Several biomarkers are useful for making treatment decisions and assessing prognosis in colorectal cancer (CRC), but others lack evidence-based support for their use outside of clinical trials, according to a new guideline.
In an effort to guide epidermal growth factor receptor (EGFR)-targeted therapies and conventional chemotherapy regimens for patients with CRC, four societies - the American Society for Clinical Pathology (ASCP), the College of American Pathologists (CAP), the Association for Molecular Pathology (AMP), and the American Society of Clinical Oncology (ASCO) - joined forces to develop evidence-based recommendations for the molecular testing of CRC tissues.
Dr. Carmen Allegra from the University of Florida Medical Center in Gainesville, co-chair of the expert panel, told Reuters Health by email, "The guidelines are dynamic and will change as new information becomes available."
For now, he said, the first four guideline statements are the most relevant:
*CRC patients being considered for anti-EGFR therapy must receive mutational testing for certain KRAS and NRAS codons.
*BRAF p.V600 mutational analysis should be performed in CRC tissue for prognostic stratification and, in deficient-mismatch-repair tumors with loss of MLH1, to evaluate for Lynch syndrome risk.
*Mismatch repair status testing should be ordered for CRC patients for the identification of those at high risk for Lynch syndrome and/or for prognostic stratification.
*There is insufficient evidence to recommend BRAF p.V600 mutational analysis to predict response to anti-EGFR inhibitors.
According to the statement, there is also insufficient evidence to recommend PIK3CA mutational analysis or PTEN analysis in CRC tissue for therapy selection outside of clinical trials.
The other 15 statements provide recommendations regarding laboratory approaches to operationalize molecular testing for predictive and prognostic molecular biomarkers, including the selection of assays, type of specimens, timing of ordering of tests, and turnaround time for testing results.
The complete guideline, along with evidence supporting each of the statements, appeared online February 6 in the Journal of Clinical Oncology.
Dr. Louis Vermeulen from the Center for Experimental and Molecular Medicine at the Academic Medical Center in Amsterdam, who was not involved with the guideline, said, "The report is very heavy on genomic tumor markers. Three fields that are entirely missed: transcriptomic classification of cancers into risk groups, for example by the consensus molecular subtypes (CMS). Also I missed the analysis of pharmacogenomic biomarkers to identify patients that should not be treated with specific agents. This is surprising. To conclude, the use of 'classic' biomarkers like CEA in serum is totally ignored; also screening is omitted with, for example, the fecal occult blood test being totally ignored."
He also noted that colon cancer and rectal cancer are covered in one guideline. "This is pretty surprising, as rectal cancer is a very different disease (not biologically but due to the location) and is treated entirely differently," Dr. Vermeulen told Reuters Health by email. "Therefore, the impact on clinical practice of specific biomarkers is very different. Only in metastatic disease can the two be compared, but in early disease implementation of specific biomarkers is likely to be entirely different."
"Unfortunately, the main message to take away from this guideline is that progress on biomarkers in CRC is very slow and that no main breakthroughs can be reported," Dr. Vermeulen concluded. "In addition, it remains unclear what to do with prognostic biomarkers without clear guidelines on how to implement them."