Competing risks analysis of microsatellite instability as a prognostic factor in colorectal cancer

Background: Despite an extensive literature suggesting that high microsatellite instability (MSI-H) enhances survival and protects against recurrence after colorectal cancer resection, such effects remain controversial as many studies show only a weak bivariate association or no multivariable association with outcome. This study examined the relationship between MSI status and colorectal cancer outcomes with adjustment for death from other causes as a competing risk. Methods: A hospital database of patients following colorectal cancer resection was interrogated for clinical, operative, pathology, adjuvant therapy and follow-up information. MSI-H status was determined by immunohistochemistry for mismatch repair protein deficiency. The cumulative incidence of recurrence and colorectal cancer-specific death was evaluated by competing risks methods. Results: Among 1009 patients who had a resection between August 2002 and December 2008, and were followed to at least December 2013, there were 114 (11.3 percent) with MSI-H (72.8 percent aged at least 70 years; 63.2 per cent women). After potentially curative resection, with adjustment for non-colorectal cancer death as a competing risk and adjustment for 22 clinical, operative and pathological variables, there was no association between MSI-H and recurrence (hazard ratio (HR) 0.81, 95 per cent c.i. 0.42 to 1.57) or colorectal cancer-specific death (HR 0.73, 0.39 to 1.35) in this patient population. For palliative resections, there was no association between MSI-H and colorectal cancer-specific death (HR 0.65, 0.21 to 2.04). MSI-H was associated with non-colorectal cancer death after both curative (HR 1.55, 1.04 to 2.30) and palliative (HR 3.80, 1.32 to 11.00) resections. Conclusion: Microsatellite instability status was not an independent prognostic variable in these patients.