Clinical implications of genomic evaluations for prostate cancer risk stratification, screening, and treatment: a narrative review

Abstract

New classification systems based on molecular features have been introduced to improve precision medicine for prostate cancer (PCa). This review covers the increasing risk of PCa and the differences in response to targeted therapy that are related to specific gene variations. We believe that genomic evaluations will be useful for guiding PCa risk stratification, screening, and treatment. We searched the PubMed and MEDLINE databases for articles related to genomic testing for PCa that were published in 2020 or earlier. There is increasing evidence that germline mutations in DNA repair genes, such as BRCA1/2 or ATM, are closely related to the development and aggressiveness of PCa. Targeted prostate-specific antigen screening based on the presence of germline alterations in DNA repair genes is recommend to achieve an early diagnosis of PCa. In cases of localized PCa, even if it has a favorable risk classification, patients under active surveillance with these gene alterations are likely to develop aggressive PCa. Thus, active treatment may be preferable to active surveillance for these patients. In cases of metastatic castration-resistant PCa, BRCA1/2 and DNA mismatch repair genes may be useful biomarkers for predicting the response to androgen receptor-targeting agents, poly (ADP-ribose) polymerase inhibitors, platinum chemotherapy, prostate-specific membrane antigen-targeted therapy, immunotherapy, and radium-223. Genomic evaluations may allow for risk stratification of patients with PCa based on their molecular features, which may help guide precision medicine for treating PCa.

Keywords: Castration resistant; Genetic testing; Prostate cancer; Prostatic neoplasms; Screening; Treatment.

Fig. 1

Schematic diagram showing clinical application of the genomic evaluation for prostate cancer screening and treatment.