Real-World Data Shows Low Adoption of Recommended Biomarker Testing in mCRC

A retrospective study has shown that only 40% of patients with metastatic colorectal cancer received biomarker testing prior to treatment, as recommended in the National Comprehensive Cancer Network guidelines. As a result, patients receive less effective therapies and experience serious adverse events, according to a press release from Guardant Health.

Stuart Goldberg, MD

A retrospective study has shown that only 40% of patients with metastatic colorectal cancer (mCRC) received biomarker testing prior to treatment, as recommended in the National Comprehensive Cancer Network (NCCN) guidelines. As a result, patients receive less effective therapies and experience serious adverse events, according to a press release from Guardant Health.1

“For over a decade, medical guidelines have recommended multigene mutation testing for mCRC 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,” said Stuart Goldberg, MD, chief scientific officer at COTA, Inc., and a lead study investigator. “Personalized medicine holds great promise for achieving better outcomes, but we will not see the benefits until genomic testing is routinely adopted into clinical practice.”

In the multicenter retrospective study, 1,497 patients were identified who had been treated between January 1, 2013, and December 31, 2017. These patients had eitherRAS-mutant,BRAF-mutant colorectal cancer, or microsatellite instability (MSI). The testing rates for these patients were 41% for patients withRASmutations, 43% for those withBRAFmutations, and 51% for those with MSI.2

Disparities were observed in the overall population of patients. Male patients were less likely to be tested than female patients (36%vs.44%; P< .01), and patients above the age of 65 were less likely to be tested than those under 65 (35% vs.44%; P< .001). Suboptimal testing was also observed in patients who progressed from early-stage disease versus metastatic disease (24% vs.42%; P< .001), and those treated in a community setting versus academic centers (29% vs.44%; P< .001) were less likely to be tested than others. There was also a subgroup of participants (12%) treated with anti-EGFR therapies (n = 177), and only 28% (n = 50) of them received the complete guideline-aligned biomarker testing that was required to determine their eligibility for anti-EGFR therapy.

Across the subgroups where testing rates varied, patients withRASand NRASmutations, testing adoption was higher in patients treated in an academic center compared with community centers (44% vs.29%; P< .001). Complete guideline-aligned testing was also more prominent in patients who presented with de novo metastatic disease versus those who progressed from an earlier stage (43% vs. 25%; P< .001), those diagnosed at age < 65 years versus age ≥ 65 years (44% vs.35%;P< .001), and in female patients versus male patients (45% vs.37%; P< .01).

In participants withBRAFmutations, individuals had higher testing rates in academic centers versus community centers (47%vs.25%;P< .001), with metastatic disease versus early-stage disease (46% vs. 23%; P< .001), and if there were female versus male (48% vs. 38%; P< .05).

The final subgroup of patients, which consisted of individuals with MSI and deficient mismatch repair, the testing rates were consistent with those observed in theRAS-,NRAS-,andBRAF-mutant&nbsp;subgroups.

Another key finding in the study was that the use of comprehensive gene panels as opposed to single-gene panels could potentially increase the guideline-recommended testing rate by 50%.

In the study, real-world data were extracted from the medical records of patients with pathologically confirmed mCRC who were treated at 23 community or academic practices throughout the United States. Additionally, 258 oncologists from in Arkansas, Maryland, Michigan, New Jersey, New York, and Tennessee contributed to these data via Business Associate Agreements.

Each medical record was reviewed by trained COTA abstractors who looked for mentions of biomarker testing in the records that included clinical progress notes, laboratory reports, and pathology reports. About 10% of the medical records went through a second review process with a different abstractor.

Patients were defined as tested patients if their record showed evidence of any type of biomarker testing from any vendor, and during any time during the course of their treatment. The study investigators considered a patient’s biomarker testing to be guideline-aligned if it was consistent with the guidelines from the NCCN.

The study population was diverse. Of the 1,497 patient records, 50% were female (n = 742) and 50% were male (n = 754), 62% of patients were younger than 65 (n = 935) and 37% were aged 65 years or older (n = 559). Patients were categorized into 5 racial groups, which were white, black, Asian, other, and undeclared. Seventy percent of patients in the study were white (n = 1047) , 9% were black (n = 131), 5% were Asian (n = 79), and 9% were identified as “other” or “undeclared (n = 141).” Eleven percent of patients were between stage 0 to III at the time of diagnosis (n = 172), while a much larger proportion of patients (89%), were stage IV or higher (n = 1,325). Additionally, the majority of the records extracted were of patients treated in an academic setting (77% ), while 23% of patients were treated in community centers.

The investigators of this retrospective study concluded that biomarker testing rates in the United States are suboptimal and that following the NCCN guidelines could improve outcomes and lower treatment costs for patients. However, the investigators also noted that more research needs to be done.

The study authors wrote, “There are multiple limitations of this study. Mainly, the study relied on medical record input for database review. Patients whose genomic testing was not documented in the medical record could have led to errors of omission. It is also possible that patients had biomarker testing before being referred to the centers included in this data set, and this testing was not documented in the record. In addition, data were collected only on patients with colon cancer. Guideline recommendations forKRAS,NRAS,BRAF, and MSI all specify testing for mCRC.

Prior studies suggest that patients with rectal cancer are tested less frequently than those with colon cancer. Therefore, true testing rates for mCRC may be lower than what is presented in this mCRC study. It is also important to note that more than three-quarters of the patients in the cohort were treated at academic centers. In 2017, 94% of the cohort was treated at academic centers. Our data demonstrate that patients were more frequently tested for NRAS,BRAF, and dMMR if they were treated at an academic center. With only 19% of the cohort being nonwhite, we were unable to make statistically significant conclusions about the impact of race on genotyping rates. This is an important factor that should be further explored in diverse patient cohorts.”

The results of the study were similar to trends observed in patients with late-stage lung cancer. In these patients, the clinical adoption of genomic profiling is well below the recommendations of the NCCN.1

“Newly available therapies routinely help some people with metastatic colorectal cancer gain a year or 2 of life, but these novel treatments cannot be applied unless comprehensive genotyping is routinely performed,” said Richard Lanman, MD, global chief medical officer, Guardant Health.


  1. Study Shows Only 40 Percent of Patients with Metastatic Colon Cancer Receive Guideline-Recommended Biomarker Testing [press release]. Redwood City, California: Guardant Health, Inc.; December 11, 2019. Accessed December 11, 2019.
  2. Gutierrez ME, Price KS, Lanman RB, et al. Genomic Profiling for KRAS, NRAS, BRAF, Microsatellite Instability, and Mismatch Repair Deficiency Among Patients With Metastatic Colon Cancer.JCO Precision Oncology. 2019 :3, 1-9.