NEW YORK – After a bumpy, three-years long journey, Opko Health's 4Kscore prostate cancer test may finally be on the verge of a crucial step toward potential Medicare coverage.
In June, the test received a proposed limited local coverage determination from Medicare Administrative Contractor Novitas, the latest development in Opko's efforts to get Medicare to cover the test. Although 4Kscore — which is used to assess a man's risk for having aggressive prostate cancer — has been covered by commercial payors since 2014, Opko has had difficulty getting coverage from the Centers for Medicare and Medicaid Services, which administers Medicare.
While receiving a proposed LCD does not guarantee Medicare coverage, it is virtually impossible to get such coverage without it.
In 2016, Novitas issued a draft local coverage determination for the test, but withdrew the decision after another MAC, Palmetto, issued a draft non-coverage determination later. In May 2018 and January 2019, Novitas issued other non-coverage determinations for the test, but withdrew those decisions, only to issue its proposed LCD during the summer.
The public comment period for the newest LCD closed Aug. 11, and the company said it expects the final decision to come sometime in the next few months, although there's no specific time frame for Novitas make a final decision. Jon Cohen, the executive chairman of BioReference Laboratories, an Opko subsidiary, didn't want to speculate on the final decision, but noted that the company remains upbeat and confident that the test will be covered.
Despite the troubles with coverage, the 4Kscore test has seen meaningful uptake with more than 4,000 urologists ordering more than 250,000 tests, the company said. In addition to providing early evaluation for high-risk patients, the test is also used to help avoid unnecessary prostate biopsies in men with low risk, said Cohen.
A study published in 2015 in European Urology found a potential 32 percent reduction in prostate biopsies when the 4K test was used. A more recent study published in the same journal found it could identify patients who had elevated prostate-specific antigen (PSA) levels but were at low risk of dying from prostate cancer in the next 20 years.
The 4Kscore has been recommended in the National Comprehensive Cancer Network's guidelines since 2015, and the European Association of Urology Prostate Cancer guidelines since 2016.
One issue surrounding PSA has been that it has led to unnecessary biopsies. Even if a patient's PSA level is raised, a biopsy is not always the best next step. The 4Kscore test, Cohen said, was developed to help clarify which patients should proceed to biopsy and which ones can skip the invasive procedure.
There's a low complication rate for prostate biopsies, but Cohen said avoiding even the chance of the complication when a biopsy isn't necessary can help, since "the complication in itself is significant if it occurs to you."
The 4Kscore test measures four kallikrein biomarkers, including intact PSA and hK2, both of which are proprietary to Opko. An algorithm then is used to determine a patient's risk of aggressive prostate cancer. The algorithm also includes prior biopsy status and age as factors to help measure risk.
Cohen noted that in conversations with Novitas regarding the coverage determination, Opko had made changes in patient and physician education surrounding the test. After speaking with the MAC, Opko made shared decision-making procedures part of the test's requisition, so patients would have to sign a release to get the test. Threading the line between education for patients and undue burden on clinicians presented a potential issue, since the company wanted to avoid the process being "too onerous" for physicians, Cohen said.
Novitas and Opko also had discussions about whom exactly the test was appropriate for, Cohen said. The ultimate decision was that the test is for patients 45 to 75 years old with a PSA between 3 and 10. For patients over 75, the PSA must be 4 to 10. Patients must also have a life expectancy of at least 10 years, since metastatic prostate cancer can take a long time to develop.
Ethnicity is another important factor, since African American men are at significantly higher risk for both getting prostate cancer and dying from it. To make sure the test worked for black patients, a clinical validation study published in the Journal of Urology was performed that involved a predominantly black population from Veterans Health Administration. There was no difference in test performance for African American and non-black men. Results from this and another clinical validation study showed a combined sensitivity of 94 percent and a negative predictive value of 95 percent for the detection of Gleason 7 or higher cancer, the company said.
Cohen was careful to emphasize that the test isn't for everyone. If a patient has a rapidly elevating PSA level, or if a large hard mass is discovered during a digital rectal exam, a biopsy may be the better option. Other high-risk factors that would lead straight to a biopsy include a strong family history or a suspicious MRI.
But the test was never intended to be used on groups with those risk factors anyway. "The role of this has always been in this indeterminate group where people just didn't know what to do, so that we could actually save thousands of men from getting biopsies," Cohen said.
The company said it plans to continue promoting the 4Kscore in urologists' office across the country, and Cohen mentioned Opko has been approached to launch the test in the international markets, although there are no further details available.