Faculty Profiles - Katayama Satoshi

Papers - Katayama Satoshi

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Discordance Between Clinical and Pathological Staging and Grading in Upper Tract Urothelial Carcinoma. International journal

Keiichiro Mori, Satoshi Katayama, Ekaterina Laukhtina, Victor M Schuettfort, Benjamin Pradere, Fahad Quhal, Reza Sari Motlagh, Hadi Mostafaei, Nico C Grossmann, Pawel Rajwa, Kristin Zimmermann, Pierre I Karakiewicz, Mohammad Abufaraj, Harun Fajkovic, Morgan Rouprêt, Vitaly Margulis, Dmitry V Enikeev, Shin Egawa, Shahrokh F Shariat

Clinical genitourinary cancer 20 ( 1 ) 95.e1-95.e6 2021.10

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

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

DOI： 10.1016/j.clgc.2021.10.002

Role of systemic immune-inflammation index in patients treated with salvage radical prostatectomy. International journal

Pawel Rajwa, Victor M Schuettfort, Fahad Quhal, Keiichiro Mori, Satoshi Katayama, Ekaterina Laukhtina, Benjamin Pradere, Reza Sari Motlagh, Hadi Mostafaei, Nico C Grossmann, Andreas Aulitzky, Andrzej Paradysz, Pierre I Karakiewicz, Harun Fajkovic, Kristin Zimmermann, Axel Heidenreich, Paolo Gontero, Shahrokh F Shariat

World journal of urology 39 ( 10 ) 3771 - 3779 2021.10

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

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

DOI： 10.1007/s00345-021-03715-4

Impact of paclitaxel, cisplatin, and gemcitabine as first-line chemotherapy in cisplatin-fit and -unfit patients with advanced/metastatic urothelial carcinoma. Reviewed International journal

Satoshi Katayama, Yasuyuki Kobayashi, Atsushi Takamoto, Kohei Edamura, Takuya Sadahira, Takehiro Iwata, Shingo Nishimura, Tomoko Sako, Koichiro Wada, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

Urologic oncology 39 ( 10 ) 731.e25-731.e32 2021.10

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

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

DOI： 10.1016/j.urolonc.2021.02.029

Choosing the Most Efficacious and Safe Oral Treatment for Idiopathic Overactive Bladder: A Systematic Review and Network Meta-analysis. International journal

Hadi Mostafaei, Hanieh Salehi-Pourmehr, Sandra Jilch, Greta Lisa Carlin, Keiichiro Mori, Fahad Quhal, Benjamin Pradere, Nico C Grossmann, Ekaterina Laukhtina, Victor M Schuettfort, Abdulmajeed Aydh, Reza Sari Motlagh, Frederik König, Claus G Roehrborn, Satoshi Katayama, Pawel Rajwa, Sakineh Hajebrahimi, Shahrokh F Shariat

European urology focus 8 ( 4 ) 1072 - 1089 2021.9

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

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

DOI： 10.1016/j.euf.2021.08.011

Prognostic role of the systemic immune-inflammation index in upper tract urothelial carcinoma treated with radical nephroureterectomy: results from a large multicenter international collaboration. International journal

Keiichiro Mori, Irene Resch, Noriyoshi Miura, Ekaterina Laukhtina, Victor M Schuettfort, Benjamin Pradere, Satoshi Katayama, David D'Andrea, Mehdi Kardoust Parizi, Mohammad Abufaraj, Wataru Fukuokaya, Claudia Collà Ruvolo, Stefano Luzzago, Sophie Knipper, Carlotta Palumbo, Pierre I Karakiewicz, Alberto Briganti, Dmitry V Enikeev, Morgan Rouprêt, Vitaly Margulis, Shin Egawa, Shahrokh F Shariat

Cancer immunology, immunotherapy : CII 70 ( 9 ) 2641 - 2650 2021.9

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

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

DOI： 10.1007/s00262-021-02884-w

Impact of enhanced optical techniques at time of transurethral resection of bladder tumour, with or without single immediate intravesical chemotherapy, on recurrence rate of non-muscle-invasive bladder cancer: a systematic review and network meta-analysis of randomized trials. International journal

Reza Sari Motlagh, Keiichiro Mori, Ekaterina Laukhtina, Abdulmajeed Aydh, Satoshi Katayama, Nico C Grossmann, Hadi Mostafai, Benjamin Pradere, Fahad Quhal, Victor M Schuettfort, Mohammad Reza Roshandel, Pierre I Karakiewicz, Jeremy Teoh, Shahrokh F Shariat, Harun Fajkovic

BJU international 128 ( 3 ) 280 - 289 2021.9

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

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

DOI： 10.1111/bju.15383

Intracorporeal versus extracorporeal urinary diversion in robot-assisted radical cystectomy: a systematic review and meta-analysis. Reviewed

