Lynch Syndrome Screening Interval: Are We “Scoping” Enough? A Single Centre 19-Year Experience

Aims Lynch syndrome (LS) is associated with pathogenic germline variants in DNA mismatch repair genes or EPCAM deletions. Since colorectal cancer (CRC) may develop through an adenoma-independent pathway, shorter interval colonoscopies could allow earlier CRC detection. We aimed to analyse the surveillance of Lynch syndrome patients at our centre and evaluate the incidence of interval CRC.

Methods Retrospective cohort study at a single centre, reviewing clinical records of patients molecularly confirmed for LS between 2005 and 2024. Analysed demographic and clinical data, and associated pathogenic variant characteristics. Evaluated the screening interval, adenoma incidence and interval CRC during colonoscopy surveillance [1].

Results Included 41 patients, 58% women (n=24), mean age at admission of 45.6±16.1 years. Identified 23 families, with 1-7 members per family. Regarding the genetic mutations: 43.5% (n=10) MLH1, 30.4% (n=7) MSH2, 17.4% (n=4) MSH6 and 8.7% (n=2) PMS2. Extra-colonic tumours occurred in 34.1% (n=14), primarily endometrial cancer (42.9%, n=4). The mean number of affected relatives with CCR was 2.8±2.2, with 82.6% having at least one first-degree relative.

51.2% (n=21) had a prior or current diagnosis of CRC at admission, mean age of 47.2±12.2 years. Of these, 81% (n=17) had right-sided CRC, with 47.6% (n=10) single lesions, 19% (n=4) synchronous and 14.3% (n=3) metachronous CRC. The mean period of surveillance was 8 years (range: 3 months-19 years). Endoscopic surveillance intervals, regardless of gene, varied by surgical history. Among patients with surgery, 23.8% (n=5) had an exam every 1/2 years, 19% (n=4) every 2 years and 42.9% (n=9) had an interval longer than 2 years. Without surgery, 45% (n=9) had an exam every 1/2 years, 40% (n=8) every 2 years and 15% (n=3) had an interval longer than 2 years. Adenomas were removed in 43.9% (n=18), with a median of 2 adenomas per patient (IQR: 1-5.25): 77.8% tubular and 27.8% with high-grade dysplasia. Adenomas incidence was 0.02 cases per person-year. Interval CRC occurred in 7.3% (n=3) patients: 23 months post-surveillance, with excellent Boston Bowel Preparation Scale (BBPS); 24 months with inadequate BBPS and 33 months with excellent BBPS. Mortality was 9.8% (n=4), attributed to distinct oncological entities.

Conclusions Our study spans a long surveillance period, with significant heterogeneity in intervals across patients and families. Although debate continues regarding the optimal surveillance interval, our current approach follows the European Hereditary Tumour Group’s guidelines. However, age and family history led us to shorten the interval. Improving the quality of colonoscopy may enhance adenoma detection, potentially preventing one of the incident cancers in our cohort. Adenoma-independent carcinogenesis may account for the other two cases.

Publikationsverlauf

Artikel online veröffentlicht:
27. März 2025

• References

• 1 Ahadova A, Seppälä TT, Engel C. et al. The "unnatural" history of colorectal cancer in Lynch syndrome: Lessons from colonoscopy surveillance. Int J Cancer 2021; 148 (4): 800-811