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The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis-free survival (MFS) was the primary outcome. Patients were stratified by prostate-specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan-Meier method and log-rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15-0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.

The US Food and Drug Administration recently defined the clinical term "bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer" as a disease state resistant to adequate bacillus Calmette-Guérin therapy. There is a significant lack of prognostication for this disease even in patients who have undergone early radical cystectomy. This study aimed to identify the clinical outcomes and prognostic factors in Japanese patients with bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer who underwent early radical cystectomy.Data from a large-scale multicenter retrospective study included 2879 patients with highest-risk or high-risk non-muscle-invasive bladder cancer who received intravesical bacillus Calmette-Guérin induction therapy between January 2000 and December 2019. A total of 141 patients (4.3%) met the criteria for bacillus Calmette-Guérin-unresponsive disease, of whom 47 (33.3%) underwent early radical cystectomy. Prognostic factors for three clinical endpoints, namely, unresectable lesion-free survival, cancer-specific survival, and overall survival, were identified.The highest-risk status at induction bacillus Calmette-Guérin was associated with short unresectable lesion-free survival (hazard ratio 7.85; P 0.05), cancer-specific survival (hazard ratio 12.24; P 0.05), and overall survival (hazard ratio 9.25; P 0.01). Moreover, extravesical tumors (pathological T3 or T4) on the radical cystectomy specimens were associated with poor prognosis and were found at a higher rate in patients with the highest-risk status at induction bacillus Calmette-Guérin than in those with high-risk status (35.7% vs 21.2%).The highest-risk status among the pre-bacillus Calmette-Guérin factors was associated with upstaging to extravesical tumors and poor prognosis despite early radical cystectomy procedures. Appropriate decision-making and the correct timing of radical cystectomy are vital to avoid treatment delays and improve outcomes.

Objectives To investigate the impact of the number of cycles and objective response to chemotherapy on overall survival in patients with metastatic urothelial carcinoma treated with pembrolizumab. Methods This multicenter, retrospective study included 755 patients from 59 institutions with advanced, chemoresistant urothelial carcinoma who received pembrolizumab. The associations of the overall survival with the number of cycles and best objective response were investigated using Cox multiple regression analysis. Results Overall, 391 patients received standard first-line chemotherapy and pembrolizumab as a second-line treatment, and were included in the final analysis. Of the 391 patients, 185 received less than four cycles, 134 received four to six cycles and 72 received more than six cycles of first-line chemotherapy. An objective response (complete or partial response) to chemotherapy was observed in 145 patients (37.1%). Univariate analysis showed that the overall survival of patients who received more than six cycles or responded to chemotherapy (complete or partial response) was significantly longer than that of patients who received less than four cycles or did not respond to chemotherapy (stable or progressive disease). At multivariate levels, no correlations were observed between overall survival and the number of cycles of or the response to chemotherapy. Conclusions Therapeutic benefit of pembrolizumab can be expected irrespective of the objective response to and number of cycles of platinum-based first-line chemotherapy.

The metastatic burden is a critical factor for decision‐making in the treatment of metastatic hormone‐sensitive prostate cancer (HSPC). This study aimed to develop and validate a novel risk model for survival in patients with de novo low‐ and high‐burden metastatic HSPC. The retrospective observational study included men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We created a risk model for overall survival (OS) in the discovery cohort (n = 1449) stratified by the metastatic burden (low vs high) and validated its predictive ability in a separate cohort (n = 951). Based on multivariate analyses, lower hemoglobin levels, higher Gleason grades, and higher clinical T‐stage were associated with poor OS in low‐burden disease. Meanwhile, lower hemoglobin levels, higher Gleason grade group, liver metastasis, and higher extent of disease scores in bone were associated with poor OS in patients with high‐burden disease. In the discovery and validation cohorts, the risk model using the aforementioned parameters exhibited excellent discriminatory ability for progression‐free survival and OS. The predictive ability of this risk model was superior to that of previous risk models. Our novel metastatic burden‐stratified risk model exhibited excellent predictive ability for OS, and it is expected to have several clinical uses, such as precise prognostic estimation., This study developed and validated a novel metastatic burden‐stratified risk model in de novo metastatic hormone‐sensitive prostate cancer. This novel metastatic burden‐stratified risk model exhibited excellent predictive ability for overall survival, and it is expected to have several clinical uses, such as precise prognostic estimation.

