Shiroki Ryoichi

OBJECTIVES: We aimed to evaluate overall survival (OS) and determine the optimal timing of cytoreductive nephrectomy (CN) in patients with metastatic renal cell carcinoma (mRCC) receiving immune checkpoint inhibitor (ICI)-based therapy. METHODS: This retrospective study reviewed medical records of 447 patients with mRCC treated with ICI at multiple Japanese institutions between January 2018 and August 2023. From this cohort, 178 patients with lymph node or distant metastases received either cytoreductive nephrectomy (CN group; n = 72) or ICI therapy without cytoreductive nephrectomy (non-CN group; n = 106) as first-line treatment. RESULTS: Median progression-free survival was 15.7 months, and median overall survival was 58.1 months. CN significantly improved OS, with the CN group's median OS not reached, compared to 29.6 months in the non-CN group (p = 0.01). Deferred CN also showed improved survival outcomes. Poor prognostic factors for immediate CN included International Metastatic Renal Cell Carcinoma Database Consortium poor risk, sarcomatoid differentiation, and a high neutrophil-to-lymphocyte ratio. CONCLUSIONS: We developed a prognostic model to guide patient selection for CN, emphasizing the need for personalized treatment strategies.

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

BACKGROUND: Acute uncomplicated cystitis (AUC) is a urinary tract infection and is generally treated using antimicrobial therapy. Escherichia coli is the main causative agent of AUC. Recently, the prevalence of fluoroquinolone (FQ)-resistant-E. coli has demonstrated a noticeable increase. In this study, we aimed to investigate the effectiveness of appropriate antimicrobial treatment in AUC caused by E. coli in real-world clinical settings. METHODS: This retrospective cohort study reviewed the records of patients with AUC treated at the urology department of Minami Cooperative Hospital between April 2016 and December 2020. Effectiveness was defined as clinical improvement. RESULTS: The study cohort of 730 patients had a median age of 65.5 years (interquartile range, 57-78 years) and 23.2% were aged <55 years. E. coli was detected in 73.4% of patients, of whom 26.7% had levofloxacin (LVFX)-resistant strains. LVFX-resistant E. coli was associated with age ≥55 years and recurrent cases. Effectiveness was determined in 75.1% of cases, of which 75% complied with the Japanese or other international guidelines. The overall treatment effectiveness was highest with β-lactam (BL)/β-lactamase inhibitor (BLI) combinations (94.7%). The effectiveness of first- and third-generation cephalosporins (CPs) was 81.1-83.3%, and that of FQs and sulfamethoxazole-trimethoprim (ST) was 82.6-83.8%. For LVFX-resistant E. coli, the treatment effectiveness was highest (100%) with BL/BLI combinations, intermediate (75-81%) with first- and third-generation CPs and ST, and lowest (50%) with FQs. CONCLUSIONS: BL/BLI combinations had the highest effectiveness for the treatment of AUC.

BACKGROUND: The treatment strategy for urothelial carcinoma has advanced with the development of enfortumab vedotin (EV); however, a comparative analysis of its therapeutic efficacy between upper urinary tract urothelial carcinoma (UTUC) and bladder cancer (BCa) has yet to be established. We aimed to compare the effects of EV after pembrolizumab treatment between the patients with UTUC and BCa. METHODS: We included the patients with advanced UC patients who received EV after pembrolizumab in this retrospective study. We investigated the impact of various clinical variables including age, primary site of disease (UTUC vs. BCa), Liver metastasis, lung metastasis, prior number of regimens before EV treatment, and ECOG PS, which influenced on prognosis and efficacy of EV treatment. RESULTS: A total of 63 male and 23 female patients were included in our study. The number of UTUC and BCa patients were 33 and 53, respectively. The UTUC cohort had a significantly older patient population and a greater incidence of lung metastases compared to the BCa group. The prognosis of UTUC patients were not significantly different from BCa patients. However, UTUC was determined as significant factor to predict better overall response rate than BCa in multiple logistic regression analysis. CONCLUSIONS: UTUC patients showed significantly better response to EV treatment than BCa patients.

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

Immune checkpoint inhibitors (ICIs) are a key component of first-line treatment for metastatic renal cell carcinoma (mRCC). However, predicting treatment-related adverse events (TRAEs) remains challenging. This study investigated the utility of eosinophil-related biomarkers as predictors of Common Terminology Criteria for Adverse Events grade ≥ 3 TRAEs in mRCC patients undergoing ICI combination therapy. In this retrospective analysis across 21 hospitals in Japan, we examined 180 patients treated with ICI/ICI therapy and 216 patients treated with ICI/tyrosine kinase inhibitor (TKI) therapy. Grade ≥ 3 TRAEs occurred in 39.4% and 31.9% of patients in the ICI/ICI and ICI/TKI groups, respectively. An elevated eosinophil proportion of ≥ 2.0% (odds ratio [OR]: 2.36; 95% CI [confidence interval] 1.23-4.54, p = 0.01) and a low neutrophil/eosinophil ratio (NER) of ≤ 40.0 (OR: 2.78, 95% CI 1.39-5.53, p = 0.004) were significant predictors of severe TRAEs in the ICI/ICI group. However, no significant associations were found in the ICI/TKI group. These findings may help identify patients who suffer from grade ≥ 3 TRAEs and help determine individualized treatment strategies in patients with mRCC.

Although glycosphingolipids (GSLs) and sterol metabolites are known to be involved in many diseases, including neurodegenerative disorders, the quantification of these molecules in humans has been scarcely investigated. Similarly, the effects of age, sex, and statin use have not been sufficiently investigated or reported in the literature. In this study, we measured the levels of human cerebrospinal fluid (CSF) GSLs of various fatty acid acyl chain lengths and sterol metabolites using hydrophilic interaction liquid chromatography and electrospray tandem mass spectrometry in a neurologically normal population. We successfully quantified the presence of glucosylated cholesterol, galactosylated cholesterol, glucosylated sitosterol, glucosylceramide (GlcCer), galactosylceramide, lactosylceramide (LacCer), and galabiosylceramide (Gb2). There were no statistically significant differences in CSF concentrations of these lipids between males and females. We also found no correlation between CSF concentration and age or statin dose, except for GlcCer d18:1-C23:1. Significant positive correlations with age were shown only in males. Our results indicate that, in future studies, age and sex should be taken into consideration when comparing CSF GSL levels in patients with neurological disorders with those in neurologically normal control subjects.

The composition of the distal ileum microbiota and the impact of fecal exposure during intracorporeal urinary diversion (ICUD) on gastrointestinal (GI) complications remain unclear. This study included 146 patients with bladder cancer who underwent ICUD without bowel preparation and received only a single day of antibiotic prophylaxis. Fecal samples were collected directly from the distal ileum during surgery, and ascitic fluid was obtained postoperatively from abdominal drains. Among the patients, 129 (88.3%) had minimal microbial growth in ileal feces, while 17 (11.7%) showed significant colonization. The most commonly identified organisms were Streptococcus, Enterococcus, Enterobacter, Klebsiella, and Candida. The incidence of GI complications was significantly higher in patients with positive ileal fecal cultures compared to those with no detectable growth (39.4% vs. 7.7%, P < 0.001), and even more pronounced in patients with positive ascitic cultures (72.5% vs. 11.3%, P < 0.001). Multivariate analysis identified positive ascitic cultures as an independent predictor of GI complications. Additionally, frailty was significantly associated with the presence of microbial growth in ascitic fluid. These findings suggest that, although the distal ileal microbiota is largely suppressed under short-term antibiotic prophylaxis, the presence of intra-abdominal bacteria or fungi is strongly linked to postoperative GI complications, including ileus. Frailty may contribute to microbial dysbiosis and the persistence of intra-abdominal pathogens, particularly Enterococcus and Enterobacter species.

OBJECTIVES: Immune checkpoint inhibitor (ICI)-based combination therapies are first-line treatments for locally advanced or metastatic renal cell carcinoma (mRCC). However, second-line treatment efficacy remains uncertain due to limited large randomized trials. This study evaluated real-world oncological outcomes after second-line treatments in patients who received combination ICIs as first-line treatment. METHODS: Among 467 patients who received ICI combination therapy as first-line treatment for mRCC between January 2018 and January 2024, those who received cabozantinib (Cabo) or axitinib (Axi) as second-line treatment were included in this study. The patient characteristics at the initiation of second-line treatment, progression-free survival (PFS), and overall survival (OS) were compared between the two groups. Prognostic factors associated with OS after the initiation of second-line treatment were evaluated. RESULTS: The Cabo and Axi groups included 87 and 45 patients, respectively. Median OS and PFS after the initiation of secondary treatment were 32 and 9 months in the Cabo group (p = 0.269), and 33 and 12 months in the Axi group (p = 0.399). Multivariable analysis identified serum C-reactive protein (CRP) ≥ 0.6 mg/dL and estimated glomerular filtration rate (eGFR) < 40 mL/min/1.73 m2 at the start of secondary treatment as independent predictors of OS. Stratification by these factors revealed a significant OS difference (p < 0.001). CONCLUSIONS: Oncological outcomes after the initiation of secondary treatment did not differ significantly between the Cabo and Axi groups. An eGFR < 40 mL/min/1.73 m2 and CRP ≥ 0.6 mg/dL at the start of Cabo or Axi treatment were independent OS predictors after secondary treatment.

