Metastasis-directed therapy in oligoprogressive prostate cancer: current evidence and future directions

Oligoprogression in prostate cancer is increasingly recognized as a clinically meaningful state with increased incidence due to effective systemic therapies and more sensitive molecular imaging, particularly prostate-specific membrane antigen positron emission tomography (PET). Broadly, oligoprogressive prostate cancer is defined as progression at a limited number of metastatic sites, commonly three to five or fewer, while the remainder of disease remains stable on ongoing therapy. In prostate cancer, however, this concept spans biologically and clinically distinct states, including repeat oligorecurrence off systemic therapy, new oligometastasis at the time of castration-resistance, and oligoprogression in castration-resistant disease. These differences are important because the goals of metastasis-directed therapy (MDT) differ across settings. In castration-sensitive disease, local therapy is often used to delay initiation or re-initiation of androgen deprivation therapy (ADT) and preserve quality of life. In castration-resistant disease, the goal is more often to ablate resistant clones, prolong the benefit of otherwise effective systemic therapy, and defer next-line treatment. Prospective randomized phase II data in oligometastatic castration-sensitive prostate cancer (CSPC) support MDT as an ADT-sparing strategy, and emerging studies suggest that repeat courses of stereotactic body radiotherapy (SBRT) may remain feasible in selected patients with serial limited-site recurrence. In metastatic castration-resistant prostate cancer (mCRPC), two randomized phase II trials and multiple prospective and retrospective series support the addition of MDT in carefully selected men. Across both disease states, local control rates are high and grade 3 or higher toxicity is uncommon. Nevertheless, major questions remain regarding optimal patient selection, imaging definitions, integration with systemic intensification, and the role of biomarkers in distinguishing durable oligoprogression from impending polyprogression. This review summarizes the biologic rationale, clinical evidence, and future directions for MDT in oligoprogressive prostate cancer.