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Objective: In December 2021, enfortumab vedotin (EV), an antibody‐drug conjugate directed against nectin‐4, was approved in Japan as a new treatment after platinum‐containing chemotherapy and PD‐1/PD‐L1 inhibitors. This study evaluated, using real‐world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). Materials and methods: Fifty‐five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non‐EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. Results: The median (range) follow‐up period after pembrolizumab discontinuation was 6.3 (0.7–31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non‐EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non‐EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non‐EV group; hazard ratio 0.26; 95% confidence interval 0.16–0.41; p < 0.001) was an independent prognostic factor for OS. Conclusion: EV prolonged OS in mUC following pembrolizumab therapy in real‐world data. [ABSTRACT FROM AUTHOR]

Approximately 1% of the general male population has azoospermia, and nonobstructive azoospermia accounts for the majority of cases. The causes vary widely, including chromosomal and genetic abnormalities, varicocele, drug‐induced causes, and gonadotropin deficiency; however, the cause is often unknown. In azoospermia caused by hypogonadotropic hypogonadism, gonadotropin replacement therapy can be expected to produce sperm in the ejaculate. In some cases, upfront varicocelectomy for nonobstructive azoospermia with varicocele may result in the appearance of ejaculated spermatozoa; however, the appropriate indication should be selected. Each guideline recommends microdissection testicular sperm extraction for nonobstructive azoospermia in terms of successful sperm retrieval and avoidance of complications. Sperm retrieval rates generally ranged from 20% to 70% but vary depending on the causative disease. Various attempts have been made to predict sperm retrieval and improve sperm retrieval rates; however, the evidence is insufficient. Further evidence accumulation is needed for salvage treatment in cases of failed sperm retrieval. In Japan, there is inadequate provision on the right to know the origin of children born from artificial insemination of donated sperm and the rights of sperm donors, as well as information on unrelated family members, and the development of these systems is challenging. In the future, it is hoped that the pathogenesis of nonobstructive azoospermia with an unknown cause will be elucidated and that technology for omics technologies, human spermatogenesis using pluripotent cells, and organ culture methods will be developed. [ABSTRACT FROM AUTHOR]

Simple Summary: Enfortumab vedotin, a targeted therapy for advanced urothelial carcinoma, has shown efficacy, especially in those treated with platinum-based chemotherapy and immune-checkpoint inhibitors. The EV-301 phase III trial reported enhanced overall survival and response rates than conventional chemotherapy. However, its effectiveness in Japanese patients needs further real-world validation. Analyzing 6007 urothelial cancer patients treated with pembrolizumab, 563 subsequently received enfortumab vedotin, while 443 switched to docetaxel or paclitaxel. Results indicated the enfortumab vedotin group had an extended overall survival compared to the paclitaxel/docetaxel group (p = 0.013, HR: 0.71). Conclusively, enfortumab vedotin offers Japanese patients better overall survival prospects after pembrolizumab treatment than docetaxel or paclitaxel. 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. [ABSTRACT FROM AUTHOR]

Background: Patient-reported outcome (PRO) measures can provide valuable information in evaluating patients' health-related quality of life (HRQoL). Post hoc analysis of the AFTERCAB study was conducted to evaluate the HRQoL benefit of enzalutamide plus androgen deprivation therapy (ADT) compared to flutamide plus ADT for the treatment of patients with castration-resistant prostate cancer (CRPC) in Japan. Methods: The open-label AFTERCAB study was conducted from November 2016 to March 2020 in Japanese men aged ≥ 20 years with asymptomatic or mildly symptomatic CRPC. Patients received enzalutamide plus ADT or flutamide plus ADT, respectively, as first-line alternative androgen therapy (AAT). HRQoL was analyzed through the Functional Assessment of Cancer Therapy–Prostate, EuroQoL 5-Dimension 5-Level instruments, Brief Pain Inventory–Short Form, and Brief Fatigue Inventory. The longitudinal changes in HRQoL, HRQoL deterioration based on minimally important difference (MID), and time to HRQoL deterioration were evaluated for first-line AAT. Results: Overall, HRQoL between the enzalutamide and flutamide groups was similar during first-line treatment. No statistically significant HRQoL difference in change from baseline to week 61 (least square mean difference; p value) was observed. Furthermore, proportions of pain progression, symptom worsening, and HRQoL deterioration based on MID, were not significantly different between groups. Conclusions: The results were similar in all subscales of each PRO, demonstrating similar HRQoL deterioration based on MID criteria between the enzalutamide and flutamide groups. [ABSTRACT FROM AUTHOR]

Objective: The prognosis of high‐risk metastatic hormone‐naïve prostate cancer is poor, and real‐world evidence of therapeutic options and sequences is lacking. The J‐ROCK study aimed to evaluate the outcomes in a real‐world setting in Japan. Methods: Patients with high‐risk metastatic hormone‐naïve prostate cancer diagnosed after May 2019 were eligible. Based on their treatment within 3 months after diagnosis, patients were allocated to either cohort 1 (androgen deprivation therapy alone or combined androgen blockade with bicalutamide) or cohort 2 (androgen deprivation therapy with abiraterone acetate+prednisolone, docetaxel, enzalutamide, or apalutamide). Results: In this first interim analysis (cut‐off January 2021), 410 patients were enrolled, including 163 patients in cohort 1 and 247 in cohort 2. The median follow‐up period was 7.6 (range 0.1–20.5) months. A higher proportion of patients in cohort 2 (42.5%) achieved nadir prostate‐specific antigen levels ≤0.2 ng/ml within a year, compared with cohort 1 (22.1%). Prostate‐specific antigen‐progression‐free survival was also more favorable in cohort 2 (adjusted hazard ratio 0.629 [95% confidence interval 0.345–1.147]). Conclusions: The higher proportion of cohort 2 suggest a paradigm shift has occurred in the real‐world treatment of high‐risk metastatic hormone‐naïve prostate cancer in Japan. Some factors including prostate‐specific antigen may affect treatment selection but need further observation. Most patients in cohort 2 received abiraterone acetate+prednisolone. The proportion of patients in cohort 1 receiving combined androgen blockade was lower than previously reported in Japan. This analysis suggest that more intensive therapy tends to prolong prostate‐specific antigen‐progression‐free survival in patients with high‐risk metastatic hormone‐naïve prostate cancer. [ABSTRACT FROM AUTHOR]

