Enzalutamide versus flutamide for castration-resistant prostate cancer after combined androgen blockade therapy with bicalutamide: the OCUU-CRPC study.

BACKGROUND: Before the androgen target therapy era, flutamide was widely used for castration-resistant prostate cancer in Japan. Enzalutamide is currently the recommended treatment; however, the efficacy and safety of enzalutamide and flutamide after combined androgen blockade therapy with bicalutamide, has not been compared. METHODS: Patients with castration-resistant prostate cancer who received combined androgen blockade therapy with bicalutamide were randomly assigned to receive either enzalutamide or flutamide. The primary endpoint for efficacy was the 3-month prostate-specific antigen response rate. This trial is registered with ClinicalTrials.gov (NCT02346578) and the University hospital Medical Information Network (UMIN000016301). RESULTS: Overall, 103 patients were enrolled. The 3- (80.8% vs. 35.3%; p < 0.001) and 6-month (73.1% vs. 31.4%; p < 0.001) prostate-specific antigen response rates were higher in the enzalutamide than in the flutamide group. The 3-month disease progression rates (radiographic or prostate-specific antigen progression) were 6.4% and 38.8% in the enzalutamide and flutamide groups, respectively [hazard ratio (HR): 0.16; 95% confidence interval (CI): 0.05-0.47; p < 0.001]; the 6-month rates were 11.4% and 51.1%, respectively (HR 0.22; 95% CI 0.09-0.50; p < 0.001). Enzalutamide provided superior prostate-specific antigen progression-free survival compared with flutamide (HR 0.29; 95% CI 0.15-0.54; p < 0.001). Median time to prostate-specific antigen progression-free survival was not reached and was 6.6 months in the enzalutamide and flutamide groups, respectively. CONCLUSIONS: As an alternative anti-androgen therapy in patients with castration-resistant prostate cancer who fail bicalutamide-combined androgen blockade therapy, enzalutamide provides superior clinical outcomes compared with flutamide. Enzalutamide should be preferred over flutamide in these patients.

Efficacy of naftopidil for nocturia in male patients with lower urinary tract symptoms: comparison of morning and evening dosing.

OBJECTIVES: To examine the difference in improvement of lower urinary tract symptoms between morning and evening dosing of α1 -blocker naftopidil. METHODS: A total of 177 male patients with nocturia were included in the present study and randomized to morning or evening dosing of naftopidil. The International Prostate Symptom Score, quality of life index and nocturia quality of life index were compared between the two study groups at 12 weeks. RESULTS: A total of 143 patients (morning group: n = 70, evening group: n = 73) were analyzed as a result of the dropout of 34 patients because of failure to give consent, adverse events and failure to attend. Nocturia, quality of life index and nocturia quality of life index at 12 weeks were significantly better in the evening group compared with the morning group. In a multivariate model, both the dosing time of naftopidil and the initial nocturia quality of life index were significantly associated with change in nocturia quality of life index. CONCLUSIONS: Evening dosing of naftopidil seems to be more effective in treating nocturia in male patients with lower urinary tract symptoms.

Pathologic complete response with pembrolizumab plus axitinib in metastatic renal cell carcinoma.

Immunotherapy-based combinations have played a central role in the treatment of metastatic renal cell carcinoma, and long-term survival of patients is expected. In this context, it is clear that a certain number of patients can achieve a complete response. However, the diagnosis of complete response is usually based on imaging, and there are few cases of pathological complete response. In this study, we report a case of a patient with metastatic renal cell carcinoma who was treated with pembrolizumab plus axitinib, followed by resection of the primary tumor and metastatic lesions, and pathologically achieved a complete response.

Time to progression to castration-resistant prostate cancer after commencing combined androgen blockade for advanced hormone-sensitive prostate cancer.

PURPOSE: The aim of our retrospective study was to determine the time to progression to castration-resistant prostate cancer (CRPC) in prostate cancer patients who undergo combined androgen blockade (CAB), as well as their prognoses. MATERIALS AND METHODS: We examined the overall survival (OS) and disease-specific survival rates, as well as the time to CRPC development, in 387 patients who were treated with CAB for prostate cancer. The disease-specific survival rate and time to CRPC were stratified by prostate-specific antigen (PSA) levels, Gleason score (GS), and presence of metastasis at diagnosis. We designated high-risk patients as those satisfying at least two of the following three criteria: extent of disease of bone metastasis grade ≥2, presence of metastasis at diagnosis, and a GS ≥8. RESULTS: The 10- and 15-year OS rates were 74.0% and 50.4%, respectively, while the corresponding disease-specific survival rates were both 86.8%. Metastasis at diagnosis was an independent prognostic factor for disease-specific survival. The median time to CRPC development was 140.7 months. A PSA level ≥20 ng/mL, a GS ≥8, and the presence of metastasis at diagnosis were independent predictors of a shorter time to CRPC development. The 10-year disease-specific survival rate in the high-risk group was significantly lower than that in the low-risk group (approximately 74% vs. 98%), and the time to CRPC development was significantly shorter (median: 20.5 months vs. not reached). CONCLUSIONS: The time to CRPC development was shorter in high-risk prostate cancer patients with metastases. Such patients require alternative novel treatment modalities.

Comparative effectiveness of radical prostatectomy and curative radiotherapy in localized prostate cancer: long-term follow-up.

We sought to investigate the long-term outcomes after radical prostatectomy (RP) and external-beam radiation therapy (EBRT) for the treatment of localized prostate cancer in Japanese patients. RP and radiation therapy are curative treatments for localized prostate cancer. However, there is controversy around which treatment is superior in Japanese patients. The aim of our retrospective study was to compare the long-term clinical outcomes of each treatment. We retrospectively evaluated the overall survival (OS), cancer-specific survival (CSS) and biochemical failure-free survival (BFS) for patients who had been diagnosed with localized prostate cancer and treated with RP (n = 248) or conventional 2D or 3D-CRT EBRT (n = 182) between 1995 and 2009. The median OS was superior in the RP group compared with that in EBRT group (P < 0.001), although CSS was comparable for both treatment groups; BFS was superior for the EBRT group compared with that for the RP group (P = 0.04). Univariate analysis identified a prostate-specific antigen count (PSA)of ≥20 vs <20 mg/ml, clinical T-stage of the tumor and Gleason score as predictors for CSS. However, multivariate analysis did not identify a factor for CSS. Subgroup analysis was also performed based on clinical T stage, PSA and Gleason score, but there was no difference in each subgroup between RP and EBRT. Both treatments provided satisfactory clinical outcomes in terms of disease control in localized prostate cancer.