Originally published May 20.
NEW YORK (GenomeWeb) – A large study presented at a medical conference this week provides further evidence that Myriad Genetics’ Prolaris prostate cancer test can be used with other clinical measures to predict patients’ survival a decade from diagnosis.
In study involving more than 750 conservatively managed prostate cancer patients, the Prolaris test provided prognostic information that was not available through traditional clinical information, researchers from the Wolfson Institute of Preventive Medicine, Myriad and other institutions reported at the American Urological Association’s annual meeting this week.
Myriad markets Prolaris, which analyzes the expression of 31 cell cycle progression genes and 15 housekeeper genes, as a tool that doctors can use to assess prostate cancer patients’ disease aggressiveness. In the post-prostatectomy setting, Prolaris can gauge which prostate cancer patients are at high risk of progression and should be followed more closely or treated with adjuvant external beam radiation therapy or systemic therapy. Doctors can also use Prolaris in the early prostate cancer setting to assess the risk of disease progression at diagnosis.
According to the company, the ability of Prolaris to detect progression of prostate cancer has been shown in 11 trials involving more than 6,000 patients. The latest study presented at AUA comes as Myriad is trying to drive adoption of Prolaris and seeking Medicare coverage for the test.
“This is the largest study using a molecular prognostic test in men [with localized prostate cancer] treated conservatively,” Michael Brawer, Myriad’s VP of medical affairs and a study investigator, told PGx Reporter. “The study more than triples the amount of information we have on patients that are biopsied and that are followed conservatively. By adding Prolaris to the standard clinical pathological parameters, we were much better able to individualize the risk, in this case [patients’ risk of] dying from prostate cancer.”
In the original study, 761 UK men diagnosed with clinically localized prostate cancer were enrolled between 1990 and 2004, and followed for a median of nearly 10 years by watchful waiting. Researchers calculated patients’ risk for disease progression at diagnosis using a variety of clinical measures, which were summarized in a so-called CAPRA score. Then, a year ago, researchers from Myriad and elsewhere generated a Prolaris risk score on these patients, but remained blinded to the patients’ disease outcomes.
When the prognostic ability of just Prolaris was assessed in nearly 600 patients with full clinical information, the test identified 30 patients as being at high risk with a score of great than 2; 110 patients as having a score between 1 and 2; 251 patients with scores between 0 and 1; and 194 with low risk scores of lower than 0. In the high risk group, patients had a 59 percent death rate. With lower Prolaris scores, the death rate in the study also declined – 36 percent for patients with scores between 1 and 2; 15 percent for those with scores between 0 and 1; and 7 percent for patients with scores less than 0. For each one-unit increase in the Prolaris score, patients’ risk of dying from prostate cancer doubled, the data show.
“As good as Prolaris is, when you add it to other ways of calculating risk, it’s even better,” Brawer said. In this study, researchers found the Prolaris score was in line with the prognostic ability of the CAPRA score, which combines Gleason score, PSA, and other clinical pathological measures and is considered the most well-validated risk assessment methodology.
“What Prolaris does is add to that,” Brawer said. In teasing out what Prolaris and CAPRA are adding to prostate cancer risk assessments, researchers found that a significant amount of prognostic information can be gleaned on a patient if Prolaris is done in addition to using the CAPRA score. By comparison, the CAPRA score also adds information to what Prolaris provides, but not nearly as much.
The latest results on Prolaris agree with findings from two other studies that Myriad has performed involving conservatively managed patients. “But this is a more contemporary series,” Brawer said. “That means that as far as the stage and the grade and the phase [of disease], it’s more [representative of] contemporary patients.”
This trial, Myriad hopes, will support increased uptake of the test by urologists. By introducing Prolaris in a study designed to follow prostate cancer patients to gauge how conservative management impacts their survival, the researchers sought to investigate whether the molecular test added useful information on top of traditional clinical prognostic information and whether it could more accurately determine which patients were at high risk of succumbing to the disease and which were at low risk of death.
“A trial like this where we have death as an endpoint … is really very helpful to the clinicians who are trying to make a decision on which patients are good candidates for conservative management or who has a cancer that looks like by standard testing to be appropriate for conservative management, but actually has more aggressive disease when tested by Prolaris, and is better suited for interventional therapy,” Brawer said.
If doctors can more accurately and earlier select which patients to conservatively manage with the help of Prolaris, that can help reduce treatment cost in these patients. “If you treat a man conservatively, but he really has more aggressive disease … then it’s an expensive proposition because you’re going to likely have to operate at a later time … and it’s a worse scenario than if you had decided on the correct risk assessment up front,” Brawer explained, noting that Prolaris can pick out these patients. “In contrast, you can take people who may look more aggressive, but when you add Prolaris, if they get a low score, then they don’t need aggressive therapy, so you can treat them more conservatively.”
The US Centers for Disease Control and Prevention estimates that each year in the US 240,000 men are diagnosed with prostate cancer and nearly 30,000 men die from the disease. But current clinical and pathological measures of determining which patients have aggressive and which have indolent disease are imprecise. Around one million men are biopsied for prostate cancer annually. Myriad estimates that as many as 85 percent of prostate cancer patients are aggressively treated, which causes 30 percent of these men to experience complications such as incontinence and impotence.
Molecular tools such as Prolaris have shown promise in being able to more accurately gauge prostate cancer patients’ prognosis and reduce unnecessary costs (see related stories, in this issue, on other molecular prostate cancer tests). According to a National Institutes of Health estimate, in 2010 the annual medical costs associated with prostate cancer in the US were $12 billion.
In addition to the large study on conservatively managed patients, Myriad reported data from two other studies at AUA involving Prolaris. In one study of 230 men with pathologic Gleason Scores of either 3+4 or 4+3, Prolaris was found to be a better prognostic indicator than Gleason Score for gauging which patients would experience biochemical recurrence after a radical prostatectomy. A third study presented at AUA concluded that Prolaris “was the strongest predictor of metastatic disease compared to other tested clinical variables.”
With this new data, Myriad is hoping to drive greater adoption and reimbursement for Prolaris.
Myriad recently submitted data from the PROCEDE 500 study to the Centers for Medicare & Medicaid Services. The study showed that Prolaris influenced treatment strategy for the majority of 150 surveyed doctors, and they changed the treatment course for two-thirds of their patients. Based on the Prolaris score, 40 percent of patient received conservative management, as opposed to expensive interventions, and 25 percent received more aggressive therapy. Doctors didn't change their treatment plans based on test results for 35 percent of patients.
The firm is hoping that the PROCEDE data will convince Medicare to cover Prolaris by the end of the 2014 fiscal year. The list price for the test is $3,400.
During its fiscal third quarter earnings call in May, Myriad officials reported there was a 24 percent increase in the number of samples the company received for analysis by Prolaris compared to the second quarter. Myriad has completed a second clinical utility study on Prolaris, called PROCEDE 1000, and plans to report outcomes from the trial by the fourth quarter. Additionally, the company is planning to ramp up its commercial efforts around Prolaris once the test garners Medicare coverage.