Survival of Squamous Cell Carcinoma Versus Adenocarcinoma in Resected Stage I-III Non-small Cell Lung Cancer

Squamous cell carcinoma (SCC) has historically been associated with worse outcomes than adenocarcinoma (AD) in non-small cell lung cancer (NSCLC). However, the prognostic significance of histology in resectable disease remains incompletely defined and warrants re-evaluation in large contemporary cohorts.

The National Cancer Database was queried for adults with resected stage I-III NSCLC diagnosed between 2004 and 2021. Histology was limited to AD and SCC using ICD-O-3 codes. Patients with in situ or occult disease, multiple primaries, death within 30 days of surgery, missing survival data, tumor size or pathologic stage, and ablative procedures were excluded. The primary outcome was 10-year overall survival. Adjusted Cox proportional hazards models were used to evaluate the association between histology and survival in the overall cohort and within pathologic stages I-III, with histology × stage interaction testing.

Among 130,731 patients, 92,598 (71%) had AD and 38,133 (29%) had SCC. Kaplan-Meier analysis demonstrated worse 10-year survival for SCC compared with AD (log-rank p < 0.001). On multivariable analysis, SCC remained associated with worse 10-year survival (aHR 1.14, 95% CI 1.12-1.17; p < 0.001). Stage-stratified models showed worse survival for SCC in stage I disease (aHR 1.24, 95% CI 1.21-1.28, p < 0.001) but not in stage II or III disease. Histology × stage interaction terms confirmed significant effect modification by stage (p < 0.001).

In resected stage I-III NSCLC, SCC remains associated with worse 10-year survival. SCC remained independently associated with worse survival in stage I disease, whereas this association was substantially attenuated in stage II and III disease.