The effectiveness and the cost-effectiveness of various colonoscopic surveillance strategies considering sex- and mismatch repair gene-specific cumulative risk of colorectal cancer in individuals with Lynch syndrome

Yoon-Jung Kang1, Michael Caruana1, Natalie Taylor1, Ian Frayling2, Alison Trainer3, Gillian Mitchell4, Finlay Macrae5, Karen Canfell1

1Cancer Council NSW, Sydney, Australia. 2 All-Wales Medical Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff, United Kingdom. 35 Parkville Familial Cancer Centre, Peter MacCallum Cancer Centre and Royal Melbourne Hospital, Department of Medicine, University of Melbourne, Melbourne, Australia. 4Centre for Cancer Research, University of Melbourne, Melbourne, Australia. 5Colorectal Medicine and Genetics, and Department of Medicine, University of Melbourne, The Royal Melbourne Hospital, Melbourne, Australia

Abstract

Objectives: The study aims to estimate sex- and MMR gene-specific cumulative risk of colorectal cancer (CRC) in individuals with Lynch syndrome (LS) without colonoscopic surveillance, and to use the estimates to evaluate the effectiveness and cost-effectiveness of various MMR gene-specific colonoscopic surveillance strategies.

Methods: We used the baseline estimates and 95% confidence intervals reported in three studies: i) PLSD estimates for sex- and MMR gene-specific cumulative CRC risks in LS individuals without previous cancer and under colonoscopic surveillance[1]; ii) hazard ratios associated with 3-yearly colonoscopic surveillance on CRC incidence reduction[2]; and iii) MMR gene-specific cumulative risk of CRC in LS individuals who are not under colonoscopic surveillance[3]. Compatible estimates for sex- and MMR gene-specific cumulative risk of CRC in LS carriers without colonscopic surveillance were found using an optimisation algorithm. Using a microsimulation model, we estimated health and economic outcomes of various colonoscopic surveillance strategies assuming: i) unified colonoscopic surveillance protocol across all MMR genes (comparator); and ii) combination of different start/end age and surveillance intervals for each of MMR genes (intervention X-Y).

Results: Analysis is underway – results will be reported for the range of CRC deaths and the number of colonoscopies over the lifetime of LS carriers and the cost-effectiveness ratios associated with MMR gene-specific colonoscopic surveillance protocols, compared to the unified approach.

Conclusions: If less intensive colonoscopic surveillance for carriers with MSH6/PMS2 mutation result in similar CRC deaths prevented compared to the unified surveillance approach, this could lead to noteworthy reductions in colonoscopy demand.

Abstract references

[1] Prospective Lynch Syndrome Database. http://www.PLSD.eu/

[2] Jarvinen HJ, Aarnio M, Mustonen H, Aktan-Collan K, Aaltonen LA, Peltomaki P, et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterology. 2000;118(5):829-34.

[3] Bonadona V, Bonaiti B, Olschwang S, Grandjouan S, Huiart L, Longy M, et al. Cancer risks associated with germline mutations in MLH1, MSH2, and MSH6 genes in Lynch syndrome. JAMA. 2011 Jun 8;305(22):2304-10.

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