To investigate the association between the onset, severity, and type of immune-related adverse events (irAEs) and the efficacy of pembrolizumab in patients with platinum-pretreated advanced urothelial carcinoma (UC), we retrospectively collected clinical datasets of 755 patients and conducted landmark analysis. Patients who survived for fewer than 3 months were excluded from the evaluation to reduce the immortal time bias. In total, 620 patients were evaluated, of whom 220 patients (35.5%) experienced grade ≥2 irAEs, including 134 patients with grade 2 irAEs and 86 with grade ≥3 irAEs. Propensity score matching extracted 198 patients with and without grade ≥2 irAEs. The onset of grade ≥2 irAEs was associated with longer median progression-free survival (PFS) (8.3 months vs. 4.5 months, p = 0.003) and overall survival (OS) (20.4 months vs. 14.3 months, p = 0.031) and a higher objective response rate (ORR) (44.8% vs. 30.2%, p = 0.004). Patients with grade 2 irAEs had significantly better oncological outcomes (PFS, OS, and ORR) than grade ≤1 and ≥3 irAEs. Patients with grade ≥3 irAEs had worse outcomes than grade 2 irAEs. Endocrine and skin irAEs were related with better survival outcomes, and the rate of severities was lower in these categories. In conclusion, the occurrence of irAEs, particularly low-grade irAEs, was predictive of pembrolizumab efficacy in patients with platinum-pretreated advanced UC.

Background The benefits of pembrolizumab in patients with advanced urothelial carcinoma (UC) and impaired performance status (PS) remain unknown. This study assessed the safety and efficacy of pembrolizumab in patients with platinum‐refractory UC and Eastern Cooperative Oncology Group PS ≥2 to identify which subgroups may benefit from this drug. Methods This retrospective nationwide cohort study collected clinicopathological information for 755 patients from 59 institutions. The overall response rate (ORR) and overall survival (OS) were compared among the patients with PS 0–1, 2, and 3–4. Multivariate analysis was conducted to identify factors predicting OS in patients with PS ≥2. Results The numbers of patients with PS 0–1, 2, and 3–4 were 602, 98, and 55, respectively; the ORRs in these groups were 29.5, 15.3, and 9.1%, respectively, and the median OS times were 14.3, 3.1, and 2.4 months, respectively. In multivariate Cox regression analysis, a neutrophil–lymphocyte ratio (NLR) ≥3.5 (hazard ratio [HR] = 1.897) and liver metastasis (HR = 2.072) were associated with OS in the PS ≥2 subgroup. The median OS of patients with PS ≥2 without either risk factor was 6.8 months, compared with 3.1 months for patients with one risk factor and 2.3 months for patients with both risk factors. Conclusions PS ≥2 portended worse ORR and OS than PS ≤1 despite a comparable safety profile. Among the patients with impaired PS, patients with NLR, Among patients who received pembrolizumab to treat urothelial carcinoma, those with Eastern Cooperative Oncology Group performance status ≥2 exhibited worse overall response rates and overall survival than those with performance status ≤1 despite their comparable safety profiles. Among the patients with impaired performance status, those with a neutrophil–lymphocyte ratio

Metastatic burden is a critical factor for therapy decision‐making in metastatic hormone‐sensitive prostate cancer. The present study aimed to identify prognostic factors in men with high‐ or low‐metastatic burden treated with primary androgen‐deprivation therapy. The study included 2450 men with de novo metastatic prostate cancer who were treated with primary androgen‐deprivation therapy at 30 institutions across Japan between 2008 and 2017. We investigated the prognostic value of various clinicopathological parameters for progression‐free survival (PFS) and overall survival (OS) in patients stratified by low‐ or high‐metastatic burden. Among the 2450 men, 841 (34.3%) and 1609 (65.7%) were classified as having low‐ and high‐metastatic burden, respectively. Median PFS of the low‐ and high‐burden groups were 44.5 and 16.1 months, respectively, and the median OS was 103.2 and 62.7 months, respectively. Percentage of biopsy‐positive core, biopsy Gleason grade group, T‐stage, and N‐stage were identified to be differentially prognostic. M1a was associated with worse PFS than was M1b in the low‐burden group, whereas lung metastasis was associated with better PFS and OS than was M1b in the high‐burden group. Differential prognostic factors were identified for patients with low‐ and high‐burden metastatic prostate cancer. These results may assist in decision‐making to select the optimal therapeutic strategies for patients with different metastatic burdens., This study investigated prognostic factors according to metastatic burden, and found that prognostic impact of some factors was different. This finding may be valuable in decision‐making to select the optimal therapeutic strategies for patients with different metastatic burdens.