OBJECTIVES: We aimed to evaluate the long-term oncological and functional outcomes after robot-assisted partial nephrectomy (RAPN) for renal hilar tumors. METHODS: A total of 22 academic hospitals in Japan participated in a prospective, multicenter, single-arm, open-label trial with a 2-year enrollment period. After undergoing RAPN, 105 patients with clinical T1 renal hilar tumors were followed up for 5 years and evaluated. Recurrence-free survival, overall survival, and trends of renal function were set as oncological and functional outcomes. RESULTS: Five-year overall survival and recurrence-free survival were 98.0% and 89.2%, respectively. Mean estimated glomerular filtration rates (eGFRs) were 69.031 mL/min preoperatively, and were 59.374, 58.334, 58.221, 56.975, and 59.602 mL/min at 1, 2, 3, 4, and 5 years after surgery, respectively. While eGFR was significantly lower than the preoperative one at all points (p < 0.001), eGFRs at 1 and 5 years after surgery did not differ significantly (p = 0.793). CONCLUSION: After long-term follow-up, RAPN for clinical T1 renal hilar tumors continues to provide functional and oncological outcomes equivalent to those in the perioperative period. TRIAL REGISTRATION: The study protocol was registered in the Japan Registry of Clinical Trials (jRCT1052190005, UMIN000023968).

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) targeting Nectin-4, has been available as standard care for metastatic urothelial carcinoma (mUC) patients who have progressed after platinum-based chemotherapy and checkpoint inhibitors (CPIs). However, the association between body mass index (BMI) and clinical outcomes for EV remains unknown. METHODS: We analyzed the records of 123 mUC patients who received EV. The cohort was divided into low BMI (< 22, n = 65) and high BMI (≥ 22, n = 58) groups. Propensity score matching was performed to reduce clinical bias between the two groups. RESULTS: In the total cohort (n = 123), the objective response rate (ORR) and disease control rate (DCR) were 46% and 68%, respectively. The ORR was significantly higher in the higher BMI group (62%, n = 58) compared to the lower BMI group (32%, n = 65). Among the pair-matched cohort (n = 100), despite reducing potential bias, the ORR remained significantly higher in the higher BMI group than in the lower BMI group (64% vs. 32%, p = 0.002). Both overall survival (OS) and radiographic progression-free survival (r-PFS) were longer in the higher BMI group compared to the lower BMI group (median OS: not reached vs. 8 months, p = 0.035; median r-PFS: 10 vs. 4 months, p < 0.001). On multivariate analyses, a higher BMI (≥ 22) was an independent predictor for achieving objective response and favorable OS in mUC patients treated with EV. CONCLUSIONS: The findings of this study suggest a potential association between high BMI and improved tumor response to EV in mUC patients with disease progression after platinum-based chemotherapy and CPIs.

PURPOSE: The purpose of this study is to determine the utility of the CANLPH score as a predictive biomarker for patients with advanced and metastatic renal cell carcinoma (a/mRCC). By validating its prognostic value, this study aims to contribute to more personalized treatment strategies for a/mRCC. METHODS: In a multicenter retrospective study by the JK-FOOT consortium, we analyzed data from 309 a/mRCC patients undergoing ICI-based therapy. The CANLPH score-a composite marker of C-reactive protein to albumin ratio (CAR), neutrophil to lymphocyte ratio (NLR), and platelet to hemoglobin ratio (PHR)-for its prognostic accuracy in predicting cancer-specific survival (CSS). Advanced statistical methods, including receiver operating characteristic (ROC) curve analysis, Cox proportional-hazard regression, and Harrell's concordance index (C-index), were employed to assess its predictive capacity against established factors. RESULTS: The median follow-up period was 17 months, revealing two-year and five-year overall survival rates of 76.8% and 62.4%, respectively, with CSS rates at 78.3% and 66.2%. The CANLPH score well stratified survival outcomes of ICI-based treatment for RCC patients (HR 5.71; P < 0.0001). C-index analysis demonstrated that the CANLPH score had the highest predictive potency for CSS among models, including IMDC score. Multivariate analysis confirmed the CANLPH score (HR, 5.59; P = 0.0007) and Karnofsky performance status (HR, 2.59; P = 0.0032) as independent prognostic factors for CSS. CONCLUSIONS: The CANLPH score emerges as a critical tool in the a/mRCC therapeutic landscape, enabling precise prediction of patient outcomes with ICI-based therapies. Limitations include the retrospective design and the single national cohort. Prospective validation studies are warranted.

OBJECTIVE: This study aimed to establish a robust predictive model for biochemical recurrence (BCR) in patients with prostate cancer who underwent robot-Assisted Radical Prostatectomy. MATERIAL AND METHODS: A cohort of 1700 patients who underwent robot-assisted radical prostatectomy (RARP) for prostate cancer between August 2009 and December 2022 was included. BCR was defined as two consecutive PSA levels exceeding 0.2 ng/mL post-radical prostatectomy. Cox proportional hazards regression identified predictive variables for BCR. Subsequently, pathologic T stage, PSA level, positive surgical margin, extraprostatic extension, and seminal vesicle involvement were retained. A nomogram was constructed using R software to predict BCR. The model was evaluated using the C-index and calibration curves. RESULTS: A total of 161 instances of BCR were observed during a median follow-up of 61.0 months (range, 12-162 months). The 5-year BCR-free survival rate for the cohort was 25 %. Univariate analysis demonstrated significant associations between BCR and PSA, clinical T stage, biopsy Gleason score, D'Amico risk classification, pathologic T stage, pathologic Gleason score, extraprostatic extension, seminal vesicle invasion, and positive surgical margins. Multivariate analysis identified high PSA ≥20 ng/mL (HR: 1.93; p = 0.034), pathologic T stage 3-4 (HR: 1.89; p < 0.001), pathologic Gleason score 8-10 (HR: 5.43; p < 0.001), extraprostatic extension (HR: 1.41; p < 0.001), seminal vesicle involvement (HR: 1.92; p = 0.018), and positive surgical margin (HR: 2.73; p < 0.001) as independent predictors of BCR. The new model exhibited a C-index of 0.743 (95 % confidence interval: 0.741-0.745). CONCLUSION: The developed nomogram accurately predicts the likelihood of BCR-free status within 3 years following RARP. This allows for tailored follow-up strategies, optimizing resource allocation, and holds significant clinical utility, warranting broader implementation and further research.

Prostate cancer (PCa) is one of the most common cancers among men worldwide, and robot-assisted radical prostatectomy (RARP) is a widely used treatment for localized PCa. Achieving pentafecta outcomes, which include continence, potency, cancer control, free surgical margins, and no major complications, is a critical measure of surgical success and long-term prognosis. However, predicting these outcomes remains challenging. In this retrospective, single-center study, we analyzed data from 1,752 patients who underwent RARP for localized prostate adenocarcinoma between August 2009 and April 2023. The pentafecta outcome was achieved in 290 patients (16.6%). Multivariate analysis revealed that bilateral nerve sparing significantly increased the likelihood of achieving the pentafecta outcome (odds ratio 10.36, 95% CI: 5.75-18.66; p < 0.001). Preoperative potency and bilateral nerve sparing were also identified as key predictors. Nomograms were developed using preoperative and postoperative variables, including age, PSA level, biopsy Gleason score, clinical stage, pathological tumor stage, tumor grade, nerve sparing, and preoperative potency. Internal validation of the nomograms was performed using bootstrapping methods, demonstrating robust predictive performance. These nomograms provide valuable tools for personalized surgical planning and patient counseling and may be applicable to broader populations, given the inclusion of universally recognized predictive factors and rigorous validation. This study presents the development and validation of nomograms to predict pentafecta outcomes before and after RARP. These nomograms provide valuable tools for clinicians to estimate the likelihood of achieving postoperative pentafecta outcomes. Incorporating these nomograms into clinical practice may improve patient counseling and shared decision-making.

