Recurrence and Emergence of New Primary Tumors in Patients with Resected Pathological Stage 1A Non-Small Cell Lung Cancer

Background Lung cancer screening has made early-stage non-small-cell lung cancer (NSCLC) more common and highly curable. However, evidence on post-treatment surveillance, new radiological findings, and distinguishing recurrence from new primary cancers remains limited. Our study aimed to assess outcomes in patients with post-surgical diagnosis of pathologic stage 0/1A first primary NSCLC, including overall survival, classification of new findings as second primaries or recurrence based on current algorithms, and propose potential improvements to these criteria. Methods We analyzed 653 patients with pathologic stage 0/1A NSCLC from the IELCART cohort (2016-2023). Radiological findings were reviewed to classify lung cancer diagnoses as second primaries or recurrences using a five-step approach based on histopathology, genetics, timing, and multidisciplinary discussions. Survival was analyzed with Kaplan-Meier curves and log-rank tests. Findings Among 653 patients (61.1% women, median age 69), 74 (11.3%) later had radiological findings confirmed as lung cancer, more frequent in men (15.7% vs. 8.5%), those with higher pack-years, and COPD. Malignancies were most common in current smokers (19.1%), followed by former (15.2%) and never smokers (1.6%) (p<.0001). Of these, 30 (5%) were second primaries, and 44 (7%) were recurrences. Non-solid cancers showed no recurrences. Recurrences peaked at 12-18 months, while second primaries occurred steadily at 0.6% annually. Overall survival differed significantly between patients groups (p < 0.0001), with overall survival of 58.2% with recurrences, 77.9% with new primaries, and 94.3% with no new cancer after a median follow-up of 3.5 years. Interpretation Among 653 patients, 7% had recurrences, while new primaries (5%) became more frequent after three years, occurring steadily at 0.6% per year, with distinct survival outcomes. New malignant events were more common in men, smokers, and those with COPD. Notably, all malignancies in non-solid cancers were new primaries. These findings emphasize the need for tailored surveillance strategies.