s10434-025-17017-1

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DOI： 10.3390/antibiotics14050468

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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：Japanese   Publisher：Okayama Medical Association  

DOI： 10.4044/joma.137.25

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I034102123

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

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DOI： 10.1111/iju.15635

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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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Major guidelines for living-donor kidney transplantation underscore the need for pre-donation evaluation of renal function, hypertension, obesity, diabetes mellitus, and albuminuria to minimize the risk of donation from marginal donors. However, validity is yet to be established. We retrospectively investigated the relationship between clinical characteristics and histological indices in baseline renal biopsies (0-h biopsies) and whether these parameters could predict renal function in living kidney donors one year post-donation. Seventy-six living kidney donors were recruited for this study. In histological analyses, glomerulosclerosis, arteriosclerosis, arteriolosclerosis, arteriolar hyalinosis, and interstitial fibrosis and tubular atrophy scores/indices were evaluated. Post-donation serum creatinine levels in kidney donors with arteriolar hyalinosis were significantly higher than those in individuals without arteriolar hyalinosis. There was a significant correlation between baseline serum uric acid levels and the arteriolar hyalinosis index, with baseline uric acid level identified as an independent factor for hyalinosis in multiple regression analysis. Additionally, the serum uric acid level was a significant prognostic factor for post-donation serum creatinine after adjustment for baseline clinical parameters. These data demonstrate that pre-donation serum uric acid levels are associated with arteriolar hyalinosis in the kidney and could predict a decline in renal function during the first year after donation in living kidney donors.

DOI： 10.1371/journal.pone.0320482

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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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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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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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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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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)日本泌尿器内視鏡・ロボティクス学会  

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

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DOI： 10.1007/s00345-024-05195-8

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OBJECTIVE: To compare the differential efficacy of first-line immune checkpoint inhibitor (ICI)-based combined therapies among patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC), as recently, the efficacy of triplet therapy comprising nivolumab plus ipilimumab plus cabozantinib has been published. PATIENTS AND METHODS: Three databases were searched in December 2022 for randomised controlled trials (RCTs) analysing oncological outcomes in patients with mRCC treated with first-line ICI-based combined therapies. We performed network meta-analysis (NMA) to compare the outcomes, including progression-free survival (PFS) and objective response rates (ORRs), in patients with intermediate- and poor-risk mRCC; we also assessed treatment-related adverse events. RESULTS: Overall, seven RCTs were included in the meta-analyses and NMAs. Treatment ranking analysis revealed that pembrolizumab + lenvatinib (99%) had the highest likelihood of improved PFS, followed by nivolumab + cabozantinib (79%), and nivolumab + ipilimumab + cabozantinib (77%). Notably, compared to nivolumab + cabozantinib, adding ipilimumab to nivolumab + cabozantinib did not improve PFS (hazard ratio 1.02, 95% confidence interval 0.72-1.43). Regarding ORRs, treatment ranking analysis also revealed that pembrolizumab + lenvatinib had the highest likelihood of providing better ORRs (99.7%). The likelihoods of improved PFS and ORRs of pembrolizumab + lenvatinib were true in both International Metastatic RCC Database Consortium (IMDC) risk groups. CONCLUSIONS: Our analyses confirmed the robust efficacy of pembrolizumab + lenvatinib as first-line treatment for patients with intermediate or poor IMDC risk mRCC. Triplet therapy did not result in superior efficacy. Considering both toxicity and the lack of mature overall survival data, triplet therapy should only be considered in selected patients.

