A Canadian Provincial Screening Program for Lynch Syndrome.

Area of Science:

• Oncology
• Genetics
• Public Health

Background:

• Manitoba established the first Canadian provincial reflex screening program for mismatch repair immunohistochemistry (MMR-IHC) in colorectal cancer (CRC) for patients 70 years or younger in December 2017.
• This initiative aimed to improve Lynch syndrome detection through universal MMR-IHC testing.
• Evaluating program compliance and referral rates for genetic assessment is crucial for optimizing CRC management and hereditary cancer surveillance.

Purpose of the Study:

• To assess the compliance rate of universal reflex MMR-IHC screening for eligible colorectal cancer patients in Manitoba.
• To determine the referral rate of MMR-deficient cases for genetic assessment and testing.
• To identify factors influencing MMR-IHC screening and genetic referral rates in a real-world provincial program.

Main Methods:

• A retrospective analysis of colorectal adenocarcinoma specimens (March 2018–December 2020) was conducted using the provincial pathology database.
• Data were cross-referenced with the Program of Genetics and Metabolism to track referrals and genetic testing uptake for MMR-deficient cases.
• Logistic regression analysis identified predictors of MMR-IHC screening and genetic referral.

Main Results:

• Of 936 patients aged 70 or younger, 89.4% received MMR-IHC screening, with individual pathologist screening rates being a significant predictor.
• An overall referral rate of 75.8% for MMR-deficient cases was achieved, with pathologists referring 53.4% and other clinicians an additional 22.4%.
• Lynch syndrome was confirmed in 1.4% of patients via germline testing, leading to cascade testing in 8 first-degree relatives.

Conclusions:

• Manitoba's Lynch syndrome screening program demonstrates high compliance with reflex MMR-IHC testing.
• The program successfully identified Lynch syndrome cases, facilitating genetic assessment and cascade testing.
• Pathologist screening rates are key drivers for program success, highlighting the importance of standardized protocols.