BACKGROUND/AIM: Cancer-induced pain (CIP) exacerbates patient's quality of life. However, it is unknown whether CIP is associated with survival in urothelial carcinoma (UC) patients treated with enfortumab vedotin (EV). This study retrospectively investigated the prognostic significance of CIP in EV-treated UC patients. PATIENTS AND METHODS: We analyzed clinical data from patients with locally advanced or metastatic UC who received EV treatment, assessing various factors such as age, metastasis site, ECOG Performance Status (PS), and CIP status prior to treatment. CIP was determined based on clinical records cancer-related pain or the use of analgesics for pain management. RESULTS: A total of 114 patients (78 males and 36 females) were included in the study. The group with CIP included significantly higher number of patients with bone metastasis. Progression-free survival of the patients with CIP was not significantly different from those without CIP. However, the patients with CIP showed worse overall survival (OS) than those without CIP. Cox proportional regression analysis showed that CIP, liver metastasis, and ECOG PS were significant predictors of poorer OS. CONCLUSION: CIP before the treatment of EV was a significant predictor of reduced OS in patients with UC. Early management of CIP or initiation of EV therapy before CIP development may improve survival outcomes.

BACKGROUND: Androgen-receptor signaling inhibitors (ARSIs) become the new standard of care for metastatic hormone-sensitive prostate cancer (mHSPC). It is unknown whether time to castration resistance (TTCR), when using the first-line ARSIs, offers predictive value in mHSPC. We sought to assess the clinical outcomes for mHSPC patients treated with first-line ARSIs focusing on the TTCR. METHODS: Data from the ULTRA-Japan study cohort from five academic institutes (496 mHSPC patients) were retrospectively analyzed. RESULTS: The median overall survival (OS) in the total cohort was 80 months with a median follow-up of 18 months. Of 496 patients, 332 (67%), 82 (16.5%), and 82 (16.5%) were treated with first-line abiraterone acetate + prednisone, enzalutamide, and apalutamide, respectively. During the follow-up, a total of 155 (31%) were diagnosed with mCRPC with a median TTCR of 10 months. In those 155 patients, TTCR > 12 months is an independent predictor of longer OS from the first-line ARSIs. Cox regression analysis of the TTCR from initiating first-line ARSI in 496 mHSPC patients revealed three variables as independent predictors of shorter TTCR, including Gleason's score (GS) ≥ 9, the extent of disease (EOD) ≥ 2, and the presence of liver metastasis. CONCLUSION: Our results indicate that mHSPC patients with those three features are likely to have primary resistance to first-line ARSIs (doublet therapy), thus requiring consideration of other options, such as the recent triplet approach.

BACKGROUND: Prostate-specific antigen (PSA) kinetics has been investigated as a prognostic marker in post hoc analyses of clinical trials. This study validated the prognostic value of rapid and deep PSA decline in metastatic hormone-sensitive prostate cancer (mHSPC) using real-world data. METHODS: In total, 1296 patients with mHSPC were retrospectively reviewed. We assessed the prognostic value of a PSA decline to ≤ 0.2 ng/mL after 12 weeks of treatment and investigated several potential risk factors for a poor PSA response. RESULTS: Of 1296 patients, 714 (cohort 1: 55.1%) were treated with conventional hormonal therapy, while 582 (cohort 2: 44.9%) received androgen signaling inhibitors. There were significant differences in progression-free survival and overall survival between patients with PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment and others (p < 0.001 for each). In addition, patients with an initial PSA ≥ 200 ng/mL, Clinical T4 and Grade Group 5 were less likely to achieve PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment, with odds ratios of 0.31 (p < 0.001), 0.67 (p = 0.039) and 0.70 (p = 0.043), respectively. CONCLUSION: Our findings suggested that PSA decline to ≤ 0.2 ng/mL by 12 weeks of treatment may be a useful prognostic biomarker for mHSPC in the real-world setting. The prognostic value of this should be further investigated in a prospective cohort, and identification of an optimal cutoff value is necessary for its application in clinical trial design or clinical practice.

BACKGROUND: Metastatic nonclear cell renal cell carcinoma (nccRCC) is a heterogeneous disease with poor prognosis. The clinical characteristics and prognostic factors of immuno-oncology (IO) combination therapy for nccRCC are not well known. This study analyzed patients with metastatic nccRCC treated with IO combination therapy. METHODS: We retrospectively collected data from 447 patients with metastatic RCC treated with IO-based combination therapy as first-line treatment between September 2018 and July 2023 in a Japanese multicenter study. The primary endpoints were objective response rate, progression-free survival (PFS), and overall survival (OS), comparing groups treated with IO-IO and IO-tyrosine kinase inhibitor (TKI) therapies. RESULTS: Seventy-five patients with metastatic nccRCC were eligible for analysis: 39 were classified into the IO-IO group and 36 into the IO-TKI group. Median PFS was 5.4 months (95% CI: 1.6-9.1) for the IO-IO group and 5.6 (95% CI: 3.4-12.0) for the IO + TKI group. Median OS was 24.2 months (95% CI: 7.5-NA) for the IO-IO group and 23.4 (95% CI: 18.8-NA) for the IO + TKI group, with no significant difference. In univariate analysis, International Metastatic Renal Cell Carcinoma Database Consortium scores, Karnofsky performance status, neutrophil-to-lymphocyte ratio, and the presence of liver metastases were significantly associated with OS, whereas in multivariate analysis, only the presence of liver metastases was significantly associated with OS (P = .035). CONCLUSIONS: There was no significant difference in OS or PFS between IO-IO and IO-TKI combination therapy as first-line treatment for patients with nccRCC. Liver metastasis is a poor prognostic factor for such patients.

BACKGROUND: Upfront androgen receptor signaling inhibitor (ARSI) along with androgen deprivation therapy is the current standard of care for metastatic castration-sensitive prostate cancer. However, evidence on second-line therapy after upfront ARSI is scarce. We aimed to evaluate the oncological outcome of ARSI versus docetaxel (DOC) after upfront ARSI therapy in a real-world clinical practice. METHODS: Subjects were metastatic castration-resistant prostate cancer (mCRPC) patients who had progressed within 2 years of upfront ARSI therapy and received ARSI (ARSI group) or DOC (DOC group) as a second-line therapy. Second-line progression-free survival (second-line PFS), and second-line overall survival (second-line OS) were assessed. Propensity score matching (PSM) was used to adjust the clinicopathological features and treatment patterns. RESULTS: A total of 101 mCRPC patients, 68 in the ARSI group, and 33 in the DOC group, were included in this analysis. Median second-line PFS was 6.3 months in the ARSI group and 4.9 months in the DOC group (p = 0.21). Median second-line OS was 25.0 months in the ARSI group and 14.2 months in the DOC group (p = 0.06). Prostate-specific antigen nadir ≤ 0.2 ng/ml during upfront ARSI therapy was significantly associated with improved second-line PFS. After PSM, no significant difference in second-line PFS and second-line OS were observed between the two groups. CONCLUSION: ARSI or DOC has comparable oncologic outcomes in terms of second-line PFS and second-line OS. Further prospective research with longer follow-ups will be needed to identify the optimal treatment after upfront ARSI therapy.

OBJECTIVE: The aim of this study was to compare prognostic outcomes of administering first- or second-generation androgen receptor signaling inhibitors in non-metastatic castration-resistant prostate cancer and to find prognostic indicators. METHODS: This retrospective study included 198 patients with non-metastatic castration-resistant prostate cancer from 14 institutions associated with Tokai Urologic Oncology Research Seminar. Forty-two patients were treated with combined androgen blockade using first-generation inhibitors (bicalutamide or flutamide), and 156 were treated with second-generation inhibitors (abiraterone/enzalutamide or apalutamide/darolutamide) after primary androgen deprivation therapy failure. We compared survival outcomes of combined androgen blockade using first-generation inhibitors and second-generation inhibitor treatments, and analyzed clinicopathological or serum parameters and survival outcome. RESULTS: Combined androgen blockade and second-generation androgen receptor signaling inhibitor groups demonstrated median progression-free survival of 10.2 (95% confidence interval: 5.5-12.3) and 26.0 (95% confidence interval: 21.9-38.4; P < 0.001) months, respectively. Cut-off levels for clinical biomarkers were targeted to <0.2 ng/ml prostate-specific antigen levels 3 months after treatment initiation for non-metastatic castration-resistant prostate cancer; the patient group that achieved this showed better progression-free survival (median 14.7 months, 95% confidence interval: 10.3-23.9 not achieved, median not applicable, 95% confidence interval: 24.6-not applicable achieved; P < 0.00001). Multivariate analysis revealed significant prognostic factors: second-generation androgen receptor signaling inhibitor as first-line treatment (odds ratio: 5.05, 95% confidence interval: 1.54-16.6) and a high hemoglobin level (odds ratio: 2.92, 95% confidence interval: 1.26-6.76). CONCLUSIONS: Our findings suggested prostate-specific antigen < 0.2 ng/ml after 3 months may be a practical prognostic indicator of survival outcomes in non-metastatic castration-resistant prostate cancer. Patients showing a high hemoglobin level should be intensively treated with second-generation androgen receptor signaling inhibitors rather than combined androgen blockade using first-generation inhibitors.

