Enzalutamide Prolonged the Duration of Drug Use in Comparison to Abiraterone Acetate and Cabazitaxel after Upfront Docetaxel: A Large Japanese Database Study.

INTRODUCTION: In the United States, a total of 268,490 men were found to have prostate cancer in 2022, thus making it the most common cancer in men, accounting for 27% of all cancers in the male population. Among all cancers in men, it was the fifth leading cause of death, with 34,500 deaths and a mortality rate of 11%. In 2019, the total number of cases was 94,748, making it the leading cancer in males, accounting for 11% of all male cancers. In terms of mortality, it ranked seventh, with 13,217 deaths and a mortality rate of 1.6%. However, new treatment options for metastatic castration-sensitive prostate cancer (mCSPC) have emerged. Docetaxel has been shown to be effective for both mCSPC and castration-resistant prostate cancer (CRPC). Upfront docetaxel has not been approved in Japan, nor has it been validated in large-scale studies. Furthermore, several agents can be used after docetaxel treatment, but it is unclear which is the most effective. We used a large Japanese health insurance database to determine which agent would be the most effective as a next-line therapy in patients who had received docetaxel. MATERIALS AND METHODS: We used data from medical institutions using the Diagnosis Procedure Combination (DPC), which provides a comprehensive evaluation of medical classifications. The Medical Data Vision database covers approximately 23% of DPC hospitals in Japan. This study analyzed 2938 patients with mCSPC who received docetaxel, followed by CRPC, between April 2008 and December 2021. The study focused on three agents: enzalutamide, abiraterone acetate, and cabazitaxel. Other agents were excluded due to the small number of patients. The following data were analyzed: age, date of CRPC diagnosis, presence of bone metastasis, drug type, and prognosis. RESULTS: This study included 1997 patients with CRPC after upfront docetaxel therapy for mCSPC (enzalutamide [ENZ] group, n = 998; abiraterone acetate [ABI] group, n = 617; and cabazitaxel [CBZ] group, n = 382). The overall survival (OS) time from drug initiation was 456 days in the enzalutamide group, which was significantly longer than that in the cabazitaxel group (p = 0.017, HR 0.94) (ENZ: ABI p = 0.54, HR 0.94; ABI: CBZ p = 0.14, HR 0.75). OS was also compared for the third-line drug in the group that received enzalutamide as the second-line drug, the group that used abiraterone acetate as the third-line drug (ENZ-ABI group), and the group that used abiraterone acetate as the second-line drug. OS from the start of the third-line drug was compared between the ENZ-ABI group and the ABI-ENZ group, which received enzalutamide as the third-line drug, but showed no significant difference (269 vs. 281 days, p = 0.85; HR 1.03). CONCLUSION: ENZ was shown to prolong OS relative to cabazitaxel after the cessation of docetaxel. ENZ was associated with a longer duration of drug use than ABI and CBZ.

Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma.

BACKGROUND: Enfortumab vedotin shows promise as a targeted therapy for advanced urothelial carcinoma, particularly in patients who have previously received platinum-based chemotherapy and an immune-checkpoint inhibitor. The EV-301 phase III trial demonstrated significantly improved overall survival and response rates compared to standard chemotherapy. However, more data, especially from larger real-world studies, are needed to further assess its effectiveness in Japanese patients. METHODS: A total of 6007 urothelial cancer patients inducted with pembrolizumab as a second-line treatment were analyzed. Among them, 563 patients received enfortumab vedotin after pembrolizumab, while 443 patients received docetaxel or paclitaxel after pembrolizumab, and all were included in the study for efficacy as a life prolonging agent. RESULTS: The enfortumab vedotin group showed a longer overall survival than the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). In multivariate analysis, enfortumab vedotin induction was the independent risk factor for overall survival (p = 0.013, HR: 0.70). There were no significant differences in cancer-specific survival. CONCLUSIONS: Enfortumab vedotin prolonged the overall survival for Japanese advanced or metastatic urothelial carcinoma patients compared to paclitaxel or docetaxel after pembrolizumab treatment.

