Deferral of systemic therapy in patients with oligorecurrent prostate cancer treated with metastasis-directed radiotherapy.

Abstract

Distant metastasis marks a critical transition in prostate cancer, separating potentially curable from canonically incurable disease. Oligometastatic disease, defined as limited metastases (e.g., less than 3, 5, or 10), can encompass different clinical scenarios, including oligorecurrent disease (characterized by a limited number of metastatic lesions that recur after initial definitive treatment), and has emerged as an intermediate or transitional state. While intensified systemic therapies are increasingly applied to metastatic cases, many patients prefer to delay starting castrating therapies. Metastasis-directed therapy (MDT) is a safe and effective alternative to systemic therapy in a subset of patients with well-defined oligometastatic disease. Recent advances in imaging technologies and emerging treatment paradigms pose clinical challenges for patient risk stratification and optimal treatment selection. Here, we explore two key developments in the field: the influence of advanced imaging on clinical decision-making and the growing role of radiotherapy (RT) in oligometastatic disease management. We explore the landscape of novel biomarkers to estimate micrometastatic disease burden, which eludes imaging, using the concept of "liquid tumor burden" (LTB) measured by blood-based markers like circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and tumor-derived extracellular vesicles (tdEVs). Promising data suggest that LTB assessment may refine patient selection for MDT and systemic treatment. These findings suggest potential for a combined approach of MDT and systemic therapy in oligometastatic prostate cancer (omPC).