DOI： 10.1111/bju.16336

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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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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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BACKGROUND AND OBJECTIVE: Although digital rectal examination (DRE) is recommended in combination with prostate-specific antigen (PSA) for detection of prostate cancer (PCa), there are limited data to support its use as a screening/early detection test. Our objective was to assess the diagnostic value of DRE in screening for early detection of PCa. METHODS: In August 2023, we queried the PubMed, Scopus, and Web of Science databases to identify prospective studies simultaneously investigating the diagnostic performance of DRE and PSA for PCa screening. The primary endpoints were the positive predictive value (PPV) and cancer detection rate (CDR) of DRE. Secondary endpoints included the PPV and CDR of both PSA alone and in combination with DRE. We conducted meta-regression analysis to compare the CDR and PPV of different screening strategies. This meta-analysis is registered on PROSPERO (CRD42023446940). KEY FINDINGS AND LIMITATIONS: We identified eight studies involving 85,798 participants, of which three were randomized controlled trials and five were prospective diagnostic studies, that reported the PPV and CDR of both DRE and PSA for the same cohort. Our analysis revealed a pooled PPV of 0.21 (95% confidence interval [CI] 0.13-0.33) for DRE, which is similar to the PPV of PSA (0.22, 95% CI 0.15-0.30; p = 0.9), with no benefit from combining DRE and PSA (PPV 0.19, 95% CI 0.13-0.26; p = 0.5). However, the CDR of DRE (0.01, 95% CI: 0.01-0.02) was significantly lower than that of PSA (0.03, 95% CI 0.02-0.03; p < 0.05) and the combination of DRE and PSA (0.03, 95% CI 0.02-0.04; p < 0.05). The screening strategy combining DRE and PSA was not different to that of PSA alone in terms of CDR (p = 0.5) and PPV (p = 0.5). CONCLUSIONS AND CLINICAL IMPLICATIONS: Our comprehensive review and meta-analysis indicates that both as an independent test and as a supplementary measure to PSA for PCa detection, DRE exhibits a notably low diagnostic value. The collective findings from the included studies suggest that, in the absence of clinical symptoms and signs, DRE could be potentially omitted from PCa screening and early detection strategies. PATIENT SUMMARY: Our review shows that the screening performance of digital rectal examination for detection of prostate cancer is not particularly impressive, suggesting that it might not be necessary to conduct this examination routinely.

DOI： 10.1016/j.euo.2023.12.005

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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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(1) Background: Intravesical chemotherapy is the standard of care in intermediate-risk non-muscleinvasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost, and practice patterns. Epirubicin (EPI), one of these agents, has been used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability are still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: This study aimed to systematically review the efficacy and safety profile of Epirubicin (EPI) in the management of non-muscle invasive bladder cancer (NMIBC) compared to other adjuvant therapies. A systematic search of the PUBMED, Web of Science, clinicaltrials.gov, and Google Scholar databases was conducted on 31 December 2023, using relevant terms related to EPI, bladder cancer, and NMIBC. The inclusion criteria targeted studies that evaluated patients treated with EPI following the transurethral resection of bladder tumors (TURBT) for NMIBC and compared oncological outcomes such as recurrence and progression with other adjuvant therapies, including Mitomycin C (MMC), Gemcitabine (GEM), and Bacillus Calmette-Guérin (BCG). Additionally, studies investigating the safety profile of EPI administered intravesically at room temperature and under hyperthermia, as well as oncological outcomes associated with hyperthermic intravesical EPI administration, were included. (3) Results: Eleven studies reported adverse events after adjuvant intravesical instillations with EPI; the most frequently reported adverse events included cystitis (34%), dysuria, pollakiuria, hematuria, bladder irritation/spasms, fever, nausea and vomiting, and generalized skin rash (2.3%). Nine studies compared EPI to BCG in terms of recurrence and progression rates; BCG instillations showed a lower recurrence rate compared to EPI, with limited or non-significant differences in progression rates. Two studies found no significant differences between EPI and MMC regarding progression and recurrence rates. One study showed statistically significant lower recurrence and progression rates with GEM in high-risk NMIBC patients. Another study found no significant differences between EPI and GEM regarding recurrence and progression. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are interesting newcomers.

DOI： 10.3390/jcm13133789

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BACKGROUND: Triplet therapy, androgen receptor signaling inhibitors (ARSIs) plus docetaxel plus androgen-deprivation therapy (ADT), is a novel guideline-recommended treatment for metastatic hormone-sensitive prostate cancer (mHSPC). However, the optimal selection of the patient most likely to benefit from triplet therapy remains unclear. METHODS: We performed a systematic review, meta-analysis, and network meta-analysis to assess the oncologic benefit of triplet therapy in mHSPC patients stratified by disease volume and compare them with doublet treatment regimens. Three databases and meeting abstracts were queried in March 2023 for randomized controlled trials (RCTs) evaluating patients treated with systemic therapy for mHSPC stratified by disease volume. Primary interests of measure were overall survival (OS). We followed the PRISMA guideline and AMSTAR2 checklist. RESULTS: Overall, eight RCTs were included for meta-analyses and network meta-analyses (NMAs). Triplet therapy outperformed docetaxel plus ADT in terms of OS in both patients with high-(pooled HR: 0.73, 95%CI 0.64-0.84) and low-volume mHSPC (pooled HR: 0.71, 95%CI 0.52-0.97). There was no statistically significant difference between patients with low- vs. high-volume in terms of OS benefit from adding ARSI to docetaxel plus ADT (p = 0.9). Analysis of treatment rankings showed that darolutamide plus docetaxel plus ADT (90%) had the highest likelihood of improved OS in patients with high-volume disease, while enzalutamide plus ADT (84%) had the highest in with low-volume disease. CONCLUSIONS: Triplet therapy improves OS in mHSPC patients compared to docetaxel-based doublet therapy, irrespective of disease volume. However, based on treatment ranking, triplet therapy should preferably be considered for patients with high-volume mHSPC while those with low-volume are likely to be adequately treated with ARSI + ADT.

