Prostate cancer expert, Matthew R. Smith, MD, PhD, shares his thoughts about importance of testing in treatment of metastatic castration-resistant prostate cancer (mCRPC).
Matthew R. Smith, MD, PhD: The patient had reported no family history of prostate cancer, but that's a relatively insensitive predictor of having an inherited alteration in a cancer susceptibility gene. The lack of a family history would not discourage me from recommending both germline and tumor genetic testing in this patient. We offer germline genetic testing to all patients with recurrent or de novo metastatic disease and specific younger individuals with high-risk localized disease for the purpose of looking for either DNA repair defects or mismatch repair. Identification of either of those alterations could inform subsequent treatment decisions. For patients who do not have germline alterations or did not have prior germline testing, we'd also recommend tumor genetic testing. We typically recommend that at progression, despite first-line treatment for mCRPC because that's the first point at which that information would currently be actionable. For patients who have an identified pathogenic mutation in a DNA repair gene, whether germline or somatic, they may be candidates for a PARP inhibitor either after an androgen receptor pathway inhibitor or after an androgen receptor inhibitor and docetaxel. The prevalence of those mutations is approximately 10% of mismatch repair alterations. MSI [microsatellite instability]high is less common at about 1% to 3%. In the rare patient who has those alterations, we would consider treatment with pembrolizumab.
Transcript edited for clarity.
Case: A 82-Year-Old Man with Metastatic Castration-Resistant Prostate Cancer