Defining Early Recurrence in Resectable Non-small Cell Lung Cancer Using Post-Recurrence Survival

This study aimed to define a data-driven threshold in NSCLC using post-recurrence survival.

Patients who underwent lung resection for stage I-IIIA NSCLC and experienced recurrence at a single institution from 2010 to 2021 were identified. Exclusion criteria included indeterminate N stage, M1 status, neoadjuvant therapy, and positive surgical margins. Time to recurrence was measured from surgery to recurrence, and post-recurrence survival from recurrence to death or last follow-up. Grid search and Kaplan-Meier analysis identified the time cut-point with the greatest survival difference, which was validated using multivariable Cox regression adjusted for age, race, tumor size, smoking history (pack-years), comorbodities, pathological N stage, histology, surgical procedure, and receipt of adjuvant therapy.

A total of 227 patients met inclusion criteria, with 50% (114/227) female and 78% (177/227) white patients. The median age was 70 years (IQR 63-76), the tumor size was 2.6 cm (IQR 1.8-4.1), and time to recurrence was 17 months (IQR 9-30). Cut-point analysis identified 12 months as the threshold most strongly associated with survival after recurrence. Median post-recurrence survival was 14 months (IQR 4-32) versus 22 months (IQR 10-40) for patients that recurred within and after 12 months, respectively (log-rank p = 0.002). On multivariable analysis, the 12-month cut-point remained associated with survival after recurrence (HR 1.49, 95% CI 1.03-2.15, p = 0.03).

Recurrence within 12 months after resection of early-stage NSCLC is associated with worse post-recurrence survival, making this cutoff a useful indicator of early recurrence.