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08-08-2011 | Gastroenterology | Article

Screening strategy ‘cost-effective’ for the Lynch syndrome


Free abstract

MedWire News: All patients newly diagnosed with colon cancer should be screened for the Lynch syndrome, an inherited defect that underlies around 3-5% of such cancers, US researchers believe.

Based on Markov risk-modeling they say that this screening strategy would be cost-effective because it would enable high-risk individuals and their relatives to receive preventative treatment, including surgery.

The Lynch syndrome is caused by mutations in one or more mismatch repair genes (MLH1, MLH2, MSH6, or PMS2) and is characterized by colorectal tumors with microsatellite instability.

At present, the Lynch syndrome is suspected on the basis of a strong family history of colon and other cancers; the best-available diagnostic criteria (the "Amsterdam" criteria) are valuable but insensitive, being fulfilled by less than half of families with the syndrome.

In this study, Uri Ladabaum (Stanford University School of Medicine, California) and team used statistical modeling to estimate the effectiveness and cost-effectiveness of different strategies to identify the Lynch syndrome.

They evaluated a range of scenarios incorporating various permutations of clinical criteria, prediction algorithms, tumor testing, germline mutation testing, tailored screening, and risk-reducing surgery.

The outcomes of interest were colorectal, endometrial, and ovarian cancers and effectiveness was measured in terms of life-years gained, cancers and deaths prevented, cost-savings, and incremental cost-effectiveness ratios.

The study, which is reported in the Annals of Internal Medicine, found that the most effective screening strategy was that in which the Lynch syndrome was identified in the relatives of an individual newly diagnosed with colorectal cancer.

In the case of a female relative who subsequently underwent hysterectomy and salpingo-oophrectomy, and regular screening for colorectal cancer, the strategy would increase life expectancy by approximately 4 years, reduce death from colorectal cancer by 7-42%, and reduce death from endometrial and ovarian cancer by 1-6%, Ladabaum et al estimate.

As expected, effectiveness and cost-effectiveness rose in line with increasing numbers of relatives tested per proband, and the widely accepted threshold of US$50,000 (€35,140) per incremental life-year gained was met when three or four relatives were tested.

In terms of specific screening strategies, the most cost-effective approach involved immunohistochemistry followed by BRAF mutation testing in all newly diagnosed individuals up to the age of 70 years, which cost US$44,000 (€30,979) per incremental life-year gained.

"A systematic approach to identify families with the Lynch syndrome makes sense clinically, because it can save lives, and economically, because its costs are comparable to other things we choose to spend our healthcare dollars on," said Ladabaum in a press release accompanying the study. "We advocate establishing similar tumor-screening systems on a national level."

Commenting on the research, Randall Burt (University of Utah and Huntsman Cancer Institute, Salt Lake City, USA) added: "Testing and counselling should probably occur in specialty clinics, but because patients whose relatives have had colorectal cancer may ask whether they can undergo testing, nonspecialty clinicians should understand the concepts and processes involved."

By Joanna Lyford

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