Assessment of the DNA Mismatch Repair System Is Crucial in Colorectal Cancers Necessitating Adjuvant Treatment: A Propensity Score-Matched and Win Ratio Analysis

Simple Summary Around 15% of sporadic colorectal cancers exhibit microsatellite instability. This unique tumor population appears to be poorly responsive to conventional chemotherapy and, conversely, reveals excellent results with immunotherapy. Our data, as demonstrated by propensity score-matched and win ratio analyses, show that there are no substantial differences between unstable and stable tumors in early colorectal cancers treated with surgery alone. On the contrary, stable tumors did much better than unstable tumors in the advanced stages of colorectal cancer undergoing conventional adjuvant treatment. Determination of the status of the DNA mismatch repair system is crucial in high-risk colorectal cancers to optimize treatment.Abstract A deficient DNA mismatch repair (MMR) system is identified in a non-negligible part of sporadic colorectal cancers (CRCs), and its prognostic value remains controversial. High tumor mutational burden, along with a poor response to conventional chemotherapy and excellent results from immunotherapy, are the main features of this subset. The aim of this study was to evaluate the predictive value of DNA MMR system status for its best treatment. Four hundred and three CRC patients, operated on from 2014 to 2021 and not treated with immunotherapy, entered this study. Immunohistochemistry and polymerase chain reaction, as appropriate, were used to unequivocally group specimens into microsatellite stable (MSS) and instable (MSI) tumors. The win-ratio approach was utilized to compare composite outcomes. MSI tumors accounted for 12.9% of all series. The right tumor location represented the most important factor related to MSI. The status of the DNA MMR system did not appear to correlate with outcome in early-stage CRCs not requiring adjuvant treatment; in advanced stages undergoing conventional chemotherapy, MSI tumors showed significantly poorer overall and disease-free survival rates and the highest win ratio instead. The determination of DNA MMR status is crucial to recommending correct management. There is clear evidence that instable CRCs needing adjuvant therapy should undergo appropriate treatments.