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Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC. Patients and methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non‐urinary tract recurrence‐free survival (NUTR‐FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer. Results: At median follow‐up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR‐FS were observed when TUR specimens were classified as pure‐urothelial carcinoma (UC), subtypes, DD, or non‐UC. Among 2449 patients diagnosed with pure‐UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre‐RC neutrophil–lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively). Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre‐RC neutrophil–lymphocyte ratio and pathological stage were independent prognostic factors for OS. [ABSTRACT FROM AUTHOR]

Objectives: In a primary analysis of data from the BRIGHT study (UMIN000035712), photodynamic diagnosis‐assisted transurethral resection of bladder tumor (PDD‐TURBT) using oral 5‐aminolevulinic acid hydrochloride reduced residual tumors in high‐risk non‐muscle invasive bladder cancer (NMIBC). We aimed to evaluate the effectiveness of PDD‐TURBT for intravesical recurrence after a second transurethral resection for high‐risk NMIBC. Methods: High‐risk NMIBC patients initially treated with PDD‐TURBT (PDD group) were prospectively registered between 2018 and 2020. High‐risk patients with NMIBC who were initially treated with white‐light TURBT (WL group) were retrospectively registered. Intravesical recurrence‐free survival after the second transurethral resection was compared between the PDD and WL groups using propensity score matching analysis. Results: In total, 177 patients were enrolled in the PDD group, and 306 patients were registered in the WL group. After propensity score matching (146 cases in each group), intravesical recurrence within 1 year was significantly less frequent in the PDD group than in the WL group (p = 0.004; hazard ratio [HR] 0.44, 95% confidence interval [CI]: 0.25–0.77). In subgroup analysis, PDD‐TURBT showed a particularly high efficacy in reducing intravesical recurrence within 1 year, especially in cases of tumors measuring less than 3 cm (p = 0.003; HR 0.31, 95% CI: 0.14–0.67), absence of residual tumor at second transurethral resection (p = 0.020; HR 0.37, 95% CI: 0.16–0.86), and no postoperative intravesical Bacillus Calmette‐Guérin therapy (p < 0.001; HR 0.27, 95% CI: 0.13–0.58). Conclusions: PDD‐TURBT may reduce short‐term intravesical recurrence in patients with high‐risk NMIBC. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to compare clinical outcomes between patients receiving second TUR after initial white‐light transurethral resection of bladder tumor (WL‐TURBT) and initial photodynamic diagnosis (PDD)‐assisted TURBT. Methods: A total of 1007 patients were divided into four groups based on the treatment pattern: WL‐TURBT with second TUR (161 patients, WL‐second group) or without second TUR (540 patients, WL‐alone group) and PDD‐TURBT with second TUR (112 patients, PDD‐second group) or without second TUR (194 patients, PDD‐alone group). Oncologic outcomes (bladder cancer recurrence, progression, urothelial cancer‐specific mortality) and rates of residual tumor and risk stratification of non‐muscle‐invasive bladder cancer (NMIBC) after second TUR were evaluated. Results: After propensity score‐matching 121 patients were included each in the WL‐alone and WL‐second groups, and 63 patients each in the PDD‐alone and PDD‐second groups. In the WL group, the second TUR was significantly associated with improved progression‐free (p = 0.012) and urothelial cancer‐specific free survival (p = 0.011), but not with recurrence‐free survival (p = 0.93). Patients initially treated with PDD‐TURBT, and with a tumor diameter <30 mm and multifocality had a relatively high benefit from second TUR. The rates of residual tumor and risk stratification of NMIBC did not significantly differ between WL‐TURBT and PDD‐TURBT groups. Conclusions: Our findings suggested that a second TUR could be omitted after an initial PDD‐TURBT in selected patients with high‐risk NMIBC. [ABSTRACT FROM AUTHOR]

