Germline Testing for Cancer Genes in Everyone With Colorectal Cancer?
Douglas K. Rex, MD, MASGE, reviewing Uson PLS Jr, et al. Clin Gastroenterol Hepatol 2021 Apr 12.
Current guidelines recommend universal screening of patients with newly diagnosed colorectal cancer (CRC) for tumor features of Lynch syndrome. This is usually done by immunohistocompatibility (IHC) staining of tumors or microsatellite instability (MSI) testing. When IHC is positive or MSI is high, genetic testing is indicated (except with MLH1 protein absence plus BRAF mutation). MSI-high cancers may be selected for PD1 or PDL1 inhibitors such as pembrolizumab.
Should genetic testing of patients with CRC be expanded? In a study from 3 related U.S. centers, consecutive patients with CRC underwent germline genetic sequencing of 83 cancer-related genes.
Among 361 patients, 56 (15.5%) had pathogenic gene variants (PGVs) in cancer genes, but 34 of those patients were considered to have clinically actionable findings that would not be detected by current guideline-recommended tumor screening or a CRC-specific gene panel. PGVs were more common in young patients, those with a family history of CRC, and those without a history of smoking, diabetes, hypertension, or obesity. PGVs were more common in rectal cancer.
Only 5 patients had actual treatment changes based on testing, including 4 patients with Lynch syndrome that was treated with immune checkpoint inhibitors and 1 patient with familial adenomatous polyposis (FAP), who also had 200 polyps at colonoscopy.
Patients with PGVs were offered genetic screening of their relatives, but only 16% had a relative accept testing.
COMMENTWill we see calls for more complete genetic screening of patients with CRC? The panel of genes tested in the assay used here includes genes with implications for treatment selection. However, of the 34 patients in this study with PGVs with the potential for treatment alterations, 5 patients had actual treatment changes based on results (4 with Lynch syndrome and 1 with FAP) that would have been recognized by current tumor screening or colonoscopy findings. Thus, the implementation of more extensive genetic testing on a systematic basis may follow from a more widespread acceptance that the findings should alter cancer treatment.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S)
Uson PLS Jr, Riegert-Johnson D, Boardman L, et al. Germline cancer susceptibility gene testing in unselected patients with colorectal adenocarcinoma: a multi-center prospective study. Clin Gastroenterol Hepatol 2021 Apr 12. (Epub ahead of print) (https://doi.org/10.1016/j.cgh.2021.04.013)
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