An observational Study of the Impact of somatic DNA Repair Mutations on the Clinical Outcomes of bone metastases in Patients with Metastatic Castration-Resistant Prostate Cancer

Background: Up to 80% of mCRPC patients develop bone metastases and about 25% ones harbor mutations in DNA damage repair (DDR) genes. This retrospective observational study evaluated the prevalence of DDR alterations in mCRPC patients and their effect on the clinical outcomes of bone metastases. Methods: The mutational status of mCRPC patients was analysed per FoundationOne® analysis in tissue biopsy or, when it was not possible, in liquid biopsy (performed at the onset of mCRPC). The impact of DDR gene mutations on bone-related efficacy endpoints was evaluated at the time of mCRPC diagnoses. Results: 121 mCRPC patients with bone metastases were included: 38 patients had mutations in at least one DDR gene, the remaining 83 ones had a non mutated DDR status. DDR mutated status was associated with bone metastases volume, but did not affect SRE incidence and time to SRE onset. Liquid and tissue biopsy were both available for 61 patients, in these patients no statistically significant difference has been found in terms incidence and type of molecular DDR alterations between tissue and liquid biopsy. Conclusions: Mutated DDR status was associated with higher bone metastases volume, although a not detrimental effect on the other bone-related efficacy endpoints was observed.