Neal D. Shore, MD, FACS
Medical Director, Carolina Urologic Research Center
Partner, Atlantic Urology Clinics
Myrtle Beach, South Carolina
Karen H. Ventii, PhD
E. David Crawford, MD, FACS
Distinguished Professor of Surgery, Urology, and
Head, Section of Urologic Oncology
University of Colorado Anschutz Medical Campus
Smilow Cancer Hospital at Yale-New Haven
Although prostate cancer (PC) is the most common solid tumor malignancy among men in the Western Hemisphere, disease-specific mortality remains low, primarily due to optimized screening, diagnosis, and treatment.
Despite this recent success, decision-making challenges remain for patients and clinicians, including whether or not to perform an initial prostate biopsy; whether or not to elect interventional treatment for low-risk disease; and whether or not to perform a repeat prostate biopsy following an initial negative result.
Clinically applicable and validated risk-analysis tools, beyond those traditionally used, are needed to assist with informing treatment decisions for patients and physicians regarding the aforementioned challenges. Biomarkers are required which can provide both prognostic and predictive information. Specifically, regarding prognostic variables, such as the historic clinical features currently used today (serum PSA [prostate-specific antigen], DRE [digital rectal exam], Gleason primary/secondary patterns, number of positive cores, and percent involvement of positive cores), there is an unmet need to inform decisionmaking optimization.
Given that traditional clinical risk-assessment tools may be less than optimal, patients with early-stage PC may benefit from more precise, personalized assessment of their tumor biology. Prognostic and predictive tools based on PCa biomarkers are already available, and more are in development. The tools now available can be roughly organized into four groups (Table 1
), each with its own unique goals for assessing clinical decision-making. Collectively, the biomarkers that fall within these four groups should be utilized to enhance risk assessment, guide diagnostic strategies, and improve treatment outcomes by allowing more targeted screening, more accurate diagnosis, and improved risk stratification. The ultimate goal is to improve treatment recommendations and subsequent selection of therapy, thereby maximizing patient outcomes and concomitantly stabilizing, or reducing, healthcare costs.1
Group 1: Biomarkers to Determine Whom to Biopsy
After its approval by the US Food and Drug Administration (FDA) more than 20 years ago, PSA dramatically influenced PC screening and diagnosis,2,3
with approximately 19 million men receiving yearly testing and more than 1.3 million biopsy procedures being conducted annually. The result was nearly 240,000 findings of newly diagnosed PC.4
Nonetheless, the interpretation of PSA has inherent challenges, including the potential for false-positive or falsenegative results regarding its assessment for malignancy. For example, most men with a PSA level above 4.0 ng/mL5
do not have PC and only about 40% of men undergoing biopsy for an elevated PSA level will actually have PC. Additionally, PSA testing does not adequately differentiate low-risk from highrisk disease;5
many newly diagnosed patients with PC may be overtreated for low-risk cancer.6
Such limitations contributed to the US Preventive Services Task Force’s recommendation against continued routine PC screening.6
In the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (which was designed to assess the effects of screening on cancer-related mortality), there was no evidence of a survival benefit for organized annual PC screening compared with usual care, which sometimes included screening, after 13 years of follow-up.