Primary site- and metastasis-directed therapies in patients with metastatic prostate cancer: A narrative review.

Metastatic prostate cancer (mPC) is primarily managed with systemic therapy based on androgen deprivation therapy, often combined with androgen receptor pathway inhibitors or chemotherapy. However, mPC is a biologically and clinically heterogeneous disease, ranging from low-volume or oligometastatic states with relatively favorable outcomes to widely disseminated disease associated with poor prognosis. In this context, primary site-directed therapy (PDT) and metastasis-directed therapy (MDT) have emerged as complementary strategies for selected patients, aiming to address both local and metastatic disease control. PDT, including prostate radiotherapy and cytoreductive radical prostatectomy, may improve outcomes by reducing tumor burden and preventing local complications. Randomized evidence supports prostate radiotherapy in low-volume metastatic hormone-sensitive PC, although its survival benefit in the setting of intensified systemic therapy remains unclear. MDT, delivered via stereotactic body radiotherapy or metastasectomy, has demonstrated clinical benefit in oligometastatic diseases-particularly metachronous oligo-recurrence-by prolonging progression-free survival, delaying systemic treatment escalation, and potentially deferring castration resistance. In oligometastatic castration-resistant PC, early randomized studies suggest that combining MDT with systemic therapy may improve progression-related outcomes. Advances in prostate-specific membrane antigen positron emission tomography have enhanced lesion detection and patient selection, although they also complicate cross-trial comparisons. Despite these advances, high-level evidence demonstrating an overall survival benefit remains limited. Ongoing clinical trials are expected to clarify the optimal integration of PDT and MDT with contemporary systemic therapies and to better define appropriate patient selection. This narrative review summarizes the current evidence and explores future perspectives on incorporating local treatment strategies into mPC management.