Abstract
BACKGROUND: This study evaluated spatial-temporal recurrence patterns after curative resection for non-small cell lung cancer (NSCLC) to clarify and recommend appropriate post-operative surveillance. METHODS: A total of 2,486 consecutive patients between January 2005 and December 2012 with NSCLC (stage I-IIIA) who underwent definitive surgical resection were retrospectively analyzed. We used a hazard rate curve to evaluate event dynamics. Disease-free survival (DFS) was evaluated by the Kaplan-Meier method. Univariate and multivariate analyses with Cox proportional hazards regression identified risk factors that predicted DFS. RESULTS: The median follow-up was 50.1 months. Recurrences were diagnosed in 852 (34.3%) patients. Four hundred eighty-nine events first occurred in the chest, 177 in the brain, 117 in the bone, and 71 in the abdomen. Of all recurrences, 78.5% occurred in the first 3 years. Univariate and multivariate analyses identified the age at diagnosis (P<0.001), histology (P=0.023), tumor size (P<0.001), pathologic N stage (P<0.001), and grade (P=0.043) as independent risk factors for intra-thoracic recurrences. Histology (P<0.001), tumor size (P<0.001), surgical method (P=0.021), pathologic N stage (P<0.001), and grade (P=0.005) were independent to predict extra-thoracic recurrences. The hazard rate curve displayed an initial surge of time to any treatment failure during 12 months after surgery. Based on sub-group analysis, both intra- and extra-recurrences increased with stage and brain recurrences in stage IIIA occurred earlier than stage II. Hazard rate curve of brain recurrences in squamous cell carcinoma showed a moderate peak during 9-15 months. Hazard rate curves of brain and bone recurrences in adenocarcinoma displayed clear peaks at 9-27 and 15-30 months, respectively. CONCLUSIONS: Intra- and extra-thoracic recurrences correlate with different clinicopathological factors. Brain MRI and bone ECT were recommended for selected patients in particular time to early detect extra-thoracic recurrences.