With more wide application of next-generation sequencing (NGS) technology in prostate cancer, increasing patients with prostate cancer have benefited from the precision treatment. Previous studies have revealed that metastatic castration-resistant prostate cancer (mCRPC) patients with DNA damage repair defects can benefit from poly (ADP-ribose) polymerase (PARP)inhibitor and platinum-based chemotherapy. As for programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, the outcome of unselected cases is limited whereas patients with mismatch repair defects have a positive response to pembrolizumab. In addition, the application of NGS plays an important role in predicting the cancer risk in family members with gene mutation.

The first edition of the NCCN Clinical Practice Guidelines in Oncology:Prostate Cancer in 2020 mentions that changes in homologous recombination DNA repair in tumors should be considered, for example: BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D and CHEK2. Consider testing mutations in these genes (germline and somatic): BRCA1, BRCA2, ATM, PALB2, FANCA; if positive, please consult genetic counseling. Currently, this information can be used for genetic counseling, early use of platinum-based chemotherapy and / or eligibility for clinical trials (eg PARP inhibitors). Clinical trials may include other candidate DNA repair genes under study as molecular biomarkers. If you find mutations in BRCA2, BRCA1, ATM, CHEK2 or PALB2 and / or have a strong family history of cancer, please consult genetic counseling to assess the possibility of hereditary breast and ovarian cancer (HBOC).

In the Standards for diagnosis and treatment of prostate cancer (2018 version), the diagnostic evaluation mentioned the role of genetic testing in the diagnosis of prostate cancer. The overall incidence of DNA repair gene mutations in male patients with metastatic or localized high-risk or low- to medium-risk prostate cancer was 11.8%, 6%, and 2%, respectively. The new understanding of the frequency of mutations in DNA repair genes is of great significance for family genetic counseling and better assessment of individual secondary cancer risk. In patients with metastatic castration-resistant prostate cancer (CRPC), the frequency of DNA repair gene mutations may be higher (up to 25%). Early research indicates that this mutation may predict the clinical benefit of poly ADP ribose polymerase (PARP) inhibitors. In particular, preliminary data indicate that the PARP inhibitor olaparib is effective in these patients. According to reports, defects in DNA repair can predict tumor sensitivity to platinum.