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Cost-Effectiveness of Microsatellite Instability Screening as a Method for Detecting Hereditary Nonpolyposis Colorectal Cancer

Scott D. Ramsey, MD, PhD; Lauren Clarke, MS; Ruth Etzioni, PhD; Mitchell Higashi, MBA; Kristin Berry, MS; and Nicole Urban, ScD
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From Fred Hutchinson Cancer Research Center and University of Washington, Seattle, Washington.

Copyright ©2004 by the American College of Physicians

Acknowledgments: The authors thank Patrice Watson, Creighton International Hereditary Colorectal Cancer Registry, for providing data essential to the analysis. They also thank Polly Newcomb, Wylie Burke, and John Potter for thoughtful comments on the analysis and the manuscript.

Grant Support: Dr. Ramsey is a recipient of the National Cancer Institute's Temin Career Development Award.

Requests for Single Reprints: Scott D. Ramsey, MD, PhD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North (MP-900), Box 19024, Seattle, WA 98109; e-mail, sramsey@fhcrc.org.

Current Author Addresses: Drs. Ramsey, Etzioni, and Urban, Ms. Clarke, and Ms. Berry: Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North (MP-900), Box 19024, Seattle, WA 98109.

Mr. Higashi: School of Pharmacy, Box 357630, University of Washington, Seattle, WA 98195.

Author Contributions: Conception and design: S.D. Ramsey, L. Clarke, R. Etzioni, N. Urban.

Analysis and interpretation of the data: S.D. Ramsey, L. Clarke, K. Berry, N. Urban.

Drafting of the article: S.D. Ramsey.

Critical revision of the article for important intellectual content: S.D. Ramsey, L. Clarke, K. Berry, N. Urban.

Final approval of the article: S.D. Ramsey, N. Urban.

Provision of study materials or patients: S.D. Ramsey.

Statistical expertise: S.D. Ramsey, K. Berry.

Obtaining of funding: S.D. Ramsey, N. Urban.

Administrative, technical, or logistic support: S.D. Ramsey.

Collection and assembly of data: S.D. Ramsey, M. Higashi.

Ann Intern Med. 2001;135(8_Part_1):577-588. doi:10.7326/0003-4819-135-8_Part_1-200110160-00008
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Background: The National Cancer Institute has published consensus guidelines for universal screening for hereditary nonpolyposis colorectal cancer (HNPCC) in patients with newly diagnosed colorectal cancer.

Objective: To determine the cost-effectiveness of screening compared with standard care in eligible patients with colorectal cancer and their siblings and children.

Design: Cost-effectiveness analysis.

Data Sources: National colorectal cancer registry data, the Creighton International Hereditary Colorectal Cancer Registry, Medicare claims records, and published literature.

Target Population: Patients with newly diagnosed colorectal cancer and their siblings and children.

Time Horizon: Lifetime (varies depending on age at screening).

Perspective: Societal.

Interventions: Initial office-based screening to determine eligibility (based on personal and family cancer history), followed by tumor testing for microsatellite instability. Those with microsatellite instability were offered genetic testing for HNPCC. Siblings and children of patients with cancer and the HNPCC mutation were offered genetic testing, and those who were found to carry the mutation received lifelong colorectal cancer screening.

Measurements: Life-years gained.

Results of Base-Case Analysis: When only the patients with cancer were considered, cost-effectiveness of screening was $42 210 per life-year gained. When patients with cancer and their siblings and children were considered together, cost-effectiveness increased to $7556 per life-year gained.

Results of Sensitivity Analysis: The model was most sensitive to the estimated survival gain from screening siblings and children, to the prevalence of HNPCC mutations among patients with newly diagnosed cancer, and to the discount rate. In probabilistic analysis, the 90% CI for the cost-effectiveness of screening patients with cancer plus their relatives was $4874 to $21 576 per life-year gained.

Conclusion: Screening patients with newly diagnosed colorectal cancer for HNPCC is cost-effective, especially if the benefits to their immediate relatives are considered.


Grahic Jump Location
Figure 1.
Decision tree for microsatellite instability test and hereditary nonpolyposis colorectal cancer (HNPCC) mutation testing of patients with newly diagnosed colon cancer and their siblings and children.(15)

The top half of the tree represents the decision pathway for those with newly diagnosed colorectal cancer (Bethesda guidelines); the lower half represents the pathway for screening of siblings and children of mutation carriers. Outcome states at the end of each branch (not shown) are either colorectal cancer followed by death or no colorectal cancer followed by death. Increased surveillance is defined as colonoscopy every 3 years; standard care is defined as standard post–colorectal cancer care . MMR = mismatch repair mutation; MSI = microsatellite instability.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Results of one-way sensitivity analyses of input variables for the cost-effectiveness model.

Analysis concerns patients with cancer and their family members. CRC = colorectal cancer; HNPCC = hereditary nonpolyposis colorectal cancer; MMR = mismatch repair mutation; MSI = microsatellite instability.

Grahic Jump Location




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