Despite Guidelines, Some with Metastatic Colon Cancer Not Tested for Biomarkers

A retrospective study found that 40% of all patients with metastatic colon cancer are not tested according to guideline recommendations for biomarker testing.

Despite guideline recommendations for biomarker testing and significant therapeutic recommendations, a study published in JCO Precision Oncology indicated that 40% of all patients with metastatic colon cancer are not tested, according to guidelines. 

Adherence to the guideline recommendations would potentially reduce exposure to expensive and less effective therapies, resulting in improved patient outcomes. 

“Newly available therapies routinely help some people with metastatic colorectal cancer gain a year or two of life, but these novel treatments cannot be applied unless comprehensive genotyping is routinely performed,” Richard Lanman, MD, Guardant Health Global chief medical officer, said in a press release. “Just as concerning was that 28% of patients received targeted treatments without being tested, and for some we would have known in advance that the treatment was not going to work.”

In this retrospective study of 1,497 patients with metastatic colon cancer from 2013-2017, guideline biomarker testing rates for RASBRAF, and microsatellite instability/mismatch repair deficiency (MSI/dMMR) over this study period were 41%, 43%, and 51%, respectively. Of the 177 (12%) of participants that received anti-epidermal growth factor receptor therapy, only 28% had complete guideline-aligned biomarker testing.

Patients were more likely to have guideline-aligned testing for RAS and BRAF if they were treated at an academic center, were diagnosed with de novo metastatic disease, and were female. Additionally, patients < 65 years of age were more likely to have guideline-aligned RAS testing.

The proportion of patients who had individual testing for KRASNRAS, and BRAF by NGS increased each year of the study; however, the number of patients receiving guideline-aligned genotyping was lower in 2017 than it was at the start of the study. These findings are consistent with the rates seen in late-stage lung cancer, where clinical adoption of genomic profiling remains below the recommended standard-of-care guidelines.

“For over a decade, medical guidelines have recommended multigene mutation testing for metastatic colon and rectal cancer patients to ensure patients receive the optimal treatment available. While the study shows that testing has improved slightly, the disappointing reality is that the majority of patients, including those receiving targeted treatments, are not being comprehensively tested,” Stuart Goldberg, MD, chief scientific officer at COTA, explained in a press release. 

Testing methodology was specified in the majority of cases (79% for KRAS, 92% for NRAS, 87% for BRAF, and 94% for MSI/dMMR). Though polymerase chain reaction (PCR) was the most common methodology for KRAS in 2013, next-generation sequencing (NGS) was the dominant testing methodology for KRAS thereafter and for NRAS and BRAF throughout the entire period of the study. 

The American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines currently recommend biomarker testing for all patients with metastatic colon cancer to screen for genomic alterations in KRAS, NRAS, BRAF, ERBB2 (HER2), NTRK and MSI, in order to help guide more effective treatment decisions. Professional guidelines continue to be updated as new therapies come to market.

Though NCCN guidelines do not currently specify a preferred methodology for biomarker testing, a sequential approach to testing multiple biomarkers increases challenges with time insufficiency, turnaround time, and cost. According to the researchers, if every patient in this study who was tested for at least 1 biomarker had a tissue- or plasma-based NGS panel with comprehensive coverage of extended RASBRAF, and MSI, they would have observed an almost 50% increase in the percentage of patients who had guideline-aligned biomarker testing (from 40% to 59%).

According to the American Cancer Society of Clinical Oncology, an estimated 145,600 adults in the U.S. will be diagnosed with colorectal cancer this year. Though colorectal cancer mainly affects older adults, there is a rising incidence in people who are younger.


1. Gutierrez ME, Price KS, Lanman RB, et al. Genomic Profiling for KRASNRASBRAF, Microsatellite Instability, and Mismatch Repair Deficiency Among Patients With Metastatic Colon Cancer. JCO Precision Oncology. doi:10.1200/P0.19.11274.

2. Study Shows Only 40 Percent of Patients with Metastatic Colon Cancer Receive Guideline-Recommended Biomarker Testing [news release]. Redwood City, California. Published December 11, 2019. Accessed December 12, 2019.

3. American Society for Clinical Oncology. Colorectal Cancer: Statistics. Doctor-Approved Patient Information ASCO website. Published November 2018. Accessed December 12, 2019.