Characterization of extracolonic cancers in individuals with Lynch syndrome: A Canadian population-based cohort.

e22658 Background: While increased risk of colorectal cancer (CRC) is well established in individuals with Lynch syndrome (LS), North American population-based data on extracolonic cancers (ECCs), especially with some gene variants, remains limited. Better understanding of ECCs in LS may improve screening, care and outcomes. Manitoba has a provincial registry of individuals with mismatch repair (MMR) germline pathogenic variants (GPVs), and a multidisciplinary clinic for individuals with LS, focused on screening, surveillance and risk-reduction strategies. The aims of this study are: (1) characterize ECCs in LS; (2) evaluate impact of clinic practices on individuals with LS. Methods: We conducted a retrospective cohort study of individuals with GPVs enrolled in the Manitoba LS registry between 1999 and 2023. Clinical and pathological data were obtained from provincial cancer and genetics databases. Outcomes included ECC type, age at diagnosis, stage, tumor MMR/MSI testing, mode of cancer detection, enrollment in LS clinic and associated screening/surveillance tests. Descriptive statistics were used. Results: 124 individuals with GPVs had 192 ECCs. Impacted GPVs were: 28.1% MLH1, 27.4% MSH2, 23.4% MSH6, 17.7% PMS2, 3.2% EPCAM. Mean age of diagnosis was 57 (SD 12.6). Common cancers were: endometrial (34.9%), genitourinary tract (8.9%) ovarian (6.3%), small bowel/stomach (5.7%), sebaceous (4.2%), hepatobiliary (2.6%). Fifty (40%) individuals had >2 ECC diagnoses. The majority of ECCs were diagnosed following symptomatic presentation (56.8%) and 8.7% were advanced or metastatic stage at diagnosis. 68 (35.4%) ECCs had tumor MMR or MSI testing and 6 (3.1%) received immunotherapy. Among individuals with ECCs, 66.1% were followed in the LS clinic. Clinic-followed individuals had higher uptake of ECC screening than those not followed (89.0% vs 66.7%), although few tests were associated with a cancer diagnosis (12%). Conclusions: While ECCs in LS are less common than CRC, they are clinically significant, particularly when of advanced stage or if limited treatment options exist. In our cohort, tumour MMR/MSI testing and receipt of immunotherapy was low, highlighting areas for improvement. Higher screening uptake among clinic-followed individuals may support a centralized care model. This underscores the need for prospective studies to optimize ECC screening and evaluate outcomes.