NEW YORK (GenomeWeb) – The National Comprehensive Cancer Network issued updated prostate cancer guidelines that include new information about the role of family history, mutations in DNA repair genes, and testing for microsatellite instability and mismatch repair status for potential treatment with the Merck drug Keytruda (pembrolizumab).
This latest update recommends that men with regional and metastatic disease should have tumor testing for homologous recombination gene mutations and have their tumors assessed for microsatellite instability or mismatch repair deficiency.
"DNA analysis for MSI and IHC for MMR are different assays measuring the same biological effect. If MSI-H or dMMR is found, refer to genetic counseling to assess for the possibility of Lynch syndrome," the NCCN states in a new footnote. "MSI or dMMR indicate eligibility for pembrolizumab in later lines of treatment for castration-resistant prostate cancer." The US Food and Drug Administration last year approved Keytruda for patients with advanced, solid tumors that were MSI-high or dMMR.
Additionally, the group suggests that clinicians consider testing patients for germline and somatic mutations in DNA repair genes BRCA1, BRCA2, ATM, PALB2, FANCA, and referring patients who have these mutations for genetic counseling. "At present, this information may be used for genetic counseling, early use of platinum chemotherapy, or eligibility for clinical trials (e.g., PARP inhibitors)," the NCCN states in a footnote.
The NCCN guidelines also includes updated language recommending germline genetic testing and counseling for all men with high risk, very high risk, regional, or metastatic prostate cancer. "The prevalence of inherited homologous recombination gene mutations in men with metastatic or localized high risk was found to be 11.8 percent and 6 percent, respectively," the group said.
In the latest guidelines, the NCCN continues to list GenomeDx's Decipher, Genomic Health's Oncotype DX Prostate Cancer, Myriad Genetics' Prolaris, and Metamark's ProMark as available molecular tests for prostate cancer prognosis for men with low or favorable intermediate risk disease. The group now suggests consideration of the Decipher assay for men with PSA persistence or recurrence (PSA levels that fail to go down after radical prostatectomy or rise again after falling.)