Clinical stage II non-small cell lung cancer: can we "just give adjuvant therapy"?

Advances in multimodal therapy have reshaped treatment paradigms for clinical stage II (cII) non-small cell lung cancer (NSCLC), yet optimal treatment sequencing remains controversial. We sought to investigate predictors of adjuvant uptake, accuracy of clinical staging, and oncologic outcomes in patients undergoing upfront surgical resection.

The retrospective analysis was completed of the National Cancer Database (NCDB) for patients with cII disease from 2015 to 2019 who underwent surgical resection. Patients were stratified by receipt of adjuvant therapy (AT). Rates of uptake, pathologic staging, and survival outcomes were analyzed. Cox regression and Kaplan-Meier curves were used to evaluate overall survival (OS) in propensity-score matched cohorts.

A total of 17,674 patients with cII NSCLC underwent surgical resection between 2015 and 2019, with 728 (4.1%) receiving neoadjuvant therapy, while the remainder (n=16,946, 95.9%) underwent upfront surgery. Of those undergoing upfront surgical resection, 8,620 (50.9%) were treated with AT and pathologic upstaging occurred in 23.3% (n=3,941) of the cohort. In patients that were pathologic stage II-IV, only 58.4% (n=8,240/14,116) received AT (P<0.001). Factors associated with lower uptake included older age, more comorbidities, and public insurance. In propensity-score matched cohorts, receipt of AT improved 5-year OS (62.2% vs. 52.2%, log-rank P value <0.001).

Despite over 80% of cII patients meeting indications for adjuvant treatment consideration, less than 60% of eligible patients receive it. Failure is associated with worse survival, particularly in upstaged patients; thus, processes should be put in place to help ensure return to intended oncologic therapy or implement practice patterns incorporating neoadjuvant protocols.