DOI： 10.1007/s10147-024-02485-4

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BACKGROUND: No head-to-head clinical trials have compared the differences in adverse events (AEs) between nivolumab plus ipilimumab (NIVO-IPI) and nivolumab plus cabozantinib (NIVO-CABO) in the treatment of metastatic renal cell carcinoma (mRCC). AIM: We analysed the two largest real-world databases, the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's VigiBase, to elucidate the differences in AEs between NIVO-IPI and NIVO-CABO. METHOD: In total, 40,376 and 38,022 records were extracted from FAERS and VigiBase, and 193 AEs were analysed. The reporting odds ratios (ROR) with 95% confidence interval were calculated using a disproportionality analysis (NIVO-CABO/NIVO-IPI). RESULTS: The reported numbers of immune-related AEs, including myocarditis, colitis, and hepatitis, were significantly higher with NIVO-IPI (ROR = 0.18 for FAERS and 0.13 for VigiBase). Contrarily, the reported numbers of other AEs, including gastrointestinal disorders (ROR = 2.68 and 2.92) and skin and subcutaneous tissue disorders (ROR = 2.94 and 3.55), considered to be potentiated by the combination of NIVO and CABO, were higher with NIVO-CABO. CONCLUSION: Our findings contribute to the selection and clinical management of NIVO-IPI and NIVO-CABO, which minimizes the risk of AEs for individual patients with mRCC by considering distinctive differences in the AE profiles.

DOI： 10.1007/s11096-024-01713-1

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CONTEXT: Active surveillance (AS) is a standard of care for patients with low-risk and selected intermediate-risk prostate cancer (PCa). Nevertheless, there is a lack of summary evidence on how to impact disease trajectory during AS. OBJECTIVE: To assess which interventions prevent PCa progression effectively during AS. EVIDENCE ACQUISITION: We queried PubMed, Scopus, and Web of Science databases to identify studies examining the impact of interventions aimed at slowing disease progression during AS. The primary endpoint was PCa progression, the definition of which must have included pathological upgrading. The secondary endpoint included treatment toxicities. EVIDENCE SYNTHESIS: We identified 22 studies, six randomized controlled trials and 16 observational studies, which analyzed the association between different interventions and PCa progression during AS. The interventions considered in the studies included 5-alpha reductase inhibitors (5-ARIs), statins, diet, exercise, chlormadinone, fexapotide triflutate (FT), enzalutamide, coffee, vitamin D3, and PROSTVAC. We found that administration of 5-ARIs was associated with improved progression-free survival (PFS; hazard ratio: 0.59; 95% confidence interval 0.48-0.72), with no increased toxicity signals. Therapies such as vitamin D3, chlormadinone, FT, and enzalutamide have shown some efficacy. However, these anticancer drugs have been associated with treatment-related adverse events in up to 88% of patients. CONCLUSIONS: The use of 5-ARIs in PCa patients on AS is associated with longer PFS. However, for the other interventions, it is difficult to draw clear conclusions based on the weak available evidence. PATIENT SUMMARY: Patients with prostate cancer managed with active surveillance (AS) who are treated with 5-alpha reductase inhibitors have a lower risk of disease progression, with minimal adverse events. Other interventions require more studies to determine their efficacy and safety profile in men on AS.