Objectives: The TITAN study is a randomized, double‐blind, placebo‐controlled, multinational trial that evaluated apalutamide with androgen deprivation therapy in patients with metastatic castration‐sensitive prostate cancer. At the first interim analysis in the Japanese subpopulation (median follow‐up 25.7 months), there was an improvement in overall survival and radiological progression‐free survival with apalutamide versus placebo. Here, we report the final analysis results for the Japanese subpopulation. Methods: Patients were randomized 1:1 to receive apalutamide 240 mg or placebo. After the first interim analysis, protocol treatment was unblinded, and crossover was allowed. Efficacy and safety were evaluated in the preplanned, event‐driven final analysis. Results: Fifty‐one patients were Japanese (apalutamide n = 28; placebo n = 23). After a median follow‐up of 46.0 months, the median overall survival was not reached neither in the apalutamide nor the placebo group; the hazard ratio was 0.45, favoring apalutamide, which was consistent with the overall population. Hazard ratios for time to cytotoxic chemotherapy (0.39), time to pain progression (0.87), and time to chronic opioid use (0.82) also favored apalutamide and were comparable with those of the overall population. Time to prostate‐specific antigen progression and progression‐free survival 2, respectively, was favored in the apalutamide group (0.21 and 0.44). Apalutamide was associated with higher incidences of rash and fracture in the Japanese subpopulation compared with the overall population. Conclusions: The efficacy of apalutamide with androgen deprivation therapy in Japanese patients was consistent with efficacy demonstrated in the overall population. No new safety concerns emerged with long‐term follow‐up. [ABSTRACT FROM AUTHOR]

Background: The purpose of the study is to evaluate real-world effectiveness and safety of enzalutamide in men with nonmetastatic castration-resistant prostate cancer (nmCRPC) in Japan. Methods: This was a retrospective evaluation of medical records from men in Japan who started enzalutamide treatment from November 1, 2014, to March 31, 2018, and received androgen deprivation therapy throughout. The primary endpoint was time to prostate-specific antigen (PSA) progression. Secondary endpoints included PSA response rate, time to first use of new antineoplastic therapy, time to first use of cytotoxic chemotherapy, and enzalutamide treatment duration. An exploratory analysis of metastasis-free survival (MFS) was also performed. Adverse events (AEs) were analyzed to assess safety. Results: Based on data from medical records of 205 men in Japan, median time to PSA progression was 27 months (95% confidence interval [CI] 19–not reached [NR]), with 82.5% and 52.0% of men achieving PSA response rates of ≥ 50% and ≥ 90%, respectively. Median time to first use of new antineoplastic therapy was 36 months (95% CI 27−NR) and median enzalutamide treatment duration was 13 months (interquartile range: 7–24). Median time to first use of cytotoxic chemotherapy was NR (95% CI 41−NR). Median MFS was 29 months (95% CI 23−35). In total, 51.7% of men experienced AEs, with malaise (18.5%), decreased appetite (10.7%), and nausea (4.9%) the most frequently reported. Conclusions: This is the first study to demonstrate the real-world effectiveness and safety of enzalutamide in men with nmCRPC in Japan, further informing healthcare providers about available treatment options for this patient population. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of enzalutamide plus androgen deprivation therapy in Japanese men with metastatic hormone‐sensitive prostate cancer. Methods: A post‐hoc analysis of the Japanese subgroup in the phase III, randomized, multinational ARCHES study (NCT02677896) was carried out. Patients with metastatic hormone‐sensitive prostate cancer were randomized to receive enzalutamide or a placebo, plus androgen deprivation therapy, stratified by disease volume and prior docetaxel therapy. The primary end‐point was radiographic progression‐free survival. Secondary end‐points included time to prostate‐specific antigen progression and overall survival. Results: Of 1150 patients, 92 Japanese patients were randomized to enzalutamide (n = 36) or a placebo (n = 56), plus androgen deprivation therapy; none received prior docetaxel. Enzalutamide plus androgen deprivation therapy reduced the risk of radiographic progression or death in Japanese patients by 61% versus the placebo, similar to the overall population. Similar results were observed with secondary end‐points, showing clinical benefit of enzalutamide plus androgen deprivation therapy in Japanese patients. Overall survival data were immature. Grade 3–4 adverse events were reported in 47% and 25% of the enzalutamide and placebo groups, respectively. Nasopharyngitis, hypertension and abnormal hepatic function were reported more frequently in Japanese patients versus the overall population. Conclusions: Enzalutamide plus androgen deprivation therapy has clinical benefit with a tolerable safety profile in Japanese men with metastatic hormone‐sensitive prostate cancer, consistent with the overall population. [ABSTRACT FROM AUTHOR]

Background: Darolutamide, an oral androgen receptor inhibitor, has been approved for treating nonmetastatic castration-resistant prostate cancer (nmCRPC), based on significant improvements in metastasis-free survival (MFS) in the ARAMIS clinical trial. Efficacy and safety of darolutamide in Japanese patients are reported here. Methods: In this randomized, double-blind, placebo-controlled phase III trial, 1509 patients with nmCRPC and prostate-specific antigen (PSA) doubling time ≤ 10 months were randomized 2:1 to darolutamide 600 mg twice daily or matched placebo while continuing androgen deprivation therapy. The primary endpoint was MFS. Results: In Japan, 95 patients were enrolled and randomized to darolutamide (n = 62) or placebo (n = 33). At the primary analysis (cut-off date: September 3, 2018), after 20 primary end-point events had occurred, median MFS was not reached with darolutamide vs. 18.2 months with placebo (HR 0.28, 95% CI 0.11–0.70). Median OS was not reached due to limited numbers of events in both groups but favored darolutamide in the Japanese subgroup. Time to pain progression, time to PSA progression, and PSA response also favored darolutamide. Among Japanese patients randomized to darolutamide vs. placebo, incidences of treatment-emergent adverse events (TEAEs) were 85.5 vs. 63.6%, and incidences of treatment discontinuation due to TEAEs were 8.1 vs. 6.1%. Conclusions: Efficacy outcomes favored darolutamide in Japanese patients with nmCRPC, supporting the clinical benefit of darolutamide in this patient population. Darolutamide was well tolerated; however, due to the small sample size, it is impossible to conclude with certainty whether differences in the safety profile exist between Japanese and overall ARAMIS populations. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of apalutamide + androgen deprivation therapy versus androgen deprivation therapy alone in Japanese patients with metastatic castration‐sensitive prostate cancer from the phase 3, randomized, global TITAN study. Methods: Men with metastatic castration‐sensitive prostate cancer randomly (1:1) received 240 mg apalutamide + androgen deprivation therapy or matching placebo + androgen deprivation therapy. The primary efficacy endpoints were radiographic progression‐free survival and overall survival. Secondary efficacy endpoints were time to cytotoxic chemotherapy, pain progression, chronic opioid use, and skeletal‐related events. Safety was also assessed. Results: Of the 1052 patients included in the TITAN study, 51 (4.85%) were Japanese (apalutamide group, n = 28; placebo group, n = 23). In all, 81.8% of patients in the apalutamide and 71.8% in the placebo group did not experience radiographic progression or death, and the hazard ratio for radiographic progression‐free survival favored treatment with apalutamide (hazard ratio 0.712, 95% confidence interval 0.205–2.466; P = 0.59). At 24 months, 85.7% of patients in the apalutamide group and 81.5% in the placebo group were alive, and the hazard ratio for overall survival favored apalutamide (hazard ratio 0.840, 95% confidence interval 0.210–3.361; P = 0.805). In the interim analysis, the median radiographic progression‐free survival and overall survival were not reached in the apalutamide group and time to cytotoxic chemotherapy was delayed following apalutamide treatment. The safety profile of apalutamide in the Japanese subpopulation was comparable with that of the global population, except for skin rash. Conclusions: The results of the present analyses suggest that apalutamide + androgen deprivation therapy in Japanese patients had favorable efficacy compared with androgen deprivation therapy alone, and these findings are comparable to those in the overall population. Apalutamide + androgen deprivation therapy can be considered as one of the therapeutic options for a broad spectrum of metastatic castration‐sensitive prostate cancer regardless of prior treatment and disease extent in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Hormone therapy is one option for some types of prostate cancer. Shared decision making (SDM) is important in the decision making process, but SDM between prostate cancer patients receiving hormone therapy and physicians is not fully understood. This study tested hypotheses: "Patients' perception of SDM is associated with treatment satisfaction, mediated by satisfaction with physicians' explanations and perceived effective decision making" and "The amount of information provided to patients by physicians on diseases and treatment is associated with treatment satisfaction mediated by patients' perceived SDM and satisfaction with physicians' explanations."Methods: This cross-sectional study was conducted using an online panel via a private research company in Japan. The participants in this study were patients registered with the panel who had received or were currently receiving hormone therapy for prostate cancer and physicians registered with the panel who were treating patients with prostate cancer. Measures used in this study included a nine-item Shared Decision Making Questionnaire, levels of satisfaction with physicians' explanations and treatment satisfaction, and effective decision making for patients (feeling the choice is informed, value-based, likely to be implemented and expressing satisfaction with the choice), and a Shared Decision Making Questionnaire for Doctors. The hypotheses were examined using path analysis.Results: In total, 124 patients and 150 physicians were included in the analyses. In keeping with our hypotheses, perceived SDM significantly correlated with the physicians' explanations and perceived effective decision making for patients, and satisfaction with physicians' explanations and perceived effective decision making for patients were both related to treatment satisfaction. Although the amount of information provided to patients was correlated with the perceived SDM, it was indirectly related to their satisfaction with physicians' explanations.Conclusions: When physicians encourage patients to be actively involved in making decisions about treatment through the SDM process while presenting a wide range of information at the start of hormone therapy, patients' effective decision making and physicians' explanations may be improved; consequently, the patients' overall treatment satisfaction may be improved. Physicians who treat patients with prostate cancer may have underestimated the importance of SDM before starting hormone therapy, even greater extent than patients. [ABSTRACT FROM AUTHOR]

