Up to 80% of castration-resistant prostate cancer (CRPC) patients develop bone metastases during the natural history of disease and about 25% harbor mutations in DNA damage repair (DDR) genes. This retrospective observational study evaluated the prevalence of DDR alterations in CRPC patients and their effect on the clinical outcomes associated with bone metastases. The mutational status of CRPC patients was analyzed per FoundationOne® analysis in tissue biopsy or, when it was not possible, in liquid biopsy performed at the onset of metastatic CRPC (mCRPC). The impact of DDR gene mutations on bone-related efficacy endpoints was evaluated at the time of mCRPC diagnoses. In total, 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 (p = 0.006), but did not affect SRE (skeletal-related events) incidence and time to SRE onset. Liquid and tissue biopsies were both available for 61 patients with no statistically significant difference in terms of incidence and type of molecular DDR alterations. Mutated DDR status was associated with higher bone metastasic volume, although a not detrimental effect on the other bone-related efficacy endpoints was observed.
International journal of molecular sciences. 2023 Aug 04*** epublish ***
Maria Concetta Cursano, Emilio Francesco Giunta, Emanuela Scarpi, Chiara Casadei, Alessandra Virga, Paola Ulivi, Sara Bleve, Nicole Brighi, Giorgia Ravaglia, Francesco Pantano, Vincenza Conteduca, Daniele Santini, Ugo De Giorgi
Department of Medical Oncology, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l., 47014 Meldola, Italy., Unit of Biostatistics and Clinical Trials, Department of Medical Oncology, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l., 47014 Meldola, Italy., Biosciences Laboratory, Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l., 47014 Meldola, Italy., Medical Oncology Department, Campus Bio-Medico University of Rome, 00128 Rome, Italy., Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, Policlinico Riuniti, University of Foggia, 71122 Foggia, Italy., Medical Oncology Department, "La Sapienza" University of Rome, 00185 Rome, Italy.