Abstract
Metastatic hormone-sensitive prostate cancer (mHSPCa) presents de novo or represents significant disease progression and requires systemic treatment. However, progression to castration resistance is inevitable. The treatment landscape has evolved with the introduction of intensified systemic therapy, including androgen deprivation therapy (ADT) combined with either androgen receptor signaling inhibitors (ARSIs) or cytotoxic chemotherapy (doublet therapy) or combined therapy with both agents (triplet therapy). Landmark trials such as CHAARTED, STAMPEDE, LATITUDE, ENZAMET, and TITAN have established combination therapies as the standard of care, demonstrating significant overall survival benefits. More recently, triplet therapy-integrating ADT, docetaxel, and an ARSI-has emerged as an effective approach, particularly in high-volume metastatic disease, as supported by ARASENS and PEACE-1. Advances in imaging, such as PSMA PET-CT, have improved disease detection, allowing earlier detection of metastasis and appropriate therapy. Similarly, genomic profiling has enabled biomarker-driven, personalized treatment strategies. The role of treatment of the primary tumor, by either radiation therapy or cytoreductive prostatectomy, in low-volume disease continues to be explored. As novel therapies, targeted agents, and immunotherapies undergo investigation, optimizing treatment selection based on disease burden, molecular characteristics, and patient factors will be essential. The future of mHSPCa management lies in multidisciplinary, precision-based approaches to improve patient outcomes while balancing treatment efficacy and tolerability.