Background: A higher incidence of apalutamide-related skin rash has been observed in Japanese patients with prostate cancer (PC).Methods: This integrated analysis of data of Japanese patients from 2 global Phase 3 studies, SPARTAN ( NCT01946204 ; patients with non-metastatic castration-resistant PC [nmCRPC]) and TITAN ( NCT02489318 ; patients with metastatic castration-sensitive PC [mCSPC]), and the Phase 1 study 56021927PCR1008 ( NCT02162836 ; patients with metastatic CRPC [mCRPC]), assessed clinical risk factors of apalutamide-related skin rash as well as the potential correlation with plasma exposure to apalutamide. Kaplan-Meier method was used for time-to-event analyses. Clinical risk factors for skin rash were assessed using odds ratio.Results: Data from 68 patients (SPARTAN: n = 34, TITAN: n = 28, 56021927PCR1008: n = 6) receiving apalutamide 240 mg orally once-daily were analyzed. Rash (13 [19.1%]) and maculo-papular rash (11 [16.2%]) were the most frequently reported skin rash. All Grade and Grade 3 skin rash occurred in 35 (51.5%) and 10 (14.7%) patients, respectively. Most (85.7%) skin rash occurred within 4 months of apalutamide initiation and resolved in a median time of 1 month following the use of antihistamines, topical or systemic corticosteroids, with/without apalutamide dose interruptions/reductions. Median time-to-remission of first incidence of rash and maximum grade incidence of rash were 1.0 month (IQR: 0.36-1.81) and 1.0 month (IQR: 0.30-2.43), respectively. No significant clinical risk factors for the incidence of skin rash were observed. Areas under the curve (0-24 h) (AUC0-24, ss) at steady-state of plasma apalutamide concentration were numerically slightly higher in patients with skin rash than those without.Conclusions: No clinical risk factors for rash could be detected. There is a potential correlation between incidence of skin rash and plasma exposure to apalutamide. In general, apalutamide-related skin rash is easily managed, with appropriate treatment with or without dose adjustment.Trial Registration: Retrospective pooled analysis of NCT01946204 , NCT02489318 , and NCT02162836 . [ABSTRACT FROM AUTHOR]

Background. The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). Methods. A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. Results. The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. Conclusions. The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients. [ABSTRACT FROM AUTHOR]

Background: ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223. Methods: Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint. Results: Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6–not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7–NE) (HR = 0.907, 95% CI 0.501–1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively. Conclusions: In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. Clinical trial registration: Clinical trial registration no: NCT02043678. [ABSTRACT FROM AUTHOR]

Introduction and Objectives. The neutrophil-to-lymphocyte ratio (NLR) has been suggested as a simple marker of the systemic inflammatory response in critical care patients. The NLR can be easily calculated from routine complete blood counts in the peripheral blood. This parameter has been reported to be an independent prognosticator for some solid malignancies. In the present study, we examined the importance of the NLR as a prognostic marker for castration-resistant prostate cancer (CRPC) patients who received docetaxel- (DOC-) based chemotherapy. Methods. We analyzed a total of 73 patients who received DOC chemotherapy for CRPC in Yokohama City University Medical Center and affiliated hospitals. Complete blood cell counts were performed, and the NLR was calculated using the neutrophil and lymphocyte counts obtained on the same day or a few days before the initiation of DOC chemotherapy. We determined the NLR cutoff value based on the sensitivity and specificity levels derived from area under the receiver operator characteristic curves for death. Results. The median overall survival (OS) after DOC was 21.0 months (range: 2.0–51.0). The median OS was shorter in patients with a high NLR (≥2.59) than in those with a low NLR (<2.59) (12.0 versus 31.6 months, p=0.001). In the multivariate analysis, the NLR and lymph node (LN) metastasis were independent predictors of the OS (hazard ratio 3.643, p=0.001; hazard ratio 2.184, p=0.038, respectively). Conclusions. The higher NLR group showed a significantly poorer OS than the lower NLR group. Pre-DOC NLR might be a new marker for predicting the prognosis of patients who receive DOC chemotherapy. [ABSTRACT FROM AUTHOR]

Granulocyte colony-stimulating factor (G-CSF)-producing bladder cancer is rare, with only 75 cases reported in Japan. A 67-year-old woman was referred to our institution for the further examination of gross hematuria. Cystoscopy revealed a 7-cm bladder tumor. The initial white blood cell count was 17,100/μL, and a transurethral resected specimen showed G-CSF expression. CT revealed that the tumor had invaded the colon. As the patient had uncontrollable schizophrenia, radical cystectomy was abandoned. We herein report a case of G-CSF-producing bladder tumor. [ABSTRACT FROM AUTHOR]

