A systems approach to enhance Lynch syndrome diagnosis through tumor testing

Abstract

BackgroundGuidelines recommend universal mismatch repair tumor (MMR) testing of colorectal adenocarcinomas (CRC) to screen for Lynch syndrome (LS). However, its implementation remains disjointed and referral for genetic testing dismal, particularly among minorities. We aimed to increase referral, cancer genetic testing, and eventually LS diagnosis by developing a systems approach which, in the second phase was automated. MethodsThis is a cohort study of all patients diagnosed with CRC at an academic center between 1/1/2012 and 1/31/2021. Tumor testing included MMR immunohistochemistry, followed by BRAF V600E/MLH1 promoter methylation testing when indicated. The intervention included a manual phase, which systematized Pathology screening and cancer genetics (CG) referral mechanisms, and an automated phase utilizing computer programming. ResultsA total of 249/1,541 CRC (17.38%) had MMR loss of expression and 129 (8.37%) qualified for CG evaluation. Referral was 27.58% in the original cohort and 92.1% in the intervention (p<0.001). Patients seen by CG among referred were 27.58% in the original cohort and 74.3 % in the intervention (P two-sided <0.001). The distribution of race/ethnicity among patients qualifying and referred for CG evaluation was not significantly different across cohorts. LS diagnosis increased from 0.56% (original cohort) to 1.43% (intervention). Cost per new diagnosis of LS decreased from $173,675 to $87,960 from original cohort to intervention. ConclusionImplementation of systematic case identification and referral support mechanisms significantly increased the proportion of patients undergoing genetic testing and doubled the percentage of patients diagnosed with Lynch syndrome with no referral differences across racial/ethnic groups.