Prostate cancer (PC) is the second most common cancer in American men, with approximately 220,000 new cases diagnosed in 2015. Assessing PC aggressiveness, based upon PSA kinetics, histopathology, and digital rectal examination – traditional clinic-pathological features – has had limited clinical utility in providing shared decision making for choosing an interventional strategy versus active surveillance.
CAPSURE/SEER data suggested that during the time frame of the early 2000s, nearly 90% of newly diagnosed men with PC received interventional treatment (surgical extirpation or radiation therapy) even though approximately half of these patients were categorized by either NCCN or AUA risk classification as either very low or low risk PC status.
Prolaris® is a rigorously validated molecular assay designed to augment patient-physician risk stratification for newly diagnosed PC and thus better inform treatment selection. The RNA expression of 31 cell-cycle progression (CCP) genes are combined to generate a CCP score, which is a measure of tumor aggressiveness. Multiple validation studies demonstrate that the CCP score predicts a variety of clinical endpoints including biochemical recurrence, metastasis, and 10-year cancer specific mortality. (See validation studies of the CCP score and references, www.prolaris.com.)
This study, the PROCEDE 1000, was a prospective open registry with 1206 eligible patients, and aimed to measure the impact the Prolaris® test had upon ultimate therapeutic decisions in patients with newly diagnosed prostate cancer adenocarcinoma. The clinical utility of the CCP score was evaluated based on changes in patient management at four stages in the decision making process from the planned treatment prior to receipt of the test results to the actual treatment captured in 3-6 months of clinical follow-up. The final treatment decision making, after both physician and patient discussion occurred, was prospectively documented and catalogued.
The study found that treatment options were altered for 576 (47.8%) individuals from the initial pre-CCP score planned treatment to the actual treatment. Of these, 415 (72.1%) individuals experienced a decrease in treatment intensity and 155 (26.9%) experienced an increase in treatment intensity. Based on receipt of a lower CCP score than anticipated, 112 men had modified management from interventional to non-interventional. Approximately the same number of men, 101, had modified management from non-interventional to interventional owing to a more worrisome CCP score.
As the largest prospective trial completed to date assessing the clinical utility of a prognostic biomarker in PC, this study provides significant insight into the use of the CCP score (Prolaris® test) at each step in the treatment decision-making process. Having a validated genomic measure of tumor aggressiveness, in conjunction with traditional clinic-pathological features, allows practitioners to identify individuals suitable for active surveillance and may also reduce additional and unnecessary treatment burden.
Written by: Neal D. Shore: Carolina Urologic Research Center, Myrtle Beach, SC.