Taking extra steps to identify a hereditary form of colorectal cancer among newly diagnosed colorectal-cancer patients and their families provides significant value for the money spent, according to Hutch research.
The study, led by Dr. Scott Ramsey of the Public Health Sciences Division, presents compelling clinical and economic rationale for identifying potential candidates for genetic testing as part of routine medical practice.
But researchers also noted that current legal, healthcare-system and insurance barriers complicate the ease of implementing it.
Using a computer simulation, researchers estimated the cost-effectiveness per life-year gained of screening newly diagnosed colorectal-cancer patients to determine their likelihood of carrying a mutation that affects their disease risk of developing cancer. They compared this data with similar data generated by not performing such screening, which is standard current practice.
Screening would mean that individuals with new colon cancers would be asked questions about their personal and family history of cancer. Those who met certain criteria would have their tumors tested for microsatellite instability, a characteristic typical in Hereditary Nonpolyposis Colorectal Cancer (HNPCC). Those with this tumor characteristic would get genetic testing for the HNPCC mutation.
The defined cost-effectiveness is the value in years of life gained for the additional costs of genetic screening. Therefore, if screening succeeds by resulting in a lengthened life, an improvement in its cost effectiveness is reflected by a lower cost per life-year gained.
The cost-effectiveness of screening only newly diagnosed colorectal-cancer patients for genetic susceptibility was $42,210 per life-year gained when costs and benefits to the person being screened were considered. When benefits and costs to siblings and children were also considered, the cost-effectiveness improved to $7,556 per life-year gained, a value that Ramsey said is impressive.
"Most people consider $50,000 per life-year gained to be pretty good value for the additional expenditure," he said, "and $7,000 per life-year gained is very good, on the order of the cost-effectiveness of some common vaccines."
The study appeared in the Oct.16 issue of Annals of Internal Medicine.
Its authors include Dr. Ruth Etzioni, Lauren Clarke, Kristin Berry and Dr. Nicole Urban of the PHS Division and Mitchell Higashi from the University of Washington School of Pharmacy.
Between 1 percent and 5 percent of all colorectal cancer cases are due to HNPCC, which is caused by a mutation in one of six genes that puts individuals at increased risk for developing the disease.
Because high cost of genetic screening - about $2,000 per individual - prohibits widespread genetic testing and counseling, the National Cancer Institute has established guidelines to identify patients at greatest risk for developing HNPCC. Known as the Bethesda guidelines, these criteria include being young when diagnosed with colorectal cancer and having a more than one first-degree relative (a parent or sibling) with the disease.
Tumors from patients at high risk under the Bethesda guidelines are recommended to undergo testing for condition known as microsatellite instability, a characteristic of HNPCC in which regions of DNA become irregular in length. Microsatellite instability also occurs in about 15 percent of tumors from non-hereditary cases of colorectal cancer.
Patients whose tumors exhibit microsatellite instability are candidates for more sensitive genetic testing, which pinpoints whether an HNPCC mutation is present in one of six known susceptibility genes.
The Hutch study used a decision-making model based on existing data on colorectal cancer incidence, life expectancies and medical care costs. It extended the Bethesda guidelines beyond patients already diagnosed with cancer, said Ramsey, who is a practicing general internist as well as an economist.
While investigators predicted that most of the benefit would come from identifying unaffected relatives with the mutation, they were surprised to find that screening those with recently diagnosed cancer is also cost-effective.
The value of screening these patients is due to changes in the type of medical treatment that can be given to those with hereditary colorectal cancer, Ramsey said.
"Several European studies have indicated that more aggressive treatment of such patients, such as prophylactic colectomy, can extend survival by preventing future malignancies," he said, referring to a surgical procedure to remove the colon.
Regular surveillance by colonoscopy of siblings and children found to be carriers can lengthen life expectancy substantially in this group.
HNPCC mutations also may boost the risk of developing several other cancers, including endometrial, gastric and ovarian. Although the researchers did not consider surveillance for those malignancies in their model, they postulated that this could further increase cost-effectiveness of the genetic screening.
Despite compelling evidence for cost-effectiveness of genetic screening for cancer, there are many barriers to its implementation. Insurance companies or patients would have to cover the added costs of testing, and releasing genetic test results to a patients' relatives may violate patient-confidentiality regulations.
A bigger challenge, Ramsey said, lies in the limitations of our country's healthcare system.
"The trick to making this work is whether we can find and get to the unaffected relatives," he said. "Right now, our healthcare system isn't set up to track families. To make this really cost-effective, we've got to implement this beyond a research setting to the general population, and so far, that's not been done."