NSAID Use After Diagnosis Improved CRC Survival in KRAS Wild-Type Patients

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Long-term survivors of wild-type KRAS colorectal cancer tumors had significantly improved survival with regular use of nonsteroidal anti-inflammatory drugs (NSAIDS), according to the results of a study published in the Journal of Clinical Oncology.

“Our results also suggest that the association between aspirin use and overall survival was more pronounced among those who initiated aspirin use after diagnosis, whereas both initiated and continued users of aspirin after diagnosis seemed to be associated with more favorable cancer-specific survival,” wrote researcher Xinwei Hua, of the Fred Hutchinson Cancer Research Center in Seattle, and colleagues.

Use of aspirin has been linked with survival improvements for patients with colorectal cancer. Here, Hua and colleagues examined whether the benefits of aspirin were limited to the timing or subtype of colorectal cancer.

The researchers used population-based cancer registries from the United States, Canada, and Australia to identify 2,419 patients aged 18 to 74 with invasive colorectal cancer diagnosed between 1997 and 2008. Patients were asked to complete questionnaires at study enrollment and at 5-year follow-up.

A little less than one-half of patients (42%) regularly used either aspirin or other NSAIDs after colorectal cancer diagnosis. Those patients who used NSAIDS were more likely to be older, male, overweight or obese, former smokers, and diagnosed with early-stage disease.

At a median of 4.9 years follow-up, 381 deaths occurred. Users of post-diagnostic aspirin had a more favorable overall survival (hazard ratio [HR], 0.76; 95% CI, 0.62–0.94) and colorectal cancer–specific survival (HR, 0.44; 95% CI, 0.25–0.71; 95% CI, 0.25–0.71) compared with non-users. These associations were similar among users of aspirin only, other NSAIDS, or aspirin and other NSAIDS.

Patients who initiated their aspirin use after diagnosis had even further improved overall survival (HR, 0.64; 95% CI, 0.47–0.86) and colorectal cancer-specific survival (HR, 0.40; 95% CI, 0.20–0.80).

Those patients with a longer duration of use had a more favorable overall and cancer-specific survival. Use of any NSAIDS for 3 years or longer significantly improved cancer-specific survival compared with any shorter duration.

The researchers looked at the survival outcomes and aspirin use in relation to tumor markers and found that the association of any NSAID use after diagnosis and overall survival differed by KRAS mutation status. Specifically, only participants with KRAS wild-type tumors had an improved overall survival with the use of any NSAID after diagnosis (HR, 0.64; 95% CI, 0.48–0.85). Patients with KRAS-mutant tumors had no improvement in survival (HR, 1.20; 95% CI, 0.75–1.91). 

“Because we collected self-reported NSAID use retrospectively, misclassification of NSAID use may have occurred,” the researchers noted. “Participants included in this study had to survive long enough after diagnosis to complete the follow-up questionnaire. Therefore our results may not apply to short-term survivors