Background: Creation of an arteriovenous fistula (AVF) as vascular access is a basic operation that should be learned by all surgeons involved in renal failure treatment. AVF creation is often challenging for inexperienced young surgeons because it requires comprehensive surgical techniques. For such young surgeons, we introduced cadaveric surgical training (CST) for AVF creation using fresh-frozen cadavers (FFCs). This study was performed to identify the differences in AVF surgical techniques between FFCs and living bodies and to examine the impact of CST on young surgeons. Methods: Twelve CST sessions were performed for AVF creation at the Clinical Anatomy Education and Research Center of Tokushima University Hospital from March 2021 to June 2022. Seven young surgeons (1st- and 2nd-year) performed the operation, and two surgeons (10th- and 11th-year) supervised it. We conducted an anonymous questionnaire survey using a 5-point Likert scale to examine the impact of CST on young surgeons. Results: Twelve CST sessions were performed on nine FFCs. All training sessions allowed completion of AVF creation with a median operative time of 78.5 min. Although veins and arteries were more difficult to identify than in a living body, other surgical operations could be performed in the same way as in a living body. All the respondents stated that it was good for them to experience CST. In addition, 86% of surgeons responded that CST improved their surgical techniques, and 71% of surgeons responded that they were less anxious about AVF creation. Conclusions: CST for AVF creation is useful for surgical education because it enables learning of surgical techniques that are almost equivalent to those in living bodies. In addition, this study suggested that CST not only contributes to the improvement of surgical skills of young surgeons but also promotes the reduction of anxiety and stress about AVF creation.

The present study aimed to evaluate the efficacy of the real‐world use of axitinib and to develop a prognostic model for stratifying patients who could derive long‐term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split‐sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model’s favorable risk group might derive a long‐term survival benefit from axitinib treatment., The accuracy of the overall survival predictions made after the initiation of axitinib treatment, area under the curve (AUC) values were calculated for each model. The adjusted AUC values at 12, 36, and 60 months after the initiation of axitinib were 0.77, 0.82, and 0.82, respectively, for the axitinib treatment prediction model, and 0.69, 0.67 and 0.56, respectively, for the International Metastatic Renal Cell Carcinoma Database Consortium model.

(Objectives) Investigation of patient-reported outcome (PRO) after ileal neobladder for bladder cancer. (Patients and methods) Forty patients who underwent radical cystectomy and ileal neobladder between July 2007 and December 2017 were asked to complete a questionnaire. PRO was evaluated using the Medical Outcomes Study Short Form-8 (SF-8) for general health-related quality of life (QOL) and the Bladder Cancer Index and the Japanese version of the Functional Assessment of Cancer Therapy-Bladder for disease specific QOL. Patients were divided into two groups according to the postoperative period (early and late), and the differences in questionnaire results between the groups were evaluated. (Results) All scores on the SF-8 were over 50 points, exceeding the Japanese national standard of 50 points for all items. The physical and mental summary scores were also favorable. For disease-specific QOL, only daytime incontinence was significantly higher in the late group, with daytime incontinence two or more times per week at 42.1%, compared to 20.0% in the early group (P=0.0403). A comparison of daytime urinary incontinence in four groups during the postoperative period showed that urinary incontinence was least frequent among patients between 64 and 101 months after surgery; patients in this group were also the youngest in age at the time of surgery. (Conclusions) Cross-sectional analysis of PRO revealed that patients with ileal neobladder had good general health-related QOL after surgery, but urinary incontinence was a significant problem.

This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC).This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression.At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression.Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.

Objectives This study aimed to evaluate how health-related quality of life (HRQOL) is related to repeat protocol biopsy compliance. Materials and methods We conducted a retrospective analysis using data from a prospective cohort in the Prostate Cancer Research International: Active Surveillance (PRIAS)-JAPAN study between January 2010 and August 2019. We used the Short Form 8 Health Survey (SF-8), as patient-reported outcomes, to assess HRQOL at AS enrollment and the first year of the protocol. The physical component summary (PCS) and mental component summary (MCS) were calculated from SF-8 questionnaires. The primary outcome was the evaluation of the association of HRQOL at enrollment on the first repeat biopsy compliance. The secondary outcome was the comparison of SF-8 scores during AS, stratified by repeat protocol biopsy compliance. Results Of 805 patients who proceeded to the first year of the protocol, the non-compliance rate was 15% (121 patients). In the adjusted model, lower MCS at enrollment was significantly associated with the first repeat protocol biopsy non-compliance (odds ratio [OR], 2.134; 95% confidence interval [CI], 1.031-4.42; P = 0.041) but not in lower PCS (OR, 0.667; 95% CI, 0.294-1.514; P = 0.333). All subscales of SF-8 were lower in the non-compliance group than in the compliance group at any point. MCS in the non-compliance group improved over time from the time of AS enrollment (2.34 increased, P = 0.152). Conclusion Our data suggest that lower MCS at AS enrollment using patient-reported outcomes was negatively associated with the first repeat protocol biopsy compliance. Our study may support the availability of a simple questionnaire to extract non-compliance.

