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Oncotype DX Test for Prostate Cancer Validated, and Now Available

Eastman, Peggy

doi: 10.1097/


A much anticipated validation study presented at the American Urological Association Annual Meeting has confirmed that the biopsy-based genomic prostate score (GPS)—the basis of the new Oncotype DX test—can predict high-grade or extracapsular prostate cancer, thus helping physicians determine which prostate cancer patients can safely choose active surveillance and which cannot.

The lead author of the study is Matthew R. Cooperberg, MD, Assistant Professor of Urology, Epidemiology and Biostatistics at the University of California, San Francisco. The GPS test, developed in collaboration with UCSF and the Cleveland Clinic, has now been validated in seven studies including approximately 1,100 patients.

As previously reported in OT ( 5/25/13 issue ), the 17-gene GPS test—now available to physicians as Oncotype DX for prostate cancer—will safely reduce the number of prostatectomies, said Steven Shak, MD, Chief Medical Officer and Executive Vice President of Research at Genomic Health, Inc., the company that makes the test, who is also a coauthor.

“This is important new news,” he said in a telephone interview. “This is a first-of-its-kind assay that will help more men confidently choose active surveillance.”

Shak said that when the test is used in clinical practice, getting the results should take about two weeks—during this waiting period, “for such a critical decision, men should take the time to be better informed about their individual disease.”

The study's principal investigator, Peter Carroll, MD, MPH, Professor and Chair of UCSF's Department of Urology, said in a news release, “The results of our study showed that the individual biological information from the Oncotype DX prostate cancer test tripled the number of patients who can more confidently consider active surveillance and avoid unnecessary treatment and its potential side effects.”

Just as important, he added, “the test identified a smaller number of patients who, despite seemingly low-risk clinical factors, had more aggressive disease and would suggest that they consider immediate treatment.” This smaller group represented about 10 percent of patients.

“Our extensive development studies tackled the key challenges inherent in prostate cancer risk assessment to identify a subset of genes that are important in both low-grade and high-grade tumors,” added another coauthor, Eric A. Klein, MD, Chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic and principal investigator for Cleveland Clinic's original development studies.

Specifically, the results presented at the AUA meeting showed that use of the GPS increased the number of patients identified as having very low-risk disease (and who were thus appropriate for active surveillance) from a range of five to 10 percent to 26 percent.

Overall, more than one third of patients initially classified as low-risk based on clinical factors were identified by the GPS as very low-risk. Two development studies showed that the 17-gene GPS test was a biopsy-based predictor of high-grade and/or pT3 disease.

In the first study, an analysis of 732 candidate genes (441 patients) identified 288 genes predictive of clinical recurrence regardless of Gleason patterns in separately sampled specimens.

A second needle biopsy study of 81 genes in low- and intermediate-risk men (167 patients) confirmed a strong association of the genes with adverse pathology. A multivariate analysis of both development studies yielded 17 genes across multiple biological pathways and a GPS algorithm.

In the validation study of 395 patients, the GPS test, assessed in biopsies with as little as one millimeter tumor length from patients who were suitable candidates for active surveillance, strongly predicted for high-grade and/or pT3 disease after adjusting for CAPRA (Cancer of the Prostate Risk Assessment) or other standard pretreatment factors.

Asked if a journal publication on these results is planned, Shak said, “Absolutely. It's important to do that as soon as possible.”

Of the 240,000 U.S. men diagnosed with prostate cancer annually, about half will be classified as low-risk using conventional measures such as the Gleason score, prostate-specific antigen level, and a physical exam. But even though multiple clinical guidelines endorse active surveillance, more than 90 percent of low-risk men undergo aggressive treatment, Shak noted.

“Use of active surveillance has been limited by the lack of risk-assessment tools. In addition, the patients become fearful themselves”—i.e., worried that a random needle biopsy may miss a focus of aggressive disease in the prostate gland, anxiety that has only increased with the continuing controversy about the PSA test. As a result, men often choose aggressive treatments such as radical prostatectomy or radiation therapy even if they could actually be safely avoided.

Of the new test, Shak said, “We designed it to specifically address that concern about adverse pathology. We sought to prove that the GPS could predict adverse pathology without having to take the prostate out to know it.”

Asked whether he expects the test to be reimbursed for clinical practice, he said, “We know that it is our job to work with the payors and the insurers” to ensure that the test will be covered. He said he expected that his previous experience with Genomic Health's Oncotype DX tests for breast and colon cancers will help in discussions with payors.

“We believe the test will actually lead to cost savings,” he said, because it has the potential to reduce the number of prostatectomies and treatment costs for side effects from aggressive treatment, some of which can last for a considerable length of time.

Asked if he thinks practicing physicians are likely to accept the new test, Shak said, “There is a range of urologists out there; we know there is still a lot of work to do to provide them with the details of the study and to educate them about the test and how it should be used.”

Carroll, who is also Co-Director of Urologic Cancer at the UCSF Helen Diller Family Comprehensive Cancer Center, is a surgeon who performs many prostatectomies but has also pioneered active surveillance for men with low-risk disease. He and one of his patients, prostate cancer survivor John Shoemaker, are featured in UCSF's multimedia ad campaign on active surveillance. Carroll has stated, “For many men, their cancers pose no risk to them left untreated. To expose them to treatment with no benefit is not good.”

Although Shoemaker initially resisted active surveillance, Carroll persuaded him that he could be safely followed and monitored without compromising his health outcome.

Also at the AUA meeting, the American Society for Radiation Oncology and the AUA announced the publication of a joint evidence-based guideline on radiation therapy after prostatectomy for patients with and without evidence of prostate cancer recurrence. The evidence-based guideline is available free online as a PDF document on the websites of both the AUA ( and ASTRO's “red journal” (

© 2013 Lippincott Williams & Wilkins, Inc.
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