While testing of colorectal cancer tumors for mismatch repair defects has been recommended for years, the majority of patients with abnormal results do not complete the next steps, including genetic testing. Skipping those steps can cause missed cancer diagnoses and unnecessary costs, as explained in a Yale study recently published in the journal Clinical Gastroenterology and Hepatology.

Completed genetic testing would determine whether a patient had Lynch syndrome (LS), a hereditary marker for a higher-than-average predisposition for developing colorectal cancer as well as other cancers, including endometrial and ovarian. Early identification of LS in a patient’s family members has the potential to reduce their cancer risk and mortality, increasing the medical benefit of and thereby ultimately lowering testing costs, the study found.

Using data from the Lynch Database, the NCI SEER program, and pre-/post-intervention cohort studies at Yale, the study found that in North America only 28% to 45% of eligible patients completed the testing to determine LS status.

A process that addresses roadblocks to completing the testing was established more than 10 years ago at Yale New Haven Health (YNHH) and doubled the Lynch syndrome diagnoses among colorectal cancer patients. Those results are shared with family members and, if they test positive as well, cancer preventive measures are implemented.

The study examined the cost-benefit ratio of three strategies for identifying Lynch syndrome. They were the current standard-of-care at most institutions; the optimized YNHH standard-of-care; and upfront germline testing for all individuals diagnosed with colorectal cancer.

This study determined that current standard-of-care was not cost effective, but both the YNHH model and universal upfront genetic testing were. Both the YNHH and universal testing options assumed that a LS diagnosis leads to at least two family members being tested for LS. The cost vs. benefit ratio improves with each family member who is tested.

“Widespread availability of genetic testing along with plummeting prices of these tests over the last few years make universal genetic testing of all individuals with colorectal cancer a cost-effective approach that will dramatically increase the number of individuals diagnosed with Lynch syndrome and they will all be able to benefit from cancer preventive measures,” says Xavier Llor, MD, PhD, co-senior author on the paper, and director of the GI and Pancreatic Cancer Prevention Program in the Department of Medicine.

Co-senior author George Goshua, MD, MSc, an assistant professor of medicine (medical oncology and hematology) at Yale School of Medicine, commented on the teamwork that made the paper possible.

“Fusing clinical knowledge with rigorous methodology, alongside working with superb colleagues across disciplines, is exactly what is needed to address real-world challenges. There are at least two different approaches to ensuring that the care of individuals with colorectal cancer is world-class and they are each cost-effective, as compared to what is currently done,” he says.

This study was supported, in part, by the NOMIS Foundation, Frederick A. DeLuca Foundation, Yale Bunker Endowment, Yale Cancer Center, the National Institutes of Health (awards 1K01HL175220 and CA-016359 ), and Yale University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.