A genomic prostate cancer test holds promise to better classify men post-radical prostatectomy for postoperative treatment decisions, "Beyond the Abstract," by Ketan K. Badani, MD

BERKELEY, CA (UroToday.com) - Almost 250,000 men are diagnosed with prostate cancer every year in the U.S., and every year around half of those men will choose to undergo radical prostatectomy (RP) to cure their localized disease. After surgery up to 50 percent of men will have one or more clinical risk factors that indicate increased chance of metastasis, and ultimately death, from prostate cancer. These men, according to standard-of-care guidelines, are candidates for secondary treatment such as radiation therapy. Very few men, however, including those classified by current guidelines as at high risk of recurrence following surgery, will experience metastasis and die of their cancer. There are no clear-cut criteria to the physician and patient if they can declare victory over the cancer.

New tools are needed to assist these men and their physicians to make better treatment decisions. The clinical utility study published in Oncotarget and referenced here shows the impact on urologists’ treatment decisions by using a new genomic classifier called Decipher that classifies a patient’s risk for developing metastatic prostate cancer following RP, independently of PSA rise and other adverse features. In this study, we evaluated the impact that Decipher has on postoperative treatment recommendations. Urologic oncologists reviewed 240 patient cases that were classified by established clinical risk factors as high risk for metastasis following prostate cancer surgery. Physicians were asked to make treatment recommendations before and after receiving Decipher genomic test results. We found that Decipher led to a change in treatment recommendations 43% (95% CI: 37-49) of the time. Significantly, recommendations for postoperative radiation were changed to observation for 31% of patient case evaluations.

Peer-reviewed manuscripts describing the clinical validity of Decipher have been published recently in the journals PLoS One and the Journal of Urology. The first study, published in PLoS One, details the development and initial validation of Decipher. To find biomarkers predictive of metastasis, researchers generated over one million data points for 639 unique patient samples that were from patients who underwent radical prostatectomy between 1987 and 2001. The 22 markers that were identified include genes associated with cell proliferation and differentiation, cell adhesion and motility, cell cycle progression, and other biological processes. Follow-up period for the patient samples used to develop Decipher was an average of 16.9 years, ensuring that the researchers could compare Decipher scores to clinical outcomes and determine which men went on to develop metastasis or not.

The second clinical validation study, published in the Journal of Urology, demonstrates that Decipher correctly reclassifies 60% of clinically “high-risk” patients as “low risk” and identifies patients 4-times more likely to develop metastatic prostate cancer. Further, Decipher could independently forecast which patients developed metastasis and showed better performance over any clinical variable or prediction model for metastasis, all of which carry limitations that can confound treatment decisions. In the study, 60 percent of patients who had a low Decipher result also had a 5-year cumulative incidence of metastasis of just 2.4 percent. In contrast, 20 percent of patients with a high Decipher result had a 22.5 percent incidence of metastasis after five years. Interestingly, data suggest that Decipher may identify a subset of men with adverse pathology features who never develop clinical metastasis.

These three papers support use of the Decipher genomic classifier to assess a patient’s risk for developing metastatic prostate cancer post radical prostatectomy. Data demonstrate that the Decipher test is as sensitive as Gleason score, but it is much more specific, given that there are cases of men having high Gleason scores that never went on to develop metastasis. In addition, this genomic classifier is more sensitive and specific than other clinical variables. The clinical utility study we performed suggests that physicians would change their treatment recommendations made for patients based on the results of our genomic classifier.

Genomic tests have the potential to radically change how men are assessed and treated after prostatectomy, and could help physicians make decisions that would spare thousands of men from permanent, life-altering side effects from secondary therapies. The compilation of peer-reviewed literature on the performance and utility of genomic classifiers should give physicians increased confidence in this move towards adopting these next generation tools for guiding treatment decisions.

Written by:
Ketan K. Badani, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Director of Robotic Surgery - NewYork Presbyterian Hospital
Associate Professor of Urology, Columbia University College of Physicians & Surgeons
Program Director, Minimally Invasive Oncology Fellowship

Impact of a genomic classifier of metastatic risk on postoperative treatment recommendations for prostate cancer patients: A report from the DECIDE study group - Abstract

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