Introduction. Nearly 80% of advanced prostate cancer patients respond to initial androgen deprivation therapy (ADT). However, ADT does not prevent the progression of prostate cancer over the long term, and the disease eventually progresses to castration-resistant prostate cancer (CRPC). Prior to the development of enzalutamide (ENZ) and abiraterone acetate, docetaxel was the only established treatment with life-prolongation for CRPC. ENZ is a second-generation anti-androgen receptor drug that has contributed to improving the prognosis of CRPC. Several studies have reported factors predicting the efficacy of ENZ; however, there are no confirmed biomarkers. The neutrophil-to-lymphocyte ratio (NLR) is an easily calculated biomarker that is associated with the prognosis of several solid malignancies. However, there were few studies investigated NLR for ENZ in patients with mCRPC. We examined the usefulness of the NLR as a predictive tool for ENZ. Methods. We retrospectively examined a total of 106 CRPC patients who were treated with ENZ until September 2016 in Yokohama City University Hospital, Yokohama City University Medical Center, and National Cancer Center Hospital East. ENZ was routinely started as a dose of 160 mg per day; the dosage was reduced in some patients due to side effects. Drug holiday for 1-2 weeks or dose reduction to 80-120mg was done and no patients discontinued ENZ treatment due to adverse effects. ENZ was stopped when cancer progression was detected based on PSA elevation, radiographic findings, and deterioration of the patient's performance status. The cut-off NLRs for overall survival (OS) and cancer-specific survival (CSS) were determined based on the receiver-operator curves. Kaplan-Meier curves were used to analyze the factors associated with OS or CSS and a log-rank test was performed. A multivariate analysis was also performed to analyze the factors associated with the prognosis. Results. We retrospectively reviewed 106 consecutive CRPC patients who were both treated with ENZ and were able to be counted before ENZ NLR. Cut-off point was 2.14 for both OS and CSS by receiver operator characteristic curve. The patients were then divided into the higher NLR group (≥2.14) and lower NLR group (<2.14). Multivariate analysis showed that NLR and predocetaxel chemotherapy were independent risk factors for both overall and cancer-specific survival. Conclusions. The NLR might be a useful biomarker for predicting the prognosis of mCRPC patients who are treated with ENZ. [ABSTRACT FROM AUTHOR]

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is,29%of Japanese physicians underestimated patients’ preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States. [ABSTRACT FROM AUTHOR]

This article adds the Japanese perspective to our knowledge of shared decision-making (SDM) preferences by surveying patients with prostate cancer (PCA) and physicians in Japan. In 2015, 103 Japanese patients with PCA were asked about their SDM preferences by using an Internet-based 5-point-scale questionnaire. Concurrently, 127 Japanese physicians were surveyed regarding their perceptions of patient preferences on SDM. Drivers of preferences and perceptions were analyzed using univariable ordinal logistic regression and graphing the fitted response probabilities. Although 41% of both patients and physicians expressed and expected a desire for active involvement in treatment decisions (a higher rate than in a similar study for the United States in 2001), almost half the Japanese patients preferred SDM, but only 33% of physicians assumed this was their choice. That is, 29% of Japanese physicians underestimated patients' preference for involvement in making treatment decisions. Patients with lower health-related quality of life (as measured by the Functional Assessment of Cancer Therapy-Prostate [FACT-P]) expressed a stronger preference for SDM. The study shows that the worse the medical situation, the more patients with PCA prefer to be involved in the treatment decision, yet physicians tend to underestimate the preferences of their patients. Perhaps in contrast to common assumptions, Japanese patients are as interested in being involved in decision making as are patients in the United States. [ABSTRACT FROM AUTHOR]

We determined whether prostate specific antigen (PSA) would decrease with immediate antiandrogen switching from bicalutamide (BCL) to flutamide (FLT) in patients receiving combined androgen blockade for advanced prostate cancer. From 2002 to 2006, 20 patients who showed PSA failure after first-line hormonal therapy with a luteinizing hormone-release hormone (LH-RH) agonist and BCL were enrolled. All patients were immediately switched from BCL to FLT, administered with an LH-RH agonist, as second-line combined androgen blockade (CAB). We evaluated the PSA response to second-line CAB. Eight patients (40%) were responsive, showing PSA decreases of at least 50%. The median (range) duration of the PSA response was 18.4 (3–26) months. Second-line CAB using FLT was effective in 40% of patients who received first-line CAB using BCL. The lower Gleason scores at the initial prostate biopsy probably reflect the response to second-line CAB. Responders showed significantly better OS and CSS in the determination of any PSA decline and 40% PSA decline. The median OS duration in nonresponders and responders (40% PSA decline) was 1433 days versus 3617 days. It is concluded that an immediate switch from BCL to FLT is effective for some CRPC patients after first-line CAB using BCL. [ABSTRACT FROM AUTHOR]

Purpose: To report 10-year outcomes of patients treated with I low-dose-rate brachytherapy (BT) for clinically localized prostate cancer. Methods: A group of 1,060 patients with clinically localized prostate cancer treated with I BT between March 2004 and December 2013 at the Yokohama City University Hospital were identified. The records of 743 patients with a minimum of 2 years of follow-up were reviewed. Cohorts were categorized according to National Comprehensive Cancer Network risk classification, and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as nadir prostate-specific antigen (PSA) level + 2 ng/mL. Univariate and multivariate Cox proportional hazards were used to determine predictors of biochemical failure. Results: A total of 743 patients met the criteria with a median follow-up of 54.6 months (range 24-114 months). The median age was 70 years (range 48-83). The 5- and 7-year overall survival rates were 98.8 and 97.6 %, and the 5- and 7-year biochemical failure-free survival rates were 92.6 and 91.0 %, respectively. With regard to distant metastases and survival, the 5- and 7-year metastatic-free survival rates were 98.2 and 95.9 %, respectively. A multivariate analysis revealed that initial PSA ( p = 0.005; HR 1.097, 95 % CI 1.028-1.170), age ( p = 0.001; HR 0.931, 95 % CI 0.893-0.971), and T stage (T1c vs. T2a) ( p = 0.002; HR2.417, 95 % CI 1.319-4.267) were independent predictors of biochemical failure. Conclusions: I low-dose-rate BT resulted in excellent survival and morbidity outcomes for localized prostate cancer at a single institution. Further studies are needed to obtain long-term outcomes. [ABSTRACT FROM AUTHOR]

