Progression-directed ablative radiotherapy improves event-free survival in oligoprogressive NSCLC

Introduction: To assess the efficacy of progression-directed radiation therapy (PDRT) in patients with oligoprogressive non-small cell lung cancer (NSCLC), with particular focus on disease progression and changes in systemic therapy. Materials and methods: From January 2020 to October 2025, a retrospective single-center analysis was conducted at our Institution, including NSCLC patients treated with PDRT for oligoprogressive disease. Oligoprogression was defined as progression involving fewer than five extracranial lesions or a total intracranial disease volume of ≤14 cc, following an initial response to systemic treatment. The primary endpoint was event-free survival (EFS), defined as the occurrence of any of the following: change in systemic therapy, progression within 6 months, or development of >3 progressive lesions. Multivariate Cox regression models were applied to identify predictors of oncological outcomes. Results: Eighty-seven patients were included, with a median age of 68 years (range: 43-87) and a median follow-up of 14 months. Adenocarcinoma was the predominant histology (75 cases, 86.2%), followed by squamous cell carcinoma (12 cases, 13.8%). PDRT was administered after first-line systemic therapy in 61 patients (70.1%). At the last assessment, 12 (13.8%) patients achieved a complete response, 29 (33.3%) a partial response, and 46 (52.9%) stable disease. The median time to event, death or last follow-up was 5 months (range: 1-48), with a one-year actuarial EFS rate of 52.1% (95% CI: 46.4-57.8%). Median time to next treatment (TTNT) was 8 months (range: 1-68), while median progression-free survival was 5 months (range: 1-39). On multivariate analysis, both PDRT directed at the primary tumor (HR = 0.28, 95% CI: 0.12-0.66; p < 0.01) and achieving a complete response prior to oligoprogression (HR = 0.31, 95% CI: 0.10-0.95; p = 0.04) were significantly associated with improved EFS. Conversely, chemotherapy use (HR = 2.33, 95% CI: 1.21-4.48; p = 0.02) and larger CTV volumes (HR = 1.01, 95% CI: 1.0004-1.0111; p = 0.03) were associated with worse outcomes. Conclusions: PDRT achieved a median EFS of 5 months and extended the median time to next systemic therapy to 8 months. These findings suggest that PDRT may represent an effective approach to maintaining disease control and postponing systemic treatment in oligoprogressive NSCLC. Larger, prospective studies with extended follow-up are warranted to confirm these results.