The treatment paradigm for non-metastatic castration-resistant prostate cancer (nmCRPC) has changed in recent years. An observational multicenter study was conducted to evaluate the effectiveness of androgen receptor signaling inhibitors (ARSIs) as a first-line treatment for patients with nmCRPC. The present study included native Japanese patients from four hospitals who received ARSIs as a first-line treatment for nmCRPC. The primary endpoint of the study was to evaluate the efficacy and safety of ARSI in patients with nmCRPC. The secondary endpoint was to develop a novel system to stratify the prognoses of these patients. In total, 160 patients were included in the present study. Within a median follow-up period of 23 months, the median overall survival (OS) was not reached, whereas the median progression-free survival was 26 months. Multivariate Cox regression analyses showed that the time to CRPC, prostate-specific antigen (PSA) level at the initiation of nmCRPC treatment and Geriatric Nutritional Risk Index (GNRI) were independent predictors of OS. The patients for whom information about all three independent OS predictors was available were subsequently divided into three groups as follows: Group 1, 57 patients with negative or one positive independent OS predictor; group 2, 38 patients with two positive independent OS predictors; and group 3, 10 patients with three independent OS predictors. The OS differed significantly among the three groups (P<0.0001). In conclusion, ARSIs as a first-line treatment may be associated with favorable outcomes in Japanese patients with nmCRPC. Time to CRPC, PSA level at the initiation of nmCRPC treatment and GNRI are potential predictors of OS in Japanese patients with nmCRPC who received ARSIs as a first-line treatment.

INTRODUCTION AND HYPOTHESIS: Robot-assisted sacrocolpopexy (RASC) is increasingly common due to the increased uptake of surgical robot systems. The aim of this retrospective study was to assess the perioperative outcomes of the first patient cohort to undergo RASC using a brand-new surgical robot system, the hinotori surgical system (robot-assisted sacrocolpopexy with hinotori surgical system [h-RASC]). This study also aimed to compare the outcomes of this group with those of the group of patients who had undergone RASC with the da Vinci surgical system (d-RASC). METHODS: This study included 15 patients per group. Operative times, blood loss, complications, overactive bladder symptom score (OABSS; subjective measure), and urodynamic outcomes (objective measure) were compared between the groups. RESULTS: All cases were completed without serious problems during RASC procedure. Perioperative outcomes were similar between the groups except for longer operation time (min) (h-RASC 266 vs. d-RASC 229; p < .01) and console time (min) (178 vs. 159; p = .02) in the h-RASC group than in the d-RASC. De novo stress urinary incontinence (SUI) and pelvic organ prolapse (POP) recurrence were comparable. LUTS improved in the postoperative OABSS total score (preoperative 6 vs. postoperative 3; p < .01) in the h-RASC group. However, OABSS assessment (h-RASC -3 vs. d-RASC -4; p = .38) was similar between the two groups. Urodynamic studies showed similar outcomes in the median Qmax (maximum flow rate) values in both groups. CONCLUSION: This is the first report focusing on RASC using the hinotori surgical system. RASC using the hinotori surgical system could provide favorable perioperative outcomes as comparable with those of the existing da Vinci system.

OBJECTIVE: To determine whether an enhanced recovery after surgery (ERAS) protocol enhances bowel recovery and reduces postoperative ileus (POI) in both non-frail and frail patients after robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: This retrospective cohort study included 186 patients (104 with and 82 without ERAS) who underwent iRARC between 2012 and 2023. 'Frail' patients was defined as those with a low Geriatric-8 questionnaire score (≤13). The primary outcomes were postoperative bowel recovery and the incidence of POI. Secondary outcomes included length of stay (LOS), 30- and 90-day complications, 90-day readmission rate, and POI predictors. RESULTS: The ERAS group exhibited a significantly shorter LOS, early bowel recovery, a lower POI rate, fewer 90-day high-grade complications, and fewer 90-day readmissions than the non-ERAS group in the entire cohort. Non-frail patients in the ERAS group had a lower rate of POI (7.1% vs. 22.1%; P = 0.008), whereas ERAS did not reduce POI in frail patients (44.1% vs. 36.6%; P = 0.50). In the multivariate analysis, ERAS was associated with a reduced risk of POI in both the entire cohort (odds ratio [OR] 0.39, P = 0.01) and in non-frail patients (OR 0.24, P = 0.01), whereas ERAS was not likely to reduce POI (OR 1.14, P = 0.70) in frail patients. Prehabilitation was identified as a favourable predictor of POI. CONCLUSIONS: The ERAS protocol did not reduce POI in frail patients after iRARC, although it enhanced bowel recovery and reduced POI in non-frail patients. Prehabilitation for frail patients might reduce POI.

OBJECTIVE: The objective of this study was to compare the prognostic outcomes between metastatic castration-sensitive prostate cancer (mCSPC) patients receiving conventional androgen deprivation therapy (ADT) and those receiving ADT plus a novel androgen-receptor signaling inhibitor (ARSI) in routine clinical practice in Japan. METHODS: This was conducted as a retrospective multicenter study including 581 mCSPC patients, consisting of 305 receiving ADT alone or in combination with bicalutamide (group 1) and 276 receiving ADT plus one of the following ARSIs: abiraterone acetate, apalutamide, or enzalutamide (group 2). Prognostic outcomes between these 2 groups were comprehensively compared. RESULTS: In the entire cohort, prostate-specific antigen-progression-free survival (PSA-PFS) in group 2 was significantly longer than that in group 1, while no significant difference was noted in overall survival (OS) between the two groups. In patients corresponding to the LATITUDE high-risk group, however, both PSA-PFS and OS in group 2 were significantly longer than those in group 1. Of several factors examined, the following were identified as independent predictors of poor PSA-PFS in the entire cohort as well as the LATITUDE high-risk group: high C-reactive protein, high lactate dehydrogenase, high alkaline phosphatase, high Gleason score, and group 1. Furthermore, it was possible to precisely classify both the entire cohort and LATITUDE high-risk group into 3 risk groups regarding PSA-PFS according to the positive numbers of independent factors: positive for ≤1 factor, favorable; 2 factors, intermediate; and ≥3 factors, poor. CONCLUSION: Combined use of ARSIs with ADT could improve the prognostic outcomes of mCSPC patients, particularly those in the LATITUDE high-risk group, in real-world clinical practice in Japan.

BACKGROUND: This study aimed to compare the efficacy of robot-assisted partial nephrectomy for completely endophytic renal tumors with the reported outcomes of conventional laparoscopic partial nephrectomy and investigate the transition of renal function after robot-assisted partial nephrectomy. METHODS: We conducted a prospective, multicenter, single-arm, open-label trial across 17 academic centers in Japan. Patients with endophytic renal tumors classified as cT1, cN0, cM0 were included and underwent robot-assisted partial nephrectomy. We defined two primary outcomes to assess functional and oncological aspects of the procedure, which were represented by the warm ischemic time and positive surgical margin, respectively. Comparisons were made using control values previously reported in laparoscopic partial nephrectomy studies. In the historical control group, the warm ischemia time was 25.2, and the positive surgical margin was 13%. RESULTS: Our per-protocol analysis included 98 participants. The mean warm ischemic time was 20.3 min (99% confidence interval 18.3-22.3; p < 0.0001 vs. 25.2). None of the 98 participants had a positive surgical margin (99% confidence interval 0-5.3%; p < 0.0001 vs. 13.0%). The renal function ratio of eGFR before and after protocol treatment multiplied by splits was 0.70 (95% confidence interval: 0.66-0.75). Factors such as preoperative eGFR, resected weight, and warm ischemic time influenced the functional loss of the partially nephrectomized kidney after robot-assisted partial nephrectomy. CONCLUSIONS: Robot-assisted partial nephrectomy for completely endophytic renal tumors offers a shorter warm ischemia time and comparable positive surgical margin rate compared with conventional laparoscopic partial nephrectomy.

