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.