Impact of locoregional recurrence versus distant metastasis on overall survival in patients with Non-Small cell lung cancer after Surgery: A secondary analysis of PORT-C RCT.

Purpose: The therapeutic advantage of postoperative radiation therapy (PORT) for non-small cell lung cancer (NSCLC) has not been shown to benefit overall survival (OS) according to two randomized controlled trials (RCTs), albeit an enhancement in locoregional-free survival was observed. We aimed to evaluate the relative influence of locoregional recurrence (LR) and distant metastasis (DM) on OS for patients with NSCLC after surgery.

Methods: This was a secondary analysis of PORT-C RCT. Patients with pN2 NSCLC undergoing complete resection followed by chemotherapy were included. A dynamic prediction model was developed to evaluate the impact of LR and DM on OS. The endpoint was OS. Age, sex, smoking history, histology, Karnofsky Performance Status, tumor side, T stage, and positive lymph node were baseline factors, whereas LR and DM status were time-dependent covariates.

Results: In total, 364 patients were eligible, including 214 and 150 in the non-PORT and PORT groups, respectively. DM significantly decreased OS in both the non-PORT (odds ratio [OR], 4.74; 95 % CI, 2.70-8.30; P < 0.01) and PORT (OR, 5.43; 95 % CI, 2.56-11.48; P < 0.01) groups. LR also significantly impacted OS in the non-PORT (OR, 2.09; 95 % CI, 1.12-3.93; P = 0.02) and the PORT (OR, 3.44; 95 % CI, 1.53-7.75; P < 0.01) groups. Multivariate Cox analysis identified the pT stage, positive lymph nodes, and histology as variables correlated with DM. A nomogram was developed to estimate the risk of DM. PORT did not significantly enhance OS in either the low (HR, 1.42; 95 % CI, 0.63-3.19, P = 0.40) or high-risk (HR, 0.62; 95 % CI, 0.35-1.09, P = 0.10) subgroup but in the medium-risk subgroup (HR, 0.20; 95 % CI, 0.05-0.86, P = 0.02).

Conclusion: DM and LR significantly impacted OS in patients with NSCLC after surgery. DM emerged as the dominant failure pattern, emphasizing more effective control of DM. PORT was beneficial for patients with a medium risk of DM.