Clinical implications of genetic aberrations in metastatic prostate cancer

The utility of tumor genetic testing in metastatic prostate cancer is rapidly evolving - especially in respect to finding prognostic and predictive biomarkers. In this review, we describe genomic aberrations in clinically relevant pathways in metastatic castration-resistant prostate cancer (mCRPC) for which therapeutic targeting is possible.

Recognizing the diverse array of genetic features within prostate cancer, the goal of testing in mCRPC is to match an individual patients' tumor with the best therapy. Approximately 20-25% of mCRPC patients have defects in DNA repair, which may be exploited with poly-ADP-ribose polymerase inhibitors, platinum-based chemotherapy, and/or immunotherapy. Choosing between the second-generation androgen inhibitors and chemotherapy may be informed through testing for androgen receptor splice variants or androgen receptor amplifications, but technology and outcomes are still being clarified. Genetic testing for mismatch repair deficiency (1% of mCRPC patients) is a standard of care, but may be expanded as other subpopulations that could respond to immunotherapy are found.

The era of precision medicine for prostate cancer is here, but is being refined. Further studies with newer technology and standardized analytical platforms are needed and must be matched with improvement in clinical care infrastructure.