Kim Van der Eecken1, Jan Vanwelkenhuyzen2, Matthew P Deek3, Phuoc T Tran3, Evan Warner4, Alexander W Wyatt5, Edmond M Kwan6, Sofie Verbeke7, Jo Van Dorpe7, Valérie Fonteyne8, Nicolaas Lumen9, Bram De Laere10, Piet Ost11. 1. Department of Pathology, Ghent University Hospital, Ghent, Belgium; Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium. Electronic address: kivdreec.vandereecken@ugent.be. 2. Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium; Center for Medical Genetics, Department of Biomolecular Medicine, Ghent University Hospital, Ghent, Belgium. 3. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 4. Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada. 5. Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada. 6. Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia; Department of Medical Oncology, Monash Health, Melbourne, Australia. 7. Department of Pathology, Ghent University Hospital, Ghent, Belgium; Cancer Research Institute (CRIG), Ghent, Belgium. 8. Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium; Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium. 9. Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium; Department of Urology, Ghent University Hospital, Ghent, Belgium. 10. Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden. 11. Cancer Research Institute (CRIG), Ghent, Belgium; Department of Human Structure and Repair, Ghent University, Belgium; Department of Radiation Oncology, Iridiumnetwerk, Antwerp, Belgium.
Abstract
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.
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.
Authors: Philip Sutera; Matthew P Deek; Kim Van der Eecken; Alexander W Wyatt; Amar U Kishan; Jason K Molitoris; Matthew J Ferris; M Minhaj Siddiqui; Zaker Rana; Mark V Mishra; Young Kwok; Elai Davicioni; Daniel E Spratt; Piet Ost; Felix Y Feng; Phuoc T Tran Journal: Prostate Date: 2022-08 Impact factor: 4.012