253 Background: An international staging collaboration for cancer of the prostate (STAR-CAP) was recently established and used for predicting oncological outcomes for patients with prostate cancer. However, the validation of STAR-CAP has not yet been performed in the Japanese cohort. Our study aimed to assess the STAR-CAP prognostic model for Japanese patients with prostate cancer and compare it to the CAPRA score for the prediction of biochemical recurrence (BCR) after radical prostatectomy. Methods: We retrospectively analyzed data from a multi-institution database of 1,645 patients who underwent radical prostatectomy between 2010 and 2020. We excluded patients with inadequate follow-up duration ( < 1 year), missing or incomplete perioperative clinical parameters relevant for STAR-CAP, and patients who received neoadjuvant therapy. BCR was defined as two consecutive prostate-specific antigen values ≥ 0.2 ng/mL. The 3-year BCR-free survival was assessed by Kaplan-Meier analyses and log-rank test. The performance of both models to predict 3-year BCR-free survival was assessed using the area under the curve (AUC). Results: The 3-year BCR-free survival ranged from 47.3% (high risk) to 93.5% (low risk) in the STAR-CAP classification ( p< 0.001) and from 62.5% (high risk) to 94.6% (low risk) in the CAPRA classification ( p< 0.001). AUCs for the 3-year BCR prediction were 0.756 and 0.784 for STAR-CAP and CAPRA, respectively. Conclusions: In Japanese patients, both STAR-CAP and CAPRA prognostic systems provide sufficient stratification and their predictive ability for 3-year BCR-free survival is comparable, with a small advantage for CAPRA (2.8%).

Objective To assess patient-reported outcomes after open radical prostatectomy, laparoscopic radical prostatectomy and permanent prostate brachytherapy. Methods patient-reported outcomes were evaluated using Expanded Prostate Cancer Index Composite scores at baseline and 1, 3, 6, 12 and 36 months after treatment, respectively, using differences from baseline scores. Results Urinary function was the same in the three groups at baseline, but worse after surgery than after permanent prostate brachytherapy until 12 months, and similar after open radical prostatectomy and permanent prostate brachytherapy and better than after laparoscopic radical prostatectomy at 36 months. Urinary bother was significantly worse at 1 month after surgery, but better after open radical prostatectomy than after permanent prostate brachytherapy and laparoscopic radical prostatectomy at 3 months, after which symptoms improved gradually in all groups. Obstructive/irritative symptoms were worse after permanent prostate brachytherapy than after open radical prostatectomy at 36 months, and worse after laparoscopic radical prostatectomy until 6 months. Urinary incontinence was worse after surgery, particularly after 1 month. This symptom returned to the baseline level at 12 months after open radical prostatectomy, but recovery after laparoscopic radical prostatectomy was slower. Bowel function after permanent prostate brachytherapy was significantly worse than after surgery at 1 month and this continued until 6 months. Bowel bother was slightly worse at 3 and 6 months after permanent prostate brachytherapy compared to these time points after surgery. Conclusion Urinary function and bother were worst after laparoscopic radical prostatectomy, especially in the early postoperative phase, whereas urinary obstructive/irritative symptom, bowel function and bother were worse after permanent prostate brachytherapy. These findings are useful and informative for the treatment of patients with prostate cancer.

(Objectives) Recently, partial nephrectomy has been recommended for patients with T1 renal cell carcinoma to preserve renal function. In this study, we retrospectively investigated the factors that affect renal function after laparoscopic or robotic partial nephrectomy using cold or warm ischemia. (Patients and methods) We reviewed 105 patients who underwent laparoscopic or robotic partial nephrectomy between March 2006 and July 2016. Patients who had a single kidney were excluded. Thirty-nine patients were managed with cold ischemia, and 66 were managed with warm ischemia. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and glomerular filtration rate (GFR) categories of the stage of chronic kidney disease (CKD). (Results) In the cold and warm ischemia groups, the duration of ischemia was significantly correlated with deterioration of the eGFR at 12 months postoperatively, but the duration of ischemia was not significantly correlated with exacerbation of the GFR categories for the stage of CKD in multivariate analyses. (Conclusions) These results suggest that the ischemia time may not have an impact on prognosis. However, due to the lack of deaths from renal carcinoma or cardiovascular events postoperatively in this study, the influence of each factor on overall survival or cardiovascular events could not be evaluated. More investigations are necessary to discern the acceptable level of deterioration and the corresponding clinical implications for postoperative eGFR.