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More Information Is Better for Prostate Cancer Screening

Cal Ripken and his doctor discuss the test that can help more men avoid biopsies — or tell them to seek one, stat

Shortstop Cal Ripken of the Baltimore Orioles signs autographs after a game in 1995

Doug Pensinger Getty Images Sport

En español | As you may have heard, baseball legend Cal Ripken Jr. received a prostate cancer diagnosis back in February and is now cancer-free. For that swift and positive outcome, he credits a new, non-invasive urine test that led him to proactively seek a biopsy — something he wants other men to know is available to them, too.

Ripken's journey began when he went for his annual physical and routine bloodwork revealed his prostate-specific antigen (PSA) — a protein produced by cells of the prostate gland — had risen over time. While between a quarter to half of the time, depending on your PSA level, this may be due to prostate cancer, much of the time it indicates something as benign as an enlarged prostate (common in men as they age) or a long bike ride. A frequent cyclist, Ripken says he thought riding his bike a lot, as he'd been doing around that time, “or a small infection” could be the reason. Otherwise, he says, “I had no symptoms whatsoever,” experiencing none of the tell-tale signs such as trouble urinating or lower back pain.

“My story had a happy ending: We caught it early, and my life went back to how it was before. All men should be able to have that."

Cal Ripken, Jr.

For years, men with an elevated PSA had two options: adopt a wait-and-see approach, or, to find out with certainty whether they had cancer, get a biopsy, a painful procedure where a physician puts a needle through the wall of the rectum and into the prostate. It also carries risk of bleeding or infection.

Instead, Ripken's urologist, Ronald Tutrone Jr., chief of the Division of Urology at the Greater Baltimore Medical Center, recommended the ExoDx Prostate Test, a newer, simple urine test that looks for genetic changes indicating prostate cancer. When that test came back elevated, Ripken went ahead with a biopsy that indeed revealed he had prostate cancer. He underwent successful surgery in March, and is now in remission.

Ripken feels fortunate his cancer was caught in the early stages, and that he was able to get the ExoDX Prostate Test. “Without it I might have decided to simply watch my PSA levels for a while, and the cancer might have spread."

For more than thirty years, the PSA has been the gold standard when it comes to detecting prostate cancer. But it's also had its share of controversy. “There have been concerns that a positive PSA test has led to overdiagnosis and overtreatment,” says James Wysock, M.D., a urologic oncologist and assistant professor of urology at Perlmutter Cancer Center at NYU Langone in New York City. In men with PSA levels in the 4.0 to 10 range, biopsy confirms cancer about 25 percent of the time. This means that the remaining 75 percent would have to undergo a procedure that's painful, anxiety-producing, and carries risks including infection and bleeding. And even if the test successfully picks up cancer, Wysock adds, many prostate cancers grow so slowly that they will not cause harm during a man's lifetime. But to be on the safe side, many men opt for treatment, which carries risk of side effects such as incontinence and impotence.

Now, not only can several new blood and urine tests more accurately measure your risk for prostate cancer, they can also detect how aggressive your cancer is, so that both you and your doctor can come up with a targeted treatment. “Not all prostate cancers need to be treated — we can sometimes do what's known as active surveillance, where you're monitored over time to see if your levels rise,” explains Wysock.

The ExoDx, which has been available since 2017, works by checking a man's urine for specific prostate cancer biomarkers that would indicate tumor cell growth. If the test comes back with a score under 15.6, it's considered low risk or benign. Anything higher could indicate cancer. Ripken's score was 45.

Similar specific tests to diagnose prostate cancer have been available for close to a decade. Two of the earliest ones were the Prostate Health Index (PHI), FDA approved in 2012, and the 4Kscore test, approved in 2015. These both combine the results of different types of PSA to get an overall score that reflects the chance a man has prostate cancer (particularly cancer that might need treatment). They've been shown to reduce the need for unnecessary biopsy by about 30 percent, while still picking up high-risk aggressive cancers.

But potentially even more accurate urine and blood tests have become available over the last couple years. “These tests rely on genomics, which means they actually analyze the genes of a patient for signs of prostate cancer,” explains Wysock. As a result, they're even more accurate then these older versions.

Along with ExoDX, such newer tests include:

SelectMDx. This urine test assesses a man's risk for aggressive prostate cancer to help identify which patients may truly benefit from a biopsy. A 2019 study published in the Journal of Clinical Oncology found that it was more useful than the Prostate Health Index in picking up aggressive cancers that required biopsy.

IsoPSA. This blood test, invented by the Cleveland Clinic and FDA approved in late 2019, identifies molecular changes in PSA that can indicate cancer, says Eric Klein, M.D., chair of Cleveland Clinic's Glickman Urological & Kidney Institute. It's been shown to reduce unnecessary prostate biopsies by about 45 percent.

miR Scientific's Sentinel Test. This urine-based test, which became available this year, can categorize patients into one of four groups: no cancer, low-risk cancer, intermediate-risk cancer or high-risk cancer.


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If you have an elevated PSA, Klein recommends following up with any of the above tests, including one of the older ones. (It may boil down to which tests are available at your medical center, and what's covered by your insurance.) If you have a test done and it's negative, you can just be followed closely with annual PSA screening. If it's positive, the next step should be a prostate MRI as well as a biopsy. An MRI is important, Klein explains, because it can show if the cancer has spread “right outside the prostate into, say, the seminal vessels.”

Ripken, for one, credits the ExoDx prostate test with convincing him to go ahead and have the biopsy. “With the uncertainty of what a PSA result means, it's easy to just dismiss it and say you'll come back in six months or a year and look at it again,” he explains. But once he got his results back, “it really gave me a different perspective. It gave me confidence that a biopsy was the right course of action.” Today, Ripken is back to doing all his regular activities, including biking, with no side effects. “My story had a happy ending: We caught it early, and my life went back to how it was before,” he says. “All men should be able to have that."

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