CASTRATION-RESISTANT PROSTATE CANCER (CRPC) ASSOCIATED WITH BRCA 1 MUTATION TREATED WITH PARP INHIBITORS: CASE REPORT AND LITERATURE REVIEW

Case Report: Male, 58 years old, surgeon, with family history of ovarian cancer, asymptomatic, sought a urologist due to rising Prostate-Specific Antigen (PSA) since 2016. On December 2017, after biopsy and confirmation by immunohistochemistry test, the diagnosis was prostate adenocarcinoma, Gleason 5 + 4, involvement varying from 15 to 90%. The staging with PSMA PET showed invasion in seminal vesicle, bladder, rectum, regional lymph nodes and presence of bone metastasis in more than 4 pelvic sites, TNM T4N1M1. On 05/22/2017, Androgen deprivation therapy (ADT) with Goserelin was started associated with chemotherapy with Docetaxel (CHAARTED TRIAL). After 8 cycles of Docetaxel, new PSMA PET showed important response, as the PSA was less than 0, 01 ng/ mg, but still persisting with metastatic lesion in the right iliac. In August 2018, developed castration-resistant prostate cancer (CRPC) having received Enzalutamide from 08/2018 to 02/2019 with short benefit and disease progression. In 02/2019, a homologous recombination repair (HRR) gene search was performed and BRCA 1 mutation with frequency of 26-30% was found. Thus, the patient was referred to study the combination of PARP inhibitors starting use of Rucaparib, obtaining complete remission of the disease. Discussion: The standard treatment of metastatic prostate cancer is androgen deprivation therapy associated with chemotherapy or new generation hormonotherapy (Abiraterone, Enzalutamide or Apalutamide). However, the association with mutation in HRR genes turns a more aggressive disease and is responsible for up to 20% of CRPC cases, which makes the conventional treatment not much effective. The most common genes affected in this scenario are BRCA1 and BRCA2, and as the patient showed a mutation in BRCA1, whose inactivation checks sensibility to PARP inhibitors, it led him to participate in the mentioned study, which has proven to be beneficial in the treatment of breast and ovarian cancer and, for this reason, studies have proposed its use for other types of tumors associated with BRCA1 / 2 mutations, including prostate cancer. Final Comments: Prostate cancer associated with mutation in DNA damage repair genes has limited therapeutic and it’s associated with higher aggressiveness and poor prognosis. Therefore, research for biomarkers in order to achieve effective target therapies are important to treatment success.