PURPOSE: Immune checkpoint inhibitor (ICI)-based combination therapy is a standard systemic treatment for metastatic renal cell carcinoma (mRCC). Although differential pharmacologic action between ICI+ICI and ICI+tyrosine kinase inhibitor (TKI) combinations may affect outcomes, comparative studies using real-world data are few. METHODS: We retrospectively analyzed the records of 447 mRCC patients treated with 1st-line ICI-based combinations at multiple institutions between January 2018 and August 2023, and selected 320 patients diagnosed with clear cell RCC (ccRCC) for further study. Cohorts were matched using one-to-one propensity scores based on IMDC risk classification. Overall survival (OS), progression-free survival (PFS), objective response rates (ORRs), and treatment-related adverse events (TrAE) were compared. RESULTS: The matching process yielded 228 metastatic ccRCC patients treated with ICI+ICI (n = 114) or ICI+TKI (n = 114). Median OS was 53 months (95%CI: 33-NA) in patients treated with ICI+ICI and was not reached (95%CI: 43-NA) with ICI+TKI (P = 0.24). Median PFS was significantly shorter for ICI+ICI (13 months, 95%CI: 7-25) than for ICI+TKI (25 months, 95%CI: 13-NA) (P = 0.047). There were no differences in second-line PFS for sequential therapy after 1st-line combinations of ICI+ICI or ICI+TKI (6 vs. 8 months, P = 0.6). There were no differences in ORR between the 2 groups (ICI+ICI: 51% vs. ICI+TKI: 55%, P = 0.8); the progressive disease (PD) rate was significantly higher in patients treated with the ICI+ICI combination (24% vs. 11%, P = 0.029). The rate of any grade TrAE was significantly higher in patients treated with ICI+TKI (71% vs. 85%, P = 0.016), but we found no differences in severe TrAE between the 2 groups (39% vs. 36%, P = 0.8). CONCLUSIONS: In a matched cohort of real-world data, we confirmed comparable OS benefits between ICI+ICI and ICI+TKI combinations. However, differential clinical behaviors in terms of PFS, PD rates, and TrAE between ICI-based combinations may enrich clinical decision-making.

BACKGROUND: Recently, various novel robotic systems have been put into clinical use. The aim of the present study was to assess the perioperative outcomes of robot-assisted radical prostatectomy (RARP) using the Hugo™ RAS system, one of brand-new robot-assisted surgical platforms. METHODS: We performed RARP with the Hugo™ RAS system in 13 cases of localized prostate cancer (PCa) between August 2023 and February 2024 at our hospital. The perioperative outcomes of these 13 patients were assessed. RESULTS: The median operative and console times were 197 (interquartile range [IQR], 187-228) and 134 min (IQR, 125-157), respectively. The median docking time was 7 min (IQR, 6-10), and the median estimated blood loss was 150 mL (IQR, 80-250). The vesical catheter was removed on postoperative day 6 in all cases. A positive surgical margin was observed in one patient (7.7%), and none experienced major perioperative complications, defined as Clavien-Dindo classification ≥3. The median postoperative length of stay was 8 days (IQR, 8-8.5). CONCLUSIONS: This was the first study to focus on RARP using the Hugo™ RAS system in Japan. Although further investigations should be conducted to assess the long-term oncological and functional outcomes, the Hugo™ RAS system could provide safe and favorable perioperative outcomes for patients with localized PCa undergoing RARP.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate that targets Nectin-4, is used for patients with metastatic urothelial carcinoma who have experienced progression on platinum-based chemotherapy and checkpoint inhibitors. Despite the widespread use of the drug, evidence remains scarce regarding clinical indicators that can predict the response to EV treatment. OBJECTIVE: We aimed to explore the predictive value of clinical indicators derived from peripheral blood tests for treatment responses to EV. METHODS: We utilized records of 109 patients with metastatic urothelial carcinoma treated by EV from our multi-institutional dataset. Receiver operating characteristic curve analyses for predicting objective responses including several indicators from blood examinations, such as C-reactive protein-albumin ratio (CAR), hemoglobin, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and lactate dehydrogenase, were performed. The optimal cutoff points were determined by the Youden index. Logistic regression analyses for achieving objective responses to EV treatment were performed among these indicators. RESULTS: The median age of the cohort was 74 years, and the median follow-up duration was 10 months for the entire group. Median overall survival and progression-free survival from the initiation of EV were 12 and 6 months, respectively. The objective response rate and disease control rate were 48% and 70%, respectively. The receiver operating characteristic curve analysis aimed at predicting the achievement of an objective response to EV showed that the concordant index for the CAR was 0.774, significantly surpassing other indicators such as hemoglobin level, neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and serum lactate dehydrogenase. The Youden index identified an optimal cutoff value of 1 for CAR (mg/L for C-reactive protein and g/dL for serum albumin level) in predicting the objective response to EV treatment. Using the cutoff value for the CAR, the cohort was divided into 32 patients (29%) with lower CAR and 77 patients (71%) with higher CAR. The objective response rate was observed to be 84% in the lower CAR group and 32% in the higher CAR group (p < 0.0001). A logistic regression analysis revealed that an Eastern Cooperative Oncology Group Performance Status ≥1 (p = 0.04) and a CAR ≥1 (p < 0.001) were identified as independent predictors for the objective response to EV. CONCLUSIONS: The evaluation of the CAR from a concise blood examination at the initiation of EV could effectively predict the treatment response to EV in patients with metastatic urothelial carcinoma after the progression of platinum-based chemotherapy and checkpoint inhibitors.

OBJECTIVES: The optimal indication and survival benefits of prophylactic urethrectomy (PU) during radical cystectomy remain unclear. Therefore, this study aims to evaluate the impact of urethra-preserving surgery (UPS) on oncological outcome including its recurrence patterns, and to establish an optimal urethral management strategy with a novel UPS technique in the robotic era. PATIENTS AND METHODS: We retrospectively analyzed 281 male patients with bladder cancer who received radical cystectomy (RC) (115 with and 166 without PU) at our institutions between 2010 and 2023. Subsequently, perioperative and oncological outcomes were assessed between propensity score-matched cohorts. RESULTS: Urethral recurrence (UR) occurred in 5 patients (5/166, 3.0%), all of whom underwent open-RC. Three among those (1.8%) with concomitant metastasis were died of cancer. There were no statistically significant differences between the PU and UPS groups in urethral-recurrence free survival (urethral-RFS) (P = .14), local-RFS (P = .59) and overall survival (OS) (P = .84) in the entire cohort. However, the UPS group showed significantly worse urethral-RFS (P = .008), local-RFS (P = .005) and OS (P = .03) in patients with high-risk of UR. Analysis of recurrence patterns revealed that UPS in high-risk patients significantly increased local recurrence (25.8% vs. 5.0%, P = .02). Conversely, a novel robotic-UPS technique demonstrated significantly favorable perioperative outcomes, comparable local-RFS (P = .79) and OS (P = .16) without UR (0/134, 0%) when compared to robotic-PU. Robotic-UPS also exhibited significantly better local-RFS (P =.007) and OS (P < .001) than open-UPS. CONCLUSIONS: UR-related death was rare and PU did not show a survival benefit for the entire cohort. However, inappropriate UPS in patients at high-risk of UR may increase local recurrence which might be responsible for poor survival after UPS rather than disease progression derived from UR. The robotic-UPS has the potential to reduce unnecessary PU, urethral and local recurrence without compromising survival.

BACKGROUND: Enfortumab vedotin (EV), an antibody-drug conjugate targeting Nectin-4, has been used for patients with metastatic urothelial carcinoma (mUC) after progressing on checkpoint inhibitors (CPIs). Re-challenging chemotherapy with platinum agents and continuing CPIs beyond progressive disease (PD) have often been chosen following PD on CPIs, and several studies indicate favorable treatment effects of re-challenging chemotherapy. There is little evidence for comparing EV and re-challenging chemotherapy in real-world clinical practice. OBJECTIVE: The aim was to reveal the real-world treatment outcomes of EV, re-challenging chemotherapy, and continuing CPIs beyond PD in mUC patients. PATIENTS AND METHODS: A multi-institutional dataset of 350 mUC patients treated with CPIs was utilized. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) were evaluated to compare the treatment arms. RESULTS: One hundred and nine mUC patients were treated with EV with a median follow-up of 6.4 months. The ORR and disease control rate (DCR) were 48% and 70%, respectively. The OS from PD on pembrolizumab exhibited significant differences among the three groups, with a median OS of 8, 14, and 29 months in continuing pembrolizumab beyond PD, re-challenging chemotherapy, and EV, respectively. When comparing the survival outcomes from the initiation of the treatment, there is neither a difference in OS (p = 0.124), PFS (p = 0.936), nor ORR (p = 0.816) between EV and re-challenging chemotherapy. Notably, the DOR in patients who achieved an objective response was significantly longer in the EV group than the re-challenging chemotherapy group (a median of 11 and 5 months, p = 0.049). For OS, the difference was not statistically significant (27 and 11 months in EV and re-challenging chemotherapy, respectively: p = 0.05). CONCLUSIONS: A superior effect of EV on patient survival compared to re-challenging chemotherapy and continuing pembrolizumab beyond PD was observed in our real-world analysis, which is attributed to the durable DOR in EV treatment despite the similar ORR to re-challenging chemotherapy.

