Survival impact of postoperative therapy modalities according to margin status in non-small cell lung cancer patients in the United States

Unlike complete (R0) resection guidelines, current National Comprehensive Cancer Network (NCCN) adjuvant therapy guidelines after incomplete (R1/R2) resection of non-small cell lung cancer (NSCLC) are based on low-level evidence. We attempted to validate them.Patients with pathologic stage I-IIIA NSCLC from 2004 to 2011 in the National Cancer Database were stratified by margin status, NCCN-specified stage groupings, and adjuvant therapy exposure (none, radiotherapy, chemotherapy, or both). Five-year overall survival (OS) and hazard ratios, adjusted for patient and institutional characteristics, were compared. We used a parallel analysis of R0 resections to validate our methodology.We analyzed 3461 R1/R2, and 78,979 R0 resections. After R0 resection, the NCCN-recommended option was associated with the best survival across all stage groups, supporting our analytic approach. Patients with R1/R2 stage IA treated with radiation had a 26% OS, compared with 58% with no treatment (P = .003). In patients with stage IB/IIA(N0) R1/R2, radiation was associated with a 25% OS compared with 47% with no treatment (P = .025) and 62% with chemotherapy (P .007). Chemoradiation was not associated with a survival benefit in either group. Patients with IIA(N1)/IIB and IIIA had better survival with chemotherapy or chemoradiation. No group had a survival benefit with radiation alone.NCCN adjuvant therapy guidelines after complete resection, based on high-level evidence, are validated, but not guidelines for patients with incompletely resected early-stage NSCLC, which are based on low-level evidence. Monomodality postoperative radiotherapy was not validated for any stage. Specific studies are needed to determine optimal management after incomplete resection.