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Objective: Novel androgen receptor axis‐targeted agents (ARATAs) have been developed for mCRPC and improved overall survival (OS). Here, we aimed to find predictors who will receive the greatest benefits from ARATAs. Methods: We previously performed a multicenter study to identify prognostic factors for metastatic hormone‐sensitive prostate cancer (mHSPC, n = 148) and mCRPC (n = 99), and showed that the bone scan index (BSI) was one of the significant prognostic factors for 3‐year OS (PROSTAT‐BSI study). mHSPC progressed to mCRPC (n = 101), for which 69 patients were treated with (n = 39) or without ARATAs (n = 30, prior to the approval of ARATAs). The 69 patients were divided into two groups according to patient factors, and these cohorts were further divided into two subgroups by usage of ARATAs. OS was compared between subgroups in each group. Results: The predictors were age (<71.4 years), serum levels of C‐reactive protein (≥0.16 ng/ml) and alkaline phosphatase (≥548 U/L), time to PSA progression after ADT (<8.9 months), the lowest PSA level (≥1 ng/ml) after ADT, and the rate of PSA decline 3 months after ADT (<0.987), whereas hemoglobin levels, PSA before ADT, Gleason scores, existence of visceral metastases, and BSI were not. Conclusions: The present study identified predictors for the effectiveness of ARATAs. The number of bone metastases (≒BSI), existence of visceral metastases, and Gleason scores, which were identified as high‐risk factors in the LATITUDE study and disease volume in CHAARTED criteria, did not appear to be useful for predicting effectiveness from ARATAs. [ABSTRACT FROM AUTHOR]

Objective: To determine prognostic factors including the Bone Scan Index in prostate cancer patients receiving standard hormonal therapy and chemotherapy. Methods: This multicenter Prostatic Cancer Registry of Standard Hormonal and Chemotherapy Using Bone Scan Index study involved 30 hospitals and enrolled 247 patients (age 71 ± 8 years) with metastatic hormone‐sensitive prostate cancer (n = 148) under hormone therapy and metastatic castration‐resistant prostate cancer (n = 99) under chemotherapy. The Bone Scan Index (%) was determined by whole‐body bone scintigraphy using 99mTc‐methylenediphosphonate. Patients were classified into tertiles and binary groups, and predictors of all‐cause death including Bone Scan Index, prostate‐specific antigen, and bone metabolic markers were determined using survival and proportional hazard analyses. Results: During a mean follow‐up period of 716 ± 404 days, 81 (33%) of the patients died, and 3‐year mortality rates were 20% and 52% in the metastatic hormone‐sensitive prostate cancer and metastatic castration‐resistant prostate cancer groups, respectively. Survival analysis showed that a Bone Scan Index >3.5% was a significant determinant of death in the metastatic hormone‐sensitive prostate cancer group, whereas prostate‐specific antigen >55 ng/mL before chemotherapy was a determinant of prognosis in the metastatic castration‐resistant prostate cancer group. A Bone Scan Index >3.5% was also associated with a high incidence of prostate‐specific antigen progression in the metastatic hormone‐sensitive prostate cancer group. Patients with metastatic hormone‐sensitive prostate cancer and a better Bone Scan Index response (>45%) to treatment had lower mortality rates than those without such response. Conclusion: The Bone Scan Index and hot spot number are significant determinants of 3‐year mortality, and combining the Bone Scan Index with prostate‐specific antigen should contribute to the management of prostate cancer patients with bone metastasis. [ABSTRACT FROM AUTHOR]

Background: To date, research has not determined the optimal procedure for adjuvant androgen deprivation therapy (ADT) in patients with locally advanced prostate cancer (PCa) treated for 6 months with neoadjuvant ADT and external-beam radiation therapy (EBRT).Methods: A multicenter, randomized, phase 3 trial enrolled 303 patients with locally advanced PCa between 2001 and 2006. Participants were treated with neoadjuvant ADT for 6 months. Then, 280 patients whose prostate-specific antigen levels were less than pretreatment levels and less than 10 ng/mL were randomized. All 280 participants were treated with 72 Gy of EBRT in combination with adjuvant ADT for 8 months. Thereafter, participants were assigned to long-term ADT (5 years in all; arm 1) or intermittent ADT (arm 2). The primary endpoint was modified biochemical relapse-free survival (bRFS) with respect to nonmetastatic castration-resistant prostate cancer (nmCRPC) progression, clinical relapse, or any cause of death.Results: The median follow-up time after randomization was 8.2 years. Among the 136 and 144 men assigned to trial arms 1 and 2, respectively, 24 and 30 progressed to nmCRPC or clinical relapse, and 5 and 6 died of PCa. The 5-year modified bRFS rates were 84.8% and 82.8% in trial arms 1 and 2, respectively (hazard ratio, 1.132; 95% confidence interval, 0.744-1.722).Conclusions: Although modified bRFS data did not demonstrate noninferiority for arm 2, intermittent adjuvant ADT after EBRT with 14 months of neoadjuvant and short-term adjuvant ADT is a promising treatment strategy, especially in a population of responders after 6 months of ADT for locally advanced PCa. [ABSTRACT FROM AUTHOR]

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 AUC0–24. 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. [ABSTRACT FROM AUTHOR]