QUANTIFYING THE IMPACT OF ADHERENCE TO HEREDITARY CANCER TESTING ON COLORECTAL CANCER BURDEN: A MICROSIMULATION MODEL
Author(s)
Sumeyye Samur, PhD1, Jade Xiao, PhD1, Gebra Cuyun Carter, MPH, PhD2, Brandie Leach, MS2, Vahab Vahdat, MSc, PhD2, Jordan Karlitz, MD2, Swati Patel, MD, MS3, Mary Linton Peters, MD, PhD4;
1Value Analytics Labs, Boston, MA, USA, 2Exact Sciences Corporation, Madison, WI, USA, 3University of Colorado, Anschutz Medical Center, Hereditary GI Cancer Center, Aurora, CO, USA, 4Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
1Value Analytics Labs, Boston, MA, USA, 2Exact Sciences Corporation, Madison, WI, USA, 3University of Colorado, Anschutz Medical Center, Hereditary GI Cancer Center, Aurora, CO, USA, 4Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
OBJECTIVES: Hereditary colorectal cancer (CRC) syndromes account for a substantial proportion of preventable CRC morbidity and mortality. Germline genetic testing (GGT) of patients with CRC enables identification of at-risk relatives, cascade testing, and CRC screening; however, its benefit is limited by insufficient adherence to testing guidelines. Our aim was to quantify the impact of adherence to guidelines on pathogenic germline variant (PGV) detection and downstream CRC outcomes among PGV-positive patients with CRC (probands) and their first-degree relatives (FDR).
METHODS: We developed a microsimulation model to evaluate three scenarios: 1) no GGT 2) real-world adherence to GGT, and 3) perfect adherence to GGT. Our model included a GGT module, simulating PGV detection in probands and their FDR following guideline-recommended testing, and a CRC screening module. PGV-specific parameters were calibrated using the published data on CRC risk and adenoma burden. PGV-specific disease progression, test performances, and real-world screening adherence inputs were informed by published sources. Model outputs were validated against reported data in the literature.
RESULTS: In the no-GGT scenario, there was no PGV detection, as expected. With real-world adherence, 42.1% of PGV-positive probands and 6.0% of PGV-positive relatives would be identified. With perfect adherence, detection further improved to 88.3% of probands and 79.3% of FDR (2.1-fold and 13-fold increases, respectively). Compared with no GGT, real-world adherence yielded minimal reductions in CRC cases and deaths (~2% for both), whereas perfect adherence resulted in substantial reductions (25% fewer CRC cases and 27% fewer CRC deaths).
CONCLUSIONS: Current adherence to GGT guidelines remains insufficient and is associated with suboptimal CRC prevention among high-risk FDRs. This study quantifies the incremental impact of identifying PGVs to enable risk-adapted surveillance and highlights the need to improve adherence to GGT. Our clinically validated model can serve as a tool for evaluating strategies to optimize CRC hereditary syndrome pathways in clinical practice.
METHODS: We developed a microsimulation model to evaluate three scenarios: 1) no GGT 2) real-world adherence to GGT, and 3) perfect adherence to GGT. Our model included a GGT module, simulating PGV detection in probands and their FDR following guideline-recommended testing, and a CRC screening module. PGV-specific parameters were calibrated using the published data on CRC risk and adenoma burden. PGV-specific disease progression, test performances, and real-world screening adherence inputs were informed by published sources. Model outputs were validated against reported data in the literature.
RESULTS: In the no-GGT scenario, there was no PGV detection, as expected. With real-world adherence, 42.1% of PGV-positive probands and 6.0% of PGV-positive relatives would be identified. With perfect adherence, detection further improved to 88.3% of probands and 79.3% of FDR (2.1-fold and 13-fold increases, respectively). Compared with no GGT, real-world adherence yielded minimal reductions in CRC cases and deaths (~2% for both), whereas perfect adherence resulted in substantial reductions (25% fewer CRC cases and 27% fewer CRC deaths).
CONCLUSIONS: Current adherence to GGT guidelines remains insufficient and is associated with suboptimal CRC prevention among high-risk FDRs. This study quantifies the incremental impact of identifying PGVs to enable risk-adapted surveillance and highlights the need to improve adherence to GGT. Our clinically validated model can serve as a tool for evaluating strategies to optimize CRC hereditary syndrome pathways in clinical practice.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
CO70
Topic
Clinical Outcomes
Topic Subcategory
Comparative Effectiveness or Efficacy
Disease
SDC: Gastrointestinal Disorders, SDC: Oncology