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Molecular Biomarker Tests for Localized Prostate Cancer
Is one of these tests right for you? Do you even need one?

You’ve got localized prostate cancer.  Deciding on treatment is easy, right?  Not always!   Molecular biomarker tests – which look at biopsy tissue for many factors, including genetic mutations and expression of certain genes or proteins in the cancer – may provide extra guidance.  Is one of these tests right for you?  Do you need one at all?  Let’s take a closer look, with the help of PCF-funded investigator and Dana-Farber Cancer Institute medical oncologist Himisha Beltran, M.D.,  who also is Director of Clinical and Translational Research at the Englander Institute for Precision Medicine at Weill Cornell Medicine.

Although by itself, localized prostate cancer (cancer that has not spread beyond the prostate) sounds fairly straightforward, knowing what to do next is not always clear, says Dr. Beltran.  Within this single category “there is a diverse spectrum of clinical courses, ranging from cancer that can be watched to cancer that needs to be treated aggressively.”

With University of Chicago urologist Scott Eggener, M.D., Dr. Beltran co-chaired a multidisciplinary panel that developed clinical practice guidelines for using molecular biomarkers to shed light on some of the nuances in localized prostate cancer.  Their results were published in the Journal of Clinical Oncology.

Beltran and colleagues focused on four commercially available genomic tests,  Oncotype Dx Prostate, Prolaris, Decipher, and ProMark, looking at specific situations where use of a tissue-based test, added to the other clinical information – factors including Gleason grade, clinical stage, PSA – can help determine treatment.  They also looked at cost:  these tests are not cheap, and they aren’t universally covered by insurance.  Are they worth it?

The answer is a resounding: Not for every man.   Even at their most helpful, notes Beltran, “these are just tools, not perfect tests.”  In fact, the panel noted that while biomarker tests may help determine treatment decisions for some men, there is not yet “high-level evidence to indicate that the results … improve quality of life or cancer-specific outcomes.”  Their recommendation:  “continued investigation of tissue-based molecular biomarkers in the context of clinical trials.”

But in some circumstances, they can add that extra piece of information that proves helpful.

Active surveillance:  The panel agreed that genomic tests may help men who are considering active surveillance but are “in a gray zone:” for example, “a man with high-volume, low-risk cancer, or a man with favorable, intermediate-risk prostate cancer.”  However:  “Routine ordering of molecular biomarkers is not recommended,” and the strength of the panel’s recommendation was “moderate.”  Note:  In another study, published after these guidelines were issued, Oncotype Dx Prostate did not prove useful for clinical decision-making in active surveillance.

Clinically significant prostate cancer:  The panel gave another moderate recommendation to using one of the four biomarkers to help identify prostate cancer that needs to be treated.  Oncotype Dx Prostate, Prolaris, Decipher, and ProMark all “may predict potentially more aggressive cancer that needs to be managed more aggressively.”

Radiation in addition to surgery:  The panel also gave a moderate recommendation to one biomarker, Decipher Genomic Classifier, to help decide whether a high-risk man gets adjuvant radiation soon after prostatectomy, or “whether he could be watched, and potentially get radiation later if his PSA rises.”  However, “in the absence of prospective clinical trial data, routine use of genomic biomarkers in the postprostatectomy setting to determine adjuvant vs. salvage radiation, or to initiate systemic therapies (such as androgen deprivation therapy or chemotherapy) should not be offered.”

MRI vs. genomics:   MRI has proven to be very valuable in identifying suspicious areas of the prostate that need to be biopsied.  However, there’s room for improvement:  “about 10 percent to 15 percent of clinically significant cancers don’t show up on MRI,” notes Beltran.  Ideally, a molecular biomarker test would provide information that the MRI does not, and vice versa.  We’re not there yet.  “These biomarkers have been developed in parallel to MRI, and it’s likely that they provide different types of information that can also help inform what’s going on in a patient with newly diagnosed prostate cancer,” adds Beltran.  “But we don’t necessarily know how well they complement each other.  There’s not enough long-term data to know.”  Although “several genomic tests have demonstrated the capacity to predict the likelihood of adverse pathologic findings at prostatectomy, risk of recurrence, metastases, or death, there have been few studies directly comparing genomics and MRI.

Are they cost-effective?  Again, nobody can say for sure yet.  “Studies are urgently needed to evaluate and compare the cost-effectiveness of each of these tests,” the panel said.  The tests range in price from $3,900 to $5,150.  The panel was very concerned with high patient out-of-pocket costs, and recommended that “clinicians discuss the use of less expensive alternatives, when practical and feasible.”   The tests discussed here are covered by Medicare but not all insurance; some financial assistance is offered by the companies, as well.

Here’s a good reason for the lack of evidence to back up using these biomarker tests:  They’re very new.   “We felt that the data showed these tests could be useful in certain situations,” says Beltran, “but what studies haven’t actually shown is that patients did better in the long term, with quality of life or length of life.  In medicine, we usually only want to order a test if we think it’s going to help someone or change something in that person’s care for the better, so that was the caveat” in the panel’s recommendations.

However, “they can potentially improve decision-making and patient counseling in cases where clinical judgment is on the fence, where having one more level of information could make a difference.”

The panel’s overall recommendation:  “If a test will be used in combination with established clinical factors, it could be considered, but not for every single patient.”  If that sounds cautious, it’s not because Beltran and the panel don’t see the potential:  They do!  “Molecular biomarkers are very promising,” she says.  “There really is an unmet need,” which these tests may be able to fill.  But “we still have a lot to learn.  We need to better understand how to stratify patients with prostate cancer, scaling back treatment for men who don’t need it, scaling up for men with very aggressive disease.  We don’t have the perfect data yet to know exactly how the tests will affect long-term outcomes, but I’ve been quite encouraged by how far we’ve come already.

This is a rapidly evolving field.  I envision that we will be subtyping patients’ tumors in a very different way in the future.  I don’t think these tests are going to replace PSA and the Gleason grade, but I think they’re only going to help us get better at understanding prostate cancer and the best way to treat it.”


Note: these tests are intended for use in men who have already had a biopsy and been diagnosed with localized prostate cancer. For information on blood and urine tests that may help determine whether and when a biopsy is needed, see the previous story in this series.

Janet Worthington
Janet Farrar Worthington is an award-winning science writer and has written and edited numerous health publications and contributed to several other medical books. In addition to writing on medicine, Janet also writes about her family, her former life on a farm in Virginia, her desire to own more chickens, and whichever dog is eyeing the dinner dish.