Impact of prior malignancy on non-small cell lung cancer presentation, management, and survival

As survival after an initial cancer diagnosis improves, an increasing number of patients are diagnosed with lung cancer after a prior malignancy. These patients represent a clinically distinct population, yet population-level data describing lung cancer presentation, treatment patterns, and outcomes in this group remain limited.

We performed a retrospective cohort study using the National Cancer Database (NCDB), including adults diagnosed with non-small cell lung cancer (NSCLC) between 2010 and 2021. Patients whose lung cancer represented their first malignancy were compared with those diagnosed with lung cancer after a prior malignancy of any type. Outcomes of interest included tumor size and stage at diagnosis, treatment strategy, and overall survival (OS).

Among 1,304,953 patients with NSCLC, 266,458 (20.4%) had a history of prior malignancy. Compared with patients with first-primary NSCLC, those with prior malignancy were older at diagnosis and more frequently presented with smaller tumors (≤3 cm: 57.2% vs. 43.8%) and earlier-stage disease (stage 0-I: 42.2% vs. 27.7%; all P<0.001). Among surgically treated patients, sublobar resection was more common in patients with prior malignancy (30.5% vs. 20.4%), including for tumors ≤2 cm (43.3% vs. 31.6%). Despite earlier stage at presentation, prior malignancy was independently associated with worse OS on adjusted analysis [adjusted hazard ratio (HR) 1.07, 95% confidence interval (CI): 1.06-1.08].

Patients diagnosed with lung cancer after a prior malignancy present with earlier-stage disease and are more frequently managed with parenchyma-sparing surgical approaches, yet experience worse adjusted OS. These findings highlight meaningful differences in presentation and management in a growing population of cancer survivors.