Background. Although patients with prostate cancer with metastatic lesions initially respond to androgen ablation therapy, most patients ultimately develop a hormone-refractory state. Effective treatment for men with hormone-refractory prostate cancer (HRPC) has not been established. We performed a clinical study of docetaxel in HRPC patients, and evaluated its efficacy. Methods. Nine patients with HRPC were administered 55mg/m² docetaxel, every 3 weeks, simultaneously with hormonal therapy, with a luteinizing hormone-releasing hormone analog, and daily oral dexamethasone. Change in serum prostate-specific antigen (PSA) was determined as the primary endpoint. Results. The mean age of the patients was 64 years (range, 49 to 76 years). Median follow-up time was 8.5 months (range, 5.3 to 16.7 months). In eight patients whose pretreatment serum PSA was elevated, six patients (75.0%) had a PSA decline of more than 50%, and four (50.0%) had a PSA decline of more than 75%. Median time to progression for all patients was 7.9 months (range, 0.0 to 11.6 months; 95% confidence interval [CI], 0.0 to 26.3). The median overall survival was 8.5 months (range, 5.3 to 16.7 months; 95% CI, 8.1 to 13.8). Four of six patients (66.7%) with pain before treatment obtained pain relief and were able to discontinue analgesic agents. This regimen was well tolerated. Grade 3 or 4 neutropenia or leukocytopenia without fever was seen in three patients (33.3%). Only one patient required administration of granulocyte-colony stimulating factor because of neutropenia. No other grade 3 or 4 toxicity was observed. Conclusion. Docetaxel was an active agent in Japanese HRPC patients, and was well tolerated in this population. To establish its efficacy and safety in Japanese HRPC patients, a large-scale study in Japan is warranted. [ABSTRACT FROM AUTHOR]

Background: We reported previously the usefulness of 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to predict prognosis of renal cell carcinoma (RCC) treated with molecular targeted agents. Herein we describe a preliminary research of nine patients who underwent FDG-PET/CT before and after initiation of nivolumab.Methods: Patients with metastatic RCC who were treated by nivolumab from October 2016 to March 2017 were enrolled in this study. All patients underwent FDG-PET/CT at baseline and 1 month as a first response assessment, and contrast-enhanced or non-contrast-enhanced CT scan at 4 month as a second response assessment. Logistic regression analysis was performed to assess the association of potential predictors, including age, gender, baseline diameter, baseline maximum standardized uptake value (SUVmax), lung or not lung metastasis, elevation of SUVmax at 1st assessment, and decrease in diameter at 1st assessment with the response at 2nd assessment (decrease in the diameter ≥ 30% or not).Results: There were 9 patients and 30 lesions. Mean days of first assessment with FDG-PET/CT and second assessment by CT scan from initiation of treatment were 32.3 ± 6.4, 115.5 ± 14.9, respectively. Lesions whose diameter decreased ≥30% at second assessment were defined as responding, and lesions whose diameter did not decrease ≥30% were defined as non-responding. There were 18 responding lesions, and 12 non-responding lesions. We compared change in diameter and SUVmax at first assessment with FDG-PET/CT, respectively. All lesions with decreased diameter and elevated SUVmax at first assessment with FDG-PET/CT showed responding at second assessment by CT scan, while most lesions with increased diameter and declined SUVmax at first assessment showed non-responding at second assessment. The multivariate logistic regression analyses revealed that only the elevation of SUVmax at 1 month was an independent predictor (P = 0.025, OR: 13.087, 95%CI: 1.373-124.716).Conclusion: Our findings suggest that the early assessment using FDG-PET/CT can be effective to predict the response of RCC to nivolumab. However, larger prospective studies are needed to confirm these preliminary results.Trial Registration: Registered in University Hospital Medical Information Network in JAPAN [ UMIN0000008141 ], registration date: 11 Jun 2012. [ABSTRACT FROM AUTHOR]

Background: Androgen deprivation therapy (ADT), administered alone, as combined androgen blockade (CAB) or as ADT plus androgen receptor signalling inhibitors (ARSIs) or ADT plus docetaxel, is the standard treatment for metastatic hormone-naïve prostate cancer (mHNPC) in Japanese real-world practice., Objective: To investigate treatment patterns and clinical outcomes in LATITUDE criteria high-risk mHNPC., Design, Setting, and Participants: The longitudinal, multicentre, J-ROCK registry study enrolled patients initiating ADT in Japan after May 2019, and categorised them as cohort 1 (ADT or CAB) or cohort 2 (ADT plus ARSIs or docetaxel)., Outcome Measurements and Statistical Analysis: Prostate-specific antigen (PSA) response, progression-free survival (PFS), time to castrate-resistant prostate cancer (CRPC), overall survival (OS), and safety were evaluated. PFS, time to CRPC, and OS were estimated via the Kaplan-Meier method and between-cohort comparisons via multivariate Cox regression models., Results and Limitations: In total, 974 patients were included (cohort 1: 38.1%, cohort 2: 61.9%). CAB was preferred (67.4%) to ADT alone in cohort 1, and abiraterone acetate plus prednisolone was used most frequently in cohort 2 (59.4%). The proportion of patients with ≥50%/≥90% PSA decline or who achieved PSA ≤0.2/≤0.1 ng/ml tended to be higher in cohort 2. PFS (adjusted hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.55), time to CRPC (0.28; 95% CI 0.23-0.36), and OS (0.54; 95% CI 0.35-0.82) were longer in cohort 2. In cohorts 1 and 2, adverse drug reactions of special interest (ADRSIs) occurred in 1.3% and 15.1%, and fatal adverse events occurred in 1.9% and 1.7%, respectively. Limitations included nonrandomised design, varying time since marketing authorisation for ARSIs, and limited safety assessments., Conclusions: ADT plus ARSIs or docetaxel was used more frequently to treat high-risk mHNPC than standard ADT/CAB and was associated with more favourable clinical outcomes. Although ADRSIs were reported more in cohort 2, the safety profile was considered tolerable., Patient Summary: Although many treatment options are available for high-risk metastatic prostate cancer, there are limited reports on real-world clinical experience with different therapies outside of the clinical trial setting. In this study, we compared clinical and safety outcomes with different treatment regimens, using a large series of patients with high-risk metastatic hormone-naïve prostate cancer across Japan. We found that androgen deprivation therapy in combination with newer androgen receptor signalling inhibitors resulted in improved response compared with androgen deprivation therapy alone or in combination with a first-generation antiandrogen., (Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aim: We aimed to determine Japanese metastatic castration resistant prostate cancer (CRPC) patients' Ra-223 treatment experience. Patients & methods: Patients answered the Cancer Therapy Satisfaction Questionnaire (CTSQ domains: Satisfaction with Therapy [SWT], Expectations of Therapy [ET], Feelings about Side Effects [FSE]), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the FACT-Bone Pain (FACT-BP) Questionnaire at baseline, during (vists 3 and 5) and after treatment (end of observation; EOO). Results: Data from 72 patients were included. Baseline median CTSQ scores SWT: 66.1 (IQR19.7), ET: 75.0 (IQR45), and FSE 68.8 (IQR 34.4) were unchanged during vists 3 and 5, but the SWT (-3.57 [IQR17.9]) and ET (-5.0 [IQR30]) decreased while FSE was unchanged (0.0 [IQR31.25]) at EOO. The median MAX-PC (18.0 [IQR 49]) score was unchanged (0.0, IQR 6) while the median FACT BP (54.0 [IQR13]) score decreased by -1.0 (IQR 8) at EOO. Conclusion: Japanese metastatic castration resistant prostate cancer patients' experience is stable during Ra-223 treatment.

