Aspirin Use and Survival After Diagnosis of Colorectal Cancer

Abstract

Randomized, placebo-controlled trials have shown that aspirin and other nonsteroidal anti-inflammatory agents significantly reduce the risk of adenomas and can prevent colorectal neoplasia. It is unclear, however, whether use of aspirin can improve the prognosis for patients with established colorectal cancer. The aim of this prospective cohort study was to investigate the effect of regular aspirin use on the colorectal cancer-specific and overall survival of patients with established colorectal cancer. The participants were 1279 health professionals with a diagnosis of stage I, II, or III colorectal adenocarcinoma who were enrolled in 2 nationwide cohorts, the Nurses' Health Study and the Health Professionals Follow-up Study. Data on aspirin use before and after diagnosis of colorectal adenocarcinoma and other information, including new cancers, was obtained from biennial questionnaires. The participants were followed from 1980 and 1986 before diagnosis until 2008. For participants alive at the end of the study, the median follow-up period from time of diagnosis was 11.8 years. The primary outcome measures were colorectal cancer-specific and overall mortality. Among the 549 participants who regularly used aspirin after colorectal cancer diagnosis, 193 total deaths (35%) and 81 colorectal cancer-specific deaths (15%) occurred. In comparison, there were 287(39%) total and 141(19%) colorectal cancer-specific deaths among the 730 participants who did not use aspirin. Multivariate analysis showed that compared to nonusers, participants who regularly used aspirin after diagnosis had a hazard ratio (HR) for colorectal cancer-specific mortality of 0.71 (95% confidence interval [CI], 0.53-0.95) and for overall mortality of 0.79 (95% CI, 0.65-0.97). Initiation of aspirin administration after diagnosis among 719 participants who did not use aspirin before diagnosis was associated with a multivariate HR for colorectal cancer-specific mortality of 0.53 (95% CI, 0.33-0.86). Immunological assessment showed that the benefit of aspirin use among participants with colorectal cancers after diagnosis appeared to be confined in tumor tissue to cyclooxygenase 2 (COX-2)-positive primary tumors. Compared to nonusers, the risk of colorectal cancer-specific mortality in patients taking regular aspirin after diagnosis was lower in primary tumors overexpressing COX-2 (multivariate HR, 0.39; 95% CI, 0.20-0.76). In contrast, there was no lower risk associated with use of aspirin after diagnosis among those with primary tumors having weak or absent COX-2 expression (multivariate HR, 1.22; 95% CI, 0.36-4.18). These findings show that use of aspirin after diagnosis of colorectal cancer is associated with improved survival from the disease, especially among patients with primary tumors that overexpress COX-2.