The picture of colorectal cancer is grim in the U.S. and abroad. In the U.S., colorectal cancer is the third most commonly diagnosed cancer, excluding skin cancers, according to the American Cancer Society. It is also the fourth leading cause of cancer-related death. Overall, the lifetime risk of developing colorectal cancer is about one in 23 for men and one in 25 for women, with a recent increase in incidence among people younger than 50 years old. Worldwide, more than 1 million cases were diagnosed in 2020 and it was expected to cause more than half a million deaths in the same year.
Considering these factors, determining if there is a genetic cause of a patient’s colorectal cancer is crucial to identifying and applying precision therapy approaches to treat the patient. Around 20% of colorectal cancer cases may be related to heredity factors, although estimates vary. By understanding an individual patient’s risk, we can best implement screening strategies aimed at early detection and better outcomes for patients and their at-risk family members.
As an oncologist dedicated exclusively to the treatment and research of patients with gastrointestinal tumors, I witness daily the important impact of the implementation of germline genetic testing (GGT) in my clinic. The benefits involve not only the stratification of the risk of developing tumors for the patient and their family members, but also in the incorporation of highly effective therapeutic options such as immunotherapy. While studies offer evidence for the clinical utility of genetic testing for patients with colorectal cancer, recent research found there is gross underutilization of GGT for patients with colorectal cancer, even when universal GGT for patients with colorectal cancer is supported by insurance medical policy. This underutilization of GGT is a major inhibitor to disease management, and obstructs patients from receiving access to precision therapies, clinical trials, and treatment based on published management recommendations.
Based on the findings of multiple studies, the National Comprehensive Cancer Network (NCCN) recently made universal GGT the standard of care for all patients with colorectal cancer. However, genetic testing has not been systematically implemented as part of the standard of care for oncology, for both colorectal cancer and other types of cancer, despite its positive impact on disease management. This was demonstrated in the study on underutilization mentioned above, where less than 5% of eligible colorectal cancer patients received GGT. The study shows that clinically actionable genetic data is not being made available to patients diagnosed with colorectal cancer, despite universal eligibility for screening according to NCCN guidelines.
Additionally, the most diverse study to-date examining germline multi-gene panel testing in colorectal cancer patients was recently published, further supporting the need for universal GGT as the standard of care for all patients with colorectal cancer. Overall, 14.2% of patients had a pathogenic variant, with most having variants with established clinical actionability — 9.1% were in genes associated with colorectal cancer and/or polyposis, and an additional 3.1% had an otherwise clinically actionable variant. Actionable pathogenic variants confer an indication for precision therapy, potential eligibility for clinical treatment trials, or application of established, gene-specific management recommendations.
Considering that perhaps as little as 5% of patients with colorectal cancer currently have the opportunity to undergo GGT, we as a medical community need to figure out ways to address the barriers to implementation of current evidence-based universal testing policies that support precision treatment and optimal care management for the patients. The lack of guideline-endorsed, medically necessary universal GGT in colorectal cancer is leading to missed opportunities, including the best precision treatment options (such as immune checkpoint inhibitors) and enrollment in clinical trials with targeted therapies. Furthermore, the lack of personalized prevention may perpetuate health disparities in colorectal cancer.
The time is now for clinicians to better understand and leverage GGT as a reflex test for all colorectal cancer patients. To win the battle against one of the most common and lethal cancers, we must overcome barriers to GGT in colorectal cancer and implement universal GGT as part of the standard of cancer care in daily medical practice.
Pedro Uson, MD, is an oncologist working at the Center for Personalized Medicine at Hospital Israelita Albert Einstein in São Paulo. He is also a research fellow with the Mayo Clinic in Phoenix, Arizona.