Aims: The treatment landscape of renal cell carcinoma has changed with the introduction of targeted therapies. While the clinical benefit of cabozantinib is well-established for Japanese patients who have received prior treatment, the economic benefit remains unclear. The objective of this study was to assess the cost-effectiveness of cabozantinib compared with everolimus, axitinib, and nivolumab in patients with advanced renal cell carcinoma who have failed at least one prior therapy in Japan., Methods: A cost-effectiveness model was developed using a partitioned survival approach and a public healthcare payer's perspective. Over a lifetime horizon, clinical and economic implications were estimated according to a three-health-state structure: progression-free, post-progression, and death. Key clinical inputs and utilities were derived from the METEOR trial, and a de novo network meta-analysis and cost data were obtained from publicly available Japanese data sources. Costs, quality-adjusted life-years, and incremental cost-effectiveness ratios were estimated. Costs and health benefits were discounted annually at 2%., Results: Cabozantinib was more costly and effective compared with everolimus and axitinib, with deterministic incremental cost-effectiveness ratios of ¥5,375,559 and ¥2,223,138, respectively. Compared to nivolumab, cabozantinib was predicted to be less costly and more effective. Sensitivity and scenario analyses demonstrated that the key drivers of cost-effectiveness results were the estimation of overall survival and treatment duration, relative efficacy, drug costs, and subsequent treatment costs., Limitations: METEOR was an international trial but did not enroll any patients from Japan. Efficacy and safety data from METEOR were used as a proxy for the Japanese population following validation by clinical experts, and alternative assumptions specific to clinical practice in Japan were evaluated in scenario analyses., Conclusions: In Japan, cabozantinib is a cost-effective alternative to everolimus, axitinib, and nivolumab for the treatment of patients with advanced renal cell carcinoma who have received at least one prior line of therapy.

Aim: This qualitative study aimed to reveal symptoms and impacts among bone metastatic castration-resistant prostate cancer (or mCRPC) Japanese patients, prior to Radium-223 (Ra-223) treatment. Materials & Methods: Twenty-three mCRPC patients designated to receive Ra-223 and three treating physicians (Ra-223 prescribers) in Japan, were interviewed. All interview data were assessed for concept frequency, themes and saturation. Results: Forty-five percent of the patients (mean age: 75.8 years) were symptomatic at the time of enrollment. Interviews with all patients revealed 47 mCRPC symptoms, including back pain and bone-specific pain, and 45 life impacts, including worry about disease progression and the impact on daily, physical activities. Conclusion: The symptoms and impacts of living with mCRPC and the associated burden of bone metastasis and skeletal-related symptoms are varied and are important considerations for treatment.

Objectives: With novel antiandrogen treatments of varying clinical benefits and risks becoming available, this study investigates how patients with castration-resistant prostate cancer (CRPC) value differences in treatment characteristics., Design: Cross-sectional observational study., Setting: A discrete choice experiment was conducted. Patients chose between two hypothetical non-metastatic CRPC (nmCRPC) treatments defined by six attributes: risk of fatigue, falls or fracture, cognitive impairment, hypertension, rashes as side effects to treatment and extension of time until cancer-related pain occurs., Participants: A total of 137 adult male patients with CRPC with no prior experience with chemotherapy and with Eastern Cooperative Oncology Group status 0-1 were recruited. Patients were excluded if they participated in an investigational programme outside of routine clinical practice, had a clinically relevant medical or psychiatric condition, or diagnosis of visceral/other metastases not related to the prostate, or were otherwise deemed ineligible by the referring physician., Primary Outcome Measures: Relative preference weights and relative importance of the attributes was estimated by hierarchical Bayesian logistic regression., Results: Among the treatment attributes, 'risk of cognitive impairment as a side effect of treatment' was the most important attribute (relative importance (RI) (95% CI): 27.47% (24.80% to 30.14%)), followed by 'extension of time until cancer-related pain occurs' (RI (95% CI): 17.87% (15.49% to 20.25%)) and the 'risk of falls or fracture' (RI (95% CI): 15.99% (14.73% to 17.25%)). The 'risk of hypertension as a side effect of treatment' (RI (95% CI): 13.77% (12.73% to 14.81%)) had similar RI as 'risk of rashes as a side effect of treatment' (RI (95% CI): 13.17% (12.15% to 14.19%)), followed by the 'risk of fatigue as a side effect of treatment' (RI (95% CI): 11.74% (10.75% to 12.73%))., Conclusions: Patients consider the risk of cognitive impairment as a side effect of treatment as the most important attribute in nmCRPC, followed by the extension of time until cancer-related pain occurs, and the risk of falls and fracture. These features should be considered in treatment decision making for nmCRPC in Japan., Competing Interests: Competing interests: DAL is an employee of Bayer Yakuhin. VG, SS and YC are employees of Kantar, Health Division., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Studies of prostate-specific antigen (PSA)-based population screening have been conducted in western countries, but there is little data in Asian populations. The objective of this study was to determine the efficacy of PSA screening in Asian men using real-world data over a period of 15 years after introducing population screening in Yokosuka City, Japan., Methods: We investigated patients with pathologically diagnosed prostate cancer at four hospitals and two clinics across the Yokosuka area (Miura peninsula) between April 2001 and March 2015. Patients were divided into two groups; the S group consisted of those diagnosed by PSA-based population screening in Yokosuka City and the NS group consisted of those diagnosed by methods other than screening. Cancer-specific survival (CSS) and overall survival (OS) rates were calculated using the Kaplan-Meier method with the log-rank test to compare survival between the two groups. Clinical and pathological factors for cancer-specific mortality were assessed with Cox regression analyses to calculate the hazard ratio (HR) and 95% confidence interval (CI)., Results: A total of 3094 patients had been diagnosed with prostate cancer over the 15-year period. The median follow-up period was 77 months. The S group and the NS group consisted of 977 and 2117 patients, respectively. Patients in the S group were younger (age: 71 years vs 73 years, P < .001) and had a lower Charlson comorbidity index (CCI) with favorable oncological factors, such as lower initial PSA, Gleason score (GS), and risk category. Kaplan-Meier curves for OS and CSS revealed significant differences between the two groups (OS: P < .001, CSS: P < .001). Analysis with Cox proportional hazards model indicated the NS group (HR: 1.584, 95% CI, 1.065-2.356, P = .023), a CCI > 4 (HR: 1.552, 95% CI, 1.136-2.120, P = .006), a GS ≥ 8 (HR: 4.869, 95% CI, 2.631-9.001, P < .001), and nonlocalized cancer (locally advanced; HR: 2.632, 95% CI, 1.676-4.133, P < .001, advanced; HR: 9.468, 95% CI, 6.279-14.278, P < .001) as independent risk factors for cancer-specific mortality., Conclusions: PSA-based population screening of prostate cancer might be useful in the Japanese population., (© 2020 Wiley Periodicals LLC.)

