Kate Johnson

June 05, 2013

CHICAGO, Illinois — A commercially available prostate cancer test (Prolaris, Myriad Genetics) is highly predictive of biochemical recurrence and death, but experts say it is not clear how this affects clinical decision-making.

A discussion followed the presentation of results from 5 retrospective studies of the test here at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO®).

The Prolaris test, launched in 2010, has recently seen competition from several newer prostate cancer tests, including Oncotype DX (Genomics Health), which was launched last month, as reported by Medscape Medical News.

"With the demand for individualized treatment, there's a huge market for this," said Scott Tomlins, MD, PhD, assistant professor of pathology and urology at the University of Michigan in Ann Arbor, who served as discussant for the study.

However, Dr. Tomlins, who is not involved with the test, told Medscape Medical News that "the challenge for us looking at the presented data is that we haven't seen how it affects clinical decision-making."

"There are many potential uses for this test that clinicians need to get comfortable with," said Jack Cuzick, PhD, from Queen Mary College University of London, United Kingdom, after he presented the company's data.

"I believe the main use will be to help in deciding which patients should be managed with active surveillance. In addition, in those who've had a radical prostatectomy, it will aid in deciding whether to use adjuvant chemo or hormones," Dr. Cuzick noted.

However, Dr. Tomlins pointed out that, for the majority of patients, standard pathology parameters can be used to arrive at the same prognosis prediction as the test. "So we're not really moving men across large categories [with the test]," he told Medscape Medical News.

Results From 5 Studies

The Prolaris test, which measures the activity of cell cycle progression (CCP) genes in prostate cancer biopsy samples, was evaluated for its ability to predict either death from prostate cancer or biochemical recurrence in 5 company-sponsored studies, Dr. Cuzick reported.

It was tested at the time of disease diagnosis in 2 conservatively managed cohorts from the United Kingdom (Lancet Oncol. 2011;12:245-255 and Br J Cancer. 2012;106:1095-1099), after radical prostatectomy in 2 cohorts from the United States (Lancet Oncol. 2011;12:245-255 and J Clin Oncol. 2013;31:1428-1434), and after external-beam radiation therapy (Freedland et al 2013, unpublished).

In the studies, formalin-fixed prostate tissue from men with prostate adenocarcinoma was analyzed. A CCP score was calculated by measuring the average RNA expression of 31 CCP genes normalized by the average expression of 15 housekeeping genes as quantitated with reverse-transcriptase polymerase chain reaction, explained Dr. Cuzick.

A hazard ratio was then calculated for every unit change in CCP score for the risk for either biochemical recurrence or death from prostate cancer.

"A unit change is essentially a doubling in the expression of these cell cycle genes," he explained.

On multivariate analysis — variables ranged in the different studies but all included Gleason score and prostate-specific antigen (PSA) level — the predictive value of the CCP score for either outcome was "dominant" and "hugely significant" (hazard ratio, 2.6; P < 1010), said Dr. Cuzick.

"PSA retained a fair amount of its predictive value, but the predictive value of the Gleason score "diminished" against the CCP score." he said. "Once you add the CCP score, there is little addition from the Gleason score, although there is some."

"Overall, the CCP score was a highly significant predictor of outcome in all of the studies," said Dr. Cuzick. "It was the dominant predictor in all but 1 of the studies in the multivariate analyses, and typically a unit change in the score was associated with a remarkably similar 2- to 3-fold increase in either death from prostate cancer or biochemical recurrence, indicating that this is a very robust predictor, and seems to work in a whole range of circumstances."

Dr. Cuzick also outlined how the CCP score can refine risk based on the Cancer of the Prostate Risk Assessment (CAPRA) score. For patients with intermediate risk (a CAPRA scores of 3 to 5) and a 10-year mortality risk of 12%, the addition of CCP scoring led to "a huge separation," boosting some patients' risk to 25% and lowering others to 5%.

"There's a lot of discrimination that is clinically useful here, probably mostly with the intermediate CAPRA scores, but it also tells us something about those with low CAPRA scores who are particularly at risk," he said.

Dr. Cuzick concluded that "the CCP score predicts prostate cancer outcome in multiple cohorts and diverse clinical settings. It provides independent information beyond classic clinical pathologic variables and can help differentiate aggressive from indolent cancers."

"Exactly how you use it is still something that's being developed," he acknowledged, "but particularly for those with low-grade (Gleason score ≤6) low-risk cancers, you can get a clear indication of which patients are truly low risk and which need more aggressive therapy."

Documented Utility in Other Cancers

According to Dr. Tomlins "there's a great deal of interest in this. Its great that people are using the test because the concept certainly has documented utility in other cancers, such as breast cancer."

However, he said, "whenever you introduce new biomarkers, you need to be able to demonstrate the ability to affect clinical management or treatment decisions."

Although genetic breast cancer tests can be predictive of a patient's response to therapy, there are no firm risk cutoffs that would steer decisions toward a different treatment in prostate cancer, he said.

"In prostate cancer, the prediction just indicates how the patient is going to do. It can certainly make some men more confident in their decision to choose active surveillance, but if you were to tell a patient that their risk goes from 4% to 8%, is that enough to change a treatment decision?"

Dr. Cuzick reports receiving honoraria and research funding from Myriad Genetics. Most of the study's coauthors report employment or other financial relationships with Myriad Genetics. Dr. Tomlins reports consulting for and receiving honoraria from Ventana/Roche, and that the University of Michigan has been issued a patent on the detection of ETS gene fusions in prostate cancer, and the diagnostic field of use has been licensed to Genprobe/Hologic and sublicensed to Ventana Medical Systems/Roche.

2013 Annual Meeting of the American Society of Clinical Oncology. Abstract 5005. Presented June 2, 2013.

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