Choosing a Chemotherapy-Based Triplet Regimen in Metastatic Castration-Sensitive Prostate Cancer

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Neal Shore, MD, FACS, provides a comprehensive analysis of the landmark ARASENS and PEACE-1 phase 3 trials, which established the efficacy of triplet therapy in high-risk patients with metastatic castration-sensitive prostate cancer. The PEACE-1 trial demonstrated superiority of abiraterone plus docetaxel plus ADT over docetaxel plus ADT alone, whereas ARASENS showed benefits of darolutamide plus docetaxel plus ADT compared with docetaxel plus ADT. These studies provide level 1 evidence for triplet therapy in appropriately selected patients.

Despite compelling clinical trial evidence, real-world utilization of intensified therapy remains suboptimal, with 25% to 30% of patients still receiving ADT monotherapy in contemporary practice. This underutilization represents a significant missed opportunity for improved outcomes, particularly given that newly diagnosed patients typically have better performance status and fewer comorbidities than those with progressive disease. The “first shot, best shot” philosophy supports early treatment intensification when patients are most likely to tolerate aggressive therapy.

Successful implementation of triplet therapy requires multidisciplinary collaboration between urologists and medical oncologists to ensure appropriate patient selection and shared decision-making. The trade-off between improved efficacy and increased toxicity must be thoroughly discussed with patients, moving away from paternalistic treatment approaches. As new agents like PARP inhibitors enter the treatment landscape, the complexity of treatment selection will continue to increase, emphasizing the need for comprehensive patient evaluation and individualized treatment planning.