Metastasis Dynamics for Non-Small-Cell Lung Cancer: Effect of Patient and Tumor-Related Factors

Event dynamics were evaluated in 1506 patients undergoing initial surgery for non-small-cell lung cancer. The hazard rate for distant metastases displayed a multipeak pattern with sex-dependent peak timing. Other patient and tumor characteristics did not modify peak position, whereas a factor-specific modulation of peak heights was also observed. The multipeak distant metastases dynamics may be an intrinsic feature of metastatic progression in non-small-cell lung cancer. Background: We studied event dynamics (probability of an event occurring over a specific time interval) in patients undergoing surgery for early-stage non-small-cell lung cancer (NSCLC) according to patient and tumor characteristics. Methods: By using a database of 1506 patients who underwent initial surgery for NSCLC, event dynamics, based on a time-specific hazard rate, were evaluated. The event of interest was the development of distant metastases, with or without a local recurrence. The effect of sex, tumor size, nodal involvement, histology, lymphovascular space invasion, pleural invasion, age, and race were studied. Results: The hazard rate for developing distant metastases was not constant over time but was characterized by specific peaks, the first being approximately 9 months after surgery and the second at 18 to 20 months for men and 24 to 26 months for women. For women, the hazard rate peaked considerably in the first year. For men, the hazard rate peaks were smaller but lasted for a longer duration. Pathologic factors associated with a higher risk of recurrence (eg, size, lymph node involvement, pleural invasion) all increased the sex-specific hazard rates. Conclusions: The probability of developing distant metastases after surgery for NSCLC peaks at specific and consistent time intervals after surgery, with specific differences between men and women. A factor-specific modulation of peak heights that ranged from no impact (eg, race) to relevant effects for primary tumor size, nodal involvement, and pleural invasion, possibly related to sex, was also observed. The bimodal distant metastases dynamics may be an intrinsic feature of metastatic progression in NSCLC. (C) 2013 Elsevier Inc. All rights reserved.