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Supported By Concordance Studies, GenomeDx Expands Decipher Test to Pre-Prostatectomy Space


NEW YORK (GenomeWeb) – After sharing several new publications during the last few months, GenomeDx has expanded its Decipher test from the post-prostatectomy space to also include a new pre-surgery indication.

The studies — one that appeared ahead of print in the Journal of Molecular Diagnostics last month and another that went up online in Urology earlier this year and will now appear in the April print edition of the journal — addressed the question of concordance between Decipher results from surgically removed prostate tissue versus matching pre-prostatectomy biopsy samples.

Decipher is a microarray-based gene expression test that predicts cancer aggressiveness using an assay of 22 markers associated with metastatic disease. Currently, the test is recommended in professional guidelines for use in men who have had a prostatectomy and who have specific clinical risk factors to help better determine their risk of metastasis in order to guide post-surgical drug treatment.

After sharing relevant research over the last few months, GenomeDx has now launched a biopsy-based version of Decipher intended to help physicians accurately determine if a patient may safely consider delaying initial local treatment or if he may benefit from earlier intensification of treatment with one or more therapies.

The company declined to discuss details of its plans for this new version of the test with GenomeWeb.

In the Urology study appearing in print this month, researchers led by Eric Klein, chairman of the Glickman Urological and Kidney Institute at the Cleveland Clinic, identified 57 patients with available biopsy specimens from a cohort of 169 men treated with radical prostatectomy in a previously reported Decipher validation study at Cleveland Clinic.

The study was funded by GenomeDx, Klein said, and was essentially an exploratory, or pilot study to determine if a biopsy-based Decipher test could predict meaningful clinical endpoints. It was "meant to help decide if larger and better designed studies were warranted," he wrote.

According to the authors, the results showed that the risk of metastasis at 10 years after prostatectomy for these patients was very similar when the test was applied to preoperative diagnostic biopsies versus prostatectomy tissues. This warrants further follow up, and offers early evidence that the test holds potential as a clinical prognostic tool to be applied before men undergo a prostatectomy, the researchers concluded.

"While further validation is required on larger cohorts, preoperative knowledge of Decipher risk derived from biopsy could indicate the need for multimodality therapy and help set patient expectations of therapeutic burden," the authors wrote.

The JMD study, though, had a broader overall focus — on evaluating the feasibility of obtaining transcriptome-wide RNA expression to measure prognostic classifiers in diagnostic prostate needle core biopsy specimens.

But aside from that larger endpoint, researchers also studied how several different gene expression classifiers, including Decipher, correlated when applied to biopsy versus surgical samples.

Overall, the study looked at 158 biopsy and prostatectomy samples from 33 men. According to the authors, Decipher scores showed a positive correlation between biopsy and matched prostatectomy tumor samples.

"This result provides preliminary evidence that the Decipher score may be predictive of disease progression in diagnostic prostate needle biopsy specimens," they wrote, adding that a "larger, adequately powered study" is needed to validate this observation.

Launching this new biopsy-based version of Decipher, GenomeDx enters more direct competition with some of the other genomic risk classifiers that are currently marketed to guide clinical decision making for men with prostate cancer, namely Myriad Genetics' Prolaris and Genomic Health's Oncotype DX Prostate Cancer, which are both currently used to assess prostate biopsy specimens to guide medical decision making regarding active surveillance versus more aggressive treatment.

According to Klein, use of all of these tests is increasing, and in his view there is good published data showing that their adoption increases the proportion of men who go on active surveillance rather than undergoing prostatectomy.

"That is my overriding goal, to reduce the overtreatment of nonlethal prostate cancers," he wrote.

Growing evidence in this area has been enough that the guidelines released by the National Comprehensive Cancer Network now include specific mentions of three tests, Prolaris and Oncotype DX for biopsies in men with low-risk cancers, and Decipher for post-prostatectomy samples in men with specific risk factors for disease recurrence.

However, Klein said, the field has yet to see a head-to-head comparison of any of these tests, and as such, clinicians lack a sense of which may be the best to use, a situation complicated by the entry of yet another test into the pre-operative biopsy space.

William Catalona, a Northwestern University urologist and director of the Urological Research Foundation, echoed Klein's sentiment on the need for a comparison between the available molecular prognostic assays, especially, he told GenomeWeb, because of the fact that due to commercial and IP considerations, each test may address different aspects of prostate cancer biology, and thus may be more or less suited to specific subsets of patients.

Prostate cancers are very heterogeneous, even within the aggressive phenotype category, he said. So, one test whose signature is focused on proliferation genes might perform better in tumors whose aggressiveness is due to high expression of those genes, but might perform less well in tumors whose aggressiveness is due to other signaling pathways that could be better measured by one of these other assays, he explained.

The manufacturers have not been willing to perform head-to-head comparisons of the tests to shed light on these issues. Ultimately, the true worth of these tests must be determined by whether patients who use them for making treatment decisions have better outcomes than those who don't.

"The manufacturers have not been willing to perform head-to-head comparisons of the tests to shed light on these issues. Ultimately, the true worth of these tests must be determined by whether patients who use them for making treatment decisions have better outcomes than those who don't," he said in an email.

Unlike Klein, Catalona is more skeptical of whether the available data on clinical utility for any of these tests — the evidence for their added value over other clinical measures — merits a patient paying a several thousand dollar price tag.   

"The bar is high to add information to routine clinical information, such as PSA, PSA density, the number and extent of biopsy cores that are involved with cancer, and the Gleason patterns present," he said.

Despite studies published by Myriad and by Genomic Health highlighting how frequently or substantially their tests change physician decision making, Catalona said that in his personal experience, it's a rare case where information from a molecular test changes what he would have recommended to a patient anyway.

He also said that based on his experience and conversations at scientific meetings, adoption of molecular prognostic testing is still low amongst clinicians who don't have a research affiliation with one or another of these companies. 

However, Catalona added, if the out-of-pocket costs of testing are reduced as these assays become covered more consistently by insurance payors, then more routine testing begins to make sense, since even an incremental added value over other currently used clinical risk factors can contribute to better patient care.

National Medicare benefit administration contractor Palmetto GBA issued a positive local coverage decision for Decipher in the post-prostatectomy space in early 2015. It also finalized an LCD for Myriad's Prolaris and for Genomic Health's Oncotype DX Prostate in August last year. 

In a call discussing its fourth quarter and full-year 2015 earnings this past February, Genomic Health said that its prostate tests delivered in the US grew 75 percent compared to the prior year and represented approximately 8 percent of its total test volume in 2015. The company added that it expects its prostate testing to represent more than 10 percent of its total test volume during 2016.

Discussing its second quarter earnings in February, Myriad said sales of its Prolaris test rose 375 percent year over year, bringing in $1.9 million in the quarter compared to $400,000 in the previous year's Q2.

In early 2015, GenomeDx said that several hundred urologists and radiation oncologists had ordered its test so far, and more than 75 percent of those clinicians were using the test to routinely inform postoperative treatment for their patients. The company declined to comment on its current adoption, or its plans for potential competition for the new pre-prostatectomy version of Decipher.