NEW YORK (GenomeWeb) – Researchers from GenomeDx Biosciences and elsewhere have published data showing that the company's 22-gene Decipher test can distinguish between prostate cancer patients at high and low risk for metastasis after surgery, and mayfurther predict which patients would benefit from adjuvant radiation therapy or would do well with salvage treatment.
Separately, GenomeDx told GenomeWeb that it is planning to submit Decipher for regulatory approval with the US Food and Drug Administration, but did not elaborate on those plans.
The company, whose R&D headquarters are in Vancouver, Canada, currently offers Decipher out of its San Diego CLIA lab. However, in light of the FDA's recently issued draft guidelines on its plan to regulate laboratory-developed tests, Decipher could end up being considered a high-risk device requiring premarket review, particularly if GenomeDx plans to market it with predictive claims for guiding therapeutic strategies in the US.
According to a company spokesperson, the latest publication in the Journal of Clinical Oncology marks the first study suggesting Decipher has predictive capabilities. GenomeDx is conducting another study to further establish the test in this regard.
The study, published in JCO and led by Robert Den of the Sidney Kimmel Medical College of Thomas Jefferson University and Jeff Karnes of the Mayo Clinic, retrospectively analyzed 188 patients with prostate cancer who received radiation treatment after a radical prostatectomy between 1990 and 2009. No patients with Decipher low scores experienced metastasis at five years after radiation therapy; 9 percent of patients with intermediate scores had metastasis; and 29 percent of patients with high scores had metastatic disease.
GenomeDx recently announced that Medicare contractor Palmetto GBA had issued a final local coverage determination (LCD) for Decipher through its MolDx program. The decision covers testing with Decipher for prostate cancer patients who are traditionally considered to have a high risk of recurrence after radical prostectomy, but who may be closely followed rather than receiving post-operative radiation therapy.
In its LCD, Palmetto noted that approximately 40,000 American men annually are determined to be at risk of cancer metastasis after surgery due to rising prostate-specific antigen (PSA) levels. According to treatment guidelines, the standard of care is to treat these patients with radiation therapy. However, data from clinical trials suggest that some patients in this subset who forgo radiation treatment do well. Those treated with radiation also do well, but experience more adverse events. "The identification of the subgroup of men who do not need [radiation treatment] is important," Palmetto stated. "However, prospective studies of outcomes of early prostate cancer (especially where there is a non-intervention arm) will take decades to complete."
Given the chance of overtreatment and unnecessary side effects using traditional risk assessment factors, GenomeDx is hoping that its test can improve doctors' ability to figure out which patients are at high risk for negative outcomes and treat them with radiation treatment immediately after surgery instead of salvage treatment after PSA levels start to rise.
In the JCO paper, researchers reported that for patients with low risk scores by Decipher, there was no difference in the incidence of metastasis between patients who received adjuvant radiation therapy after surgery versus salvage radiation treatment; the p-value of this finding was 0.7. Among patients with high risk scores, metastasis rates were lower for those treated with adjuvant radiation (6 percent) compared to those who received salvage treatment (23 percent). This analysis was statistically significant.
"We demonstrate that the genomic classifier is highly prognostic in the setting of post-prostatectomy radiation therapy and that the genomic classifier may be a predictive marker that can help determine which patients will benefit from adjuvant radiation therapy as opposed to salvage radiation therapy," the study authors wrote. "Although a biomarker should not substitute for the shared patient-physician decision-making process, the integration of a genomic classifier can provide additional insights into the aggressiveness of a man's prostate cancer and more appropriately guide his post-prostatectomy therapy selection."
The GenomeDx spokesperson noted that the company is continuing to update Palmetto's MolDx program with new data on Decipher. The latest results "were provided upon acceptance by the journal," the spokesperson said. The results "were given consideration in the coverage decision for the indicated test population of all intermediate- and high-risk prostate cancer patients after surgery."
To further study the predictive component for Decipher, the company is conducting analysis of a retrospective, randomized controlled trial with "a major NCI cooperative trial group," the company spokesperson noted. Results from this trial are expected to be reported by year end.
GenomeDx began offering testing on Decipher two years ago. Since then several hundred urologists and radiation oncologists have ordered the test, according to the company, and more than 75 percent of those clinicians are using the test to routinely inform postoperative treatment for their patients. GenomeDx began marketing the test nation-wide at the start of this year.