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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. [ABSTRACT FROM AUTHOR]

Objectives: We examined the outcomes of eight weekly bacillus Calmette–Guérin induction therapy after second transurethral resection, and investigated risk factors for intravesical recurrence or disease progression in high‐risk non‐muscle‐invasive bladder cancer patients. Methods: This retrospective study included 146 high‐risk non‐muscle‐invasive bladder cancer patients who received eight weekly bacillus Calmette–Guérin instillations without a maintenance schedule between 2000 and 2019. Intravesical recurrence‐free and progression‐free survival rates were evaluated using the Kaplan–Meier method. The Cox proportional hazards model was used to identify risk factors. Results: Pathological T staging in the first transurethral resection was pTa in 56 patients (38.4%), pT1 in 75 (51.4%) and primary carcinoma in situ in 15 (10.2%). A total of 109 (83.2%) with pTa–1 disease underwent second transurethral resection before bacillus Calmette–Guérin induction therapy, and residual disease was detected in 54 (49.5%). The completion rate of eight instillations was 82.2%. The 2‐ and 5‐year intravesical recurrence‐free survival rates were 80.7% and 75.2%, whereas the 2‐ and 5‐year progression‐free survival rates were 85.7% and 82.0%. Recurrent tumors (hazard ratio 6.5830, P = 0.0007) and residual tumors at the second transurethral resection (hazard ratio 4.0337, P = 0.0021) were risk factors for intravesical recurrence. Multiple tumors (hazard ratio 5.8056, P = 0.0302), pT1 disease (hazard ratio 3.7351, P = 0.0447) and residual tumors at second transurethral resection (hazard ratio 3.2552, P = 0.0448) were associated with disease progression. Conclusions: Accurate disease staging and disease elimination by second transurethral resection followed by eight weekly bacillus Calmette–Guérin instillations achieved good disease control. Our protocol (without a maintenance schedule) after thorough surgical resection has potential as a treatment option in the current bacillus Calmette–Guérin shortage. [ABSTRACT FROM AUTHOR]

Although prostate cancer control using radiotherapy is dose‐dependent, dose–volume effects on late toxicities in organs at risk, such as the rectum and bladder, have been observed. Both protons and carbon ions offer advantageous physical properties for radiotherapy, and create favorable dose distributions using fewer portals compared with photon‐based radiotherapy. Thus, particle beam therapy using protons and carbon ions theoretically seems suitable for dose escalation and reduced risk of toxicity. However, it is difficult to evaluate the superiority of particle beam radiotherapy over photon beam radiotherapy for prostate cancer, as no clinical trials have directly compared the outcomes between the two types of therapy due to the limited number of facilities using particle beam therapy. The Japanese Society for Radiation Oncology organized a joint effort among research groups to establish standardized treatment policies and indications for particle beam therapy according to disease, and multicenter prospective studies have been planned for several common cancers. Clinical trials of proton beam therapy for intermediate‐risk prostate cancer and carbon‐ion therapy for high‐risk prostate cancer have already begun. As particle beam therapy for prostate cancer is covered by the Japanese national health insurance system as of April 2018, and the number of facilities practicing particle beam therapy has increased recently, the number of prostate cancer patients treated with particle beam therapy in Japan is expected to increase drastically. Here, we review the results from studies of particle beam therapy for prostate cancer and discuss future developments in this field. [ABSTRACT FROM AUTHOR]

