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From WSJ: New Prostate Cancer Tests



By Melinda Beck

When Al Piazza learned he had prostate cancer, his first thought was, “Let’s get this out and be done with it,” he says. But his urologist, Jeremy Lieb, said the side effects of treatment could be more harmful than the cancer itself.


Dr. Lieb ran a genetic test on the patient’s biopsy sample, which calculated that Mr. Piazza, then 70 years old, had only a 3% chance of dying from prostate cancer over the next 10 years if he left the tumor untreated.

Four years later, the retired AT&T manager from Discovery Bay, Calif., has been monitoring his cancer with regular blood tests and imaging scans and says he is comfortable leaving it alone. “My feeling is—it’s there, but it’s not going to kill me,” Mr. Piazza says.

Al Piazza learned he doesn’t require treatment for prostate cancer after a genetic test performed on his biopsy sample revealed small odds of harm if the tumor was left untreated.

The procedure done on Mr. Piazza’s tumor sample, called Prolaris by Myriad Genetics, is one of several new prostate-cancer tests that aim to reduce detection and treatment of tumors that are likely to be harmless while still spotting those that are lethal.

That has been a daunting challenge in recent years. Routine screenings for prostate cancer, using blood tests for prostate-specific antigen, or PSA, have dramatically increased early detection of the disease. More than 99% of cases are curable today. Most of the cancers that prostate screenings find are so slow-growing they are effectively harmless, experts say. Still, because some cancers are aggressive and deadly, most men have opted for treatment with surgery or radiation despite a significant risk of incontinence or impotence.

The ratio of potential benefit to harm is so small that the U.S. Preventive Services Task Force recommended in 2012 that men not be screened for prostate cancer at all.


Many experts recommend against routine PSA blood screening for prostate cancer, leaving many men to wonder whether they should get one.

The new tests, using blood, urine and tissue samples, go well beyond PSA tests and aim to tell men, in advance, not simply if they have prostate cancer, but also if it is aggressive enough to warrant locating and treating or if it can be safely monitored instead. (Gleason scores, which pathologists use to grade prostate cancers found on biopsies, help classify them as low, intermediate or high risk but don’t always reflect the cancer’s true aggressiveness.)

“The solution isn’t to stop screening. The better idea is to use more specific tests,” says Stacy Loeb, an assistant professor of urology and population health at New York University School of Medicine, who led a session on the new tests at the American Urological Association’s annual meeting, May 6 to May 10.

Dr. Stacy Loeb, a New York University urologist, led a session on new prostate-cancer tests at the American Urological annual meeting this month.

The new tests, however, don’t provide useful information for every patient and add significantly to the cost, Dr. Loeb and other urologists caution. Few of them have been vetted by the Food and Drug Administration. And while most have been validated in retrospective studies, there’s little data on how they compare with each other or whether they will improve prostate-cancer care long term.

“It’s very exciting to have these tests available, but it’s sort of the wild west now,” says Scott Eggener, a University of Chicago urologist and a spokesman for the American Urological Association.


Several of the new tests aim to reduce the number of needless prostate biopsies. More than 1 million U.S. men undergo the painful, intrusive procedure each year mainly because of an elevated PSA level. Overall, fewer than 20% of biopsies find prostate cancer.

The 4Kscore, developed at Memorial Sloan Kettering Cancer Center in New York, analyzes four different types of PSA-related proteins in blood samples and calculates the likelihood, from 1% to 100%, that a biopsy would find an aggressive cancer, defined as a Gleason score of 7 or above.

“It’s frightening for a patient to be diagnosed with cancer that doesn’t need to be treated. If it’s not going to bother him, then why find it?” says Peter Scardino, chairman of surgery at Memorial Sloan Kettering who advises the test’s maker, OPKO Health Inc., and is eligible for stock options. The 4Kscore became available in 2014 and costs about $1,000.

Another PSA-based test, Prostate Health Index, or PHI, from Beckman Coulter Inc., costs only about $100. It calculates the likelihood that a biopsy will find cancer but not how aggressive the cancer might be.

Other new tests check urine samples for gene fragments of prostate cancer to assess whether it is likely to be high-risk. SelectMDx, available from MDxHealth in the U.S. since April, requires a digital rectal exam first.

A new test from Exosome Diagnostics, expected to be available in June, checks for the presence of exosomes, the chemical messengers that can pave the way for cancer’s spread. A study in JAMA Oncology in March found the Exosome test correctly identified 97% of cancers that were later found to be aggressive in biopsies.

