Volume 23, Number 3Prostate CancerIncorporation of IsoPSA Into Clinical Practice in the Management of Elevated Prostate-Specific Antigen Based on Current GuidelinesAidan KennedyJason HafronProstate cancer is a highly prevalent malignancy among men worldwide. Optimal management depends on early detection and accurate surveillance. Several screening and surveillance tools are available to men with prostate cancer, including prostate-specific antigen (PSA) testing, digital rectal examination, prostate biopsy, imaging modalities, and a plethora of biomarkers. Prostate-specific antigen, though widespread in its use, is limited in its specificity. Many adjunctive tests to PSA have been developed. One such test is IsoPSA (Cleveland Diagnostics), a novel PSA assay that focuses on structural differences among PSA isoforms to aid in detecting clinically significant prostate cancer. With an improved understanding of the capability and uses of IsoPSA, physicians can enhance patient outcomes through more accurate risk assessment and save costs by reducing the number of unnecessary prostate biopsies and imaging generated resulting from a nonspecific elevation in serum PSA. This review describes the performance and use of IsoPSA.Prostatic neoplasmsBiomarkerProstate-specific antigen (PSA)Prostate-specific antigenBiomarkers
Volume 16, Number 4Review ArticlesA Guide for Clinicians in the Evaluation of Emerging Molecular Diagnostics for Newly Diagnosed Prostate CancerDiagnosis UpdateMichael J KemeterPhillip G FebboSteven E CanfieldAdam S KibelH Jeffrey LawrenceJudd W MoulProstate-specific antigen (PSA) screening is associated with a decline in prostate cancerrelated mortality. However, screening has also led to overdiagnosis and overtreatment of clinically insignificant tumors. Recently, certain national guidelines (eg, US Preventive Services Task Force) have recommended against PSA screening, which may lead to a reverse-stage migration. Although many prostate tumors are indolent at presentation, others are aggressive and are appropriate targets for treatment interventions. Utilization of molecular markers may improve our ability to measure tumor biology and allow better discrimination of indolent and aggressive tumors at diagnosis. Many emerging commercial molecular diagnostic assays have been designed to provide more accurate risk stratification for newly diagnosed prostate cancer. Unfamiliarity with molecular diagnostics may make it challenging for some clinicians to navigate and interpret the medical literature to ascertain whether particular assays are appropriately developed and validated for clinical use. Herein, the authors provide a framework for practitioners to use when assessing new tissue-based molecular assays. This review outlines aspects of assay development, clinical and analytic validation and clinical utility studies, and regulatory issues, which collectively determine whether tests (1) are actionable for specific clinical indications, (2) measurably influence treatment decisions, and (3) are sufficiently validated to warrant incorporation into clinical practice. [Rev Urol. 2014;16(4):172-180 doi: 10.3909/riu0644] © 2014 MedReviews®, LLCProstate cancerBiomarkerClinical utilityGenomic prostate scoreAdverse pathologyClinical validationMolecular diagnostics
Volume 17, Number 1Review ArticlesFinding the Wolf in Sheep’s Clothing: The 4Kscore Is a Novel Blood Test That Can Accurately Identify the Risk of Aggressive Prostate CancerDiagnosis and Screening UpdateDipen J ParekhSanoj PunnenMASNicola PavanBetter biomarkers that can discriminate between aggressive and indolent phenotypes of prostate cancer are urgently needed. In the first 20 years of the prostate-specific antigen (PSA) era, screening for prostate cancer has successfully reduced prostate cancer mortality, but has led to significant problems with overdiagnosis and overtreatment. As a result, many men are subjected to unnecessary prostate biopsies and overtreatment of indolent cancer in order to save one man from dying of prostate cancer. A novel blood test known as the 4Kscore® Test (OPKO Lab, Nashville, TN) incorporates a panel of four kallikrein protein biomarkers (total PSA, free PSA, intact PSA, and human kallikrein-related peptidase 2) and other clinical information in an algorithm that provides a percent risk for a high-grade (Gleason score ≥ 7) cancer on biopsy. In 10 peer-reviewed publications, the four kallikrein biomarkers and algorithm of the 4Kscore Test have been shown to improve the prediction not only of biopsy histopathology, but also surgical pathology and occurrence of aggressive, metastatic disease. Recently, a blinded prospective trial of the 4Kscore Test was conducted across the United States among 1012 men. The 4Kscore Test replicated previous European results showing accuracy in predicting biopsy outcome of Gleason score ≥ 7. In a recent case-control study nested within a population-based cohort from Västerbotten, Sweden, the four kallikrein biomarkers of the 4Kscore Test also predicted the risk for aggressive prostate cancer that metastasized within 20 years after the test was administered. These results indicate that men with an abnormal PSA or digital rectal examination result, and for whom an initial or repeat prostate biopsy is being considered, would benefit from a reflex 4Kscore Test to add important information to the clinical decision-making process. A high-risk 4Kscore Test result may be used to select men with a high probability of aggressive prostate cancer who would benefit from a biopsy of the prostate to prevent an adverse and potentially lethal outcome from prostate cancer. Men with a low 4Kscore Test result may safely defer biopsy. [Rev Urol. 2015;17(1):3-13 doi: 10.3909/riu0668] © 2015 MedReviews®, LLCProstate cancerBiomarkerScreeningHigh-grade prostate cancer
Volume 21, Number 4Case ReviewUsing 17-OHP as Serum Biomarker to Monitor Therapy in Patients With Hypogonadotropic HypogonadismA MouzannarM NarasimmaP PatelR RamasamyExogenous testosterone administration decreases intratesticular testosterone (ITT) significantly, an essential hormone for spermatogenesis. Therefore, treatment of patients with hypogonadotropic hypogonadism (HH) who desire infertility can be challenging. These patients are treated with recombinant follicle-stimulating hormone (FSH), clomiphene citrate, and human chorionic gonadotropin (hCG) to increase their ITT. However, there is no approved serum biomarker for ITT and it can only be measured via invasive testicular biopsy or aspiration. Previous authors have speculated that serum 17-hydroxyprogestrone (17-OHP) can be used as serum biomarker for ITT. In our case report, we demonstrate increase in 17-OHP associated with spermatogenesis after commencing treatment for infertility in patient with HH. [Rev Urol. 2019;21(4):180–182] © 2020 MedReviews®, LLCBiomarkerInfertility17-HydroxyprogesteronIntratesticular testosteroneHypogonadotropic hypogonadism