There are regional and/or ethnic differences in tumorigenic pathways among several types of cancer, including prostate cancer (PCa). However, information on genome‑wide gene alterations and the transcriptome is currently only available for PCa patients from Western countries. In order to profile the genetic alterations in Japanese patients with PCa, new panels were created to examine nucleotide sequence variations in 71 selected PCa‑related genes (KCC71) and to detect all fusion RNA transcripts known in PCa (PCaFusion). An analysis of 21 Japanese PCa cases identified 33 different somatic variants in 24 genes in the KCC71 panel, including 2 in SPOP (F102V and F133L), 2 in BRCA2 (I1859fs and R2318ter, resulting in premature termination of the polypeptide), and 1 each in BRAF (K601E), CDH1 (E880K) and RB1 (R621S), as pathogenic alterations. Unexpectedly, the TMPRSS2‑ERG fusion transcript was detected in only 1 case, although the SLC45A3‑ELK4 and USP9Y‑TTTY15 fusion transcripts, known as transcription‑mediated chimeric RNAs, were detected in all examined cases. A new pathway analysis with The Cancer Network Galaxy (TCNG), a cancer gene regulatory network database, was also applied in an attempt to predict molecular pathways implicated in PCa in the Japanese population. Based on the 24 genes having somatic variants identified by the panel analysis as initial seed genes, a putative core network was finally established, including 5 identified genes, namely TNK2, SOX9, CDH1, FOXA1 and TP53, with high commonality from TCNG datasets. These genes are expected to be involved in tumor development, as revealed by the results of an enrichment analysis with Gene Ontology terms. This analysis must be further extended to include more cases in order to verify this method and also to elucidate the characteristics of PCa in Japanese patients.

Background: Sarcopenia is defined as a low skeletal muscle volume. Recent studies have reported that sarcopenia is associated with a poor prognosis in various cancers. The purpose of this study is to evaluate the correlation between the psoas muscle volume and recurrence-free survival in patients with localized clear cell renal cell carcinoma (ccRCC)., Methods: A total of 316 male patients with localized ccRCC who underwent radical nephrectomy at Yokohama City University Hospital (Yokohama, JAPAN) and Kanagawa Cancer Center (Yokohama, JAPAN) between 2002 and 2018 were enrolled in this study. The psoas muscle index (PMI) was calculated by normalizing the psoas muscle area on the contralateral side of the tumor on axial CT, which was calculated at the level of L4 (mm2) divided by the square of the body height (m2). We divided patients into two groups based on the median PMI (409.64mm2/m2)., Results: The lower PMI group showed poorer recurrence-free survival (RFS) than the higher PMI group (p = 0.030). Regarding 5-year RFS, a lower PMI was a significant predictor of recurrence (p = 0.022, hazard ratio (HR): 2.306) and a multivariate analysis revealed that a lower PMI (4 cm (p = 0.044, HR: 2.341), and pathological stage >2 (p<0.001, HR: 3.660) were independent risk factors for poor RFS., Conclusions: The presence of sarcopenia (lower PMI) was found to be associated with poor RFS in male ccRCC patients. The PMI might serve as a measure of patient frailty and might be useful for prognostic risk stratification in ccRCC., Competing Interests: The authors have declared that no competing interests exist.

Background: Apalutamide, a nonsteroidal potent androgen receptor antagonist, was safe and effective in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic-CRPC (mCRPC) in global studies. In this phase 1 study, safety, pharmacokinetics (PK), and efficacy of apalutamide were evaluated in Japanese patients with mCRPC., Methods: In this open-label, multi-center study, patients received apalutamide 240 mg (once-daily, orally) for first 1 week (PK week) during which PK parameters were assessed. 1 week later (Cycle 1 Day1), after reassessing safety, continuous daily dosing (4 weeks/cycle; once-daily orally) was initiated. Endpoints evaluated were: safety, tolerability, PK and antitumour efficacy of apalutamide. Dose-limiting toxicities (DLTs) were evaluated during PK week and Cycle 1., Results: All six patients received apalutamide. The most common treatment-emergent adverse events (TEAEs) were abdominal discomfort, nasopharyngitis, dysgeusia, rash, and hot flush [2/6 patients (33.3%) each]. No death or DLTs were reported. Grade 3 TEAEs were spinal-cord compression and renal disorder (1/6 patient each). In continuous daily dosing period, PK steady-state of apalutamide was reached approximately by week 4. A significant accumulation of apalutamide was observed (mean accumulation index 3.55), based on AUC 0-24 . Median (range) serum prostate-specific antigen level decreased from 54.42 (8.92-310.11) ng/mL at baseline to 11.70 (0.37-47.74) ng/mL at week 12 with ≥ 50% reduction in 4/6 (66.7%) patients and 90% reduction in 2/6 (33.3%) patients., Conclusion: Apalutamide had manageable safety profile, without any DLT or any new safety signals, and favourable efficacy in Japanese mCRPC patients. Thus, it was ascertained to be an adequate dosage regimen in Japanese mCRPC patients., Trial Registration: ClinicalTrials.gov identifier: NCT02162836.

Background: Cabazitaxel is an efficacious treatment for patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel, but febrile neutropenia during the first cycle is a frequent complication. Asian patients are at increased risk of febrile neutropenia. Although primary prophylaxis with granulocyte colony-stimulating factor can reduce the incidence, its efficacy has not been prospectively demonstrated in Japanese patients with cabazitaxel treatment., Methods: PEGAZUS, a prospective, single-arm study conducted at eight clinical sites in Japan, enrolled 21 heavily pretreated patients with metastatic castration-resistant prostate cancer. Patients received cabazitaxel 25 mg/m2 every 3 weeks, up to 10 cycles. Oral prednisolone 10 mg was taken daily. Pegfilgrastim 3.6 mg was administered at least 24 h after the cabazitaxel infusion. The primary endpoint was the incidence of febrile neutropenia in the first cycle., Results: The median number of treatment cycles was seven. The relative dose intensity of cabazitaxel was 67.4% (range, 53.2-91.3%). Two of 21 patients (9.5%) experienced febrile neutropenia in the first cycle. This rate was lower than the rate (43%) previously observed without prophylactic granulocyte colony-stimulating factor in a similar patient population. Six patients showed a prostate-specific antigen response (28.6%). Three of four patients evaluable for tumor response had stable disease and one had progressive disease. Grade ≥3 diarrhea was not observed. Primary prophylaxis with granulocyte colony-stimulating factor significantly reduced the incidence of febrile neutropenia in this study., Conclusions: Cabazitaxel plus granulocyte colony-stimulating factor is safe and effective for Japanese patients with metastatic castration-resistant prostate cancer who have previously progressed on docetaxel. Clinical trial registration: ClinicalTrials.gov (NCT02441894)., (© The Author(s) 2019. Published by Oxford University Press.)

