Prostate cancer is the most common non-cutaneous malignancy affecting men in the United States, with the incidence of metastatic disease rising. Despite modern androgen deprivation therapy (ADT), nearly all cases of metastatic prostate cancer develop castration resistance. Informed by successes in the treatment of metastatic castration-resistant prostate cancer (mCRPC), novel treatment modalities have emerged as part of the armamentarium for metastatic hormone-sensitive prostate cancer (mHSPC). In this review, we detail treatments such as cytotoxic chemotherapy, androgen receptor pathway inhibitors (ARPIs), radiotherapy, radiopharmaceutical therapy, immunotherapy, and poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of mHSPC, synthesizing current evidence and guiding clinical decision-making. With technological advances and insight from molecular studies, we discuss emerging biomarkers as indicators to guide prognostication and therapeutic decisions. As a result of these developments, the treatment landscape for mHSPC is evolving toward a precision oncology paradigm incorporating combined systemic therapies.
Journal of immunotherapy and precision oncology. 2026 May 12*** epublish ***
Elias A Castro, Yash C Jani, Mehmet A Bilen
Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Department of Medicine, Medical College of Georgia at Augusta University, Augusta, GA, USA., Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, USA.