INTRODUCTION: Postoperative Legionella pneumonia is very rare. CASE PRESENTATION: A 71-year-old male patient with prostate cancer (cT2bN0M0) underwent a robotic-assisted radical prostatectomy. On the 5th postoperative day, the patient developed chills and a fever of 39.2°C. Chest radiography revealed decreased permeability in the right middle lung field, leading to the diagnosis of postoperative pneumonia. Antimicrobial therapy was initiated immediately. Blood tests on postoperative day 10 revealed mild liver function abnormalities, electrolyte abnormalities, and a markedly elevated inflammatory response. Legionella pneumonia was suspected based on blood sample results and systemic symptoms, such as diarrhea and nausea. Furthermore, Legionella antigens were detected in the patient's urine, prompting further administration of levofloxacin. The patient's subsequent clinical course was favorable. CONCLUSION: When bacterial pneumonia fails to respond to antimicrobial therapy and systemic symptoms develop, atypical pneumonia, caused by pathogens such as Legionella pneumophila, should be considered even in cases of postoperative pneumonia.

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.

OBJECTIVES: Enfortumab vedotin (EV) is a novel antibody-drug conjugate approved for metastatic urothelial carcinoma (UC) refractory to prior treatment with immune checkpoint inhibitors (ICIs). However, the difference in efficacy of EV after each ICIs and prognostic factors are not well known. We aimed to compare the efficacy of EV in patients with metastatic UC who were treated with avelumab or pembrolizumab and to identify the prognostic factors. METHODS: The records of 100 patients with advanced metastatic UC who received EV after the administration of either avelumab or pembrolizumab were retrospectively collected from five academic hospitals in Japan. RESULTS: The median follow-up period was 6.7 months. The median overall survival (OS) and progression-free survival (PFS) in the EV after avelumab/pembrolizumab group were not reached/14.7 months (p = 0.17) and 10.4/5.2 months (p = 0.039), respectively. The objective response rates (ORR) were 66.6% and 46.8% in EV after avelumab and EV after pembrolizumab groups, respectively (p = 0.14). Multivariate analysis identified histological variants, liver metastasis, low serum albumin levels, and high serum CRP level as significant poor prognostic factors. The median OS and PFS of cachexia patients with both low serum albumin levels and high serum CRP levels were 6.0 months and 0.93 months, respectively. CONCLUSION: PFS was superior in patients treated with EV after avelumab to EV after pembrolizumab. However, OS showed no significant difference between the two groups. Because the prognosis of patients with cachexia is extremely poor, the initiation of EV should be discussed in these patients.

OBJECTIVE: To evaluate the safety and efficacy of robot-assisted radical cystectomy using an intracorporeal ileal conduit in older compared to younger patients. METHODS: We retrospectively analyzed 122 patients who underwent robot-assisted radical cystectomy with an intracorporeal ileal conduit at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2012 and 2022. Patients were categorized into two groups: older (age ≥ 75 years; n = 53) and younger (age < 75 years; n = 69). Perioperative outcomes, complications, recurrence-free survival, cancer-specific survival, and overall survival were compared between the cohorts. RESULTS: The groups had no significant differences in perioperative outcomes, such as estimated blood loss, operative time, and blood transfusion rate. However, hospital stay was longer in the older patients than in the younger group (19 vs. 16 days; p < 0.001). The 30-day minor and major complication rates were 33.3% and 13.0%, respectively, for the younger group and 50.9% and 9.4% for the older group (p = 0.11). Urinary tract infection and bowel ileus were the most common complications in both groups. No significant differences were observed in recurrence-free survival, cancer-specific survival, and overall survival between the groups (p = 0.58, p = 0.75, and p = 0.78), and subgroup analysis in ≥cT3 revealed the older group tended to have poorer cancer-specific survival and overall survival (p = 0.07 and p = 0.01). Multivariate analysis indicated that older age was not associated with high-grade complications and cancer-specific survival. CONCLUSIONS: Robot-assisted radical cystectomy with an intracorporeal ileal conduit is a safe and effective treatment option for older patients.

BACKGROUND: The interaction between lymph node dissection (LND) during radical cystectomy (RC) and neoadjuvant chemotherapy (NAC) remains unclear. This study aimed to evaluate the role of LND in patients undergoing RC after NAC. PATIENTS AND METHODS: We retrospectively analyzed 259 patients with muscle-invasive bladder cancer (MIBC) who underwent RC following NAC at Fujita Health University Hospital and Fujita Health University Okazaki Medical Center between 2010 and 2022. Baseline characteristics, pathological outcomes, recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS) were compared between propensity score (PS)-matched cohorts. RESULTS: PS matching analysis resulted in 94 matched pairs from the adequate (standard or extended template) and inadequate (limited template or unilateral- or no-LND) LND groups. The median number of dissected nodes was significantly higher in the adequate LND group than in the inadequate LND group (19 vs. 5, P < .001). Similarly, a higher pathological node-positive rate (ypN+) was observed in the adequate group than in the inadequate group (18.1% vs. 7.4%, P = .03). The adequate LND group identified more ypN+ with ≤ ypT1 cases than the inadequate group (4 vs. 1). There were no statistically significant differences between the adequate and inadequate groups in RFS (P = .94), CSS (P = .54), and OS (P = .65). Subgroup analysis also showed comparable survival rates, even in patients with ≥ pT3 or cN+ disease. ypN+ was an independent predictor of OS in the Cox regression analysis, while adequate LND and the number of lymph nodes removed (≥10 or ≥15) were not associated with survival. CONCLUSIONS: Although adequate LND did not show a significant therapeutic effect in RC after NAC, adequate LND may have an important diagnostic role in detecting ypN+, which is a robust predictor, and is a useful biomarker to perform appropriate adjuvant immunotherapy especially in ≤ ypT1 cases.

INTRODUCTION: It is well known that patients with objective response to pembrolizumab have a durable duration of response, leading to favorable survival outcomes. We investigated the possibility of predicting the objective response with concise indicators obtained from daily clinical practice. METHODS: In our multi-institutional cohort, 220 platinum-refractory metastatic urothelial carcinoma (mUC) patients treated with pembrolizumab for at least 6 weeks with complete information of objective response were investigated. RESULTS: The median follow-up was 7.3 months, and 119 patients deceased during the follow-up. A multivariate logistic regression analysis exhibited two independent variables predicting the objective response, including the neutrophil-lymphocyte ratio (NLR) change at 6 weeks of treatment and liver metastasis. We proposed a risk group using these two indicators. Patients with no predictive indicators/one of those were assigned to favorable (42%)/intermittent (47%) risk groups. Patients with both indicators were assigned to poor risk (11%). Notably, the objective response rate was well delineated in 41%, 25%, and 0% for favorable-, intermediate-, and poor-risk groups, respectively (p &lt; 0.001). Distinct overall survival (OS) between the risk groups was also confirmed with the median OS of 14.1, 11.7, and 4.2 months in favorable-, intermediate-, and poor-risk groups, respectively. CONCLUSIONS: At the 6 weeks of the pembrolizumab treatment, our risk model predicts the objective response rate precisely. Notably, those classified as "poor risk" - marked by liver metastasis and an increased NLR - should be considered for alternative therapy with a different mode of action, highlighting a critical decision point in treatment optimization.

BACKGROUND: To investigate the impact of different urinary diversion (UD) techniques on the peri- and postoperative complications of robot-assisted radical cystectomy (RARC) with ileal conduit. METHODS: We retrospectively analyzed 373 patients undergoing RARC with ileal conduit at 11 institutions in Japan between April 2018 and December 2021. Propensity score weighting was performed to adjust for confounding factors such as age, sex, body mass index, performance status, American Society of Anesthesiologists score, previous abdominal surgery, neoadjuvant chemotherapy, and preoperative high T stage (≥ cT3) and high N stage (≥ cN1). Perioperative complications were then compared among three groups: extracorporeal, intracorporeal, and hybrid urinary diversion (ECUD, ICUD, and HUD, respectively). RESULTS: A total of 150, 68, and 155 patients received ECUD, HUD, and ICUD, respectively. Bowel reconstruction time and UD time were significantly shorter in the ECUD group (p < 0.001), and console time was significantly longer and blood loss was significantly higher in the ICUD group (p < 0.001). For postoperative complications (Clavien-Dindo Classification grade ≥ 3), surgical site infection (p = 0.004), pelvic abscess (p = 0.013), anastomotic urine leak (p = 0.007), and pelvic organ prolapse (p = 0.011) significantly occurred in the ECUD group. For all grades, ileus was more common in the HUD group, whereas anastomotic stricture was more common in the ECUD group compared with the other groups (p < 0.05). CONCLUSIONS: Severe complications did not increase after HUD and ICUD compared with ECUD; however, console time tended to be longer and blood loss was slightly higher during RARC.

