Background: To assess the outcome of neoadjuvant chemohormonal therapy comprising complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy in Japanese patients with a high risk of localized prostate cancer (PCa). Methods: Complete androgen blockade followed by 6 cycles of docetaxel (30 mg/m²) with estramustine phosphate (560 mg) were given to 18 PCa patients before radical prostatectomy. Subsequently, the clinical and pathological outcomes were analyzed. Results: No patients had severe adverse events during chemohormonal therapy, and hence they were treated with radical prostatectomy. Two patients (11.1%) achieved pathological complete response. Surgical margins were negative in all patients. At a median follow-up of 18 months, 14 patients (77.8%) were disease-free without PSA recurrence. All 4 patients with PSA recurrence had pathologic T3b or T4 disease and 3 of these 4 patients had pathologic N1 disease. Conclusion: We found that neoadjuvant chemohormonal therapy with complete androgen blockade followed by treatment with docetaxel and estramustine phosphate before radical prostatectomy was safe, feasible, and associated with favorable pathological outcomes in patients with a high risk of localized PCa.

Although recent evidence has suggested that a high-fat diet (HFD) plays an important role in prostate carcinogenesis, the underlying mechanisms have largely remained unknown. This review thus summarizes previous preclinical studies that have used prostate cancer cells and animal models to assess the impact of dietary fat on prostate cancer development and progression. Large variations in the previous studies were found during the selection of preclinical models and types of dietary intervention. Subcutaneous human prostate cancer cell xenografts, such as LNCaP, LAPC-4, and PC-3 and genetic engineered mouse models, such as TRAMP and Pten knockout, were frequently used. The dietary interventions had not been standardized, and distinct variations in the phenotype were observed in different studies using distinct HFD components. The use of different dietary components in the research models is reported to influence the effect of diet-induced metabolic disorders. The proposed underlying mechanisms for HFD-induced prostate cancer were divided into (1) growth factor signaling, (2) lipid metabolism, (3) inflammation, (4) hormonal modulation, and others. A number of preclinical studies proposed that dietary fat and/or obesity enhanced prostate cancer development and progression. However, the relationship still remains controversial, and care should be taken when interpreting the results in a human context. Future studies using more sophisticated preclinical models are imperative in order to explore deeper understanding regarding the impact of dietary fat on the development and progression of prostate cancer.

Sunitinib is a tyrosine kinase inhibitor and used as the first-line treatment for advanced renal cell carcinoma (RCC). Nevertheless, inter-individual variability of drug’s toxicity was often observed among patients who received sunitinib treatment. This study is to investigate the association of a functional germline variant on ABCG2 that affects the pharmacokinetics of sunitinib with sunitinib-induced toxicity of RCC patients in the Japanese population. A total of 219 RCC patients were recruited to this pharmacogenetic study. ABCG2 421C>A (Q141K) was genotyped by using PCR-Invader assay. The associations of both clinical and genetic variables were evaluated with logistic regression analysis and subsequently receiver operating characteristic (ROC) curve was plotted. About 43% (92/216) of RCC patients that received sunitinib treatment developed severe grade 3 or grade 4 thrombocytopenia according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 3.0, the most common sunitinib-induced adverse reaction in this study. In the univariate analysis, both age (P = 7.77x10^-3, odds ratio (OR) = 1.04, 95%CI = 1.01–1.07) and ABCG2 421C>A (P = 1.87x10^-2, OR = 1.71, 95%CI = 1.09–2.68) showed association with sunitinib-induced severe thrombocytopenia. Multivariate analysis indicated that the variant ABCG2 421C>A is suggestively associated with severe thrombocytopenia (P = 8.41x10^-3, OR = 1.86, 95% CI = 1.17–2.94) after adjustment of age as a confounding factor. The area under curve (AUC) of the risk prediction model that utilized age and ABCG2 421C>A was 0.648 with sensitivity of 0.859 and specificity of 0.415. Severe thrombocytopenia is the most common adverse reaction of sunitinib treatment in Japanese RCC patients. ABCG2 421C>A could explain part of the inter-individual variability of sunitinib-induced severe thrombocytopenia.

Nivolumab plus ipilimumab (NIVO+IPI) demonstrated superior efficacy over sunitinib (SUN) for previously untreated advanced renal cell carcinoma (aRCC) in CheckMate 214, with a manageable safety profile. We report efficacy and safety with extended follow-up amongst Japanese patients. CheckMate 214 patients received NIVO (3 mg/kg) plus IPI (1 mg/kg) every 3 weeks for four doses, then NIVO (3 mg/kg) every 2 weeks; or SUN (50 mg) once daily for 4 weeks (6-week cycle). This subgroup analysis assessed overall survival (OS), objective response rate (ORR) and progression-free survival (PFS) per investigator in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk and intent-to-treat (ITT) patients and safety (ITT patients). Of 550 and 546 patients randomized to NIVO+IPI and SUN, 38 and 34, respectively, were Japanese. Of these, 31 (NIVO+IPI) and 29 (SUN) patients were IMDC intermediate/poor-risk. In IMDC intermediate/poor-risk patients with 30 months’ minimum follow-up, there was a delayed trend in OS benefit with NIVO+IPI (hazard ratio [HR] 0.56; 95% confidence interval [CI]: 0.19–1.59; P = 0.2670), and 24-month OS probability favoured NIVO+IPI (84%) versus SUN (76%). The ORR was 39% with NIVO+IPI and 31% with SUN (P = 0.6968). PFS was similar in both treatment arms (HR 1.17; 95% CI: 0.62–2.20; P = 0.6220). Efficacy in ITT patients was similar to IMDC intermediate/poor-risk patients. Grade 3–4 treatment-related adverse event incidence was lower with NIVO+IPI versus SUN (58 versus 91%). Japanese patients with untreated aRCC in the NIVO+IPI arm had a numerically higher ORR and improved safety profile versus patients in the SUN arm. A delayed OS benefit appears to be emerging with NIVO+IPI. Longer follow-up is needed. https://clinicaltrials.gov/ct2/show/NCT02231749?term=NCT02231749&rank=1 identifier: NCT02231749.

Urinary bladder capacity is reduced in patients undergoing long-term dialysis, which may increase the risk of vesicoureteral reflux (VUR) to a transplanted kidney. This study investigated the correlations between dialysis duration, pretransplant and posttransplant bladder capacity, and prevalence of VUR to the graft. Voiding cystography was performed in 101 adult renal transplant recipients without neurogenic disorders immediately before and 1 year after transplantation to evaluate bladder capacity and VUR. Nonstented extravesical antireflux ureteroneocystostomy was performed in all patients. The median dialysis duration and pretransplant bladder capacity were 32 months (range 1-426 months) and 120 mL (range 15-450 mL), and 21 patients (20.8%) underwent dialysis for more than 120 months, and 30 patients (29.7%) had a pretransplant bladder capacity of less than 80 mL. Dialysis duration was correlated with pretransplant bladder capacity (R=0.466, P<0.001). Bladder capacity expanded more than 6-fold from pretransplantation to posttransplantation, and all recipients had a bladder capacity greater than 150 mL at 1 year posttransplantation. Thirty patients had VUR to the graft. Dialysis duration longer than 60 months (P=0.021) and pretransplant bladder capacity of less than 130 mL (P=0.024) were associated with VUR. VUR was associated with lower graft function. Although bladder capacity decreased because of long-term dialysis, it exceeded 150 mL at 1 year posttransplantation. A small bladder can be used in renal transplantation, but it may increase the risk of VUR.