Lung cancer remains the leading cause of cancer death worldwide and the search for modifiable risk factors to improve survival is ongoing. There is a growing appreciation for a biological relationship between opioids and lung cancer progression. Our goal is to evaluate the association between perioperative opioid use and long-term survival after lung cancer resection.

Retrospective analysis of 2006-2012 SEER-Medicare datasets identified all patients undergoing pulmonary resection for non-small cell lung cancer (NSCLC) stages I-III. Patients were stratified by only filling opioid prescriptions 30 days pre or postoperatively (Standard Group), filling opioid prescriptions >30 days preoperatively (Chronic Group), or filling opioid prescriptions >90 days postoperatively but not preoperatively (Prolonged Group). Kaplan-Meier survival analysis compared each group and risk-adjusted survival analysis was performed using Cox Proportional Hazards model.

A total of 3,273 patients were identified including 1,385 in the Standard Group (42.3%), 1,441 in the Chronic Group (44.0%), and 447 in the Prolonged Group (13.7%). Of previously opioid-naïve patients, 24.4% (447/1832) became new prolonged opioid users. Kaplan-Meier survival analysis illustrates lower overall and disease specific survival in Chronic and Prolonged opioid groups (both p<0.0001). After risk-adjustment, Chronic (HR 1.27, 95% CI 1.09-1.47, p<0.01) and Prolonged (HR 1.42, 95% CI 1.17-1.73, p<0.01) opioid use were independently associated with reduced long-term survival.

Chronic and prolonged opioid use were independently associated with reduced long-term, disease specific survival following lung cancer resection. These findings provide epidemiologic support for a biological relationship between opioid use and lung cancer progression.