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

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.