Objectives Pressure flow studies are regarded as the gold standard for evaluating both bladder outlet obstruction and detrusor contractility, but none of the current methods for evaluating bladder contraction patterns are well validated. Impaired bladder contraction results in a lower peak Watts factor and poorly sustained detrusor contractions. From this viewpoint, the maximum Watts factor and its pattern should be considered separately. To examine detrusor contraction pattern in patients after radical prostatectomy by using multiple parameters. Methods A total of 37 patients with clinically localized prostate cancer underwent both pre- and post-radical prostatectomy urodynamic evaluations. The examined urodynamic parameters included the maximum flow rate, post-void residual volume, detrusor pressure at maximum flow, maximum Watts factor and relative volume (maximum Watts factor). Some parameters were defined from the Watts factor curve throughout micturition. Relative volume (maximum Watts factor) was the relative bladder volume at the maximum Watts factor. A normal detrusor contractility pattern involves an increase in Watts factor at the initiation followed by further gradual increases until the end of micturition. Results Maximum flow rate increased significantly after radical prostatectomy (pre: 13.0 ± 6.5, post: 17.3 ± 7.7 mL/min; P < 0.01), whereas detrusor pressure at maximum flow and post-void residual volume decreased significantly (pre: 49.6 ± 21.6 and 31.4 ± 18.2 cmH2O; post: 48.6 ± 66.1 and 10.1 ± 28.5 mL; P < 0.05). Maximum Watts factor did not change significantly after radical prostatectomy (pre: 10.5 ± 3.1 W/m2, post: 11.0 ± 3.2 W/m2), but relative volume (maximum Watts factor) decreased significantly (pre: 0.48 ± 0.3, post: 0.20 ± 0.20; P < 0.001). Maximum Watts factor represents the maximum power of bladder contraction at a particular point in time, whereas relative volume (maximum Watts factor) can be used to detect changes in detrusor contraction pattern. Conclusions Evaluation of relative volume (maximum Watts factor) confirms that radical prostatectomy restores the normal detrusor contractility pattern in prostate cancer patients. [ABSTRACT FROM AUTHOR]

Objective To evaluate the association between the RENAL nephrometry score and annual growth rates of renal masses presumed to be renal cell carcinoma. Methods The current study included 47 renal tumors followed up for at least 12 months, of which 26 tumors were found to be pathologically proven renal cell carcinomas. Annual tumor growth rates were calculated from changes in the maximal diameter on computed tomography, and RENAL nephrometry scores were recorded on initial imaging by two senior urologists. The associations between clinical characteristics including the RENAL nephrometry score and annual growth rates were analyzed using a linear regression model. Results The median tumor size at diagnosis was 1.7 cm (range 0.6-5.8). The median nephrometry score at diagnosis was 7 (range 4-10). Overall, the median tumor growth rate was 0.34 cm per year (range −0.19-2.0). Linear regression analysis showed that the annual tumor growth rate was associated with the RENAL nephrometry score ( P < 0.0001), but it was independent of the age at diagnosis, sex and initial tumor size. In addition, the correlation between the RENAL nephrometry score and annual growth rate remained significant in the 26 pathologically proven renal cell carcinomas. Conclusions The RENAL nephrometry score is associated with the annual growth rate of renal masses. Our findings further support the association between the RENAL nephrometry score and tumor biology. [ABSTRACT FROM AUTHOR]

Objective To determine the differences in the type, incidence, and severity of 90-day morbidity after radical cystectomy between two different methods of urinary diversion, ileal conduit and neobladder. Methods We carried out a retrospective multi-institutional study by reviewing the records of 668 patients treated with open radical cystectomy, and ileal conduit ( n = 493) or neobladder substitution ( n = 175) between 1997 and 2010. All complications within 90 days after surgery were divided into 11 specific categories as reported by the Memorial- Sloan Kettering Cancer Center, and graded according to the modified Clavien system. Type, incidence and severity of the 90-day morbidity between the two different types of urinary diversions were compared. Results There was no significant difference in the overall complication rates between the two groups (ileal conduit: 72% [353/493], neobladder: 74% [129/175], P = 0.5909), whereas the neobladder group had fewer major (grade 3 or more) complications (13 vs 20%, respectively, P = 0.0271). The neobladder group had more infectious complications (43 vs 31%, respectively, P = 0.0037), mainly as a result of urinary tract infection, whereas the ileal conduit group had more wound-related complications (24 vs 14%, respectively, P = 0.0068), mainly as a result of surgical site infection. The 90-day mortality rates were 1.1% (2/175) in the neobladder group and 1.6% (8/493) in the ileal conduit group ( P = 0.6441). Conclusions There was no significant difference in the overall complication rates between the two methods, and patients with neobladder had fewer major complications. The neobladder group had more infectious complications, whereas the ileal conduit group had more wound-related complications. [ABSTRACT FROM AUTHOR]

