Genomic Markers in Prostate Cancer Decision Making

Published on Nov 1, 2017in European Urology17.30
· DOI :10.1016/j.eururo.2017.10.036
Vito Cucchiara4
Estimated H-index: 4
(UC Davis: University of California, Davis),
Matthew R. Cooperberg55
Estimated H-index: 55
(UCSF: University of California, San Francisco)
+ 4 AuthorsChristopher H Evans108
Estimated H-index: 108
(UC Davis: University of California, Davis)
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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.
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