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

Objective 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. Methods 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. Results 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. Conclusions 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.