DOI： 10.1016/j.euo.2023.10.010

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

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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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OBJECTIVE: To evaluate the impact of adjuvant therapy on oncological outcomes in patients with intermediate-risk non-muscle-invasive bladder cancer (NMIBC), as due to the poorly-defined and overlapping diagnostic criteria optimal decision-making remains challenging in these patients. PATIENTS AND METHODS: In this multicentre study, patients treated with transurethral resection of bladder tumour for Ta disease were retrospectively analysed. All patients with low- or high-risk NMIBC were excluded from the analysis. Associations between adjuvant therapy administration with recurrence-free survival (RFS) and progression-free survival (PFS) rates were assessed in Cox regression models. RESULTS: A total of 2206 patients with intermediate-risk NMIBC were included in the analysis. Among them, 1427 patients underwent adjuvant therapy, such as bacille Calmette-Guérin (n = 168), or chemotherapeutic agents, such as mitomycin C or epirubicin (n = 1259), in different regimens up to 1 year. The median (interquartile range) follow-up was 73.3 (38.4-106.9) months. The RFS at 1 and 5 years in patients treated with adjuvant therapy and those without were 72.6% vs 69.5% and 50.8% vs 41.3%, respectively. Adjuvant therapy was associated with better RFS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.70-0.89, P < 0.001), but not with PFS (P = 0.09). In the subgroup of patients aged ≤70 years with primary, single Ta Grade 2 <3 cm tumours (n = 328), adjuvant therapy was not associated with RFS (HR 0.71, 95% CI 0.50-1.02, P = 0.06). While in the subgroup of patients with at least one risk factor including patient age >70 years, tumour multiplicity, recurrent tumour and tumour size ≥3 cm (n = 1878), adjuvant intravesical therapy was associated with improved RFS (HR 0.78, 95% CI 0.68-0.88, P < 0.001). CONCLUSION: In our study, patients with intermediate-risk NMIBC benefit from adjuvant intravesical therapy in terms of RFS. However, in patients without risk factors, adjuvant intravesical therapy did not result in a clear reduction in the recurrence rate.

DOI： 10.1111/bju.16371

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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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To evaluate the oncological outcomes and safety of primary retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) II seminomatous testicular germ cell tumor (TGCT). A literature search using PubMed, Scopus, and Cochrane Library was conducted on July 2023 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta Analysis (PRISMA) guidelines. The pooled recurrence rate and treatment-related complications were calculated using a random effects model. Overall 8 studies published between 1997 and 2023 including a total of 355 patients were selected for systematic review and meta-analysis with the overall median follow-up of 38 months. The overall and infield recurrence rate were 0.14 (95% CI: 0.08-0.22) and 0.04 (95% CI: 0.00-0.11), respectively. The overall pooled rate of ≥ Clavien Dindo grade III complications was 0.04 (95% CI: 0.01-0.10); there was no significant heterogeneity (I^2 = 35.10%, P = 0.19). Antegrade ejaculation was preserved with the overall pooled rate of 0.98 (95% CI: 0.95-1.00); there was no significant heterogeneity on Chi-square and I2 tests (I^2 = 0.00%, P = 0.58). Primary RPLND is a safe and effective treatment option for patients with CS II seminomatous TGCT resulting highly promising cure rates combined with low treatment-associated adverse events, at medium-term follow-up. However, owing to the lack of comparative studies to the current standard of care and the limited follow-up, individual decision must be made with the informed patient in a shared decision process together with a multidisciplinary team.

DOI： 10.1016/j.urolonc.2024.01.014

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

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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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Authorship：Lead author  

DOI： 10.21873/anticanres.16822.

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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：一般社団法人 日本移植学会  

【目的】腎移植における術前栄養状態と骨格筋評価がレシピエントの腎予後に関与するかについて検討した。【対象と方法】2009年5月~2022年12月に当院で腎移植を行った144症例。術前栄養状態としてcontrolling nutritional status: CONUT score（血清アルブミン、総コレステロール、末梢リンパ球数による栄養評価指標、cut off値3）、骨格筋評価として腹部CTを用いたpsoas muscle mass index: PMI(腰椎第3レベル、cut off値:男性6.36cm2/m2、女性3.92cm2/m2)をそれぞれ算出し、全腎生着率を比較検討した。【結果】年齢中央値や性別、透析歴、免疫学的リスク、術前脱感作歴に差はなかった。術前低栄養群で糖尿病罹患率が高く(11.7% vs 30.0%, p=0.011)、低骨格筋群でBMI低値であった(22.2kg/m2 vs 20.9kg/m2, p=0.032)。周術期合併症や急性拒絶有無に関して各群間で差を認めなかったが、低栄養群で術後1年以内に入院を要した感染症発生率が高かった (23.4% vs 46.0%, p=0.008)。術前低栄養かつ低骨格筋群は術前低栄養もしくは低骨格筋群、術前栄養・骨格筋正常群と比較し、5年移植腎生着率の低下を認めた(77.0% vs 89.4% vs 92.7%, P=0.013)。移植腎廃絶のリスク因子として、術前低栄養かつ低骨格筋量 (HR; 4.88, 95% CI 1.48-16.1, P=0.009)が認められた。【結語】術前低栄養かつ低骨格筋量を認める腎移植レシピエントは、腎生着悪化のリスクを有することが示唆された。

