Efficacy and safety of metastasis-directed therapy for oligometastatic cancer: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Metastasis-directed therapy (MDT) is a promising therapeutic strategy in oligometastatic cancer, but its safety and efficacy remains uncertain. This systematic review and meta-analysis aims to evaluate the efficacy and safety of MDT interventions in randomized controlled trials (RCT) of oligometastatic cancer. METHODS: This study was prospectively registered in PROSPERO (CRD420251075947). A literature search of MEDLINE, Embase, and Cochrane CENTRAL was conducted from inception to June 9, 2025. Eligible RCTs compared MDT interventions with standard of care in patients with oligometastatic cancer (≤5 lesions). Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and adverse event (AE) rates were pooled using random-effects meta-analysis. RESULTS: Thirty seven records representing 3,500 participants were included. Subgroup analyses showed upfront MDT improved both PFS (HR = 0.45, 95% CI 0.32-0.64) and OS (HR = 0.49, 95% CI 0.38-0.64), while consolidation MDT improved PFS only (HR = 0.56, 95% CI 0.40-0.78). In de novo oligometastatic disease, MDT improved PFS (HR = 0.50, 95% CI 0.32-0.78) but not OS, while recurrent oligometastatic disease benefited in both PFS (HR = 0.57, 95% CI 0.42-0.78) and OS (HR = 0.70, 95% CI 0.52-0.93). MDT was associated with an increased odds of Grade ≥ 2 adverse events (OR = 1.77, 95% CI [1.30-2.41]). CONCLUSION: The addition of MDT to standard of care improves OS and PFS in oligometastatic cancer patients, with a moderate increase in adverse events. MDT is a valuable component of multimodal therapy for oligometastatic disease, warranting further study of optimal timing, patient selection, and long-term outcomes.