Is It Time to Broaden Use of Multigene Panel Testing in Patients With Colorectal Cancer?

Sarah Coughlin, MD


May 24, 2022

Sarah Coughlin, MD

Genetic testing has been a game changer in cancer care and prevention, but could we be doing more? Could we use multigene panel testing more broadly to identify both more precise treatments and cancers earlier in patients and their family members?

In the study, "Multigene Panel Testing Yields High Rates of Clinically Actionable Variants Amongst a Large Colorectal Cancer Cohort," presented at Digestive Disease Week 2022, we set out to better understand the potential yield of broadening genetic testing for hereditary cancer risk variants among patients diagnosed with colorectal cancer (CRC).

We conducted a retrospective cohort study of people with a diagnosis of CRC who underwent multigene panel testing of more than 10 genes at a commercial laboratory between March 2015 and May 2021. The panels were looking for inherited gene variants associated with an increased risk of developing cancer.

We analyzed data for 34,210 patients who underwent germline testing during the more than 6-year study period. Among those patients, 13.4% had at least one pathogenic or likely pathogenic germline variant, nearly 9% had a variant specifically associated with increased risk for CRC or polyposis, and 2.9% had an otherwise clinically actionable variant. Across all ages, panel sizes, and races/ethnicities, the rate of clinically actionable variants was 7.8% or greater.

Our results support an expanded role for multigene panel testing in patients who are diagnosed with CRC. Identifying pathogenic or likely pathogenic variants has implications for the medical management of individual patients, and also for family members who may carry the same variant and thus may be at increased cancer risk as well. Armed with knowledge about inherited risk, we can screen for cancers more often, detect cancers earlier, provide more effective treatments, and even prevent some cancers from developing outright.

This study represents the largest and by far the most diverse cohort of patients with CRC in which multigene panel testing has been looked at to date.

It is a step toward understanding what germline genetic testing might look like for everyone diagnosed with CRC. It certainly supports expanding the criteria for which patients with CRC are eligible for genetic testing, as current guidelines only recommend testing those with CRC who are younger than 50 years, as well as those with other high-risk personal or family history characteristics.

However, there are always costs associated with increasing genetic testing.

In addition to the resources necessary to conduct the genetic testing, it is also important to have enough experienced providers, including cancer-focused genetic counselors — of whom there is a current shortage — to be able to interpret and provide recommendations based on the genetic testing results. We need to be cognizant of the burden to the system and to individual patients, and weigh it against the clinical benefits to patients and their family members.

Our data suggest that expanding the use of multigene panel testing for patients diagnosed with CRC could benefit many of those with CRC and their families through identification of clinically actionable variants in cancer risk genes.

Sarah Coughlin, MD, is an a dvanced endoscopy fellow in the Division of Gastroenterology at the University of Pennsylvania.

Dr Coughlin presented findings of the study, "Multigene Panel Testing Yields High Rates of Clinically Actionable Variants Among a Large Colorectal Cancer Cohort," poster Tu1104, on Tuesday, May 24, at 12:30 PM PDT, at the Familial Cancer Syndromes and Cancer Genetics session. This research was funded by the Jason and Julie Borrelli Lynch Syndrome Research Fund and the Scott and Suzi Lustgarten Colon Cancer Research Fund at the University of Pennsylvania.

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