As a result of recent research revealing that a significant number of colorectal cancer patients with actionable variants are missed under previous genetic testing guidelines, the National Comprehensive Cancer Network (NCCN) announced new guidelines calling for testing to be available to all patients diagnosed with colorectal cancer.

Specifically, NCCN recommended that germline multigene panel testing should be offered to all individuals with CRC aged under 50 and be considered for all others, particularly for, but not restricted to, those with evidence of mismatch repair in their tumor or suggestive family history. These new recommendations expand the current testing criteria, which limited testing to certain age groups and types of cancer. 

The new NCCN guidelines follow recent landmark studies published in JAMA Oncology and Clinical Gastroenterology and Hepatology by Invitae and Mayo Clinic supporting universal genetic testing for all cancer patients, regardless of cancer type, age, stage or family history.

The data showed that nearly one in six colorectal cancer patients had inherited gene mutations that increased their risk of cancer. Additionally, more than 10% of patients in the study had changes to their cancer treatments based on genetic testing findings—many of whom would have been missed by previous limited testing guidelines. The study also found that patients diagnosed with colorectal cancer at a younger age were more likely to have heritable genetic changes linked to an increased risk of cancer.

The new NCCN guidelines have the potential to impact millions, as colorectal cancer is the third most diagnosed cancer and an estimated 5 million people worldwide currently live with colorectal cancer according to the American Cancer Society. The lifetime risk of developing colorectal cancer according to ACS is about 1 in 23 for men and 1 in 25 for women, and there’s recently been an increase in incidence among people younger than 50 years old. Understanding risk and implementing screening strategies is essential to early detection and better outcomes for patients.

“As the medical community’s understanding of genetic links to cancer evolves, genetic testing guidelines must evolve with it,” says Robert Nussbaum, MD, chief medical officer of Invitae, who co-authored a letter in January 2022 to the NCCN formally requesting universal germline testing for patients with CRC be added to their guidelines. “In addition to excluding older people from receiving access to medically actionable information about their disease, previous guidelines were based on studies with an overrepresentation of individuals of European origin, potentially biasing and exacerbating existing disparities to those of non-European background.”

“The number of genes with targeted therapeutic or clinical management implications for colorectal cancer has significantly increased in recent years,” Nussbaum continued. “At the same time, genetic testing has become more affordable. These new guidelines will help identify more patients and their family members who might benefit from genetic assessment.”

Jewel Samadder, MD, enterprise co-leader precision/individualized cancer medicine, Mayo Clinic Comprehensive Cancer Center, added: “The INTERCEPT study supports the use of universal germline genetic testing for patients with colorectal cancer, and has shown the clinical impact of this strategy in targeted therapy implementation, personalized clinical management and cascade family testing for prevention. The NCCN update will improve access for patients with colorectal cancer to the gene-directed precision care they need.”

In addition to recommending testing be either offered or considered for all diagnosed colorectal cancer patients, the NCCN guidelines recommend subsequent cascade testing of family members of colorectal cancer patients who have pathogenic variants identified in cancer risk genes.

“This is one of the biggest challenges related to germline multigene panel testing for all colorectal cancer patients,” says Ed Esplin, MD, PhD, FACMG, FACP, clinical geneticist at Invitae and a co-author of the INTERCEPT study. “Alerting other family members to be tested to determine increased risk and implementing more intensive surveillance could lead to earlier diagnosis, significantly higher chance of curative treatment and ultimately, prevention of colorectal cancer entirely for those at increased risk.”