Treatment Strategies for Metastatic Castration-Sensitive Prostate Cancer: From “All-Comers” to “Personalized” Approach

Standard treatment for metastatic castration-sensitive prostate cancer (mCSPC) was androgen-deprivation therapy (ADT) for >7 decades, and this was termed the “all-comers” approach. A remarkable evolution in the treatment of mCSPC has been noted in the previous several years. High-quality clinical trials have shown that the addition of docetaxel or androgen receptor pathway inhibitors, such as abiraterone acetate, enzalutamide, and apalutamide, to ADT improves the overall survival (OS) as compared to ADT alone. The first 2 trials demonstrated the benefits of docetaxel and abiraterone acetate in terms of OS in high-volume and high-risk cancer subgroups, respectively. The later trials indicated that upfront combination therapies were associated with improved OS in all patients, irrespective of tumor volume and risk category. Upfront combination therapies are becoming a standard of care for all patients with mCSPC. However, meta-analyses have failed to show that all upfront combination therapies provide significant survival benefits in all patient subgroups. In the low-volume subgroup, significance was observed only for treatment with enzalutamide and radiation to the prostate. Men with low-volume low-risk cancer who have favorable response to ADT achieve long-term survival with ADT only, and toxicities induced by combination therapies would exceed the benefit for these patients. Treatments should be tailored to each patient because mCSPC has marked diversity in its biological and clinical features. Recent advances in diagnostic and molecular technologies will provide useful prognostic and predictive biomarkers, and the treatment strategy will shift from the “for all-comers” to the “individualized” approach.