Timing of Surgery after Neoadjuvant Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer

Abstract

Introduction: A subset of patients with potentially resectable clinical stage IIIA NSCLC are managed with trimodality therapy. However, little data exist to guide the timing of surgery after neoadjuvant therapy. This study examined whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical resection affects overall survival.

Methods: Patients with clinical stage IIIA disease (T1-3 N2) NSCLC who underwent NCRT were identified in the National Cancer Data Base (NCDB) between 2004 and 2012 and categorized on the basis of the interval between chemoradiation and surgery (0 to ≤3, >3 to ≤6, >6 to ≤9, and >9 to ≤12 weeks). Other clinical stages were excluded. The Kaplan-Meier method and log-rank tests were used to compare overall survival rates, and a bootstrapped Cox proportional hazards model was used to determine significant contributors to overall survival.

Results: Of the 1623 patients identified, 7.9% underwent an operation 0 to 3 weeks or less after NCRT, 50.5% underwent an operation greater than 3 and less than or equal to 6 weeks after NCRT, 31.9% underwent an operation greater than 6 and less than or equal to 9 weeks after NCRT, and 9.6% underwent an operation greater than 9 and less than or equal to 12 weeks after NCRT. Multivariate survival analysis demonstrated no significant difference in survival in those who underwent an operation within 6 weeks of NCRT. However, significant drops in overall survival were observed in those who had an operation greater than 6 and less than or equal to 9 weeks after NCRT (hazard ratio = 1.33, 95% confidence interval: 1.01-1.76, p = 0.043) and greater than 9 and less than or equal to 12 weeks after NCRT (hazard ratio = 1.44, 95% confidence interval: 1.04-2.01, p = 0.030).

Conclusions: The findings from this retrospective study suggest that overall survival may be significantly lower in patients with clinical stage IIIA N2 NSCLC who undergo an operation later than 6 weeks after NCRT. These results discourage unnecessary delays in surgery.

Keywords: Chemotherapy; NSCLC; Radiation therapy; Surgery; Survival; Trimodality therapy.