Circulating Biomarkers Predictive of Treatment Response in Patients with Hormone-sensitive or Castration-resistant Metastatic Prostate Cancer: A Systematic Review.

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.

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.

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).

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.

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.

European urology oncology. 2024 May 31 [Epub ahead of print]

Michael Baboudjian, Arthur Peyrottes, Charles Dariane, Gaëlle Fromont, Jérôme Alexandre Denis, Gaëlle Fiard, Diana Kassab, Sylvain Ladoire, Jacqueline Lehmann-Che, Guillaume Ploussard, Morgan Rouprêt, Philippe Barthélémy, Guilhem Roubaud, Pierre-Jean Lamy

Department of Urology, North Academic Hospital, AP-HM, Marseille, France., Service d'Urologie et de Transplantation Rénale, Hôpital Saint-Louis, AP-HP, Université de Paris, Paris, France., Department of Urology, European Hospital Georges-Pompidou, University Paris Cité, Paris, France; UMR-S1151, CNRS UMR-S8253 Institut Necker Enfants Malades, Paris, France., INSERM UMR1069, Nutrition Croissance et Cancer, University of Tours, Tours, France; Department of Pathology, CHRU de Tours, Tours, France., INSERM UMR_S938, CRSA, Biologie et Thérapeutiques du Cancer, Saint-Antoine University Hospital, Sorbonne Université, Paris, France; Service de Biochimie Endocrinienne et Oncologique, Oncobiologie Cellulaire et Moléculaire, GH Pitié-Salpêtrière, AP-HP, Paris, France., Department of Urology, CHU Grenoble Alpes, University of Grenoble Alpes CNRS, Grenoble INP, TIMC, Grenoble, France., Association Française d'Urologie, Paris, France., Department of Medical Oncology, Platform of Transfer in Biological Oncology, Georges François Leclerc Cancer Center, Dijon, France; University of Burgundy-Franche Comté, Dijon, France; INSERM U1231, Dijon, France., INSERM U976, Immunologie Humaine, Pathophysiologie, Immunothérapie, Université Paris Cité, Paris, France; UF Oncologie Moléculaire, Hôpital Saint-Louis, AP-HP, Paris, France., Department of Urology, La Croix du Sud Hospital, Quint-Fonsegrives, France; Department of Urology, Institut Universitaire du Cancer Toulouse-Oncopole, Toulouse, France., Department of Urology, University Hospital Pitié-Salpêtrière, Paris, France; Faculty of Medicine, Sorbonne University, Paris, France., Medical Oncology Department, Institut de Cancérologie Strasbourg Europe, Strasbourg, France., Department of Medical Oncology, Institut Bergonié, Bordeaux, France., Biopathologie et Génétique des Cancers, Institut Médical d'Analyse Génomique, Imagenome, Inovie, Montpellier, France; Unité de Recherche Clinique, Clinique Beausoleil, Montpellier, France. Electronic address: .