New Molecular Biomarkers in Colorectal Cancer Guideline Released

New Molecular Biomarkers in Colorectal Cancer Guideline Released

Dr. Antonia Sepulveda, credit Michael Dames
A new molecular biomarkers in colorectal cancer guideline was published in the American Journal of Clinical Pathology, the Journal of Molecular Diagnostics, the Archives of Pathology & Laboratory Medicine, and the Journal of Clinical Oncology. It represented an unprecedented collaboration between four organizations: the College of American Pathologists, the American Society for Clinical Pathology, the Association for Molecular Pathology, and ASCO.

The guideline, organized into 21 recommendations of how to use molecular biomarkers to diagnose and treat patients with colorectal cancer, is the direct result of an extensive literature search conducted by the joint clinician–pathologist panel.

Antonia Sepulveda, MD, PhD, of the Columbia University College of Physicians and Surgeons, represented the Association for Molecular Pathology on the panel. She said the new guideline’s comprehensive scope is what distinguishes it from previous guidelines. 

Dr. Carmen J. Allegra
“This guideline is fundamentally different because we address all known molecular biomarkers that can be used for treatment decisions in patients with colorectal cancer,” Dr. Sepulveda said. “Other guidelines have essentially focused on one or a fairly limited number of biomarkers.”

Carmen J. Allegra, MD, of the University of Florida Health, represented ASCO on the panel. He said some of the biomarkers featured for the first time in the new guideline include RAS, PTEN, BRAF, and PIK3CA.

“Prior guidelines might simply focus on a few specific KRAS mutations,” Dr. Allegra said.

Not only does the guideline feature a more comprehensive list of molecular biomarkers implicated in colorectal cancer, but it is one of the first to address the clinical along with the pathologic applications of these biomarkers, Dr. Sepulveda said.

In terms of clinical practice, Dr. Allegra said the guideline might help an oncologist decide whether to treat a patient with MMR-deficient colorectal cancer with immunotherapy.

Dr. Stanley R. Hamilton
MMR-deficient colorectal cancer is “responsive to new immunotherapies like checkpoint inhibitors,” Dr. Allegra said. “There were pretty interesting data presented at the ASCO Annual Meeting 2 years in a row that supported this concept.”

The guideline also recommends that patients with RAS, KRAS, or NRAS mutations should not be treated with anti-EGFR antibodies. Testing for these mutations is valuable, as it can help patients avoid unnecessary treatment costs and toxicities associated with anti-EGFR treatment.

Stanley R. Hamilton, MD, of The University of Texas MD Anderson Cancer Center, represented the College of American Pathologists on the panel. He said the guideline will inform pathologists and their lab scientists of the diagnostic tests available and how often to perform them.

According to Dr. Hamilton, the guideline conveys the importance of testing colorectal cancers for MMR deficiency—not only for diagnosis of Lynch syndrome, but for prognostic stratification as well.

Although most of the recommendations in the guideline are based on current cancer research, Dr. Allegra said some point to areas where future research is needed, such as for patients with BRAF-mutant colorectal cancer.

“Clinical trials are testing combination therapies that might substantially and rapidly alter guidance on BRAF inhibitors for BRAF-mutant tumors,” Dr. Sepulveda said.

And when these clinical trials are completed, she is confident the guideline panel will be ready to incorporate the results.

“Our guidelines are being developed to provide frequent, as-needed updates to keep them current,” Dr. Sepulveda said. “Updates that may be needed soon are MMR or microsatellite instability testing for checkpoint immunotherapies and recommendations on the use of liquid biopsies for colorectal cancer management.”

–Danielle Prieur