Background: Non-muscular invasive bladder cancer (NMIBC) has a high risk of recurrence. As androgen receptor (AR) reportedly affects bladder cancer, we assessed the correlation between NMIBC recurrence and tumor AR expression in Japanese patients., Methods: We retrospectively reviewed 53 specimens of non-metastatic NMIBC, with recurrence-free survival (RFS) as the primary endpoint. We used real-time quantitative polymerase chain reaction to quantify AR mRNA expression. Kaplan-Meier product-limit estimators were used to assess RFS distribution, log-rank tests to analyze differences in RFS between high- and low-risk groups; and multivariate analyses of AR mRNA expression and other clinicopathological factors to predict independent factors for RFS., Results: The high AR mRNA-expressing group (n = 43) tended to have a longer median RFS (not reached) than did the low-AR group (n = 10; 9.04 months; P = 0.112). Multivariate analysis showed female sex (hazard ratio [HR]: 7.360, 95% CI: 1.649-32.856, P = 0.009), tumor size ≥3 cm (HR: 23.697, 95% CI: 4.383-128.117, P < 0.001) and low AR mRNA expression (HR: 0.202, 95% CI: 0.048-0.841, P = 0.028) to be independent predictors of shorter RFS., Conclusion: Our study showed that low AR mRNA expression level is an independent risk factor for RFS in Japanese patients with NMIBC. Further studies are necessary but AR expression might be a new indicator of recurrence of NMIBC.

Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open-label, parallel-arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non-inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end-point was the cumulative castration rate from day 28 to day 364 and the non-inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non-inferiority of the 3-month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate-specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non-inferiority of the 3-month formulation of degarelix to goserelin was shown for testosterone suppression. The 3-month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170)., (© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Background: The safety, tolerability, pharmacokinetics (PK) and anti-tumor activity of enzalutamide were investigated in patients with castration-resistant prostate cancer (CRPC) in Japan through a multicenter phase I/II study., Methods: In phase I, patients with progressive metastatic CRPC received single, then multiple, ascending doses of enzalutamide 80, 160 or 240 mg/day. After assessment of tolerability at multiple doses of 160 mg/day for 4 weeks, post-docetaxel patients with CRPC and measurable disease were enrolled into phase II; receiving long-term administration of enzalutamide 160 mg/day., Results: Nine and 38 patients were enrolled in phase I and II, respectively. During phase I, enzalutamide was well tolerated in each cohort; PK parameters were similar to those of non-Japanese populations in other studies. By week 12, overall response rate was 5.3 % and clinical benefit rate was 47.4 %. Prostate-specific antigen response rate (≥50 % reduction from baseline) was 28.9 %. Treatment-emergent adverse events reported in >20 % of patients in phase II were decreased weight, decreased appetite and constipation. No seizures were observed., Conclusion: Enzalutamide at 160 mg/day was well tolerated, with PK and safety profiles similar to the non-Japanese population. Anti-tumor activity was observed in post-docetaxel Japanese patients with metastatic CRPC. Apparent differences in anti-tumor activity compared with the AFFIRM study (a phase III trial in a diverse population of patients with CRPC post-docetaxel) may be attributed to differences in treatment history prior to starting enzalutamide. Particularly in Japan, the influence of sequence in hormone treatments, including combined androgen blockade therapy, should be considered., Trial Registration: ClinicalTrials.gov NCT01284920.

Background: We analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis., Methods: From 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validation data set, the nomogram was assessed for discriminatory ability, and the predictions were assessed for calibration accuracy by plotting actual survival against predicted risk., Results: Of the 361 patients in the training data set, 205 (56.8%) patients died, 169 (46.8%) deaths of which were due to prostate cancer. The median follow-up period was 55.2 months. In the multivariate analysis, patient age, serum prostate-specific antigen level, clinical T stage, extent of disease on bone scan, and biopsy Gleason sum were independent prognostic factors. We developed a prognostic model comprising these five factors for patients with bone-metastatic prostate cancer. This nomogram can be used to estimate 1-, 3-, and 5-year survival probability. External validation of this model using 102 validation data sets showed reasonable accuracy (concordance index, 0.719)., Conclusion: Our pretreatment prognostic nomogram might be useful for Japanese patients with bone-metastatic prostate cancer.

Purpose: In the present study, we compared 12- with 16-core biopsy in patients with prostate- specific antigen (PSA) levels of 4.0-20.0 ng/mL., Materials and Methods: Between 2003 and 2010, 332 patients whose serum PSA level was between 4.0 and 20.0 ng/mL underwent initial transrectal ultrasound (TRUS)-guided needle biopsy. Of those patients, 195 underwent 12-core biopsy and 137 underwent 16-core biopsy., Results: In the 12-core prostate biopsy group, 66 (33.8%) patients were found to have prostate cancer. On the other hand, in the 16-core prostate biopsy group of 137 patients, 61 (44.5%) were found to have prostate cancer. Among all patients, the prostate cancer detection rate was slightly higher in the 16-core biopsy group than in the 12-core biopsy group. Moreover, in patients with prostate volume > 30 mL or PSA density (PSAD) < 0.2, the prostate cancer detection rate was significantly higher in the 16-core biopsy group than in the 12-core biopsy group. There was no significant difference in pathological tumor grade, indolent cancer probability, or biopsy complication rate between the two groups., Conclusion: In order to detect prostate cancer, 16-core prostate biopsy is safe and feasible for Japanese patients with serum PSA level of 4.0-20.0 ng/mL.

Purpose: In Japan, sometimes a patient with malignant fatal disease is not informed the diagnosis. We tried to investigate if the informed consent of cancer notification is acceptable and suitable for aged Japanese prostate cancer patients., Materials and Methods: From January to June 2003, we distributed a questionnaire to outpatients who had been followed up for more than 6 months after the diagnosis of prostate cancer. These patients declared a wish to be notified the true diagnosis in their first visit to our department and were informed that they had prostate cancer just after the diagnosis. Ninety-one per cent of patients (54 patients, mean age was 74.8 +/- 6.1 years old) answered to our questionnaire. Clinical stage consisted of 14 cases of B1, 13 cases of B2, 15 cases of C, 3 cases of D1, and 9 cases of D2. The histopathological grade consisted of 6 cases of well differentiated carcinoma, 32 cases of moderately differentiated carcinoma, and 16 cases of poorly differentiated carcinoma. Eleven cases underwent total prostatectomy (B1 and B2) and 44 cases had androgen deprivation therapy., Results: Seventy-six per cent of patients understood and accepted their illness within a few days. However, 11% of patients took more than 3 months to accept their malignant disease. They answered that they could accept their illness given with a relationship of mutual trust between themselves as patients and the medical staff, effective medical treatment, and with the help of their family. They also answered that the most important emotional support was given by their wives (46.3%) and doctors (27.8%). In the early days following the diagnosis, they worried about their remaining days, the risks or side effects of the treatment, their family, and their job. Several months following the diagnosis, they were concerned about recurrence of the disease, their family, medical expenses, and their old age. Those who did not worry at all doubled from 11.1% immediately after the diagnosis to 22.2% several months later. More than 90% of the patients were satisfied with our medical care. And none answered that they might have been happier without cancer notification., Conclusions: Cancer notification is acceptable and suitable in aged Japanese prostate cancer patients who declare a wish to know their malignant illness. A good relationship between the patients and the medical staff, and emotional support from the wife are important.