Impact of the coronavirus disease 2019 pandemic on the number of undergoing radical nephroureterectomy and postoperative adjuvant systematic therapy for upper tract urothelial carcinomas in Japan: A multicenter retrospective study.

OBJECTIVES: The coronavirus disease 2019 pandemic has affected cancer management worldwide. For upper tract urothelial carcinomas, delays in treatments are not recommended even during the pandemic. We investigated the impact of the pandemic on patients with these carcinomas who underwent radical nephroureterectomy (RNU) and adjuvant systematic therapy before and after COVID-19 spread in Japan. METHODS: This multicenter retrospective study included 304 patients who underwent RNU for upper tract urothelial carcinomas between May 1, 2019, and December 31, 2021, in Aichi, Japan. The patients were categorized into three groups based on whether they underwent surgery in the prepandemic (before infection spread in Japan), early pandemic (between confirmation of the first case and vaccination initiation), and late pandemic (after the start of vaccination in Japan) phases. The patient characteristics, diagnostic methods, pathological findings, and postoperative therapy were compared among the three phases. RESULTS: Overall, 74, 152, and 78 patients underwent RNU in the prepandemic, early pandemic, and late pandemic phases, respectively. The number of patients who underwent preoperative ureteroscopy decreased significantly from the prepandemic phase to the late pandemic phase due to pandemic-related restrictions (p = 0.016). There was no difference in the time to the first visit or pathological findings. Among patients classified as high-risk according to existing clinical trials, the proportion receiving adjuvant systematic therapy after RNU decreased significantly from 52.3% to 19% (p = 0.003). CONCLUSIONS: There was no difference in the pathological findings. The number of patients receiving appropriate adjuvant systematic therapy decreased during the pandemic.

Presence of constipation predicts the therapeutic efficacy of pembrolizumab in metastatic urothelial cancer patients.

OBJECTIVES: To study bowel function in urothelial cancer patients treated with pembrolizumab and to assess its association with treatment efficacy. METHODS: This retrospective study was analyzed for patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment between December 2017 and June 2019 at Nagoya University and affiliated hospitals in Japan. The association between bowel dysfunction (defined as constipation or need for laxatives) and treatment efficacy was investigated. RESULTS: We retrospectively enrolled 73 patients with metastatic urothelial cancer who received immune checkpoint inhibitor treatment. All patients received pembrolizumab at 200 mg per bodyweight administered intravenously every 3 weeks. Performance status was 0-1 in 58 patients (79.5%), and liver metastasis was detected in 22 patients (30.1%). The median age was 72 years (range 40-89 years). A total of 45 patients had constipation. The median progression-free survival and overall survival from the start of immune checkpoint inhibitor treatment was 4.0 months (95% confidence interval 1.0-17.3) and 6.6 months (95% confidence interval 1.0-18.0), respectively. Patients with constipation had a significantly higher risk of disease progression (P = 0.005). There was no significant association between constipation and overall survival (P = 0.131). However, complete response was observed among two patients treated with immune checkpoint inhibitor, both of whom did not present constipation. CONCLUSION: The presence of constipation might be a prognostic factor for urothelial cancer patients undergoing immune checkpoint inhibitor treatment.

Impact of Histological Variants on Clinical Responses to Pembrolizumab in Patients With Metastatic Urothelial Cancer.

BACKGROUND: The efficacy of anti-programmed celldeath protein 1 treatment in patients with urothelial carcinoma (UC) with molecular subtypes of histological variants has not been investigated. This study aimed to examine the impact of histological variants classified according to molecular subtypes on clinical outcomes in patients with platinum-resistant metastatic UC treated with pembrolizumab. PATIENTS AND METHODS: Data of 168 patients with metastatic UC who received intravenous pembrolizumab after platinum-based chemotherapy between December 2017 and November 2020 were retrospectively reviewed. Relationships between histological variant type (basal or luminal molecular subtypes) and survival outcome and response to immunotherapy were examined. Clinicopathological factors were analyzed using the Cox proportional hazards model. RESULTS: UC with histological variants was identified in 19 (11.3%) cases (basal subtype in 12; luminal subtype in 7). The median age of the patients was 72.5 years (range=40-89 years). The performance status was 0-1 in 151 (89.9%) patients. Liver metastasis was detected in 44 (26.2%) patients. The median progression-free survival was 3.5 months (range=0.5-34.3 months). Treatment with immune checkpoint inhibitors resulted in an overall mean survival (from the start of treatment) of 8.1 months (range=1.2-34.3 months). Patients with basal-type UC had significantly shorter progression-free survival and cancer-specific survival than those with pure UC (p=0.010 and p=0.035, respectively). A complete response was observed in eight patients (seven with pure UC, one with basal type). CONCLUSION: The basal histological variant might be a potential prognostic indicator in patients with platinum-resistant metastatic UC treated with pembrolizumab.