Satoshi Katayama, Keiichiro Mori, Benjamin Pradere, Hadi Mostafaei, Victor M Schuettfort, Fahad Quhal, Reza Sari Motlagh, Ekaterina Laukhtina, Marco Moschini, Nico C Grossmann, Yasutomo Nasu, Shahrokh F Shariat, Harun Fajkovic

International journal of clinical oncology 26 ( 9 ) 1587 - 1599 2021.9

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

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

DOI： 10.1007/s10147-021-01972-2

Differences in oncological and toxicity outcomes between programmed cell death-1 and programmed cell death ligand-1 inhibitors in metastatic renal cell carcinoma: A systematic review and meta-analysis. International journal

Keiichiro Mori, Benjamin Pradere, Fahad Quhal, Satoshi Katayama, Hadi Mostafaei, Ekaterina Laukhtina, Victor M Schuettfort, David D'Andrea, Shin Egawa, Karim Bensalah, Manuela Schmidinger, Thomas Powles, Shahrokh F Shariat

Cancer treatment reviews 99 102242 - 102242 2021.9

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

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

DOI： 10.1016/j.ctrv.2021.102242

Comparison of intracorporeal versus extracorporeal urinary diversion after robot-assisted radical cystectomy at a medium-sized facility.

Takehiro Iwata, Yasuyuki Kobayashi, Yuki Maruyama, Tatsushi Kawada, Takuya Sadahira, Yuko Oiwa, Satoshi Katayama, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Koichiro Wada, Kohei Edamura, Motoo Araki, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

International journal of clinical oncology 26 ( 9 ) 1714 - 1721 2021.9

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

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

DOI： 10.1007/s10147-021-01957-1

The Value of Preoperative Plasma VEGF Levels in Urothelial Carcinoma of the Bladder Treated with Radical Cystectomy. International journal

Keiichiro Mori, Victor M Schuettfort, Satoshi Katayama, Ekaterina Laukhtina, Benjamin Pradere, Fahad Quhal, Reza Sari Motlagh, Hadi Mostafaei, Nico C Grossmann, Pawel Rajwa, Frederik König, Abdulmajeed Aydh, Francesco Soria, Marco Moschini, Pierre I Karakiewicz, Yair Lotan, Douglas Scherr, Martin Haydter, Peter Nyirady, Jeremy Y C Teoh, Shin Egawa, Eva Compérat, Shahrokh F Shariat

European urology focus 8 ( 4 ) 972 - 979 2021.8

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

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

DOI： 10.1016/j.euf.2021.08.006

The role of lymph node dissection in salvage radical prostatectomy for patients with radiation recurrent prostate cancer. International journal

Fahad Quhal, Pawel Rajwa, Keiichiro Mori, Ekaterina Laukhtina, Nico C Grossmann, Victor M Schuettfort, Frederik König, Abdulmajeed Aydh, Reza S Motlagh, Satoshi Katayama, Hadi Mostafai, Benjamin Pradere, Giancarlo Marra, Paolo Gontero, Romain Mathieu, Pierre I Karakiewicz, Alberto Briganti, Shahrokh F Shariat, Axel Heidenreich

The Prostate 81 ( 11 ) 765 - 771 2021.8

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

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

DOI： 10.1002/pros.24173

Androgen receptor axis-targeted agents for non-metastatic castration-resistant prostate cancer impact on overall survival and safety profile: an updated systematic review and meta-analysis. International journal

Keiichiro Mori, Fahad Quhal, Satoshi Katayama, Hadi Mostafaei, Ekaterina Laukhtina, Victor M Schuettfort, Reza Sari Motlagh, Nico C Grossmann, Pawel Rajwa, Guillaume Ploussard, Alberto Briganti, Takahiro Kimura, Shin Egawa, Rocco Papalia, Diego M Carrion, Cristian Fiori, Shahrokh F Shariat, Francesco Esperto, Benjamin Pradere

Minerva urology and nephrology 74 ( 3 ) 292 - 301 2021.7

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

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

DOI： 10.23736/S2724-6051.21.04431-1

The Efficacy and Safety of Relugolix Compared with Degarelix in Advanced Prostate Cancer Patients: A Network Meta-analysis of Randomized Trials. International journal

Reza Sari Motlagh, Mohammad Abufaraj, Keiichiro Mori, Abdulmajeed Aydh, Pawel Rajwa, Satoshi Katayama, Nico C Grossmann, Ekaterina Laukhtina, Hadi Mostafai, Benjamin Pradere, Fahad Quhal, Pierre I Karakiewicz, Dmitry V Enikeev, Shahrokh F Shariat

European urology oncology 5 ( 2 ) 138 - 145 2021.7

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

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

DOI： 10.1016/j.euo.2021.07.002

Association of Severe Microscopic Hematuria with Successful Conservative Treatment of Single Uncomplicated Ureteral Calculus: A Multicenter Cohort Study. International journal

