Comparative effectiveness for early-stage NSCLC without lymph node involvement based on prospective studies.

Background: There is ongoing uncertainty in comparing surgical and nonsurgical therapies, with or without systemic options, in heterogeneous early-stage non-small cell lung cancer without lymph node involvement (eNSCLC-N0).

Materials and methods: We conducted an integrated evidence synthesis of prospective randomized controlled trials (RCTs) and non-RCTs, covering four databases through 1 September 2024. Treatment effects were evaluated using single-arm, pair-wise, and Bayesian random-effects network meta-analyses. Primary outcomes were overall survival (OS) and disease-free survival (DFS); secondary outcomes included recurrence and grade ≥3 adverse events.

Results: This report included 31 clinical trials (24 RCTs) with 12,049 patients. In the network-analyses, adjuvant targeted therapy (ATKI) (rank 1) significantly improved DFS compared with mixed radical resection (RR) (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.05-0.90; rank 14; GRADE, very low) in the overall population. For patients with wild-type/unknown EGFR status, stereotactic body radiation therapy (SBRT) plus immune checkpoint inhibitors (I-SBRT) (rank 1) showed DFS benefit over SBRT alone (HR, 0.17; 95% CI, 0.03-0.83; rank 3; GRADE, high) and was non-inferior to adjuvant platinum-based chemotherapy (HR, 0.18; 95% CI, 0.02-1.65; rank 2; GRADE, very low).

Conclusion: These findings suggest the combination of systemic therapies, such as surgery plus ATKI or SBRT plus immunotherapy, superior approaches for patients with eNSCLC-N0 depending on the genomic mutation status and patient tolerability.