Another urine-based test, the University of Michigan’s Michigan Prostate Score, has been available since 2013 and has been shown to reduce the number of negative biopsies by 50% while delaying the finding of just 1% of high-risk cancers.


The typical 12-core prostate biopsy, which samples only about 1% of the prostate gland, can miss about 25% of cancers. In the past, men with a negative biopsy who still have other signs of prostate cancer, such as a rising PSA, have undergone second, third or fourth biopsies to search for tumors.

A new test called ConfirmMDx, also from MDxHealth, searches biopsied tissue for precancerous changes known as the “field” or “halo,” suggesting a tumor may be lurking nearby. In a 2013 study in the Journal of Urology, ConfirmMDx identified two-thirds of prostate cancers missed on first biopsy, and correctly identified two-thirds of patients who could correctly forgo a repeat biopsy.


Some urologists are using advanced imaging studies known as multiparametric MRIs, or mpMRIs, to guide initial and repeat biopsies. Several recent studies show a technique called fusion biopsy, combining MRI and ultrasound images, results in much higher accuracy for biopsies.

Dr. Mark Scholz at Prostate Oncology Specialists in Marina del Rey, Calif., says an mpMRI can yield much of the same information as a biopsy and far less invasively.

Some urologists are using mpMRI instead of biopsies for patients who opt for active surveillance of low-risk prostate cancers.

Mark Scholz, a prostate oncology specialist in Marina del Rey, Calif., maintains that an mpMRI can yield much of the same information as a biopsy and far less invasively. Low-risk prostate cancers barely register, he says, adding, “When patients find out they have a choice between 12 harpoon sticks to the prostate through the rectum or an MRI, they are on board big time.”

Joel Copeland, 62 years old, has been monitoring his PSA closely for a decade; his two brothers were diagnosed with prostate cancer. He opted for an MRI instead of a biopsy when his PSA bounced up in 2013. “I don’t like needles, but that’s not the point,” Mr. Copeland says. “The point is, biopsies can cause infection and miss cancers.”

Other urologists cite studies showing mpMRIs can miss an many as 16% of significant cancers and suggest patients also get a traditional biopsy. “Just because you have a negative MRI doesn’t mean you don’t have cancer,” Dr. Eggener says.

The biopsy is positive – now what?

Traditionally, urologists have urged men whose biopsies show prostate cancer with a Gleason score of 7 or higher to proceed immediately with surgery or radiation. Increasingly, doctors are counseling those with a Gleason 6 score, the lowest possible, to opt for “active surveillance” of the cancer.

Now, though, even some Gleason 7s are thought to be indolent, while about 20% of Gleason 6s are found to have been aggressive if the prostate was removed.

Dr. Jeremy Lieb, of Pacific Urology, says the new tests are useful in part because they reassure patients with low-risk cancers that it’s OK to watch and wait.

The new tests aim to provide better predictive information by analyzing the genetic makeup of tissue sampled in a biopsy. Even for patients with low-risk cancers, “it helps to have some validation to tell them, ‘you can just wait and watch it’,” says Jeremy Lieb, Mr. Piazza’s urologist in Walnut Creek, Calif., who has participated in some Prolaris test studies.

Prolaris examines the RNA expression of 46 genes involved in tumor-cell growth and predicts a patient’s likelihood of dying from prostate cancer in the next 10 years. OncotypeDx, by Genomic Health, studies a different set of 17 genes and predicts the patient’s chance of having a “favorable pathology,” or a cancer that won’t metastasize.

The two tests each cost from $3,000 to $4,000. They are covered by Medicare and most insurers for patients with low or very low risk cancers.

ProMark, by MetaMark Genetics, measures protein levels of eight biomarkers in tumor tissue to predict aggressiveness. GenomeDx Biosciences announced in March that its Decipher test, which predicts the risk of cancer recurrence after a prostatectomy, can be used to evaluate cancers in newly diagnosed patients as well.

Dr. Loeb of NYU says the tests are most useful when a patient’s cancer pathology is borderline. “If the patient already has aggressive disease, we don’t need a test to tell us,” she says. “And if it’s very low risk, only a tiny amount of Gleason 6, there’s already good data that shows we can use active surveillance.”

Prostate cancer experts say more tests are needed to spot and derail aggressive prostate cancers that kill about 26,000 Americans a year. “The goal should be that we can see a man’s prostate cancer coming from so far away that it never harms him,” says Jonathan Simons, president of the nonprofit Prostate Cancer Foundation, which helps fund research.

Write to Melinda Beck at HealthJournal@wsj.com

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