Abstract
PURPOSE: In patients with oligometastatic disease (OMD), local therapy to metastatic sites has gained acceptance despite uncertainty regarding its long-term benefits or whether some subgroups would benefit more than others. Here, we report a meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of adding stereotactic radiation to metastases versus the standard of care (SOC) in treating OMD. METHODS AND MATERIALS: A meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were identified from Medline and Embase databases from inception to July 16, 2024. The inclusion criteria comprised RCTs involving adults with oligometastatic solid tumors receiving metastasis-directed therapy (MDT) compared to SOC alone. OMD was divided into 4 groups according to the time of intervention: upfront therapy, consolidation therapy, unselected and oligoprogression. The primary outcomes were progression-free survival (PFS), overall survival (OS), time to new lesion (TNL), and treatment toxicity. Hazard ratios (HR) for PFS, OS, and TNL were extracted. Odd ratios (ORs) were calculated for adverse events grade 3 or higher. Data were analyzed using random effects models, with statistical significance set at P < .05. RESULTS: Fifteen RCTs comprising 1414 patients were included. MDT significantly improved PFS [HR: 0.48, 95% confidence interval (CI), 0.42-0.54, P < .01] and OS (HR, 0.60; 95% CI, 0.49-0.75; P < .001) compared to SOC. Subgroup analysis revealed a consistent benefit in nonmutated non small cell lung cancer (NSCLC), prostate, and epidermal growth factor receptor (EGFR)-mutated NSCLC, but not in breast cancer. The benefits of MDT were significant across all intervention points: upfront, consolidation, and unselected. No significant benefit was observed in oligoprogressive disease (HR, 0.69; P = .11). MDT did not prolong the TNL compared to SOC (HR, 0.81; 95% CI, 0.62-1.08; P = .15). MDT was associated with a higher odds of adverse events (odd ratio: 1.46, P = .03). CONCLUSIONS: MDT provides significant improvement in PFS and OS, though these effects were not observed in breast cancer or in oligoprogressive disease.