Prospective Study of Homologous Recombination Repair Gene Mutation Prevalence in Patients With Advanced Prostate Cancer From Latin America: Challenges and Future Approaches.

The prevalence of homologous recombination repair gene mutations (HRRm) in patients with metastatic castration-resistant prostate cancer (mCRPC) in Latin America and the Caribbean (LAC) is unknown. Prevalence of homologous Recombination repair (HRR) gene mutatiOns in patientS with metastatic castration resistant ProstatE Cancer in LaTin America (PROSPECT) aimed to determine this prevalence and to describe the demographic and clinical characteristics of the participants.

This was a prospective, cross-sectional, multicenter study across 11 cancer centers in seven LAC countries. After informed consent, all eligible participants underwent genomic testing by provided blood samples for germline HRR testing; they also provided PC tissue blocks if available for somatic HRR testing.

Between April 2021 and April 2022, 387 patients (median age, 70 years [49-89], 94.3% Eastern Cooperative Oncology Group 0-1) with mCRPC were enrolled in the study. Almost 40% of them had a family history of cancer, and the overall time from their initial PC and mCRPC diagnosis was 3 years and 1 year, respectively. The overall prevalence of germline HRRm was 4.2%. The mutations detected included the genes CHEK2 (n = 4, 1%), ATM (n = 3, 0.8%), BRCA2 (n = 3, 0.8%), BRIP1 (n = 2, 0.5%), RAD51B (n = 2, 0.5%), BRCA1 (n = 1, 0.3%), and MRE11 (n = 1, 0.3%). The prevalence of somatic HRRm could not be assessed because of high HRR testing failure rates (79%, 199/251) associated with insufficient DNA, absence of tumor cells, and poor-quality DNA.

Despite the study's limitations, to our knowledge, PROSPECT was the first attempt to describe the prevalence of HRRm in patients with PC from LAC. Notably, the germline HRRm prevalence in this study was inferior to that observed in North American and European populations. The somatic HRR testing barriers identified are being addressed by several projects to improve access to HRR testing and biomarker-based therapies in LAC.

JCO precision oncology. 2024 May [Epub]

Ray Manneh, Carmen Alaez Verson, Angel Martin, Arturo Delgado, Pedro H Isaacsson Velho, Alejandro Manduley, Luis Tejado, Yolanda Rodríguez, Carmen Vargas, Pedro C Barata

Sociedad de Oncología y Hematología del Cesar, Valledupar, Colombia., Laboratorio de Diagnóstico Genómico, Instituto Nacional de Medicina Genómica, Ciudad de Mexico, Mexico., Instituto Alexander Fleming, Buenos Aires, Argentina., Centro Médico Nacional Siglo XXI, Ciudad de Mexico, Mexico., Hospital Moinhos de Vento, Porto Alegre, Brazil., Centro de Especialidades Urológicas de Panama, Panama City, Panama., AstraZeneca, Ciudad de Mexico, Mexico., AstraZeneca AG, Baar, Switzerland., University Hospitals Seidman Cancer Center, Cleveland, OH.