TY - JOUR
T1 - Tissue- and Blood-derived Genomic Biomarkers for Metastatic Hormone-sensitive Prostate Cancer
T2 - A Systematic Review
AU - Van der Eecken, Kim
AU - Vanwelkenhuyzen, Jan
AU - Deek, Matthew P.
AU - Tran, Phuoc T.
AU - Warner, Evan
AU - Wyatt, Alexander W.
AU - Kwan, Edmond M.
AU - Verbeke, Sofie
AU - Van Dorpe, Jo
AU - Fonteyne, Valérie
AU - Lumen, Nicolaas
AU - De Laere, Bram
AU - Ost, Piet
N1 - Publisher Copyright:
Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2021/12/1
Y1 - 2021/12/1
N2 - CONTEXT: Multiple studies have reported on the genomic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC). The impact of these findings on prognostication, treatment selection, and clinical trial design remains unclear. OBJECTIVE: To summarise genomic alteration prevalences in liquid and/or tissue biopsies, infer their clinical implications, and compare genomic alteration frequencies across different disease states and clinical phenotypes. EVIDENCE ACQUISITION: The PubMed and Web of Knowledge databases were systematically searched up to January 2021. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal tools. EVIDENCE SYNTHESIS: In total, 11 studies encompassing 1682 mHSPC patients were included. High-volume disease was associated with more frequent alterations in TP53, DNA damage repair, and Wnt pathways. Tumours from patients with de novo mHSPC were enriched for alterations in TP53 and CDK12 compared with recurrent disease. Alterations in AR, TP53, cell cycle signalling, and MYC were associated with a poorer clinical outcome. A comparative analysis of gene alteration frequencies across disease states revealed a relative increase from localised to castration-resistant tumours, with noteworthy enrichment of CTNNB1 alterations in mHSPC (5%), which warrants further investigation. This study was limited by variability in methodology and definitions used among the eligible studies, including differences in sequencing methods, analytes (being either tissue or liquid), alteration calling thresholds, and target patient populations with a relative under-representation of recurrent metastatic disease. CONCLUSIONS: Several genomic alterations are associated with differential prognosis and clinical phenotypes in mHSPC. We urge that emerging data on these potential predictive biomarkers must be validated in biomarker-driven randomised controlled trials before any clinical implementation. Alignment of the assay methodology and reporting will be critical for ensuring rapid scalability. PATIENT SUMMARY: We reviewed current data on genomic alterations of metastatic hormone-sensitive prostate cancer, and summarised key genomic subtypes that associate with specific clinical phenotypes and treatment outcomes.
AB - CONTEXT: Multiple studies have reported on the genomic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC). The impact of these findings on prognostication, treatment selection, and clinical trial design remains unclear. OBJECTIVE: To summarise genomic alteration prevalences in liquid and/or tissue biopsies, infer their clinical implications, and compare genomic alteration frequencies across different disease states and clinical phenotypes. EVIDENCE ACQUISITION: The PubMed and Web of Knowledge databases were systematically searched up to January 2021. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal tools. EVIDENCE SYNTHESIS: In total, 11 studies encompassing 1682 mHSPC patients were included. High-volume disease was associated with more frequent alterations in TP53, DNA damage repair, and Wnt pathways. Tumours from patients with de novo mHSPC were enriched for alterations in TP53 and CDK12 compared with recurrent disease. Alterations in AR, TP53, cell cycle signalling, and MYC were associated with a poorer clinical outcome. A comparative analysis of gene alteration frequencies across disease states revealed a relative increase from localised to castration-resistant tumours, with noteworthy enrichment of CTNNB1 alterations in mHSPC (5%), which warrants further investigation. This study was limited by variability in methodology and definitions used among the eligible studies, including differences in sequencing methods, analytes (being either tissue or liquid), alteration calling thresholds, and target patient populations with a relative under-representation of recurrent metastatic disease. CONCLUSIONS: Several genomic alterations are associated with differential prognosis and clinical phenotypes in mHSPC. We urge that emerging data on these potential predictive biomarkers must be validated in biomarker-driven randomised controlled trials before any clinical implementation. Alignment of the assay methodology and reporting will be critical for ensuring rapid scalability. PATIENT SUMMARY: We reviewed current data on genomic alterations of metastatic hormone-sensitive prostate cancer, and summarised key genomic subtypes that associate with specific clinical phenotypes and treatment outcomes.
KW - Circulating tumour DNA
KW - Genomics
KW - Hormone sensitive
KW - Liquid biopsy
KW - Metastatic prostate cancer
KW - Precision oncology
KW - Sequencing
KW - Tissue biopsy
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U2 - 10.1016/j.euo.2021.10.005
DO - 10.1016/j.euo.2021.10.005
M3 - Review article
C2 - 34801437
AN - SCOPUS:85122842631
SN - 2588-9311
VL - 4
SP - 914
EP - 923
JO - European Urology Oncology
JF - European Urology Oncology
IS - 6
ER -