Objectives: We assessed preoperative factors predicting the poor therapeutic efficacy of holmium laser enucleation of the prostate (HoLEP) in benign prostatic hyperplasia (BPH) patients. Methods: The present study included 159 patients who underwent HoLEP between August 2015 and June 2021 at our institution. Overall therapeutic efficacy was divided into good and poor therapeutic efficacies according to changes in the international prostate symptom score (IPSS), IPSS quality of life (IPSS‐QOL), and the maximum urinary flow rate. Patients were divided into good and poor therapeutic efficacy groups based on findings obtained 3 months after HoLEP, and comparative assessments were performed between the two groups. Results: The therapeutic efficacy of HoLEP was poor in 53 (33.3%) out of 159 patients. Intravesical prostatic protrusion (IPP), IPSS, IPSS‐QOL, post‐void residual volume (PVR), and the presence of overactive bladder (OAB) were significantly higher in the poor therapeutic efficacy group than in the good therapeutic efficacy group. A multivariable analysis of several factors identified the preoperative presence of OAB and short IPP as independent risk factors for the poor therapeutic efficacy of HoLEP. When treatment efficacy was divided according to risk factors, poor therapeutic efficacy was observed in only 14% of patients with prolonged IPP and the absence of OAB. Conclusions: The therapeutic efficacy of HoLEP may be poor in patients with OAB and short IPP, resulting in the significant deterioration of lower urinary tract symptoms. Accordingly, it is important to consider the presence or absence of OAB and IPP measurements when selecting indications for HoLEP. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to assess the prognostic outcomes in mRCC patients receiving second‐line TKI following first‐line IO combination therapy. Methods: This study retrospectively included 243 mRCC patients receiving second‐line TKI after first‐line IO combination therapy: nivolumab plus ipilimumab (n = 189, IO–IO group) and either pembrolizumab plus axitinib or avelumab plus axitinib (n = 54, IO–TKI group). Oncological outcomes between the two groups were compared, and prognostication systems were developed for these patients. Results: In the IO–IO and IO–TKI groups, the objective response rates to second‐line TKI were 34.4% and 25.9% (p = 0.26), the median PFS periods were 9.7 and 7.1 months (p = 0.79), and the median OS periods after the introduction of second‐line TKI were 23.1 and 33.5 months (p = 0.93), respectively. Among the several factors examined, non‐CCRCC, high CRP, and low albumin levels were identified as independent predictors of both poor PFS and OS by multivariate analyses. It was possible to precisely classify the patients into 3 risk groups regarding both PFS and OS according to the positive numbers of the independent prognostic factors. Furthermore, the c‐indices of this study were superior to those of previous systems as follows: 0.75, 0.64, and 0.61 for PFS prediction and 0.76, 0.70, and 0.65 for OS prediction by the present, IMDC, and MSKCC systems, respectively. Conclusions: There were no significant differences in the prognostic outcomes after introducing second‐line TKI between the IO–IO and IO–TKI groups, and the histopathology, CRP and albumin levels had independent impacts on the prognosis in mRCC patients receiving second‐line TKI, irrespective of first‐line IO combination therapies. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to assess the clinical outcomes following combined treatment with pembrolizumab and axitinib as first‐line therapy for patients with advanced RCC. Methods: This study retrospectively included 47 consecutive Japanese patients who were diagnosed with advanced RCC and subsequently received pembrolizumab and axitinib between February 2020 and January 2022. Efficacy and safety of this combined therapy in these patients were comprehensively investigated. Results: The 47 included patients were classified into the following 3 groups by the IMDC system: favorable, 7 (14.9%); intermediate, 24 (51.1%) and poor, 16 (34.0%). Responses to this combined therapy in the 47 patients were as follows: CR, 8 (17.0%); PR, 20 (42.6%); SD, 16 (34.0%) and PD, 3 (6.4%); thus, the ORR was 59.6%. During the observation period, disease progression and death occurred in 19 (40.4%) and 9 (19.1%) patients, respectively, and the median PFS and OS were 18 months and not reached, respectively. Univariate analyses identified the following significant predictors for poor prognostic outcomes: lack of nephrectomy, liver metastasis, bone metastasis, elevated CRP and IMDC poor risk for PFS; and lack of nephrectomy, non‐CCC and elevated CRP for OS. AEs and those corresponding to grade ≥ 3 occurred in all (100%) and 30 (63.8%) patients, respectively. Conclusions: To our knowledge, this is the first study focusing on real‐world outcomes following pembrolizumab and axitinib for treatment‐naïve advanced Japanese RCC patients, which showed the efficacy and safety of this combined therapy being similar or even superior to those in clinical trial. [ABSTRACT FROM AUTHOR]

Objectives: The present study comprehensively investigated the significance of several factors reflecting the therapeutic effects of anticancer treatment on overall survival (OS) in advanced urothelial cancer (UC) patients receiving sequential systemic therapy. Methods: This study included 101 consecutive advanced UC patients who received first‐line platinum‐based combination chemotherapy followed by second‐line pembrolizumab. The impacts of the following factors on OS in these patients were analyzed: responses to chemotherapy, responses to pembrolizumab, progression‐free survival (PFS) with chemotherapy, PFS with pembrolizumab, and second PFS (PFS2). Results: The median age of patients was 71 years, and 35 and 66 had UC in the upper urinary tract and bladder, respectively. objective response rate to first‐line chemotherapy and second‐line pembrolizumab were 37.6% and 19.8%, respectively. Median PFS with chemotherapy, pembrolizumab, and PFS2 were 5, 4, and 9 months, respectively. Uni‐ and multivariate analyses of the five factors examined identified PFS with pembrolizumab and PFS2 as independent surrogates for OS, with PFS2 (hazard ratio [HR] = 0.23) being more closely associated with OS than PFS with pembrolizumab (HR = 0.31). Furthermore, uni‐ and multivariate analyses of various prognostic parameters showed the independent impacts of baseline performance status (PS) and neutrophil‐to‐lymphocyte ratio (NLR) on PFS2. Conclusions: The present results suggest the potential of PFS2 as an optimal surrogate for OS in advanced UC patients receiving standard sequential systemic therapy and indicate that intensive treatment needs to be considered for those with poor PS and/or high NLR prior to the introduction of first‐line chemotherapy. [ABSTRACT FROM AUTHOR]

Objectives: To validate the risk stratification newly defined in the Japanese Urological Association guidelines 2019 for non‐muscle invasive bladder cancer and provide a more accurate stratification model for a heterogeneous intermediate‐risk group. Methods: A total of 1610 patients, who underwent transurethral resection, diagnosed with non‐muscle invasive bladder cancer in nine collaborating hospitals were retrospectively reviewed. They were classified into low‐risk, intermediate‐risk, high‐risk, and highest‐risk groups, and recurrence‐free survival, progression‐free survival, cancer‐specific survival, and overall survival were compared among the groups. The intermediate‐risk group was subdivided into two groups based on the multivariable Cox regression model of recurrence and progression risk factors, and a revised risk model was created. Results: The progression‐free survival, cancer‐specific survival, and overall survival were well stratified, while the recurrence‐free survival of the intermediate‐risk group was the shortest among the four groups (p < 0.001). The independent risk factors for recurrence and progression‐free survival in the intermediate‐risk group were as follows: age ≥ 70 years, sex, multiple tumors, tumor size ≥3 cm, and recurrent cases. The intermediate‐risk group was subdivided into two groups: favorable intermediate‐risk group and unfavorable intermediate‐risk group. The revised risk model showed significant differences. Conclusion: We validated the Japanese Urological Association guidelines 2019 stratification model. The revised risk model provided a more accurate treatment selection for this disease subset. [ABSTRACT FROM AUTHOR]