Vito Cucchiara1, Matthew R Cooperberg2, Marc Dall'Era1, Daniel W Lin3, Francesco Montorsi4, Jack A Schalken5, Christopher P Evans6. 1. Department of Urology, School of Medicine, University of California, Davis, Sacramento, CA, USA. 2. Departments of Urology and Epidemiology & Biostatistics, University of California, San Francisco, San Francisco, CA, USA. 3. Department of Urology, University of Washington, Seattle, WA, USA. 4. Department of Urology, Urological Research Institute, Vita-Salute University, San Raffaele Scientific Institute, Milan, Italy. 5. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands. 6. Department of Urology, School of Medicine, University of California, Davis, Sacramento, CA, USA. Electronic address: cpevans@ucdavis.edu.
Abstract
CONTEXT: Although the widespread use of prostate-specific antigen (PSA) has led to an early detection of prostate cancer (PCa) and a reduction of metastatic disease at diagnosis, PSA remains one of the most controversial biomarkers due to its limited specificity. As part of emerging efforts to improve both detection and management decision making, a number of new genomic tools have recently been developed. OBJECTIVE: This review summarizes the ability of genomic biomarkers to recognize men at high risk of developing PCa, discriminate clinically insignificant and aggressive tumors, and facilitate the selection of therapies in patients with advanced disease. EVIDENCE ACQUISITION: A PubMed-based literature search was conducted up to May 2017. We selected the most recent and relevant original articles and clinical trials that have provided indispensable information to guide treatment decisions. EVIDENCE SYNTHESIS: Genome-wide association studies have identified several genetic polymorphisms and inherited variants associated with PCa susceptibility. Moreover, the urine-based assays SelectMDx, Mi-Prostate Score, and ExoDx have provided new insights into the identification of patients who may benefit from prostate biopsy. In men with previous negative pathological findings, Prostate Cancer Antigen 3 and ConfirmMDx predicted the outcome of subsequent biopsy. Commercially available tools (Decipher, Oncotype DX, and Prolaris) improved PCa risk stratification, identifying men at the highest risk of adverse outcome. Furthermore, other biomarkers could assist in treatment selection in castration-resistant PCa. AR-V7 expression predicts resistance to abiraterone/enzalutamide, while poly(ADP-ribose) polymerase-1 inhibitor and platinum-based chemotherapy could be indicated in metastatic patients who are carriers of mutations in DNA mismatch repair genes. CONCLUSIONS: Introduction of genomic biomarkers has dramatically improved the detection, prognosis, and risk evaluation of PCa. Despite the progress made in discovering suitable biomarker candidates, few have been used in a clinical setting. Large-scale and multi-institutional studies are required to validate the efficacy and cost utility of these new technologies. PATIENT SUMMARY: Prostate cancer is a heterogeneous disease with a wide variability. Genomic biomarkers in combination with clinical and pathological variables are useful tools to reduce the number of unnecessary biopsies, stratify low-risk from high-risk tumors, and guide personalized treatment decisions.
CONTEXT: Although the widespread use of prostate-specific antigen (PSA) has led to an early detection of prostate cancer (PCa) and a reduction of metastatic disease at diagnosis, PSA remains one of the most controversial biomarkers due to its limited specificity. As part of emerging efforts to improve both detection and management decision making, a number of new genomic tools have recently been developed. OBJECTIVE: This review summarizes the ability of genomic biomarkers to recognize men at high risk of developing PCa, discriminate clinically insignificant and aggressive tumors, and facilitate the selection of therapies in patients with advanced disease. EVIDENCE ACQUISITION: A PubMed-based literature search was conducted up to May 2017. We selected the most recent and relevant original articles and clinical trials that have provided indispensable information to guide treatment decisions. EVIDENCE SYNTHESIS: Genome-wide association studies have identified several genetic polymorphisms and inherited variants associated with PCa susceptibility. Moreover, the urine-based assays SelectMDx, Mi-Prostate Score, and ExoDx have provided new insights into the identification of patients who may benefit from prostate biopsy. In men with previous negative pathological findings, Prostate Cancer Antigen 3 and ConfirmMDx predicted the outcome of subsequent biopsy. Commercially available tools (Decipher, Oncotype DX, and Prolaris) improved PCa risk stratification, identifying men at the highest risk of adverse outcome. Furthermore, other biomarkers could assist in treatment selection in castration-resistant PCa. AR-V7 expression predicts resistance to abiraterone/enzalutamide, while poly(ADP-ribose) polymerase-1 inhibitor and platinum-based chemotherapy could be indicated in metastatic patients who are carriers of mutations in DNA mismatch repair genes. CONCLUSIONS: Introduction of genomic biomarkers has dramatically improved the detection, prognosis, and risk evaluation of PCa. Despite the progress made in discovering suitable biomarker candidates, few have been used in a clinical setting. Large-scale and multi-institutional studies are required to validate the efficacy and cost utility of these new technologies. PATIENT SUMMARY:Prostate cancer is a heterogeneous disease with a wide variability. Genomic biomarkers in combination with clinical and pathological variables are useful tools to reduce the number of unnecessary biopsies, stratify low-risk from high-risk tumors, and guide personalized treatment decisions.
Authors: Michael C Haffner; Wilbert Zwart; Martine P Roudier; Lawrence D True; William G Nelson; Jonathan I Epstein; Angelo M De Marzo; Peter S Nelson; Srinivasan Yegnasubramanian Journal: Nat Rev Urol Date: 2020-12-16 Impact factor: 14.432
Authors: Richard M Martin; Jenny L Donovan; Emma L Turner; Chris Metcalfe; Grace J Young; Eleanor I Walsh; J Athene Lane; Sian Noble; Steven E Oliver; Simon Evans; Jonathan A C Sterne; Peter Holding; Yoav Ben-Shlomo; Peter Brindle; Naomi J Williams; Elizabeth M Hill; Siaw Yein Ng; Jessica Toole; Marta K Tazewell; Laura J Hughes; Charlotte F Davies; Joanna C Thorn; Elizabeth Down; George Davey Smith; David E Neal; Freddie C Hamdy Journal: JAMA Date: 2018-03-06 Impact factor: 56.272
Authors: Freddie C Hamdy; Jenny L Donovan; J Athene Lane; Malcolm Mason; Chris Metcalfe; Peter Holding; Julia Wade; Sian Noble; Kirsty Garfield; Grace Young; Michael Davis; Tim J Peters; Emma L Turner; Richard M Martin; Jon Oxley; Mary Robinson; John Staffurth; Eleanor Walsh; Jane Blazeby; Richard Bryant; Prasad Bollina; James Catto; Andrew Doble; Alan Doherty; David Gillatt; Vincent Gnanapragasam; Owen Hughes; Roger Kockelbergh; Howard Kynaston; Alan Paul; Edgar Paez; Philip Powell; Stephen Prescott; Derek Rosario; Edward Rowe; David Neal Journal: Health Technol Assess Date: 2020-08 Impact factor: 4.014