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. Simran, MD, MBBS - Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario
Simran1,2, S. Panda3, K. Shin4, K. Olabode5,6, L. Martinka5,6, S. Puri7, J. Gray7, A. N. Saltos7, T. Tanvetyanon7, S. A. Rosenberg6, T. J. Dilling6, S. K. Jabbour8, and J. Kim9,10; 1Department of Radiation Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, India, 2Moffitt Cancer Center, Tampa, FL, 3All India Institute of Medical Sciences(AIIMS), Raipur, Raipur, India, 4Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Morsani College of Medicine, University of South Florida, Tampa, FL, 6Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 7Department of Thoracic Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, 8Department of Radiation Oncology, Rutgers Cancer Institute, New Brunswick, NJ, 9Department of Radiation Oncology, Moffitt Cancer Center, Tampa, FL, 10Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL
Purpose/Objective(s):
Oligometastatic non–small cell lung cancer (NSCLC) represents a potentially curable intermediate state. Although phase II trials suggest improved survival with metastasis-directed therapy (MDT) after systemic therapy, the magnitude of benefit across treatment eras remains uncertain. We conducted a systematic review and meta-analysis to evaluate survival outcomes associated with MDT in oligometastatic NSCLC.
Materials/Methods:
PubMed/MEDLINE, Embase, Cochrane CENTRAL, and Web of Science were searched from inception to January 2026. Eligible studies included adults with histologically confirmed oligometastatic NSCLC, defined as =5 metastases in =3 organs (including residual disease after systemic therapy). Treated and controlled brain metastases were permitted. Randomized phase II and comparative cohort studies evaluating radiotherapy-based MDT, with limited surgical contribution, after first-line systemic therapy were included. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were pooled using a random-effects model; heterogeneity was assessed using I².
Results:
Thirteen studies (3 randomized, 10 comparative) comprising 3,929 patients met inclusion criteria; 823 (21.0%) received MDT. Among studies reporting metastatic burden, 2,814 patients (71.6%) had 1–3 metastatic lesions. Brain metastases were permitted in 11 of 13 studies. Median age was 60.5 years ( range, 59–63); 46.2% of studies included ECOG 0–2 patients, and 84.6% involved predominantly non-squamous histology. The pooled median follow-up was 22.5 months (9.6–52.3). Radiotherapy was the principal modality, delivered in 684 patients (83.1%). Surgery was performed in 96 patients (11.7%), including 41 (5.0%) who received combined radiotherapy and surgery. Among radiotherapy techniques, SBRT/SABR was used in 402 patients (48.8%), SRS in 87 (10.6%), WBRT in 54 (6.6%), and conventional fractionated radiotherapy in 141 (17.1%), with SBRT/SRS typically delivered in 1–5 fractions (21–37.5 Gy or up to 50 Gy in 4 fractions) and conventional regimens ranging from 30–40 Gy (10–20 fractions) to 60–70 Gy (30–34 fractions). Non-surgical ablative techniques were used in 43 patients (5.2%), most commonly microwave ablation (n=29) and cryoablation (n=13). MDT significantly improved OS (HR 0.39, 95% CI 0.22–0.68; I²=85.3%) and PFS (HR 0.41, 95% CI 0.29–0.58; I²=69.7%). Meta-regression showed no significant interaction by study design, sample size, or inclusion of brain metastases.
Conclusion:
MDT after systemic therapy improves OS and PFS in selected oligometastatic NSCLC (=5 metastases in =3 organs), including patients with controlled brain metastases. These findings reinforce the role of MDT as an integral component of multidisciplinary management in carefully selected patients and underscore the need for adequately powered phase III trials to define optimal patient selection, timing, and treatment sequencing in the modern systemic therapy era.
