Debate 3: Metastasis Directed Therapy in Oligometastatic Prostate Cancer

Abstract

Oligometastatic prostate cancer (OMPC), characterized by limited metastatic burden (≤5 lesions), encompasses 3 major subtypes: de novo synchronous oligometastatic hormone-sensitive prostate cancer (om-HSPC), metachronous oligorecurrent HSPC (or-HSPC), and oligoprogressive castrate-resistant prostate cancer (op-CRPC). Metastasis-directed therapy (MDT), particularly stereotactic body radiotherapy (SBRT), has been widely adopted and offers a noninvasive approach for delaying disease progression and achieving durable local control while maintaining the quality of life (QoL). This review examines the evolving evidence supporting MDT across OMPC spectrum. In de novo om-HSPC, early prospective studies suggest benefit when combining MDT with systemic therapy and local prostate radiation therapy (RT). However, conclusive randomized evidence for benefit of MDT in de-novo om-HSPC is lacking. For or-HSPC, randomized trials (STOMP, ORIOLE) demonstrate that SBRT-MDT safely delays systemic therapy initiation and prolongs progression-free survival (PFS). In nodal or-HSPC, the PEACE V-STORM trial has shown superior biochemical and locoregional control with elective nodal radiotherapy (ENRT) compared to SBRT alone. For well selected patients with OMPC, systemically augmented MDT (SBRT with short-course ADT±ARPI) is an attractive strategy to improve outcomes with no added QoL detriment and has shown more durable responses than either modality alone (EXTEND, RADIOSA trials). The recent WOLVERINE meta-analysis has shown that MDT improves PFS and overall survival across OMPC subtypes. Patient selection remains crucial, with PSA kinetics, PSMA-PET findings, and genomic factors emerging as potential biomarkers for personalizing the OMPC therapeutic landscape. While several phase III trials are ongoing, current evidence supports MDT integration into clinical practice for appropriately selected OMPC patients.