Associations of Aspirin and Non-Aspirin Non-Steroidal Anti-Inflammatory Drugs With Colorectal Cancer Mortality After Diagnosis

Abstract

Background: Aspirin use reduces colorectal cancer (CRC) incidence, but there is limited evidence regarding associations of aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) with CRC-specific survival.

Methods: This prospective analysis includes women and men from the Cancer Prevention Study-II Nutrition Cohort who were cancer free at baseline (1992 or 1993) and diagnosed with CRC during incidence follow-up through 2015. Detailed information on aspirin and non-aspirin NSAID use was self-reported on questionnaires at baseline, in 1997, and every 2 years thereafter. Pre- and postdiagnosis data were available for 2686 and 1931 participants without distant metastases, respectively, among whom 512 and 251 died from CRC during mortality follow-up through 2016. Secondary analyses examined associations between prediagnosis aspirin use and stage at diagnosis (distant metastatic vs localized or regional). All statistical tests were 2-sided.

Results: Long-term regular use of aspirin (>15 times per month) before diagnosis was associated with lower CRC-specific mortality (multivariable-adjusted hazard ratio [HR] = 0.69, 95% confidence interval [CI] = 0.52 to 0.92). Postdiagnosis regular aspirin use was not statistically significantly associated with risk of CRC-specific mortality overall (HR = 0.82, 95% CI = 0.62 to 1.09), although participants who began regular aspirin use only after their diagnosis were at lower risk than participants who did not use aspirin at both the pre- and postdiagnosis periods (HR = 0.60, 95% CI = 0.36 to 0.98). Long-term aspirin use before diagnosis was also associated with lower odds of diagnosis with distant metastases (multivariable-adjusted odds ratio = 0.73, 95% CI = 0.53 to 0.99).

Conclusions: Our results suggest that long-term aspirin use before a diagnosis of nonmetastatic colorectal cancer may be associated with lower CRC-specific mortality after diagnosis, consistent with possible inhibition of micrometastases before diagnosis.

© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Figures

Figure 1.

Forest plots depicting potential effect modifiers of the association between aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) use pre- (A, C, respectively) and postdiagnosis (B, D, respectively) and colorectal cancer–specific mortality. The diamonds represent hazard ratios, and the error bars represent 95% confidence intervals (CIs). P values were 2-sided and were calculated via multiplicative interaction terms and the likelihood ratio test. CVD = cardiovascular disease; RR = relative risk; SEER = Surveillance, Epidemiology, and End Results.