title: A guide for clinicians in the evaluation of emerging molecular diagnostics for newly diagnosed prostate cancer.
abstract: Prostate-specific antigen (PSA) screening is associated with a decline in prostate cancer-related 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.
authors.affiliation: Division of Urology, Department of Surgery, The University of Texas Medical School at Houston, Houston, TX.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Canfield
authors.affiliation: Division of Urology, Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kibel
authors.affiliation: Departments of Medical Affairs and Oncology Development, Genomic Health, Inc., Redwood City, CA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kemeter
authors.affiliation: Departments of Medical Affairs and Oncology Development, Genomic Health, Inc., Redwood City, CA.
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Febbo
authors.affiliation: Departments of Medical Affairs and Oncology Development, Genomic Health, Inc., Redwood City, CA.
authors.forename: H Jeffrey
authors.initials: HJ
authors.lastname: Lawrence
authors.affiliation: Division of Urologic Surgery and Duke Cancer Institute, Duke University Medical Center, Durham, NC.
authors.forename: Judd W
authors.initials: JW
authors.lastname: Moul
keywords: Adverse pathology; Biomarker; Clinical utility; Clinical validation; Genomic prostate score; Molecular diagnostics; Prostate cancer