Objective To determine the type, incidence and severity of 90-day morbidity after radical cystectomy in our institution and our affiliated hospitals in accordance with a standard reporting methodology. At present, most studies on complications associated with open radical cystectomy are derived from Western academic high-volume centres and data from Japan and other Asian countries remain very limited., Patients and Methods The study comprised a retrospective multi-institutional study., The records were reviewed of 928 patients who underwent open radical cystectomy between 1997 and 2010., All complications within 90 days of surgery were categorized into 11 specific categories and graded in accordance with the modified Clavien system., Multivariate regression models were used to determine predictors of complications., Results At least one complication was observed in 635 (68%) patients and a major (grade 3-5) complication was observed in 156 (17%) patients., The most common complication categories were infectious (30%), gastrointestinal (26%), wound-related (21%) and genitourinary (15%)., The 30-day mortality rate was 0.8% and the 90-day mortality rate was 2%., A multivariate regression model showed that previous cardiovascular comorbidity and type of urinary diversion (i.e. ileal conduit or neobladder) were significant factors for any and major complications., Conclusions Surgical complication-related radical cystectomy is significant and both previous cardiovascular comorbidity and the type of urinary diversion were found to be significant factors for any and major complications., The 90-day mortality rate was 2%, which is compatible with reports from Western high-volume centres. [ABSTRACT FROM AUTHOR]

The aims of the present study were to: (i) develop a clinically useful prognostic classification in Asian patients with metastatic renal cell carcinoma ( RCC) by combining metastatic features with several pretreatment parameters; and (ii) evaluate the validity of this prognostic classification. Baseline characteristics and outcomes were collected for 361 patients who underwent interferon-α-based therapy between 1995 and 2005. Relationships between overall survival ( OS) and potential prognostic factors were assessed using Cox's proportional hazard model. The predictive performance of the model was evaluated using bootstrap resampling procedures and by using an independent dataset obtained from randomly selected institutions. The predictive accuracy was measured using the concordance index (c-index). Four factors were identified as independent prognostic factors: time from initial diagnosis to treatment, anemia, elevated lactate dehydrogenase ( LDH), and poor prognostic metastatic group (liver only, bone only, or multiple organ metastases). Each patient was assigned to one of three risk groups: favorable risk (none or one factor; n = 120), in which median OS was 51 months; intermediate risk (two factors; n = 101), in which median OS was 21 months; and poor risk (three or four factors; n = 102), in which median OS was 10 months. The c-index was 0.72 in the original dataset and 0.72 in 500 random bootstrap samples. In the independent dataset for external validation, the c-index was 0.73. Thus, the new prognostic classification is easily applicable for Asian patients with previously untreated metastatic RCC and should be incorporated into patient care, as well as clinical trials performed in Asia. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the influence of baseline renal function and dose reduction of chemotherapeutic agents on the outcome of metastatic urothelial carcinoma patients with renal impairment. Methods: A total of 57 patients with metastatic urothelial carcinoma treated by systemic chemotherapy were included in the present study. The 24 h-creatinine clearance was measured before each cycle and dose reduction was carried out according to our guidelines. Patients were divided into two groups according to baseline 24 h-creatinine clearance: fit group (60 mL/min/1.48 m2≤) and unfit group (60 mL/min/1.48 m2>). Clinical characteristics and final outcomes were compared between the two groups. Results: There was no significant difference in the total number of chemotherapy cycles of each patient between the two groups (fit group: median 5; unfit group: median 4; P = 0.7466), although dose reduction was carried out significantly more often in the unfit group than in the fit group during treatment (fit group: median 0 cycles; unfit group: median 3.5 cycles; P = 0.0016). Overall, the median survival was 16 months. There was a significant survival difference between the two groups (fit group: median 17 months; unfit group: median 10 months; P = 0.0419). On multivariate analyses, impaired renal function at the baseline remained an adverse factor (HR 2.27, P = 0.01). Conclusions: 'Unfit' was a poor prognostic factor for metastatic urothelial carcinoma. The dose reduction strategy contributed to continuous treatment in the unfit group. However, its contribution to the prognosis of unfit patients is uncertain. [ABSTRACT FROM AUTHOR]

