非轉移性去勢抗性攝護腺癌中雄性素受體路徑抑制劑之真實世界比較性療效分析

馮思中、邵翊紘、謝瑾瑄、張孜璇、林柏宏、虞凱傑、甘弘成、李宗霖、莊正鏗

 林口長庚紀念醫院 外科部 泌尿腫瘤科

Real-world Comparative Outcomes of Androgen Receptor Pathway Inhibitors in Nonmetastatic Castration-Resistant Prostate Cancer

See-Tong Pang、I-Hung Shao、Chin-Hsuan Hsieh、Tzu-Hsuan Chang、Po-Hung Lin、Kai-Jie Yu、Hung-Cheng Kan、Chung-Lin Lee、Cheng-Keng Chuang

Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch, Taiwan.

Purpose: Patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) and high-risk features frequently progress to life-threatening metastasis in the absence of androgen receptor pathway inhibitors (ARPIs). Evidence from cohorts prior to the approval of these agents highlights a substantial unmet clinical need in this population. However, real-world evidence from Taiwan remains limited, particularly regarding treatment discontinuation, progression to metastatic CRPC (mCRPC), and safety outcomes. This study aimed to report real-world clinical experience from Taiwan and evaluate the effectiveness and tolerability of ARPIs in routine clinical practice.

Materials and Methods: This retrospective cohort study evaluated patients with nmCRPC treated with ARPIs, including apalutamide, darolutamide, and enzalutamide, in routine clinical practice and aimed to compare their efficacy and safety. Clinical outcomes assessed included the rate and risk of treatment discontinuation, progression to mCRPC, and the incidence of adverse events (AEs). Survival analyses were performed using the Kaplan–Meier method, and Cox proportional hazards models were applied to estimate the risk of treatment discontinuation and disease progression across treatment groups.

Results: A total of 114 patients were included in this study, comprising 57 treated with darolutamide, 35 with apalutamide, 10 with enzalutamide, 2 with abiraterone, and 10 who did not receive ARPIs. Baseline characteristics were generally comparable across these groups. The apalutamide group demonstrated a higher incidence of adverse events, particularly skin rash. Discontinuation rates due to adverse events varied among treatment groups, with patients receiving darolutamide showing a lower likelihood of treatment discontinuation compared with apalutamide and enzalutamide. Regarding disease progression, patients treated with darolutamide showed a trend toward a reduced risk of progression to mCRPC compared with enzalutamide, while outcomes were generally comparable with apalutamide and abiraterone. The most common reason for treatment discontinuation was disease progression, followed by adverse events. Overall, darolutamide demonstrated a favorable safety profile compared with other ARPIs.

Conclusions: This real-world study provides important insights into the utilization of ARPIs for nmCRPC in the Taiwanese population. Variations in adverse event profiles across different treatments highlight the need for individualized therapeutic decision-making in routine clinical practice. Darolutamide demonstrated a favorable safety profile and improved treatment persistence compared with other agents. These findings support the integration of regional real-world evidence into clinical practice and may help inform treatment selection and optimize clinical outcomes for patients with nmCRPC.