Statin chemoprevention with minimal surveillance could prevent 96 percent of colon cancers

Ulcerative colitis affects about one out of every 2,000 Americans, and after living with the disease for 30 years, nearly 22 percent of those people will develop colon cancer.

For those patients, the current standard of care in colon cancer prevention is frequent colonoscopic surveillance and random biopsies every one to two years, which may lead to the surgical removal of the colon and significantly decrease a patient's quality of life. But a new study from the University of Michigan Health System suggests that there may be better and more cost-effective means to prevent colon cancer in patients with ulcerative colitis, an inflammatory bowel disease.

Researchers from the U-M Health System's Division of Gastroenterology examined the cost-effectiveness of chemoprevention of colorectal cancer with statins, a class of medications commonly used to lower cholesterol. The investigators found that statin chemoprevention alone, or with infrequent colonoscopies, may be a more promising strategy for the management of patients with chronic ulcerative colitis than the current standard of care.

Results of the study will be presented May 16 at the Digestive Disease Week annual meeting in Chicago.

The cost-effectiveness of any strategy of prevention for colon cancer mortality in ulcerative colitis depends not only on the efficacy of surveillance or chemoprevention, but also on complication rates, costs, and quality of life of the patient, says lead author Joel Rubenstein, M.D., M.Sc., a lecturer in the Division of Gastroenterology and Hepatology in the Department of Internal Medicine at the U-M Medical School.

"Surveillance prevents cancer by leading patients to have colectomies, the surgical removal of part or the entire colon, which can significantly decrease their quality of life," says Rubenstein, who also is a staff physician at the Veteran's Affairs Ann Arbor Healthcare System. "But our study shows the possibilities of other interventions in terms of extending and improving quality of life. It highlights the pitfalls of surveillance strategies and the potential strength of chemoprevention."

For the cost-utility analysis of colon cancer prevention in patients with ulcerative colitis, Rubenstein and his colleagues created a Markov model, a mathematical simulation of hypothetical patients over time. No real patients were enrolled in this study.

The hypothetical patients consisted of 35-year-old men with an eight year history of ulcerative colitis, which was inactive at the time of enrollment in the study. Using this model, the study followed the cohort until age 90 or until death, whichever occurred first.

To determine if statin chemoprevention is more cost-effective than the current standard of care, the study compared seven strategies for colon cancer prevention, including doing nothing, annual colonoscopy, colonoscopy every five years, statin alone, and statin in combination with colonoscopy annually, every five years or every 10 years.

By age 47, 6.3 percent of patients in the "do nothing" strategy, meaning they did not receive statins or undergo surveillance, developed colon cancer. During the course of their lives, 37.5 percent of patients in this group developed colon cancer and incurred an average cost of $103,801 for care.

While annual surveillance without statin chemoprevention prevented 96 percent of cancers, 57 percent of patients in this group underwent a colectomy, and their lifetime cost for care was $103,348. However, with surveillance every five years, 39 percent of patients underwent a colectomy and 57 percent of cancers were prevented at an annual cost of $96,977.

Statin chemoprevention without surveillance prevented 90 percent of cancers, and 15 percent of patients required a colectomy. The average cost for lifetime care for this group was $108,051.

Even more promising, patients receiving statins and undergoing surveillance lived longer than patients who underwent surveillance alone, and had a better quality of life. Patients who received statins and underwent surveillance once every 10 years had 96 percent of their cancer prevented – the same proportion as those who underwent annual surveillance without statins.

"Ultimately, we found that statin chemoprevention of colon cancer is a promising strategy for the management of patients with chronic ulcerative colitis, and demonstrated the shortcomings of surveillance," says Rubenstein. "This study adds to a growing body of cost-effectiveness analyses that demonstrate a common principle: effective prevention with medicines is cost-effective compared to surveillance followed by just-in-time interventions, such as surgery."

Statins were originally developed to lower cholesterol, but also have been found to induce the programmed cell death of colorectal cancer cells in the laboratory, and observational studies suggest statins protect patients with ulcerative colitis from developing colon cancer, says study co-author Peter Higgins M.D., Ph.D., lecturer in the Division of Gastroenterology and Hepatology in the Department of Internal Medicine at the U-M Medical School.

"The results of our study are preliminary. More research is still needed to precisely determine the effectiveness of statins in the prevention of colon cancer, the accuracy of colonoscopy in the detection of pre-cancerous changes, and the quality of life of people with ulcerative colitis following a colectomy," says Higgins. "However, this study does prove the principle that chemoprevention is an effective strategy for the prevention of ulcerative colitis-associated colon cancer. If we can prove that medications like statins are an effective means to prevent cancer at a reasonable cost, chemotherapy may be the best alternative to frequent colonoscopy in patients with ulcerative colitis."

In addition to Rubenstein and Higgins, the study was co-authored by Akbar Waljee, M.D., house officer, the Department of Internal Medicine at the U-M Medical School; Joanne Jeter, M.D., with the Division of Hematology/Oncology at the U-M Medical School; and John M. Inadomi, M.D., associate professor, the Department of Internal Medicine at the U-M Medical School, and interim chief and director of endoscopy, Veteran's Affairs Ann Arbor Healthcare System.