For patients with testicular tumors who need the surgical management, open retroperitoneal lymph node dissection (O-RPLND) is considered the gold standard treatment. However, recently, robot-assisted RPLND (R-RPLND) has gained popularity as a minimally invasive therapy alternative to O-RPLND and laparoscopic RPLND. Here, we report the case of a 32-year-old man presenting with a left testicular teratoma with several enlarged left para-aortic lymph nodes. After the orchiectomy, the patient underwent R-RPLND with an operation time of 279 min, console time of 189 min, bleeding volume of 59 mL, and no significant complications, resulting in a successful outcome. To the best of our knowledge, this is the first reported case of R-RPLND in Japan. Based on our experience, R-RPLND may provide safe and effective outcomes; however, further research is required before the widespread implementation of this technique.

BACKGROUND: Recently, robot-assisted surgery has been widely used to treat several urological cancers. Robot-assisted radical nephrectomy (RARN) was approved by the health insurance system in April 2022; however, RARN with inferior vena cava tumor thrombectomy (IVCTT) is still challenging. Also, its safety and feasibility have not yet been established owing to lack of literature, especially in Japan. CASE DESCRIPTION: We performed RARN with IVCTT in four patients between April 2022 and March 2023 at Fujita Health University Hospital. To reduce the risk of tumor embolism and major hemorrhage, an "IVC-first, kidney-last" robotic technique was developed. The safety and feasibility of RARN with IVCTT were evaluated by assessing the perioperative outcomes. Three women and one man were enrolled in this study. The median age was 72 years, and the tumor was on the right side in all cases. According to the Mayo Clinic thrombus classification, two patients were classified as level I, and the others were classified as level II. The two patients at level I did not undergo presurgical treatments, whereas the others at level II underwent presurgical treatments, which were combinations of tyrosine kinase inhibitors and immune-checkpoint inhibitors. The median operation and console times were 341 and 247 min, respectively. The median bleeding volume was 577 mL, and no complications beyond grade III of the Clavien-Dindo classification were observed. The median length of postoperative hospital stay was 10 days. CONCLUSIONS: Although the sample size was relatively small, we demonstrated the safety and feasibility of RARN with IVCTT in the Japanese population.

OBJECTIVES: To explore the characteristics of patients and assess the effectiveness of enfortumab vedotin (EV) in those with treatment-resistant advanced urothelial cancer in a real-world setting. PATIENTS AND METHODS: A multicenter observational study was conducted on 103 evaluable patients with advanced urothelial cancer who received EV. Outcomes were assessed by radiographic response, progression-free survival (PFS), and overall survival (OS), with treatment-related adverse events (trAEs). Radiographic response was assessed using Response Evaluation Criteria in Solid Tumors version 1.1, while trAEs were studied in line with Common Terminology Criteria for Adverse Events version 5.0. RESULTS: The median follow-up was 8.9 months (range, 0.1-16.4). The observed objective response rate was 50.5%. The median PFS was 6.0 months (95% CI: 4.7-9.8), and the median OS was 14.5 months (95% CI: 12.4-not reached). Out of the 103 patients, 19 (18.4%) had an Eastern Cooperative Oncology Group performance status of 2 or more, 14 (14.7%) had an non-urothelial carcinoma histology, and 40 (38.3%) had at least one pre-existing comorbidity. There were 26 (25.2%) patients who reported 49 trAEs, with 9 (18.3%) being grade 3 or higher. The most common trAEs included rash, occurring in 18.4%. CONCLUSIONS: This study describes the characteristics and outcomes of patients with previously treated advanced urothelial cancer receiving EV. The findings demonstrate that EV showed robust anti-tumor activity and had manageable safety profiles outside the clinical trial setting.

Malnutrition is associated with prognosis in cancer. The geriatric nutritional risk index (GNRI), based on the ratio of actual to ideal body weight and also serum albumin level, is a simple screening tool for assessing nutrition. We investigated the GNRI as a prognostic factor for oncological outcomes in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC) using a Japanese multicenter cohort. This study included a total of 175 patients with LATITUDE high-risk mHSPC, of whom 102 had received androgen deprivation therapy (ADT) plus upfront abiraterone acetate, and 73 had received ADT plus bicalutamide (Bica), from 14 institutions associated with the Tokai Urologic Oncology Research Seminar. Patients were classified into GNRI-low (<98) or GNRI-high (≥98) groups. The GNRI was based on the body mass index and serum albumin level. Kaplan-Meier analysis revealed that the median overall survival (OS) of a GNRI-low group (median 33.7 months; 95% confidence interval [CI]: 26.2-not reached [NR]) was significantly worse than that of a GNRI-high group (median: NR; 95% CI: NR-NR; p < 0.001). Multivariate analysis identified Bica and low GNRI (<98) as independent prognostic factors for reduced times to both castration-resistant prostate cancer and OS, and, therefore, a poor prognosis. Our findings indicate the GNRI may be a practical prognostic indicator in the evaluation of survival outcomes in patients with LATITUDE high-risk mHSPC.

BACKGROUND: There is little evidence of abiraterone acetate (AA) plus prednisone for patients with non-metastatic castration-resistant prostate cancer (nmCRPC). In this study, we conducted a comparative analysis of real-world survival outcomes between AA plus prednisone and enzalutamide (Enz) in patients with nmCRPC, utilizing our consortium dataset. MATERIALS AND METHODS: The clinical records of 133 nmCRPC patients treated with first-line Enz or AA plus prednisone were analyzed. The primary endpoints of the study were overall survival (OS) and cancer-specific survival (CSS). Cumulative incidence function (CIF) using Fine and Gray models was also utilized to assess non-cancer-caused death considering the competing risk of cancer-caused death. RESULTS: During a median follow-up of 36 months, 34 patients (25.6%) had deceased, with a median OS of 99 months in the entire cohort. There were no significant differences in comorbidities between the Enz and AA groups. Time to PSA progression (TTPP: HR 0.81, 95% CI 0.51-1.30, P = 0.375) and CSS (HR 1.32, 95% CI 0.55-3.44, P = 0.5141) were comparable between the two groups. However, intriguingly, there was a trend towards shorter OS in patients treated with AA plus prednisone compared to Enz (HR 0.57, 95% CI 0.29-1.12, P = 0.0978, median of 99 and 69 months in Enz and AA groups, respectively). CIF analysis revealed that nmCRPC patients treated with AA plus prednisone were more likely to result in non-cancer-caused death than those treated with Enz (HR 5.22, 95% CI 1.88-14.50, P = 0.0014). CONCLUSIONS: Our real-world survival analysis suggests that while AA plus prednisone may demonstrate comparable treatment efficacy to Enz in the context of nmCRPC, there may be an increased risk of non-cancer-caused death. Physicians should take into consideration this information when making treatment decisions for patients with nmCRPC.

BACKGROUND: Immune checkpoint inhibitors can cause various immune-related adverse events (irAEs). This study aimed to evaluate the association between the incidence of irAEs and oncological outcomes of metastatic renal cell carcinoma (mRCC) treated with nivolumab plus ipilimumab as first-line therapy. PATIENTS AND METHODS: We retrospectively analyzed data from 69 patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy between September 2018 and September 2021 at 4 institutions. Cox regression analyses were performed to investigate the important factors affecting overall survival (OS) in patients with mRCC treated with nivolumab plus ipilimumab as first-line therapy. RESULTS: During observation with a median follow-up of 9.1 months, the median OS was not reached, while the median progression-free survival was 6.0 months. Patients with irAEs had significantly prolonged OS and progression-free survival than those without irAEs (p = .012 and .002, respectively). Multivariate analysis showed that 3 independent factors, including C-reactive protein (CRP), irAEs, and performance status (PS), were significantly associated with OS (p = .04, .02, and .01, respectively). The patients were subsequently divided into 3 groups as follows: group 1, 20 patients with all 3 independent OS predictors; group 2, 18 patients with irAE predictors alone or 2 positive independent OS predictors (irAEs + CRP or irAEs + PS); group 3, 31 patients with 3 negative independent S predictors. OS varied significantly among the 3 groups (p = .004). CONCLUSION: The appearance of irAEs could predict OS in patients with mRCC treated with nivolumab plus ipilimumab as the first-line therapy.