Satoshi Katayama, Takashi Yoshioka, Tomoko Sako, Wataru Murao, Motoo Araki, Toyohiko Watanabe, Tadasu Takenaka

European urology focus 7 ( 4 ) 812 - 817 2021.7

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

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

DOI： 10.1016/j.euf.2020.04.004

Accuracy of Frozen Section Analysis of Urethral and Ureteral Margins During Radical Cystectomy for Bladder Cancer: A Systematic Review and Diagnostic Meta-Analysis. International journal

Ekaterina Laukhtina, Pawel Rajwa, Keiichiro Mori, Marco Moschini, David D'Andrea, Mohammad Abufaraj, Francesco Soria, Andrea Mari, Wojciech Krajewski, Simone Albisinni, Jeremy Yuen-Chun Teoh, Fahad Quhal, Reza Sari Motlagh, Hadi Mostafaei, Satoshi Katayama, Nico C Grossmann, Dmitry Enikeev, Kristin Zimmermann, Harun Fajkovic, Petr Glybochko, Shahrokh F Shariat, Benjamin Pradere

European urology focus 8 ( 3 ) 752 - 760 2021.6

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

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

DOI： 10.1016/j.euf.2021.05.010

Impact of the preoperative modified glasgow prognostic score on disease outcome after radical cystectomy for urothelial carcinoma of the bladder. International journal

Victor M Schuettfort, Kilian Gust, David D'Andrea, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Michael Rink, Mohammad Abufaraj, Pierre I Karakiewicz, Stefano Luzzago, Morgan Rouprêt, Dmitry Enikeev, Kristin Zimmermann, Marina Deuker, Marco Moschini, Reza Sari Motlagh, Nico C Grossmann, Satoshi Katayama, Benjamin Pradere, Shahrokh F Shariat

Minerva urology and nephrology 74 ( 3 ) 302 - 312 2021.6

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

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

DOI： 10.23736/S2724-6051.21.04216-6

Accuracy and Clinical Utility of a Tumor Grade- and Stage-based Predictive Model in Localized Upper Tract Urothelial Carcinoma. Reviewed International journal

Satoshi Katayama, Keiichiro Mori, Victor M Schuettfort, Benjamin Pradere, Hadi Mostafaei, Fahad Quhal, Pawel Rajwa, Reza Sari Motlagh, Ekaterina Laukhtina, Marco Moschini, Nico C Grossmann, Motoo Araki, Jeremy Yuen-Chun Teoh, Morgan Rouprêt, Vitaly Margulis, Dmitry Enikeev, Pierre I Karakiewicz, Mohammad Abufaraj, Eva Compérat, Yasutomo Nasu, Shahrokh F Shariat

European urology focus 8 ( 3 ) 761 - 768 2021.5

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

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

DOI： 10.1016/j.euf.2021.05.002

Photodynamic diagnostic ureteroscopy using the VISERA ELITE video system for diagnosis of upper-urinary tract urothelial carcinoma: a prospective cohort pilot study. International journal

Koichiro Wada, Motoo Araki, Ryuta Tanimoto, Takuya Sadahira, Shogo Watari, Yuki Maruyama, Yosuke Mitsui, Hirochika Nakajima, Herik Acosta, Satoshi Katayama, Takehiro Iwata, Shingo Nishimura, Atsushi Takamoto, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Yasutomo Nasu

BMC urology 21 ( 1 ) 45 - 45 2021.3

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

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

DOI： 10.1186/s12894-021-00819-2

Intravesical Therapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Network Meta-analysis of Disease Recurrence. International journal

Ekaterina Laukhtina, Mohammad Abufaraj, Abdallah Al-Ani, Mustafa Rami Ali, Keiichiro Mori, Marco Moschini, Fahad Quhal, Reza Sari Motlagh, Benjamin Pradere, Victor M Schuettfort, Hadi Mostafaei, Satoshi Katayama, Nico C Grossmann, Harun Fajkovic, Francesco Soria, Dmitry Enikeev, Shahrokh F Shariat

European urology focus 8 ( 2 ) 447 - 456 2021.3

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

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

DOI： 10.1016/j.euf.2021.03.016

A panel of systemic inflammatory response biomarkers for outcome prediction in patients treated with radical cystectomy for urothelial carcinoma. International journal

Victor M Schuettfort, David D'Andrea, Fahad Quhal, Hadi Mostafaei, Ekaterina Laukhtina, Keiichiro Mori, Frederik König, Michael Rink, Mohammad Abufaraj, Pierre I Karakiewicz, Stefano Luzzago, Morgan Rouprêt, Dmitry Enikeev, Kristin Zimmermann, Marina Deuker, Marco Moschini, Reza Sari Motlagh, Nico C Grossmann, Satoshi Katayama, Benjamin Pradere, Shahrokh F Shariat

BJU international 129 ( 2 ) 182 - 193 2021.3

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

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

DOI： 10.1111/bju.15379

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