DOI： 10.11386/jst.59.supplement_s323_2

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Non-metastatic upper urinary tract carcinoma (UTUC) is a comparatively rare condition, typically managed with either kidney-sparing surgery (KSS) or radical nephroureterectomy (RNU). Irrespective of the chosen therapeutic modality, patients with UTUC remain at risk of recurrence in the bladder; in patients treated with KSS, the risk of recurrence is high in the remnant ipsilateral upper tract system but there is a low but existent risk in the contralateral system as well as in the chest and in the abdomen/pelvis. For patients treated with RNU for high-risk UTUC, the risk of recurrence in the chest, abdomen, and pelvis, as well as the contralateral UT, depends on the tumor stage, grade, and nodal status. Hence, implementing a risk-stratified, location-specific follow-up is indicated to ensure timely detection of cancer recurrence. However, there are no data on the type and frequency/schedule of follow-up or on the impact of the recurrence type and site on outcomes; indeed, it is not well known whether imaging-detected asymptomatic recurrences confer a better outcome than recurrences detected due to symptoms/signs. Novel imaging techniques and more precise risk stratification methods based on time-dependent probabilistic events hold significant promise for making a cost-efficient individualized, patient-centered, outcomes-oriented follow-up strategy possible. We show and discuss the follow-up protocols of the major urologic societies.

DOI： 10.3390/cancers16010044

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Authorship：Lead author   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/cancers15245873

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DOI： 10.1007/s12672-023-00816-x

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Authorship：Lead author   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/iju.15221

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DOI： 10.2217/imt-2023-0039

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DOI： 10.2217/imt-2022-0309

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DOI： 10.1002/iju5.12599

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DOI： 10.3390/jpm13040641

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DOI： 10.1097/MOU.0000000000001095.

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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)日本インターベンショナルラジオロジー学会  

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Publishing type：Research paper (scientific journal)  

DOI： 10.3390/curroncol30020170

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

DOI： 10.3892/mco.2022.2603

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Authorship：Lead author  

DOI： 10.11302/jserjje.35.2_290

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Authorship：Lead author  

DOI： 10.18926/AMO/63906.

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Language：Japanese   Publisher：一般社団法人 日本移植学会  

【緒言】生体腎移植ドナーの長期的予後は、一般人口と同様でQOLも損なわないことが示されている。しかし、高血圧や年齢などの医学的問題を抱えたマージナルドナー(MD)のQOLに関する報告は少ない。今回、当院におけるMDの腎提供後5年間のQOL変化をスタンダードドナー(SD)と比較した。【対象・方法】2009年2月~2021年4月の間に当院で腎提供を経験した症例のうち、SF-36v2を使用したQOL評価を腎提供後1年以上継続して行えた81例(SD40例、MD41例)を対象とし、国民標準値50点と比較した。また、術後の腎機能推移、CVD併発、新規悪性腫瘍発生についても比較検討した。【結果】両群間で術後の腎機能推移、CKD 3b以上の症例数に有意差なく(各群10例ずつ)、CVDや悪性腫瘍発生についても有意差を認めなかった。術前において3つのQOLサマリースコアは国民標準値と比較し高く、両群間で有意差を認めなかった。術後の身体的QOLサマリースコア(PCS)において、術後2か月(53.3 vs 50.1, P=0.03)、術後1年(55.3 vs 52.5, P=0.03)、術後4年(53.8 vs 51.8, P=0.01)、術後5年(53.9 vs 49.5, P=0.03)でMD群はSD群と比較し有意に低下していた。術後の精神的QOLサマリースコア(MCS)、社会的QOLサマリースコア(RCS)においては国民標準値と比較し高く、両群間で有意差を認めなかった。【結語】マージナル生体腎移植ドナーの術前QOLは国民標準値と比べ良好であるが、術後PCSにおいてSD群、さらには一般人口と比較し長期的に低下する可能性があり、今後更なる調査が必要である。