Objective: Epstein-Barr virus (EBV) has been implicated in the genesis of a variety of human cancers. We aimed to confirm the presence and define the role of EBV in bladder cancer. Methods: A total of 39 bladder cancer specimens were analyzed. Ten urinary bladder tissues obtained at autopsy were used as a normal control. EBV-encoded RNA (EBER) was evaluated by in situ hybridization (ISH). Frozen material available from 18 EBER-positive cases was analyzed by using reverse transcription-polymerase chain reaction for BZLF1, an early lytic gene product. The expression of CD20, CD3, ZEBRA (BZLF1 product) and transforming growth factor β1 (TGFβ-1) was assessed using an immunohistochemical technique. Results: Infiltration of EBER-expressing lymphocytes was detected in 26 of 39 bladder cancer cases (66.7%). A small fraction of the tumor cells as well as the infiltrating lymphocytes were positive in two cases. All normal urinary bladder specimens showed negative results. The incidence of EBV-positive lymphocyte infiltration was significantly higher for advanced stage cancers than those in earlier stages (Ta-152% vs T2-4 93%, P = 0.013). The presence of BZLF1 mRNA was demonstrated in seven out of the 18 EBER-positive cases. Conclusions: Infiltration of EBV-harboring lymphocytes occurs in a large subset of bladder cancers cases. It is more frequently associated with advanced stages. EBV infection in tumor cells is very limited. Our findings suggest that EBV-positive lymphocytes might play a role in bladder cancer progression. [ABSTRACT FROM AUTHOR]

Objectives: Our goal was to identify changes in urodynamic parameters and lower urinary tract symptoms (LUTS) in men followed for1 year after radical prostatectomy (RP) compared to the preoperative measures with a specific focus on detrusor contractility. Methods: This study enrolled 43 patients who received RP (laparoscopic 27, retropubic: 16) and pressure flow studies (PFS) pre-RP as well as 12 months (M) after RP. No patients complained of urinary incontinence preoperatively. Urodynamic studies and questionnaires regarding LUTS and urinary continence were conducted before and 12 M after RP. Detrusor underactivity (DU) was defined as <10 (W/m2) in preoperative maximum watts factor value. Results: Urodynamics demonstrated that RP improved urodynamic parameters by releasing bladder outlet obstruction without affecting overall detrusor contractility. Meanwhile, RP did not affect bladder capacity, bladder compliance, or detrusor contractility. LUTS in the International Prostate Symptom Score (IPSS), including the IPSS subscore, was not improved. The quality of life score was significantly better at 12 M after RP and continence rates were gradually improved to be at a satisfactory level in more than 80% of patients by 12 M after RP. DU was preoperatively identified in 21(49%) patients, influencing urodynamic parameters and LUTS preoperatively. However, DU did not affect urodynamic parameters and LUTS after RP. Conclusion: Although RP improves urodynamic parameters, it does not significantly affect LUTS. Urinary continence gradually improves and is satisfactory within 1 year after RP. The status of preoperative detrusor contractility did not affect urodynamic parameters or LUTS after RP. [ABSTRACT FROM AUTHOR]