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Benefits of Colonoscopic Surveillance and Prophylactic Colectomy in Patients with Hereditary Nonpolyposis Colorectal Cancer Mutations

Sapna Syngal, MD, MPH; Jane C. Weeks, MD, MSc; Deborah Schrag, MD, MPH; Judy E. Garber, MD, MPH; and Karen M. Kuntz, ScD
[+] Article and Author Information

For author affiliations and current author addresses, see end of text. Grant Support: In part by the National Cancer Institute (5R25CA57711) and an American College of Gastroenterology Clinical Research Award (Dr. Syngal). Requests for Reprints: Karen M. Kuntz, ScD, Center for Risk Analysis, Harvard School of Public Health, 718 Huntington Avenue, 2nd Floor, Boston, MA 02115-5924. Current Author Addresses: Drs. Syngal, Weeks, Schrag, and Garber: Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1998;129(10):787-796. doi:10.7326/0003-4819-129-10-199811150-00007
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Background: Predisposition genetic testing is now possible for many hereditary cancer syndromes, including hereditary nonpolyposis colorectal cancer. The optimal management of the elevated risk for cancer in carriers of mutations for hereditary nonpolyposis colorectal cancer is unclear.

Objective: To assess the life expectancy and quality-adjusted life expectancy benefits derived from endoscopic surveillance and prophylactic colectomy for persons who carry a mutation associated with hereditary nonpolyposis colorectal cancer.

Design: Decision analysis model. Lifetime risk for colorectal cancer, efficacy of surveillance and colectomy, stage-specific colorectal cancer mortality, and quality of life were included in the model.

Setting: Decision about a cancer prevention strategy at the time of a positive result on genetic testing.

Patients: Carriers of a mutation for hereditary nonpolyposis colorectal cancer who were 25 years of age.

Interventions: Immediate prophylactic colectomy; delayed colectomy on the basis of age, adenoma, or diagnosis of colorectal cancer; and endoscopic surveillance. Prophylactic surgical options were proctocolectomy with ileoanal anastomosis and subtotal colectomy with ileorectal anastomosis.

Measurements: Life expectancy and quality-adjusted life expectancy.

Results: All risk-reduction strategies led to large gains in life expectancy for carriers of a mutation for hereditary nonpolyposis colorectal cancer, with benefits ranging from 13.5 years for surveillance to 15.6 years for prophylactic proctocolectomy at 25 years of age compared with no intervention. The benefits of colectomy compared with surveillance decreased with increasing age and were minimal if colectomy was performed at the time of colorectal cancer diagnosis. When health-related quality of life was considered, surveillance led to the greatest quality-adjusted life expectancy benefit (3.1 years compared with proctocolectomy and 0.3 years compared with subtotal colectomy).

Conclusions: Colonoscopic surveillance is an effective method of reducing risk for cancer in carriers of a mutation for hereditary nonpolyposis colorectal cancer. The individual patient's choice between prophylactic surgery and surveillance is a complex decision in which personal preferences weigh heavily.

Figures

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Figure 1.
General model framework.

Schematic overview of Markov model. A cohort of 25-year-old carriers of a mutation for hereditary nonpolyposis colorectal cancer who are cancer-free enter the model. Each circle represents states of health within the model. Each of the four main categories, depicted in bold, contains several subsets that depend on whether the patient is undergoing surveillance (surveillance status), undergoes colectomy (colon status), or has a polyp diagnosed and on the patient's stage of cancer (if colorectal cancer has occurred). The arrows represent potential transitions between health states and transition probabilities that vary depending on the strategy. Each year, a patient may remain in the same health state, die, or move to another health state, as shown in the flow diagrams.

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Figure 2.
Schematic representation of surveillance and colectomy if adenoma is found.Top.Bottom.

The patient enters the Markov tree (the encircled letter M), which depicts the clinical events that may occur during each 1-year period as a patient is followed until death. Circles represent chance nodes. Because surveillance occurs every 3 years, a patient may or may not undergo surveillance in a given year. Colorectal cancer may be diagnosed on the basis of symptoms or at the time of colonoscopy. Death may occur as a result of colorectal cancer, surgical or surveillance procedures, or causes not related to colorectal cancer. Surveillance. If colorectal cancer develops, segmental resection of the cancer is performed; the patient must continue to undergo surveillance and is at risk for a second primary tumor. Surveillance and colectomy if adenoma is found. If colorectal cancer or an adenoma develops, colectomy is performed. If subtotal colectomy is performed, the patient must continue to undergo surveillance and is at risk for a second primary tumor. If total proctocolectomy with ileoanal anastomosis is performed, the risk for a second primary cancer is eliminated and continued surveillance is not necessary. Other colectomy strategies examined follow similar paths, with variations of timing of colectomy based on the particular strategy being evaluated.

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Figure 3.
Two-way sensitivity analysis varying the utilities associated with total and subtotal colectomy and their effects on quality-adjusted life expectancy.

The lines represent thresholds at which the strategy leading to the greatest quality-adjusted life expectancy changes.

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