Perioperative Use of Nonsteroidal Anti-inflammatory Drugs Decreases the Risk of Recurrence of Cancer After Colorectal Resection: A Cohort Study Based on Prospective Data

Background. Perioperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) is known to reduce inflammatory response in relation to surgery. Inflammation may promote recurrence of cancer, thus inhibition by use of NSAIDs could reduce recurrence after surgery. Objective. The aim of this study was to examine the association between perioperative use of NSAIDs and cancer recurrence, as well as disease-free survival (DFS) and mortality after colorectal cancer surgery. Methods. This was a cohort study based on data from a prospective clinical database, electronic medical records, and nationwide registers, and included patients from six major colorectal centers in Denmark. The primary outcome was cancer recurrence, while secondary outcomes included 5-year mortality and DFS. Results. Overall, 2308 patients undergoing colorectal cancer surgery between 1 January 2006 and 31 December 2009 were included. A total of 909 patients received at least 2 days of treatment with NSAIDs, of whom 702 (77.2%) received ibuprofen and 204 (22.4%) received diclofenac. Cox regression analysis adjusting for NSAIDs resulted in decreased recurrence risk (adjusted hazard ratio [HRadjusted] 0.84, 95% confidence interval [CI] 0.72-0.99; p = 0.042). Competing risk analysis confirmed the finding, with an HRadjusted of 0.76 (95% CI 0.60-0.97; p = 0.026). There was no significant effect on mortality or DFS. Sensitivity analysis of the effect of ibuprofen reported an HRadjusted of 0.83 (95% CI 0.70-1.00; p = 0.047). In restricted analyses of localized disease only (Union for International Cancer Control [UICC] I-II) and elective surgery only, no effect was found (localized: HRadjusted 0.81, 95% CI 0.62-1.06, p = 0.12; elective: HRadjusted 0.85, 95% CI 0.72-1.01, p = 0.063). Conclusions. Perioperative use of NSAIDs was associated with a reduced risk of cancer recurrence after resection for colorectal cancer. No effect on 5-year mortality or DFS was found.