May 08, 2013—After men undergo a needle biopsy of their prostate gland and receive a positive diagnosis of cancer, they often face a difficult question: should they consent to aggressive therapy, with surgery or radiation, both of which may cause serious side effects such as sexual, bowel or bladder dysfunction, or should they opt for a program of active surveillance that monitors men over time for signs of cancer progression? Doctors know that the majority of prostate cancers are slow-growing and non-lethal, but pinpointing exactly which cancers fall into this category has been historically difficult. Thus, many men and their physicians err on the side of caution.
– Dr. Peter Carroll, Chairman of Urology, UCSF
The ability for physicians to look a man in the eye and say with 100 percent certainty: ‘you may safely forgo aggressive treatment of your prostate cancer at this time’ is an ultimate goal of prostate cancer diagnostics. While that goal has yet to be reached, today marks an important step forward toward that goal.
Today at the American Urological Association (AUA) meeting in San Diego, Genomic Health Inc., a cancer diagnostics company that already has a genomic test on the market that helps women with breast cancer determine how likely chemotherapy is to help them—announced they are now marketing a genomic test for men diagnosed with prostate cancer that will give men better information on how likely it is that their prostate cancer is an aggressive form of the disease needing immediate treatment, or a slow-growing, low-risk form of prostate cancer that can safely be monitored over time for signs of progression.
The new assay, Oncotype DX Prostate Cancer Test, will potentially give tens of thousands of men increased confidence that they can safely forgo aggressive treatment and instead enter a program of active surveillance, where their tumor is monitored over time, deferring surgery or radiation and potentially avoiding the sexual and/or bowel and bladder dysfunction side-effects that can result from those treatments. The new test—a 17-gene predictive “signature”—measures the amount of RNA expressed by these various genes, with some genes making large amounts of RNA and others making little. Research has shown that in men whose tumors turned out to be high-risk, those men tended to test positive for this 17-gene “signature,” say those involved with the test. At the AUA meeting, Genomic Health reported that they have validated these results in seven separate studies involving over 1,000 men diagnosed at biopsy with prostate cancer.
“This test represents the beginning of a personalized approach to the management of prostate cancer, whereby patients and their physicians are given additional information about the characteristics of a tumor that can be used to select the most appropriate course of action,” said Dr. Ballantine Carter, the director of the Division of Adult Urology at Johns Hopkins Medicine in Baltimore.
Prostate Cancer Foundation fingerprints on this 17-gene predictive “signature”
The Prostate Cancer Foundation (PCF) is a long-time funder of instrumental research that fostered the development of this 17-gene signature test. The process of finding this 17-gene signature began with a series of studies, done at the Cleveland Clinic under the leadership of Dr. Eric Klein, that followed a group of men over time, analyzing the genetics of their tumors. It was through these initial analyses that a group of over 700 candidate genes was winnowed down to the current 17 subset used in the predictive signature test now offered by Genomic Health. Read more here about the test’s development and how it evolved and why it’s pertinent even when an initial biopsy indicates low-risk cancer with traditional scoring.
- PCF partnered with the Safeway Foundation as they generously and presciently provided over $2 million in funding towards the development of this 17-gene predictive signature. This was instrumental in funding and facilitating the establishment of massive biobanks of prostate cancer tissue samples that could be analyzed over time for a genetic fingerprint signature or signatures associated with high-risk tumors.
- PCF and Safeway funded key researchers involved in the validation and evolution of this 17-gene signature. For example:
Dr. Peter Carroll , professor and chair of the UCSF Department of Urology, led a large validation study of the 17-gene signature. (As reported at AUA, this validation study of the Oncotype DX prostate cancer 17-gene test tripled the number of patients who could confidently begin a program of active surveillance, staving off surgical and radiation-induced side effects.
Dr. Matt Cooperberg, a PCF Young Investigator, also at UCSF, was also an investigator on the large clinical validation study. Cooperberg worked closely with Genomic Health in a sterling example of how academia can and should partner with biotechnology companies to move research into the clinic.
Dr. Ballantine Carter of Johns Hopkins Medicine who developed the foundation for highly successful active surveillance programs and helped launch the National Proactive Surveillance Network (NPSN), a $5 million program launched by PCF in conjunction with Johns Hopkins Medicine and Cedars Sinai Medical Center that tracks the progression of prostate cancer in men whose tumors have been designated as low-risk. This valuable data collection set was used in the development of the 17-gene signature and is being used to develop other prognostic tests.
- PCF’s chief science officer, Dr. Howard Soule facilitated the virtuous cycle of information sharing amongst academic, private and non-profit entities that generated the crosstalk that helped bring to market this gene signature test.
Moving toward Precision Medicine and 100% certainty levels
“The Oncotype DX Prostate Cancer Test will finally allow us to begin leaving the PSA era and enter a world of true prostate-specific molecular diagnostics and accurate predictive biomarkers,” said Dr. Stuart Holden, director the of Louis Warschaw Prostate Cancer Center at Cedars-Sinai Medical Cancer Center in Los Angles and PCF Medical Director. (The PSA, or prostate-specific antigen test, is a routine blood test that may or may not indicate prostate cancer, and recently was the subject of significant controversy when a governmental task force recommended against the use of PSA as a general prostate cancer screening method.)
Dr. Jonathan Simons, president and CEO of the Prostate Cancer Foundation hails the market entrance of Oncotype DX Prostate Cancer Test as an important milestone towards a day when physicians can make that 100 percent pronouncement that a prostate cancer is non-lethal. “The Gleason score—where a pathologist looks at tumor samples under a microscope to determine, or score the aggressiveness of a tumor sample—is often inaccurate, up to 25 percent of the time, in fact,” said Simons. “This 17-gene signature test is showing a 95 percent accuracy rate in its ability to predict a tumor’s aggressive nature,” he adds. Simons said he’s pleased with this highly positive movement from 75 percent accuracy to 95 percent. “That’s more than statistics; that’s men’s lives saved,” added Simons who said that this 17-gene genetic fingerprint signature test is just one of many that will soon be available and that, he hopes, will boost doctors and men to that 100 percent certainty level when opting for active surveillance as a safe choice for them.