NSAIDs reduce mortality in colorectal cancer

Prediagnosis regular nonsteroidal anti-inflammatory drug (NSAID) use and prolonged duration of NSAID use were independently associated with decreased overall mortality and colorectal cancer (CRC) mortality in women with a first primary invasive CRC, according to a large cohort study. In addition, the researchers found that NSAID duration (more than 5 years) reported among women with subsequent CRC diagnosis was associated with a 50% (unadjusted) and 60% (adjusted) lower risk of CRC-specific mortality.

CRC is the third most common cancer among men and women in the United States; in 2007 there were an estimated 112,000 new cases of colon cancer and 41,000 cases of rectal cancer. The current study conducted by Jason A. Zell, DO, MPH, and colleagues from University of California, sought to clarify the wide body of evidence that suggests NSAID (including aspirin and ibuprofen) use reduces the risk of CRS and that use after diagnosis enhances survival.

The researchers studied women aged 85 years or fewer who were participating in the California Teachers Study cohort; they identified 621 CRC cases. Of the 621 CRC cases, 222 (36%) died during the study period; 145 (65%) of the 222 deaths were from CRC and 15 (6.8% of all deaths) were from heart disease.

CRC patients who used NSAIDs for at least 5 years prior to diagnosis had a statistically significant decreased risk of overall mortality after adjustment for clinically relevant factors compared with those patients who did not use NSAIDs (HR, 0.55; 95% CI, 0.37-0.84). There was also a statistically significant decreased risk of CRC-specific mortality for patients reporting at least 5 years of NSAID use before diagnosis compared with patients who did not report such use (HR, 0.40; 95% CI, 0.23-0.71). There were not statistically significant associations with overall or CRC-specific mortality for patients reporting less than 5 years duration of using NSAIDs compared with those reporting no NSAID use.

There was a significant reduction in CRC-specific mortality (HR, 0.46; 95% CI, 0.23-0.94), but not overall mortality (HR, 0.65; 95% CI, 0.40-1.05) among colon cancer patients who used NSAIDs for at least 5 years before diagnosis. There were no significant differences observed for subset analysis of NSAID duration among rectal cancer patients. Aspirin-only survival effects were similar to that observed for all NSAIDs.

The researchers note that NSAIDs exert their antiproliferative effects on colonic cells by inhibiting prostaglandin synthesis through reversible binding to cyclooxygenase (COX) and through other mechanisms. They report that aspirin reduces adenomatous polyp recurrence in patients with moderate risk and acceptable toxicity, but this is not the case with COX-2 selective inhibitors. COX-2 selective NSAIDs result in substantial reduction in adenoma recurrence, but result in an increase in cardiovascular events.

Consequently, the researchers cannot support a general recommendation for NSAID use as a tertiary prevention of colorectal patients among CRC patients. They urge future validation studies to better understand prediagnostic and postdiagnostic NSAID use among CRC patients and clinical trials of NSAID tertiary prevention in these patients.