Efficacy of Platinum-based Chemotherapy in Patients With Metastatic Urothelial Carcinoma With Variant Histology.

BACKGROUND/AIM: Variant urothelial carcinoma (VUC, defined herein as urothelial carcinoma with any histological variant) is frequently observed at an advanced stage. However, the efficacy of systemic chemotherapy against VUC in metastatic disease has rarely been reported. This study assessed the therapeutic response and survival outcomes of platinum-based chemotherapy as first-line treatment in patients with metastatic VUC. PATIENTS AND METHODS: We retrospectively analyzed consecutive patients with metastatic bladder and upper urinary tract cancer who received gemcitabine plus cisplatin (or carboplatin) at the University of Occupational and Environmental Health Hospital between November 2008 and November 2022. Progression-free survival and overall survival were evaluated using the Kaplan-Meier method and Cox proportional hazard models. RESULTS: Out of 131 patients recorded, 86 (65.6%) had pure urothelial carcinoma (PUC) and 45 (34.4%) had VUC. The most common variant element was squamous differentiation (44.4%). Compared to those with PUC, patients with VUC showed a comparable objective response rate (33.3% vs. 41.9%, p=0.451) and disease control rate (64.5% vs. 75.6%, p=0.221). They also had poorer progression-free survival (median=4.9 months vs. 7.9 months, p=0.014) and overall survival (median=10.9 months vs. 18.2 months, p=0.037) than those with PUC. On multivariate analysis, VUC was an independent predictor of progression (hazard ratio=1.79; 95% confidence interval=1.19-2.69; p=0.005) and mortality (hazard ratio=1.64; 95% confidence interval=1.08-2.48; p=0.020). CONCLUSION: Although the response of metastatic VUC to platinum-based chemotherapy was not inferior to that of PUC, VUC had progressed faster than PUC. VUC was significantly associated with a poor prognosis after platinum-based chemotherapy as first-line treatment.

Efficacy and Tolerability of Enfortumab Vedotin for Metastatic Urothelial Carcinoma: Early Experience in the Real World.

BACKGROUND/AIM: This study retrospectively investigated the impact of enfortumab vedotin (EV) monotherapy on the oncological outcome, safety profile, and health-related quality of life (HRQoL) in patients with metastatic urothelial carcinoma. PATIENTS AND METHODS: We assessed 26 consecutive patients who had received EV monotherapy after failure of platinum-based chemotherapy and immune checkpoint blockade therapy at our single institution from December 2021 to January 2023. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), incidence of adverse events (AEs), and EORTC QLQ-C30 as an HRQoL instrument were evaluated. RESULTS: The ORR and DCR were 57.7% and 80.8%, respectively. EV was effective regardless of the patient and tumor characteristics, including the efficacy of previous systemic therapy, performance status, number of Bellmunt risk factors, and presence of variant histology. With a median follow-up time of 7.5 months, the median durations of PFS and OS were 5.4 months and 10.3 months, respectively. Grade ≥3 AEs included neutropenia (15.4%), fatigue (7.7%), appetite loss (7.7%), rash (3.8%), febrile neutropenia (3.8%), hyperglycemia (3.8%), and interstitial pneumonia (3.8%). AEs resulting in withdrawal of EV, interruption of EV, and dose reduction occurred in two (7.7%), nine (34.6%), and 13 patients (50.0%), respectively. The EORTC QLQ-C30 scores from baseline to post-EV introduction remained stable. CONCLUSION: EV monotherapy demonstrated promising anti-tumor activity and tolerability in patients with metastatic urothelial carcinoma.

Real-world treatment outcomes of patients with penile cancer in the Kyushu-Okinawa area of Japan in the pre-guideline era.

