Beyond PSA: What's Next for Prostate Cancer Detection?

Stacy Loeb, MD

Prostate-specific antigen (PSA) screening, while a great tool, has significant limitations for prostate cancer detection when used alone, explains Stacy Loeb, MD, assistant professor of Urology and Population Health at NYU Langone Medical Center.

“PSA is not like a pregnancy test; it’s not black and white where you either see the pink line or you don’t,” she says. “Since a PSA elevation is nonspecific, it can be increased because the prostate is growing, there’s a tumor growing, or there is an infection.”

Fortunately, several new tests are on the market that, often times in conjunction with PSA, can give oncologists and urologists more insight into prostate cancer risk. These include the Prostate Health Index, 4Kscore, PCA3, and ConfirmMDx.

“Since we don’t really know the cause of increased PSA in many cases, the purpose of these tests is to help sort out, through various ways, if it is due to a significant prostate cancer or just something else,” explains Loeb.

OncLive: How has the use of prostate biopsy evolved in recent years?

In an interview with OncLive, Loeb discusses how these tests work, what their benefits are, and what urological specialists need to know in order to best utilize them.Loeb: Historically, one PSA threshold was used to decide if a biopsy was necessary. Back in the early 1990s, the FDA approved PSA screening with a threshold of 4. That means that levels above 4 were considered abnormal, so it didn’t matter if you were 50 years old or 80 years old, or if you were known to have a big prostate or any other factors. Basically, if it was above 4, irrespective of any other issues, then you were referred for a biopsy. Actually, because the randomized studies of PSA screening were designed in the early 1990s, one PSA cutoff was used to decide on biopsy for everyone.

Since then, it has become clear that PSA really cannot be dichotomized like that. It’s actually a spectrum. Therefore, as the level gets higher, the risk increases continuously and makes it hard to draw a line in the sand.

What are some of those new markers?

We have learned a lot since the early 1990s on how to use PSA better, and there are new markers available that are more specific to help us make better decisions regarding biopsy.There are two blood tests called the Prostate Health Index and the 4Kscore. They are actually very similar to each other. They perform similarly and are both based on PSA. They use different forms of PSA combined together, which jointly do a better job than just looking at total PSA. Both of these tests are recommended as options in the 2015 NCCN Guidelines.

If a man has a PSA that’s above 3, and you’re trying to decide whether he should proceed with biopsy, both of these tests can be used to help make that decision. This is because the Prostate Health Index and the 4Kscore are specific to clinically significant disease. If these tests are high, that means that this man has a higher risk of having significant prostate cancer.

There are also other types of markers, including PCA3. This is a urine test and is also FDA approved, but only for men who already had a prostate biopsy that was negative and we have to decide if they need another biopsy. This is also commercially available; it was FDA approved in 2012.

The problem is that there is conflicting data on whether it actually predicts significant prostate cancer. The other 2 tests that I spoke on earlier—the Prostate Health Index and the 4Kscore—are consistently, across all studies, associated with aggressive disease. Whereas, with PCA3, some studies show a relationship and some don’t. It’s important that we focus on markers that will actually help us in this quagmire of trying to find the important cancers and not unearth indolent cancers.

There is also a tissue test called ConfirmMDx. This is also for men who had a negative biopsy. Unlike the other tissue tests on the market, which look at tumor tissue, this is actually looking at a negative biopsy. It examines benign tissue and asks the question, “Are there suspicious changes in the benign tissue that suggest that there’s a tumor somewhere lurking that was missed on the biopsy?”

Are there challenges in terms of accessibility of these newer tests or a lack of knowledge on how to use them?

If they are there, then that would suggest the need to re-biopsy and it would show us where we need to be looking. All of these tests are commercially available. It’s great that we have some more testing options because so many men are in the position of trying to decide if they should have a biopsy or they have already had one or more negative biopsies and are trying to decide if they should get another one.Definitely. I think it’s a major challenge because there’s just been such an expansion of the number of tests on the market.

There is confusion among physicians and patients on which test should be used in which setting. Some of the tests can be difficult to obtain in certain areas, but that’s also why it’s nice that there are multiple options available. If it is difficult to obtain one of these tests in your region, hopefully one of the others are available.

A good example of this is MRI. We do a lot of prostate MRI at NYU. We have a very longstanding program for this, and I think MRI is one of the most important tools in our armamentarium for prostate cancer nowadays. However, it’s still at the beginning in many places, and there are many people who tell me that they don’t have a lot of experience with it or have radiologists who are experienced with it.

What does the urology community need to know about these tests?

Until people become more experienced using MRI, it’s very helpful to have some objective marker tests available that are not dependent on the level of experience. Also, they can be ordered from anywhere, as long as you can obtain a blood test or a urine sample.They need to understand what is the state of the evidence on each of these tests and the role that each test has in our clinical decision-making process. Is the test used to help with the initial biopsy decision, to help with the repeat biopsy decision, or designed for men who already have prostate cancer to help predict prognosis and make management decisions?

Some tests span more than 1 of these decision points and others do not. Because there are so many, much education is needed so that the right patient can receive the right testing options that may really help them.

The ultimate goal is to have an improvement in patient care by taking advantage of the fact that we do have more specific options available to provide more information and make better decisions.