Recurrence Dynamics for Non–Small-Cell Lung Cancer: Effect of Surgery on the Development of Metastases

Abstract

We study event rates over time (event dynamics) in patients undergoing surgery for early-stage non-small-cell lung cancer (NSCLC). Using a database of patients undergoing initial surgery for NSCLC, the event dynamics, based on the hazard rate, were evaluated. Events evaluated included time to any treatment failure, local recurrence, distant metastasis (DM), and development of a second primary lung cancer. Among 1506 patients, time to any treatment failure dynamics demonstrated an initial surge in the hazard rate 9 months after surgery, followed by two smaller peaks at the end of the second and fourth years, respectively. This pattern was dominated by DM events. Two distinguishable peaks were noted for local recurrence in the first and second years. In contrast, the hazard rate for second primary lung cancer exhibited a more uniform pattern over time. The DM dynamics was analyzed by sex and three peaks emerged for both sexes. The timing of the first peak was similar for both sexes, at 7 to 9 months after surgery. The second peak occurred earlier in men (18-20 months) than women (24-26 months). For both sexes the third peak appeared during the fourth year. Recurrence dynamics of resected early-stage NSCLC displays a multipeak pattern, which supports the hypothesis of a metastasis growth model previously described for early-stage breast cancer. The model assumes both cellular and micrometastatic tumor dormancy and a transient phase of acceleration of metastatic growth following surgical excision of the primary tumor.