DOI： 10.11386/jst.57.supplement_s286_2

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OBJECTIVES: To determine whether neoadjuvant hormonal therapy improves oncological outcomes of patients with localized prostate cancer treated with permanent brachytherapy. METHODS: Between January 2004 and November 2014, 564 patients underwent transperineal ultrasonography-guided permanent iodine-125 seed brachytherapy. We retrospectively analyzed low- or intermediate-risk prostate cancer based on the National Comprehensive Cancer Network guidelines. The clinical variables were evaluated for influence on biochemical recurrence-free survival, progression-free survival, cancer-specific survival and overall survival. RESULTS: A total of 484 patients with low-risk (259 patients) or intermediate-risk disease (225 patients) were evaluated. Of these, 188 received neoadjuvant hormonal therapy. With a median follow up of 71 months, the 5-year actuarial biochemical recurrence-free survival rates of patients who did and did not receive neoadjuvant hormonal therapy were 92.9% and 93.6%, respectively (P = 0.2843). When patients were stratified by risk group, neoadjuvant hormonal therapy did not improve biochemical recurrence-free survival outcomes in low- (P = 0.8949) or intermediate-risk (P = 0.1989) patients. The duration or type of hormonal therapy was not significant in predicting biochemical recurrence. In a multivariate analysis, Gleason score, pretreatment prostate-specific antigen, clinical T stage, and prostate dosimetry, primary Gleason score and positive core rate were significant predictive factors of biochemical recurrence-free survival, whereas neoadjuvant hormonal therapy was insignificant. Furthermore, neoadjuvant hormonal therapy did not significantly influence progression-free survival, cancer-specific survival or overall survival. CONCLUSIONS: In patients with low- or intermediate-risk disease treated with permanent prostate brachytherapy, neoadjuvant hormonal therapy does not improve oncological outcomes. Its use should be restricted to patients who require prostate volume reduction.

DOI： 10.1111/iju.13555

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OBJECTIVES: To describe the frequency of and to determine predictive factors associated with Radiation Therapy Oncology Group urinary toxicity in prostate brachytherapy patients. METHODS: From January 2004 to April 2011, 466 consecutive Japanese patients underwent permanent iodine-125-seed brachytherapy (median follow up 48 months). International Prostate Symptom Score and Radiation Therapy Oncology Group toxicity data were prospectively collected. Prostate volume, International Prostate Symptom Score before and after brachytherapy, and postimplant analysis were examined for an association with urinary toxicity, defined as Radiation Therapy Oncology Group urinary toxicity of Grade 1 or higher. Logistic regression analysis was used to examine the factors associated with urinary toxicity. RESULTS: The rate of Radiation Therapy Oncology Group urinary toxicity grade 1 or higher at 1, 6, 12, 24, 36 and 48 months was 67%, 40%, 21%, 31%, 27% and 28%, respectively. Grade 2 or higher urinary toxicity was less than 1% at each time-point. International Prostate Symptom Score was highest at 3 months and returned to normal 12 months after brachytherapy. On univariate analysis, patients with a larger prostate size, greater baseline International Prostate Symptom Score, higher prostate V100, higher prostate V150, higher prostate D90 and a greater number of seeds had more acute urinary toxicities at 1 month and 12 months after brachytherapy. On multivariate analysis, significant predictors for urinary toxicity at 1 month and 12 months were a greater baseline International Prostate Symptom Score and prostate V100. CONCLUSIONS: Most urinary symptoms are tolerated and resolved within 12 months after prostate brachytherapy. Acute and late urinary toxicity after brachytherapy is strongly related to the baseline International Prostate Symptom Score and prostate V100.

DOI： 10.1111/iju.12050

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Language：Japanese   Publishing type：Research paper (scientific journal)  

Scopus

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00345-011-0738-4

Web of Science

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Language：English  

DOI： 10.1200/jco.2012.30.5_suppl.321

Web of Science

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J-GLOBAL

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

J-GLOBAL

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Language：Japanese   Publisher：東京 : 科学評論社  

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Other Link： https://ndlsearch.ndl.go.jp/books/R000000004-I032529687

Language：English   Publishing type：Research paper, summary (international conference)  

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