Management of Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): an Evolving Treatment Paradigm

Combination systemic therapy is now standard of care for all men with metastatic, hormone-sensitive prostate cancer (mHSPC). Patients with mHSPC should be treated with standard androgen deprivation therapy (ADT) and abiraterone acetate with prednisone or docetaxel (chemohormoanl therapy) unless there are contraindications to combination therapy. Based on the Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer (CHAARTED) study subgroup analysis, chemohormonal therapy may be most beneficial in men with high-volume disease burden, as men with low-volume metastatic disease do not appear to experience a survival benefit with chemohormonal therapy, while abiraterone in combination with ADT appears to be beneficial across both disease volume subgroups. Decisions regarding whether to use chemohormonal therapy or abiraterone and ADT for men with mHSPC should integrate consideration of volume of disease burden, quality of life effects, duration of therapy, and patient preferences for treatment as there is no formally powered prospective head-to-head comparison of these options demonstrating superiority of one approach over the other. Treatment of the primary tumor with radiation should be considered in men with de novo low-volume metastatic disease as radiation is associated with prolonged survival and a tolerable toxicity profile. Men with de novo high-volume metastatic disease do not appear to have improved survival with radiation of the primary tumor. Numerous clinical trials are ongoing to evaluate treatment approaches that may benefit men with mHSPC. Radical prostatectomy in men with mHSPC in combination with optimal systemic therapy is currently being assessed in a clinical trial, but should not be considered outside of a clinical trial. Metastasis-directed therapy with radiotherapy directed at metastatic lesions is still investigational, but can be considered in clinical trials in men with oligometastatic disease. Multiple studies are enrolling worldwide for men with mHSPC, and these should be considered for all interested patients.