3rd Annual Jefferson Urology Symposium: Men’s Health Forum

© The Canadian Journal of Urology TM : International Supplement, August 2020 Uhr et al. Confirm MDx (MDxHealth, Irvine, California, USA) is a non-invasive test that relies on archival on prior negative prostate biopsy specimens collected within the past 30months in patients with persistent abnormal PSA who are considering a repeat biopsy. It uses a three-gene ( GSTP1 , APC , and RASSF ) PCR assay to identify an epigenetic field surrounding cancer cells and map DNA methylation which may help guide future biopsy targets. A positive result provides risk prediction for Gleason ≥ 7 disease. A negative result with no areas of DNAmethylation corresponds with a 96% NPV for Gleason ≥ 7 disease and 90% NPV for all prostate cancer. 17,18 For patients with biopsy proven prostate cancer considering active surveillance or treatment, or post prostatectomy patients considering adjuvant therapy Oncotype DX - Genomic Prostate Score (GPS) (GenomicHealth Inc., RedwoodCity, California, USA) is a non-invasive test on biopsy tissue used to identify the aggressiveness of disease and provide a personalized risk assessment in NCCN-defined very low risk, low risk, and intermediate risk cancer patients. The assay predicts tumor aggressiveness based on 17 gene panel (12 prostate cancer related genes and 5 housekeeping controls) within cellular communication pathways including androgen signaling, stromal response, and cellular organization and proliferation stages. Results are reported as a GPS score from 0-100 where higher scores correlate with higher risk of aggressive disease. Risk of adverse pathology (Gleason> 4+3 and/or pT3+), metastatic disease and prostate cancer death at 10 years is also predicted. 19 Decipher (GenomeDx Biosciences, Vancouver, BC, Canada) is a genome wide test reflecting multiple biological pathways inpatientswithNCCN-categorized very low, low, or favorable intermediate risk cancer after a positive biopsy. It is reported as a continuumrisk score from 0-1 and is independent of clinical or pathological features. It predicts the likelihood of high grade disease, 5 year metastasis, and 10 year cancer specific mortality. It has also been shown to be an independent predictor of adverse pathology and metastasis. Decipher can be performed on post radical prostatectomy specimens and is useful in patients who have adverse pathology (pT3 disease, positive surgical margins) or biochemical persistence/recurrence to help identify patients likely to benefit from adjuvant or salvage radiation. In patients with a risk score ≥ 0.4, there was a 6% versus 23% incidence of metastatic disease at 5 years after adjuvant versus salvage radiation. 20,21,22 Prolaris (Myriad Genetics, Salt Lake City, Utah, USA) is also a tissue biopsy based test that combines RNA expression of 46 genes (31 cell cycle progression genes and 15 housekeeping controls) with clinical and pathologic features to stratify 10 year risk of metastasis after definitive treatment and disease specific mortality if managed conservatively. This test can also be useful in post prostatectomy specimens to predict 10 year risk of biochemical recurrence to help identify patients who may benefit most from adjuvant therapy. 23 For patients with advanced disease and in the decision for systemic therapies** AR-V7 (GenomicHealth Inc., RedwoodCity, California, USA) is a blood-based test useful in patients with metastatic castrate-resistant prostate cancer who have previously or are currently on androgen-receptor (AR) targeted medications to help determine appropriate future systemic therapy. AR-V7 is a truncated AR circulating tumor cells that is activated independent of androgen binding, and may be present in men with previous or current AR targeted therapy. AR-V7 positive patients have poor response to AR blockade, and therefor may benefit more from chemotherapy or other non-androgen pathway therapies. In contrast, AR-V7 negative patientsmay respond to all therapeutic agents. 24,25 Conclusion Prostatecancercanbeahighlyvariableandheterogeneous disease, making diagnosis, prognosis and treatment a challenging task. Historically, management decisions have been based on clinico-pathologic features and PSA trends. With an increasing number of aging men in the population at risk for this disease, there are significant implications of these biopsy and subsequent treatment decisions. Risk stratificationwill help avoidunnecessary biopsies and over-treatment in low risk patients, and guide treatment strategies in high risk patients who will derive the most benefit. Biomarkers are becoming useful adjunctive tools to help risk stratify patients and ultimately guide individual management, either at the decision for initial biopsy or in determining between active surveillance or active treatment with radiation or surgery for localized disease. 4 Each of the biomarkers presented have unique performancecharacteristicsandaresubject toproprietary considerations. Sincemultiple biomarker tests currently existwithmanymore indevelopment, itmay be difficult for clinicians to decide onwhich test to use. Large scale prospective studiesmay help validate biomarker usage 26