Defining Patient Benefits from High-intensity Intermittent Therapy for Hormone-sensitive Prostate Cancer

Intensification of systemic therapy beyond androgen deprivation therapy (ADT) with the addition of novel androgen receptor pathway inhibitors (ARPIs) is associated with better overall survival (OS) in comparison to ADT alone in metastatic hormone-sensitive prostate cancer (mHSPC). However, continuous use of ARPIs, as is currently standard in routine practice, may be associated with long-term toxicities, lower quality of life (QOL), and higher health care costs. Post hoc analyses of contemporary ARPI trials suggest that the depth of the initial prostate-specific antigen (PSA) response is associated with favorable long-term outcomes. While a prior large randomized trial (S9346) failed to demonstrate noninferiority of intermittent ADT in patients with HSPC, evaluation of high-intensity intermittent therapy is warranted. This involves a strategy whereby more potent systemic therapy is interrupted by treatment breaks in selected patients with mHSPC as a means to improve QOL and reduce costs, while not impacting cancer-related outcomes. PATIENT SUMMARY: Intensified hormonal treatment is a standard of care in advanced prostate cancer. Treatment breaks may be beneficial in patients with an outstanding response to therapy. Further trials are warranted to identify which subgroups of patients may benefit from this approach.