Findings from a meta-analysis, including data from five independent patient cohorts, show that a novel genetic test is a powerful prognostic predictor of prostate cancer outcome across diverse clinical settings.
Chicago-Findings from a meta-analysis, including data from five independent patient cohorts, show that a novel genetic test is a powerful prognostic predictor of prostate cancer outcome across diverse clinical settings.
The commercially available Prolaris test (Myriad Genetics, Inc., Salt Lake City, UT) calculates a cell cycle progression (CCP) score based on the expression of 31 cell cycle progression genes in prostate cancer tissue.
The five studies evaluating its prognostic performance were all retrospective and used tissue from needle biopsy, transurethral resection of the prostate, or radical prostatectomy surgical specimen for determining the CCP score. They included two studies determining 10-year prostate cancer-specific mortality in newly diagnosed, conservatively managed patients (686 patients total) and three studies that assessed biochemical recurrence after radical prostatectomy (two studies, 779 patients total) or external beam radiotherapy (one study, 141 patients).
CCP score hazard ratio (HR) was calculated for a 1-unit increase in CCP score, which corresponds to about a doubling of the CCP gene expression profile as well as to the median size of the interquartile range of the CCP scores across the five cohorts. In univariate analyses for each study, a 1-unit increase in CCP score was associated with a twofold or greater increase in risk of the specified outcome (HR range, 2.0 to 2.9).
Results of multivariate analyses showed the CCP score remained a highly significant independent predictor of outcome after adjusting for known clinicopathologic risk factors. The HR per unit of CCP score change ranged from 1.7 to 2.6 across the five studies and was 2.27 in a pooled analysis. In addition, findings from multivariate analyses showed CCP score was a more powerful predictor of outcome than Gleason score or PSA in all cohorts except one of the radical prostatectomy groups.
“These findings show the CCP score performed remarkably consistently in predicting outcomes of prostate cancer for patients representing a variety of clinical contexts, including when using tissue from needle biopsy. They also indicate that the CCP score is the single best prognostic variable we have and provides information beyond current clinicopathologic variables,” said co-author Jack Cuzick, MD, head of the Cancer Research UK Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, St. Bartholomew’s Medical School, Queen Mary University of London.
“The 1-unit effect size for the CCP score appears robust in being able to separate out newly diagnosed men with more than a twofold difference in 10-year risk of dying from prostate cancer as well as those with a more than twofold difference in risk of biochemical recurrence after radical prostatectomy or radiotherapy. Based on these data, we believe this test will be very useful in differentiating men with indolent versus aggressive prostate cancer and in helping clinicians make management decisions for their patients with prostate cancer,” added Dr. Cuzick, who presented the findings at the American Society of Clinical Oncology annual meeting in Chicago.
Dr. Cuzick acknowledged that more experience is needed to determine how best to use the test in clinical practice. However, he suggested that it might have its greatest value for guiding decisions on choosing radical versus conservative management for men with apparently low-grade cancer (Gleason score 6 and possibly Gleason 7). In addition, it may have a role in helping to determine whether to begin androgen deprivation therapy or chemotherapy after radical therapy.
Dr. Cuzick receives honoraria and research funding from Myriad Genetics. Several of his co-authors are consultant/advisers for, have employment/leadership positions with, own stock in, and/or receive other remuneration from the company.UT
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