Risk Reduction depends on the Level of Compliance with Surveillance for Colorectal Cancer in Lynch syndrome

Lars Joachim Lindberg 1, Maria Rasmussen 1, Klaus Kaa Andersen 2, Mef Nilbert 2, 1,3, Christina Therkildsen 1

1 Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark. 2 The Danish Cancer Society Research Centre, Copenhagen, Denmark. 3 Department of Oncology and Pathology, Lund University, Lund, Sweden

Abstract

Objectives

Lynch syndrome confers an increased risk of colorectal cancer, which motivates colonoscopic surveillance programs to reduce morbidity and mortality. The effect from these surveillance programs depends on individual risk factors and levels of compliance, which vary during life and complicate risk modelling. We determined how different levels of compliance relates to individual factors and influences risk of colorectal cancer in the Danish Lynch syndrome cohort.

Methods

In a nationwide, prospective observational register study covering 1223 individuals, we estimated the risk of colorectal cancer and assessed clinicopathological data in relation to compliance. We developed a time-based model classifying time at-risk as fully, partially and non-compliant with recommended biennial colonoscopies and estimated the cumulative life-time risk and hazard rate ratios of first and metachronous colorectal cancer.

Results

During the study period, 99 first and 48 metachronous colorectal cancers developed. Compliance was associated with female gender, previous history of cancer and age <75 years. The risk of colorectal cancer was proportionally related to the level of compliance with cumulative incidences at age 75 of 38% (95% CI 27-50%) for full compliance, 48% (95% CI 29-67%) for partial compliance, and 72% (95% CI 61-83%) for non-compliance. Full compliance gave a 4-fold risk reduction (HR = 0.28), while partial compliance resulted in a 2-fold risk reduction (HR = 0.47) compared to non-compliance.

Conclusions

The colorectal cancer risk reduction gained from colonoscopic surveillance in Lynch syndrome is related to the level of compliance, which calls for motivational initiatives to optimise benefit.

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