Taro Iguchi

PURPOSE: In patients who received enzalutamide, we characterized the development of radiographic progression (rPD) without prostate-specific antigen (PSA) rise or progression in metastatic hormone-sensitive prostate cancer (mHSPC) and nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods: We conducted a post hoc analysis in two phase III trials (N = 2,551; ARCHES [ClinicalTrials.gov identifier: NCT02677896 ]; PROSPER [ClinicalTrials.gov identifier: NCT02003924 ]) for co-occurrence of rPD ± Prostate Cancer Working Group 2/3-defined PSA progression, and rPD ± any PSA rise from baseline/nadir by treatment. Kaplan-Meier methods were used for overall survival (OS) outcomes. RESULTS: In ARCHES, 3.5% and 8.5% of 574 patients with mHSPC treated with enzalutamide plus androgen-deprivation therapy (ADT) had no PSA rise or PSA progression at rPD, respectively. Of 79 patients with rPD who received enzalutamide plus ADT, 25.3% had no PSA rise and 62.0% did not meet PSA progression criteria compared with 7.4% and 38.3% of 188 patients with rPD treated with ADT alone, respectively. In PROSPER, 4.4% and 10.3% of 933 patients with nmCRPC treated with enzalutamide plus ADT had no PSA rise or PSA progression, respectively, at rPD. However, of 187 patients with rPD who received enzalutamide plus ADT, 21.9% had no PSA rise and 51.3% did not meet PSA progression criteria compared with 3.6% and 18.8% of 224 patients treated with placebo/ADT, respectively. Liver metastases were >5-fold higher in enzalutamide-treated patients with rPD events versus control, although sample size was small. Compared with no rPD, enzalutamide-treated patients with rPD ± PSA rise or progression had worse OS. CONCLUSION: Given the frequent discordance and poor prognosis of imaging-based progression in the absence of PSA changes during enzalutamide treatment in mHSPC and nmCRPC, periodic surveillance using imaging is recommended.

This third edition of the Japanese Clinical Practice Guidelines for Urinary stones (2023) has been developed under the leadership of the Japanese Urological Association, the Japanese Society of Endourology and Robotics, and the Japanese Society on Urolithiasis Research. This revision adheres to the Minds Manual for Guideline Development (2017) and incorporates new findings from a nationwide survey conducted in 2015, which highlighted the epidemiological characteristics of urolithiasis in Japan since the previous guidelines were published in 2013. A significant advancement in this edition is the systematic review (SR) methodology applied to formulate recommendations for 12 clinical questions (CQs). Both quantitative and qualitative SRs were performed, leading to recommendations determined through consensus among 21 members of the guideline development group. Additionally, nine algorithms were created to support clinical decision‐making based on these findings. Topics not addressed by the CQs, considered as foundational knowledge, are outlined in an “Explanation of Related Matters” section, which includes 26 items. This article provides an overview of these guidelines. This section ensures that practitioners have access to comprehensive information, covering aspects of urolithiasis management beyond the scope of the systematic reviews. This article provides an overview of the guidelines, emphasizing their relevance and importance in improving the management and treatment outcomes for patients with urinary stones. The guidelines are designed to be a practical resource for clinicians, facilitating evidence‐based care in the evolving landscape of urolithiasis treatment.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In primary analysis, enzalutamide plus androgen deprivation therapy (ADT) improved radiographic progression-free survival (rPFS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC); however, overall survival data were immature. In the phase III, double-blind, global ARCHES trial (ClinicalTrials.gov identifier: NCT02677896 ), 1,150 patients with mHSPC were randomly assigned 1:1 to enzalutamide (160 mg once daily) plus ADT or placebo plus ADT, stratified by disease volume and prior docetaxel use. Here, we report the final prespecified analysis of overall survival (key secondary end point) and an update on rPFS, other secondary end points, and safety. After unblinding, 180 (31.3%) progression-free patients randomly assigned to placebo plus ADT crossed over to open-label enzalutamide plus ADT. As of May 28, 2021 (median follow-up, 44.6 months), 154 of 574 patients randomly assigned to enzalutamide plus ADT and 202 of 576 patients randomly assigned to placebo plus ADT had died. Enzalutamide plus ADT reduced risk of death by 34% versus placebo plus ADT (median not reached in either group; hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P < .001). Enzalutamide plus ADT continued to improve rPFS and other secondary end points. Adverse events were generally consistent with previous reports of long-term enzalutamide use. In conclusion, enzalutamide plus ADT significantly prolongs survival versus placebo plus ADT in patients with mHSPC.

Prostate cancer is a common malignancy and patients may progress to castration-resistant prostate cancer (CRPC). Among patients with CRPC, fatigue is a common symptom associated with current treatm...

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.