Reassessing perioperative risks: impact of neoadjuvant therapy on mortality in pneumonectomy

The INT0139 trial [2009] raised concerns about the safety of pneumonectomy after chemoradiation due to high perioperative mortality rates. Recent clinical trials have supported the use of neoadjuvant treatment as a viable option for stage Ib or greater lung cancer. We hypothesized that neoadjuvant treatment does not increase perioperative mortality risk in patients undergoing pneumonectomy.

Adult patients with nonmetastatic non-small cell lung cancer (NSCLC) from the 2004-2021 National Cancer Database undergoing pneumonectomy were analyzed in a retrospective cohort study. Exclusions included missing study variables, non-adenocarcinoma/squamous histology and pneumonectomy after neoadjuvant radiation alone. Multivariate logistic regression analyzed 30- and 90-day mortality and included laterality and neoadjuvant treatment interactions.

Of 14,522 patients, 58.6% underwent right pneumonectomy and 41.4% underwent left pneumonectomy. Neoadjuvant treatment was received by 14.9% (systemic therapy alone: 1,008; systemic therapy + radiation: 1,156). The 90-day mortality was higher for right versus left pneumonectomy (17.2% vs. 9.8%, P<0.001). Neoadjuvant therapy was not associated with higher 90-day mortality compared to surgery alone (10.4% vs. 13%, P=0.04). Independent predictors of mortality included right-sided pneumonectomy [odds ratio (OR) =2.01, 95% confidence interval (CI): 1.78-2.28], advanced age (OR =1.05, 95% CI: 1.04-1.06), and Charlson-Deyo index ≥ 3 (OR =1.98, 95% CI: 1.53-2.57). Interaction analysis showed no increased risk with neoadjuvant therapy for either side.

This analysis reiterates known elevated risk associated with right pneumonectomy but disputes the dogma that neoadjuvant treatment increases the risk of pneumonectomy, suggesting that neoadjuvant treatment is not a contraindication to receipt of pneumonectomy.