NEW YORK (GenomeWeb) – At a medical meeting last week, researchers presented data from a study that included a large number of biopsy samples from African-American men and concluded that Myriad Genetics' prostate cancer aggressiveness test Prolaris can accurately determine the risk of metastases in this group with a high disease burden.
In the study presented at the American Urological Association's annual meeting, researchers used Prolaris to retrospectively test samples from nearly 700 men — 38 percent were African American — who were diagnosed with localized prostate cancer at the Ochsner Clinic in New Orleans and treated between 2006 and 2011. Investigators led by Stephen Bardot, a urologist at the Ochsner Clinic Foundation in Louisiana, and Steven Stone, VP of cancer genomics at Myriad, found that the Prolaris score was a strong predictor of which patients would see their cancer metastasize over 10 years and whether they'd experience biochemical recurrence.
Prolaris analyzes expression of 46 genes that can drive tumor growth, and provides a score that translates to high, intermediate, and low risk of disease mortality. Myriad has evaluated Prolaris in a dozen published studies in order to show that men deemed low risk by the test can be candidates for active surveillance, while those with high-risk scores may require additional therapy. The analysis presented at AUA characterizes Prolaris' prognostic capabilities in African Americans, a population that has three-to-four times the mortality risk from prostate cancer compared to white men.
However, counter to previous studies suggesting that African-American men tend to have more aggressive disease compared to Caucasian men, Bardot and colleagues reported in their evaluation that the distribution of Prolaris scores didn't differ by race, though this was not a statistically significant finding. "Contrary to expectations, this large study found no evidence that African-American men have more aggressive prostate cancer than non-African-American men after accounting for all molecular and clinical information," Myriad said in a statement announcing the results of the study.
The researchers concluded that this data provides further support that Prolaris significantly predicts which men are likely to progress to metastatic disease, regardless of race, risk group, or treatment. The Bardot et al. study is Myriad's second evaluation of Prolaris' ability to gauge risk of prostate cancer metastasis.
Previously, researchers led by Jay Bishoff from Intermountain Healthcare published in the Journal of Urology in 2014 that the Prolaris score was associated with biochemical recurrence and metastatic disease in three cohorts totaling close to 600 men. The second study by Bardot and colleagues builds on that earlier data, and enabled Myriad to add a metastasis risk score to its Prolaris report.
"This study adds significantly to data on Prolaris' ability to predict risk of developing metastatic disease after definitive therapy," Michael Brawer, senior VP of medical affairs at Myriad Genetic Laboratories, said in an interview. "But the reason we did this study was to respond to data … that in African-American men we couldn't rely on standard clinical pathological parameters to identify who is or is not a good candidate for active surveillance."
The data Brawer is referencing comes from a 2013 Journal of Clinical Oncology publication by Sundi et al., which studied 1,800 men, of whom 250 where African Americans. This evaluation found that African-American men deemed to be at very low risk of prostate cancer by National Comprehensive Cancer Network criteria tended to have more adverse pathology at radical prostatectomy compared to Caucasian men or men of other races. This study suggested that African-American men may have unique biological features driving their disease that may not be captured by standard pathological parameters.
Myriad explored this finding further in its own study, and worked with the Ochsner Clinic, which is located in New Orleans and treats a large number of African-American men. Bardot and colleagues reported that after factoring in molecular and clinicopathologic data, they found no evidence that African Americans have more aggressive disease than men of other races.
"Prolaris behaved exactly the same in African Americans and in non-African Americans as to identifying the risk of developing metastases," Brawer said. The finding is intriguing from a public health standpoint, since prostate cancer has a high toll in the African-American population.
The incidence of prostate cancer is 60 percent higher for African-American men, compared to white men; they tend to present with features indicative of more aggressive disease (i.e. larger tumors and elevated prostate-specific antigen levels); and they are two-to-three times more likely to die from the disease. At a time when the US Preventive Services Task Force recommends against PSA screening for men, these statistics have raised calls for a separate set of guidelines for African-American men.
"But there has always been a question as to whether there is a biologic basis for [these differences] or if there is a detection bias," Brawer reflected. This question has been at the center of a number of analyses, recognizing that African-American men tend to be underserved when it comes to access to screening.
Studies conducted by the US Department of Veterans Affairs have found that when healthcare access was equal among white and African-American men, mortality was similar among prostate cancer patients, regardless of race. Reviews of the published literature, however, have painted a more complex interaction between disease biology, socio-economic, and cultural determinants.
"I really don't know whether the difference in the [Sundi et al. study] was a reflection of non-equal access … and maybe Ochsner Clinic has more equal access," Brawer said. "These are questions for epidemiologists, and we're going to try to figure some of this out based on these findings."
The co-lead authors of that study, Debasish Sundi at MD Anderson Cancer Center and Edward Schaeffer at Northwestern University, declined to comment on the latest study by Bardot and colleagues. Schaeffer has been a consultant to Myriad and has a financial interest in GenomeDx, another firm selling prognostic molecular tests for prostate cancer.
Sam Chang, professor of urologic surgery and oncology at Vanderbilt University, wasn't surprised by the finding that after factoring in molecular characteristics of patients' tumors there was no difference in prostate cancer aggressiveness by race. "We don’t know of any other cancer where race would make a difference in terms of the genetic and chromosomal changes," he said. "I think this [study] makes sense. I personally wouldn't have expected an African-American cohort to have more aggressive disease."
Chang wasn't involved in the analysis by Bardot's group, but has used Prolaris and other prognostic molecular tests in his practice. He acknowledged that there is data suggesting that it may not be safe to do active surveillance on African-American men based on standard risk assessments because they may have more aggressive disease. But he also cited a retrospective analysis of records from the SEARCH database, which found that disease aggressiveness, survival, and biochemical recurrence were similar between African-American and Caucasian men.
The Bardot study aligns with Chang's understanding that "if you're careful with follow up and monitoring of African-American men with prostate cancer, with low-risk disease, they don't have a higher chance of treatment failure compared to Caucasians." Within the active surveillance population at Vanderbilt, close to 10 percent of prostate cancer patients are African American, he noted.
Myriad believes that the present analysis in the African-American population speaks to the broad applicability of its test in determining prostate cancer aggressiveness. Although the present finding with regard to the race-specific performance of Prolaris wasn't statistically significant, he highlighted that in two other studies, one by Freedland et al. in the International Journal of Radiation Oncology and another by Bishoff et al. in the Journal of Urology, similarly showed that test scores were similar for African-American and non-African-American men. Data from all these studies, Brawer said, gives him and his colleagues greater confidence in the broad utility of the Prolaris test.
The accumulating data on the performance of Prolaris in African-America men could be a differentiating factor in a market crowded with molecular diagnostic testing options for prostate cancer aggressiveness. "When you step back and ask where do we need the biggest [impact] in prostate cancer in the US, it's unequivocally in African-American men," Brawer said.
Myriad has already discussed these data with payors. Since 2015, the Centers for Medicare & Medicaid Services has been covering Prolaris for men who are at low risk and very low risk for prostate cancer according to NCCN criteria. Medicare contractor Palmetto hasn't yet finalized a draft local coverage determination for Prolaris for men who have favorable intermediate risk by NCCN criteria.
"This [latest data] will resonate well with the payors," Brawer said, adding that knowing the risk for metastasis allows patients to then consider adjuvant therapy, more active monitoring, or clinical trials. "It's where we need to make the biggest bang [and] … where we really need to improve our risk stratification if we're going to change the almost 30,000 men who are going to die of this disease."