Integrating BRCA testing into routine prostate cancer care: a multidisciplinary approach by SIUrO and other Italian Scientific Societies

Abstract

Prostate cancer (PCa) ranks among the most prevalent malignancies in men, with notable associations to Hereditary Breast and Ovarian Cancer Syndrome (HBOC) and Lynch Syndrome, both linked to germline likely pathogenetic variant/pathogenetic variant (LPV/PV) in genes involved in DNA repair. Among these genes, BRCA2 in PCa patients is the most frequently altered. Despite progresses, challenges in BRCA carriers detection persist, with a quarter of PCa cases lacking family history.To address these challenges, a multidisciplinary expert panel from six Italian Scientific Societies, formulated a care pathway to integrate BRCA testing into routine clinical practice in different Italian geographical areas.The development process, promoted by the Italian Society of Uro-Oncology (SIUrO), involved three key stages. A preliminary meeting convened teams from different Italian regions to establish minimal requirements for a mini-counseling program (defined as a pre-test consultation carried out by clinicians responsible of patients' management) and propose care pathway models. At the same time, a comprehensive survey was launched to highlight regional variations in BRCA testing and identify eventual obstacles to testing activities. A subsequent meeting synthesized care pathway proposals and formulated a unified framework, acknowledging regional legislative variations as enriching factors. Lastly, implementation of the unified framework was promoted by the project faculty and identified regional team leaders.Survey results revealed significant regional disparities in BRCA testing, reimbursement policies, and access to genetic counseling. The proposed mini-counseling program outlined essential steps for patient identification, information provision, and multidisciplinary review, aiming to streamline BRCA testing processes.Expert recommendations emphasized offering tumor genetic testing to metastatic PCa patients eligible for PARP-i treatment and outlined criteria for genetic counseling and germline testing. Key considerations included family history and tumor characteristics.In conclusion, the proposed care pathway represents a critical step towards integrating BRCA testing into routine PCa care, aiming to optimize patient management and familial risk assessment within the constraints of the Italian healthcare system.

Keywords: BRCA; Care pathway; Genetic counseling; Mini-counseling; Prostate cancer.

Fig. 1

Flowchart of care pathway Patients affected by metastatic Prostate Cancer: The multidisciplinary team selects patients affected by metastatic prostate cancer eligible for PARP inhibitor treatment. Caring clinicians conduct pre-test mini counseling, gathering personal and family history through a proposed questionnaire (Annex 1) and obtaining written informed consent or dissent. Regardless of familial risk clinicians will proceed with a BRCA tumor testing. If archival tissue is inadequate for analysis, clinicians should consider re-biopsy of the metastatic site. Alternatively, liquid biopsy or germline testing should be considered. If BRCA (likely) pathogenetic variants are detected at the somatic level (+), patients will have access to PARP inhibitor treatment and genetic counseling for germline testing. In the case of positive (+) germline testing, patients and family members will be referred to a geneticist for testing and eventual surveillance. Patients affected by localized Prostate Cancer: The multidisciplinary team selects patients affected by localized Prostate Cancer who meet criteria for personal or familial risk. Caring clinicians conduct pre-test mini counseling, gathering personal and family history through a proposed questionnaire (Annex 1), and require genetic counselling. The geneticist will decide whether to perform germline testing and which panel to use based on the familial risk. In case of a positive germline test, patients and family members will be referred to a geneticist for testing and surveillance