OBJECTIVES: To understand the real-world outcomes for patients with penile cancer in the Kyushu-Okinawa area before the introduction of practice guidelines in Japan. METHODS: We retrospectively collected medical information on patients with penile squamous cell carcinoma and penile intraepithelial neoplasia at 12 university hospitals and their affiliated hospitals in the Kyushu-Okinawa area from January 2009 to December 2020. Patients with unknown clinical stage were excluded. Patient background characteristics and survival, as well as pretreatment factors involved in survival, were investigated. RESULTS: A total of 196 patients were included. Patients with clinical stage 0, I, IIA, IIB, IIIA, IIIB and IV comprised 9.7, 26.0, 22.4, 2.6, 10.7, 14.3 and 14.3%, respectively. The median follow-up was 26 months, and the mean 5-year overall survival and cancer-specific survival rates were 74.3 and 79.8%, respectively. On univariate analysis, tumor diameter ≥ 30 mm, penile shaft tumor, Eastern Cooperative Oncology Group performance status ≥ 1, cT ≥ 3, cN ≥ 2 and cM1 were associated with significantly poorer cancer-specific survival. On multivariate analysis, pretreatment factors of cN ≥ 2 (hazard ratio, 32.5; 95% confidence interval, 5.08-208; P = 0.0002), Eastern Cooperative Oncology Group performance status ≥ 1 (4.42; 1.79-10.9; P = 0.0012) and cT ≥ 3 (3.34; 1.11-10.1; P = 0.0319) were identified as independent prognostic factors. CONCLUSIONS: The study revealed basic data for future penile cancer treatment and research, including survival rates according to clinical stages, and identified cN ≥ 2, Eastern Cooperative Oncology Group performance status ≥ 1 and cT ≥ 3 at initial diagnosis as independent prognostic factors. Evidence for penile cancer in Japan is particularly scarce, and future large-scale prospective studies are warranted.

[Clinical Statistics From 2017 to 2019 in the Department of Urology, Hospital of the University of the Occupational and Environmental Health, Japan].

We introduced the da Vinci Xi surgical system (Intuitive Surgical G.K. CA) in January 2018, and here we report clinical statistics on outpatients, inpatients, and surgical procedures for the 3-year period from January 2017 to December 2019. The number of new outpatients since 2017 has remained almost unchanged at 1,406, 1,530, and 1,494 per year. There was an increasing trend in the number of inpatients, from 862 to 1,021 to 1,239. The main diseases of the inpatients over the 3-year period were bladder cancer in 676 (21.7%), renal cancer in 374 (12.0%), prostate cancer in 268 (8.6%), and urolithiasis in 263 (8.4%). The total number of surgeries in the three years was 1,931. The numbers of transurethral surgeries and laparoscopic surgeries, including robotic surgeries, were 1,063 (55.0%) and 396 (20.5%), respectively. The numbers of inpatients and surgery have been increasing year by year. Medical resources are limited and need to be distributed more efficiently.

Impact of the Use of Proton Pump Inhibitors on Pembrolizumab Effectiveness for Advanced Urothelial Carcinoma.

BACKGROUND/AIM: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated. RESULTS: The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis. CONCLUSION: The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab.

Evaluation of the Extent of Variant Histology in Urothelial Carcinoma as a Predictive Marker of Clinical Outcomes After Radical Cystectomy.

Background/Aim: This study investigated the impact of the extent of variant histology (VH) on the prognosis of patients with bladder cancer (BC). Patients and Methods: We retrospectively evaluated consecutive patients with muscle-invasive BC who were treated with radical cystectomy (RC) at our institution between 2005 and 2018. Recurrence-free survival (RFS) and overall survival (OS) rates were evaluated using Kaplan-Meier analysis and Cox regression. Results: We identified 103 and 47 patients with pure urothelial carcinoma (UC) and a VH in UC, respectively. At the cutoff of 80%, univariate analysis identified significant differences in RFS (p=0.046) and OS (p=0.038) between patients with ≥80% VH (n=21) and those with <80% VH (n=26). Multivariate analysis revealed that the presence of ≥80% VH was significantly associated with RFS and OS. Conclusion: The presence of ≥80% VH in UC could be an independent predictor of recurrence and mortality after RC.

Oncological Outcome After Radical Prostatectomy without Pelvic Lymph Node Dissection for Localized Prostate Cancer: Follow-up Results in a Single Institution.

The oncological benefit of pelvic lymph node dissection (PLND) is still debatable because data on clinical outcomes of radical prostatectomy (RP) without PLND are lacking. In this study, we reported oncological outcome in consecutive 146 patients who underwent RP without PLND. Although 27% of our patients developed biochemical recurrence, the estimated 5-year overall survival rates were 100%, 96.3%, and 95.7% in the low-, intermediate-, and high-risk groups, respectively. These data in our patients were not inferior to those in previous reports that investigated the survivals in patients who received PLND during RP. The therapeutic significance of PLND should be re-evaluated.