Prognosis and recurrence patterns in patients with early stage lung cancer: a multi-state model approach

Background: We aimed to assess whether recurrence patterns affect survival and to use a multi-state model to predict the prognosis of early stage non-small cell lung cancer in patients who underwent surgical resection. Methods: Patients with early stage non-small cell lung cancer who underwent surgical resection at two tertiary medical centers between 2010 and 2015 were retrospectively analyzed. A multi-state model was employed with one initial state (surgery), two intermediate states (locoregional recurrence, distant metastasis), and one absorbing state (death), comprising five transitions: surgery to locoregional recurrence, surgery to distant metastasis, surgery to death without recurrence, locoregional recurrence to death, and distant metastasis to death. Cox proportional hazards models stratified for these transitions were performed with the risk factors; transition probabilities for each patient were predicted. Results: A total of 949 patients were identified [median age: 67 years, male: 614 (64.6%)]. Recurrence occurred in 194 (20.4%) patients (locoregional recurrence: 7.3%, distant metastasis: 13.1%). Hazard ratios for distant metastasis after surgery were higher for older age (hazard ratio: 1.03, 95% confidence interval: 1.01–1.06) and adenocarcinoma (hazard ratio: 1.67, 95% confidence interval: 1.06–2.61). Lower lobe location exhibited a higher hazard ratio for death after surgery without recurrence (hazard ratio: 1.59, 95% confidence interval: 1.00–2.53). Stage IIB lung cancer showed a higher probability of transition to distant metastasis after surgery than other stages. Cumulative transition hazards rapidly increased in both recurrence patterns until approximately two years after surgery (locoregional recurrence: 0.052; distant metastasis: 0.104). Patients with distant metastasis were more likely to die within 5 years of surgery than those with locoregional recurrence (6.8% and 2.6%, respectively). Conclusions: With the multi-state model, risk factors and post-relapse survival probabilities differed between locoregional recurrence and distant metastasis. These findings may enable clinicians to establish personalized follow-up strategies for patients undergoing curative resection for early stage non-small cell lung cancer.