FROM THE JOURNAL OF CLINICAL ONCOLOGY
Current evidence supports testing colorectal cancers for genetic mutations in the epidermal growth factor receptor (EGFR) signaling pathway because the results provide clinically actionable information, according to a new clinical practice guideline published in the Journal of Clinical Oncology.
In contrast, the evidence is inadequate at this time to recommend either for or against several other mutational analyses, such as PIK3CA, PTEN, or BRAF V600 testing. This guideline is intended “to help establish standard molecular biomarker testing, guide targeted therapies, and advance personalized care for colorectal cancer patients,” said Antonia R. Sepulveda, MD, PhD, and her associates on the guideline committee.
The guideline is meant for use by oncologists and other clinicians, pathologists, laboratory employees, molecular diagnostics professionals, scientists, government agencies, nonprofit organizations, patients, and patient advocates. It includes 21 recommendations and was developed jointly by the American Society for Clinical Pathology, the College of American Pathologists, the Association for Molecular Pathology, and the American Society of Clinical Oncology. The groups based these recommendations on a comprehensive review of 123 randomized controlled studies, comparative studies, existing practice guidelines, consensus documents, and meta-analyses published in the medical literature or presented at meetings since 2008, said Dr. Sepulveda, professor of pathology and cell biology at Columbia University, New York, and her associates (J Clin Oncol. 2017 Feb 6. doi: 10.1200/JCO.2016.71.9807.
Among the strongest recommendations based on the highest-quality evidence:
• Patients with colorectal carcinoma who are being considered for anti-EGFR therapy must undergo RAS mutational testing, and KRAS and NRAS mutations are reliable predictors that this therapy will not be beneficial.
• Analysis of BRAF and MMR mutations have clear prognostic value, and MMR status is emerging as predictive in patients with advanced disease being considered for anti-PD-1/PD-L1 treatment.
• Laboratories must use validated molecular testing methods and follow accepted standards for molecular diagnostic tests. They should include in their reports a “results and interpretation” section readily understandable to oncologists and pathologists.
• Laboratories must incorporate colorectal carcinoma molecular biomarker testing methods into their overall quality improvement programs and must participate in formal proficiency testing programs or an appropriate alternative.
Several recommendations address the importance of timeliness in performing genetic testing on colorectal cancers. Professionals and staff must expedite sending specimens to specialty laboratories, performing all biomarker tests, and reporting all test results to clinicians. It is “suggested” that molecular diagnostics laboratories aim for a benchmark of 90% of reports available within 10 working days from date of receipt of the specimen.