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.
Int J Mol Sci. 2023 Aug 4;24(15):12436. doi: 10.3390/ijms241512436.
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 ( = 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.
多达 80%的去势抵抗性前列腺癌（CRPC）患者在疾病的自然史中会发生骨转移，约 25%的患者存在 DNA 损伤修复（DDR）基因的突变。本回顾性观察研究评估了 CRPC 患者 DDR 改变的发生率及其对与骨转移相关的临床结局的影响。在组织活检中按 FoundationOne 分析对 CRPC 患者的突变状态进行分析，在发生转移性 CRPC（mCRPC）时无法进行组织活检，则在液体活检中进行分析。在 mCRPC 诊断时评估 DDR 基因突变对骨相关疗效终点的影响。共纳入 121 例有骨转移的 mCRPC 患者：38 例患者至少有一种 DDR 基因突变，其余 83 例患者的 DDR 状态未突变。DDR 突变状态与骨转移体积相关（ = 0.006），但不影响 SRE（骨骼相关事件）的发生率和 SRE 发病时间。液体和组织活检均适用于 61 例患者，在分子 DDR 改变的发生率和类型方面无统计学差异。DDR 突变状态与更高的骨转移体积相关，尽管对其他骨相关疗效终点没有不利影响。
