目的:转移性前列腺癌(mPCa)的基因组改变可以预测靶向治疗的疗效。这些改变不仅可以在组织中识别,而且可以直接在生物液体中识别(即,液体活检),主要是血。液体活检可能代表监测接受mPCa治疗的患者的更安全且侵入性较小的替代方案。当前的研究集中在新型预测生物标志物的描述和验证,以改善mPCa中的精准医学。我们的目的是系统地回顾目前关于液体活检生物标志物预测mPCa治疗反应的证据。
方法:我们系统地搜索了Medline,WebofScience,和2013年3月至2024年2月期间mPCa循环生物标志物出版物的循证网站进行审查。终点是:总生存期的预测,生化或放射学治疗后无进展生存期(化疗,雄激素剥夺疗法,雄激素受体途径抑制剂[ARPIs],免疫疗法,或PARP抑制剂[PARPIs])。对于每个生物标志物,临床有效性的证据水平(LOE)归因于:LOEIA和IB,高水平的证据;LOEIIB和IIC,中级水平;以及LOEIIIC和LOEIV-VD,弱水平。
在转移性激素敏感性(mHSPC)和去势抵抗性前列腺癌(mCRPC)中评估了每种生物标志物对几种疗法的反应的预测值。在mCRPC患者中,BRCA1/2或ATM突变预测对ARPIs(LOEIB)和PARPIs(LOEIIB)的反应,而循环肿瘤细胞(CTC)中的AR-V7转录物或AR-V7蛋白水平可预测对ARPIs和紫杉烷类(LOEIB)的反应。CTC定量预测对卡巴他赛的反应,阿比特龙,和镭-223(LOEIIB),而TP53改变预测对177Lu前列腺特异性膜抗原放射性配体治疗(LOEIIB)的反应。在第一个治疗线之前和随后的治疗线之前,循环肿瘤DNA中的AR拷贝数预测了对多西他赛的反应,卡巴他赛,和ARPIs(LOEIIB)。在mHSPC中,淋巴细胞中的DNA损伤预示着对镭-223(LOEIIB)的反应。
结论:BRCA1/2,ATM,在液体活检中检测到的AR改变可能有助于临床医生管理mPCa患者。其他循环生物标志物未达到常规临床应用所需的LOE,应在前瞻性独立研究中进行验证。
结果:我们回顾了评估血液或尿液中生物标志物治疗转移性前列腺癌价值的研究。证据表明,一些生物标志物可以帮助选择符合特定治疗条件的患者。
OBJECTIVE: Metastatic prostate cancer (mPCa) harbors genomic alterations that may predict targeted therapy efficacy. These alterations can be identified not only in tissue but also directly in biologic fluids (ie, liquid biopsies), mainly blood. Liquid biopsies may represent a safer and less invasive alternative for monitoring patients treated for mPCa. Current research focuses on the description and validation of novel predictive biomarkers to improve precision medicine in mPCa. Our aim was to systematically
review the current evidence on liquid biopsy biomarkers for predicting treatment response in mPCa.
METHODS: We systematically searched Medline, Web of Science, and evidence-based websites for publications on circulating biomarkers in mPCa between March 2013 and February 2024 for
review. Endpoints were: prediction of overall survival, biochemical or radiographic progression-free survival after treatment (chemotherapy, androgen deprivation therapy, androgen receptor pathway inhibitors [ARPIs], immunotherapy, or PARP inhibitors [PARPIs]). For each biomarker, the level of evidence (LOE) for clinical validity was attributed: LOE IA and IB, high level of evidence; LOE IIB and IIC, intermediate level; and LOE IIIC and LOE IV-VD, weak level.
UNASSIGNED: The predictive value of each biomarker for the response to several therapies was evaluated in both metastatic hormone-sensitive (mHSPC) and castration-resistant prostate cancer (mCRPC). In patients with mCRPC, BRCA1/2 or ATM mutations predicted response to ARPIs (LOE IB) and PARPIs (LOE IIB), while AR-V7 transcripts or AR-V7 protein levels in circulating tumor cells (CTCs) predicted response to ARPIs and taxanes (LOE IB). CTC quantification predicted response to cabazitaxel, abiraterone, and radium-223 (LOE IIB), while TP53 alterations predicted response to 177Lu prostate-specific membrane antigen radioligand treatment (LOE IIB). AR copy number in circulating tumor DNA before the first treatment line and before subsequent lines predicted response to docetaxel, cabazitaxel, and ARPIs (LOE IIB). In mHSPC, DNA damage in lymphocytes was predictive of the response to radium-223 (LOE IIB).
CONCLUSIONS: BRCA1/2, ATM, and AR alterations detected in liquid biopsies may help clinicians in management of patients with mPCa. The other circulating biomarkers did not reach the LOE required for routine clinical use and should be validated in prospective independent studies.
RESULTS: We reviewed studies assessing the value of biomarkers in blood or urine for management of metastatic prostate cancer. The evidence indicates that some biomarkers could help in selecting patients eligible for specific treatments.