Pentafecta (continence, potency, cancer control, free surgical margins, and no complications) is an important outcome of prostatectomy. Our objective was to assess the pentafecta achievement between nerve-spring and non-nerve-sparing robot-assisted radical prostatectomy (RARP) in a large single-center cohort. The study included 1674 patients treated with RARP between August 2009 and November 2022 to assess the clinical outcomes. Cox regression analyses were performed to evaluate the prognostic significance of RARP for pentafecta achievement, and 1:1 propensity score matching (PSM) was performed between the nerve-sparing and non-nerve-sparing to test the validity of the results. Pentafecta definition included continence, which was defined as the use of zero pads; potency, which was defined as the ability to achieve and maintain satisfactory erections or ones firm enough for sexual activity and sexual intercourse. The biochemical recurrence rate was defined as two consecutive PSA levels > 0.2 ng/mL after RARP; 90-day Clavien-Dindo complications ≤ 3a; and a negative surgical pathologic margin. The median follow-up period was 61.3 months (IQR 6-159 months). A multivariate Cox regression analysis demonstrated that pentafecta achievement was significantly associated with nerve-sparing (NS) approach (1188 patients) (OR 4.16; 95% CI 2.51-6.9), p < 0.001), unilateral nerve preservation (983 patients) (OR 3.83; 95% CI 2.31-6.37, p < 0.001) and bilateral nerve preservation (205 patients) (OR 7.43; 95% CI 4.14-13.36, p < 0.001). After propensity matching, pentafecta achievement rates in the NS (476 patients) and non-NS (476 patients) groups were 72 (15.1%) and 19 (4%), respectively. (p < 0.001). NS in RARP offers a superior advantage in pentafecta achievement compared with non-NS RARP. This validation study provides the pentafecta outcome after RARP associated with nerve-sparing in clinical practice.

BACKGROUND: We recently reported the importance of deep learning (DL) of pelvic magnetic resonance imaging in predicting the degree of urinary incontinence (UI) following robot-assisted radical prostatectomy (RARP). However, our results were limited because the prediction accuracy was approximately 70%. AIM: To develop a more precise prediction model that can inform patients about UI recovery post-RARP surgery using a DL model based on intraoperative video images. METHODS AND RESULTS: The study cohort comprised of 101 patients with localized prostate cancer undergoing RARP. Three snapshots from intraoperative video recordings showing the pelvic cavity (prior to bladder neck incision, immediately following prostate removal, and after vesicourethral anastomosis) were evaluated, including pre- and intraoperative parameters. We evaluated the DL model plus simple or ensemble machine learning (ML), and the area under the receiver operating characteristic curve (AUC) was analyzed through sensitivity and specificity. Of 101, 64 and 37 patients demonstrated "early continence (using 0 or 1 safety pad at 3 months post-RARP)" and "late continence (others)," respectively, at 3 months postoperatively. The combination of DL and simple ML using intraoperative video snapshots with clinicopathological parameters had a notably high performance (AUC, 0.683-0.749) to predict early recovery from UI after surgery. Furthermore, combining DL with ensemble artificial neural network using intraoperative video snapshots had the highest performance (AUC, 0.882; sensitivity, 92.2%; specificity, 78.4%; overall accuracy, 85.3%) to predict early recovery from post-RARP incontinence, with similar results by internal validation. The addition of clinicopathological parameters showed no additive effects for each analysis using DL, EL and simple ML. CONCLUSION: Our findings suggest that the DL algorithm with intraoperative video imaging is a reliable method for informing patients about the severity of their recovery from UI after RARP, although it is not clear if our methods are reproducible for predicting long-term UI and pad-free continence.

BACKGROUND: Because of the organ shortage, donation after cardiac death (DCD) kidney transplantation (KTx) is an alternative way of achieving KTx using brain-dead donors (BDs). Although the prognosis of DCD-KTx is improving, the graft suffers from delayed graft function (DGF), the management of which is essential. With progress in understanding the characteristics of cell-free DNA (CF-DNA), we consider plasma total CF-DNA (tCF-DNA) to be a useful biomarker for predicting DGF in DCD-KTx. STUDY DESIGN AND METHOD: Consecutive patients from living donors (LDs; n = 9), BDs (n = 8), or DCD donors (n = 13) were enrolled. Plasma samples were collected after KTx and on postoperative days 3 and 5. CF-DNA was isolated, and tCF-DNA was quantified using the TapeStation 2200 software program. RESULTS: The tCF-DNA levels after BD-KTx and DCD-KTx were higher than those after LD-KTx (LD, 78 ± 27 (ng/mL); BD, 99 ± 20; DCD, 150 ± 23); the difference between DCD-KTx and LD-KTx was statistically significant (P < .05). The tCF-DNA levels declined at postoperative day 5 (LD, 45 ± 10; BD, 51 ± 11; DCD, 66 ± 13). tCF-DNA levels were significantly increased in patients with DGF after KTx (DGF, 139 ± 22; immediate function, 91 ± 18; P < .05). The tCF-DNA level was correlated with the duration of DGF (r = 0.5825, P < .05). CONCLUSION: Although the mechanism underlying DNA release from transplanted grafts into the recipient circulation remains unclear, cell death by apoptosis or necrosis and the active secretion of the immune system may play important roles in DGF. These data suggest that monitoring tCF-DNA may help predict graft recovery after DCD-KTx.

The advent of second-generation androgen receptor axis-targeted agents (ARATs) has revolutionized the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Biochemical recurrence-free survival (BRFS) was used to compare the efficacy of each ARAT. This multicenter retrospective study included 581 patients with newly diagnosed mHSPC who received first-line hormone therapy. The characteristics of patients treated with different ARATs were compared as well as changes in the usage of each drug over time. For BRFS, the apalutamide (Apa) and enzalutamide (Enza) groups, as well as the abiraterone acetate (Abi) and Apa/Enza groups, were compared. In addition, multivariate analysis was performed to determine predictive factors for biochemical recurrence (BCR). The use of second-generation ARATs tended to increase after May 2020. No significant difference in BRFS was found between patients receiving Apa and Enza (p = 0.490) and those receiving Abi or Apa/Enza (p = 0.906). Multivariate analysis revealed that the neutrophil-to-lymphocyte ratio (NLR) ≥ 2.76 and PSA ≥ 0.550 ng/mL were independent predictors of BCR. There were no significant differences in patient characteristics or BRFS in patients with mHSPC receiving different ARATs as first-line treatment. NLR and PSA may be prognostic factors following the first-line treatment of patients with mHSPC.

BACKGROUND AND PURPOSE: Pembrolizumab has now become a standard of care in metastatic urothelial carcinoma (mUC), although the treatment effect of the drug substantially differs among individuals. Emerging evidence suggests that radiotherapy exerts a synergistic effect with PD-1 blockade. We sought to elucidate the survival outcomes in patients who underwent palliative radiation with the pembrolizumab treatment. METHODS: We retrospectively investigated our multi-institutional dataset of 235 platinum-refractory mUC patients treated with pembrolizumab as second-line treatment, collected from January 2018 and October 2021. Propensity score matching was performed to reduce biases by potential confounding factors for overall survival (OS). RESULTS: With a median follow-up of 6.8 months, the median OS from the initiation of pembrolizumab was 13 months in 235 patients. Palliative radiation was performed in 71 (30.2%) patients for whom the median radiation dose and fraction were 30 Gy and 10 fractions, respectively. Irradiated sites were bone in 24 (33.8%), lymph node in 17 (23.9%), lung in 3 (4.2%), brain in 8 (11.3%), and other sites in 19 (26.8%). OS from the initiation of pembrolizumab was significantly longer in patients who underwent concurrent palliative radiation with pembrolizumab (39 patients: median OS: 21 months) than in both patients with palliative radiation before pembrolizumab (32 patients: median OS: 9 months) (p = 0.001) and those without palliative radiation throughout the follow-up (164 patients: median OS: 13 months) (p = 0.019). After the propensity-score matching by putative confounding factors, longer OS in patients treated with concurrent palliative radiation with pembrolizumab (n = 36) was still observed compared to patients without the concurrent palliative radiation (n = 36) in the pair matched cohort (median OS of 29 and 13 months, respectively, p = 0.033). CONCLUSIONS: Our findings suggest that the concurrent administration of palliative radiation with pembrolizumab offers a favorable effect on OS in platinum-refractory mUC patients.