Use of metallic and polymeric ureteral stents in malignant ureteral obstruction.

Background: Malignant ureteral obstruction (MUO) is often caused by advanced intra-abdominal cancers. Effective management must be attempted, but the treatment policy is unclear. Metallic ureteral stents are one of the latest options in managing MUO. Metallic ureteral stents are superior to traditional polyurethane stents. The present study retrospectively reviewed our four institutions' experiences with treating MUO using metallic ureteral stent. Methods: A total of 45 patients who required metallic ureteral stent placement for MUO at Yokohama City University Medical Center (Yokohama, JAPAN) between January 2014 and May 2016 were analyzed. We defined stent failure as having to change the ureteral stent before the scheduled ureteral stent exchange time or having to perform percutaneous nephrostomy (PCN). Complications were defined as an unscheduled hospital visit or hospitalization caused by incompatibility, infection, and pain of the metallic ureteral stent, etc., unrelated to the primary disease. We compared stent failure and the overall survival (OS) between metallic and polymeric ureteral stents. To evaluate the workload of the medical staff, we used the NASA Task Load Index (NASA-TLX) in a total of 11 urologists. Results: During the observation period, 8 (17.8%) patients in the metallic ureteral stent group and 10 (27.8%) in the control group developed stent failure. Complications were noted in 14 (31.1%) patients in the metallic ureteral stent group and 15 (41.7%) patients in the control group. A Kaplan-Meier analysis and log-rank test showed no significant differences between two groups in the overall survival (P = 0.673). One or more complications developed in 19 (32.2%) patients in the metallic ureteral stent group and 18 (38.3%) patients in the control group (P = 0.409). Renal dysfunction after the replacement of the ureteral stent developed in 9 (15.3%) patients in the metallic ureteral stent group and 14 (29.8%) patients in the control group. No patients developed a urinary tract infection (UTI) that required hospitalization in the metallic ureteral stent group, whereas 3 (6.4%) patients in the control group had a UTI that was treated with hospitalization. The average workload score in the six subscales was analyzed, and the scores for mental demand and performance were higher in the metallic ureteral stent group, although there was no significant difference between the metallic and polymeric ureteral stent groups. Conclusions: Metallic ureteral stents showed favorable ureteral stent patency and reduced the workload for urologists.

[PREDICTIVE AND PROGNOSTIC SIGNIFICANCE OF PRE-TREATMENT LYMPHOCYTE COUNT IN PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA TREATED WITH PLATINUM-BASED FIRST-LINE CHEMOTHERAPY].

(Purpose) Pre-treatment low lymphocyte count may result from cytokine secretion by the tumor microenvironment, in association with aggressive tumor biology. We sought to establish the prognostic impact of the absolute lymphocyte count (ALC) in advanced urothelial carcinoma. (Patients and method) We retrospectively reviewed 63 patients with unresectable or metastatic urothelial carcinoma who were treated with platinum-based first-line systemic chemotherapy between January 2011 and April 2018. We evaluated the importance of the ALC in patients who underwent systematic chemotherapy. (Results) Thirty-eight patients (60%) died from urothelial carcinoma, with a median follow-up interval of 12.2 months. The median overall survival (OS) duration was 15.3 months. The mean ALC in the stable and progressive disease group was lower than that in the complete and partial response group (1,312 /µL and 1,666 /µL, respectively, p=0.004). The ALC of 1,460 /µL was determined as the cut-off on Receiver operating characteristic curve analysis. The log-rank test revealed that the lymphocytopenia group (ALC <1,460 /µL) showed significantly poorer prognoses than the non-lymphocytopenia group (p=0.001). Multivariate analyses showed that lymphocytopenia was an independent poor prognostic factor (hazard ratios of 3.46, p=0.002). (Conclusions) Pre-treatment low lymphocyte count is an independent poor prognostic factor in patients with urothelial carcinoma who underwent platinum-based first-line systemic chemotherapy.