What Are The Best Practices For Prostate Cancer Screening?

IRA FLATOW: This is Science Friday. I’m Ira Flatow. Former President Joe Biden was diagnosed with an aggressive form of prostate cancer a few weeks ago. The cancer had already spread to the bone. The news got a lot of people, including myself, thinking, how did his doctors not catch that cancer sooner, and what exactly are the best practices for screening for prostate cancer? Turns out it’s a bit more complicated than it might seem on the surface.

Prostate cancer is a world filled with confusing advice for diagnosis and treatment of patients, so we’re going to try to through it. And joining me now to help unpack those complexities are my guests, Dr. Matthew Cooperberg, urologic oncologist and professor at the University of California, San Francisco, and Dr. Andrew Vickers, a statistician who studies prostate cancer screening at Memorial Sloan Kettering Cancer Center here in New York. Welcome to Science Friday, both of you.

ANDREW VICKERS: Glad to be here.

MATTHEW COOPERBERG: Good to be here.

IRA FLATOW: Nice to have you. Dr. Cooperberg, let me start with you. Let’s start by going over some basics about prostate cancer screening. Many people are familiar with the famous PSA test. Tell us what exactly what it measures and what it means.

MATTHEW COOPERBERG: Sure. So PSA stands for prostate-specific antigen. It is a protein made by the prostate gland, a small portion of which gets out into the bloodstream, and we can measure that. And it’s an indicator of what’s going on in the prostate. Now, it’s prostate-specific, not prostate cancer specific.

And other things that affect the prostate can raise the PSA. And that issue is kind of what gets to the heart of the controversy. The reality is that PSA is probably the best screening test in the history of oncology, if it is used well, and the problem and the controversy all relate to how it gets used. As men age, the PSA will tend to drift up, because other things happen to the prostate.

Most commonly, it grows, a phenomenon called BPH or benign prostatic hyperplasia, which happens to almost all men to some extent as they get older. And that means as men get older, interpreting the PSA in terms of its prediction for prostate cancer, which is the main use for the test, gets more difficult.

IRA FLATOW: So just to reiterate, it’s not detecting prostate cancer, it’s just assessing a risk factor for it.

MATTHEW COOPERBERG: Correct. PSA is a first screening test. It does not diagnose prostate cancer. People who have an elevated PSA need to think about secondary testing. In the old days, that would mean a biopsy. Today, we have MRI and eight different urine and blood tests that we use to figure out who is actually at risk of having a higher grade prostate cancer that might actually need treatment.

IRA FLATOW: Yeah. We’ll talk about that a little more in detail. I want to get some more background information first.

MATTHEW COOPERBERG: We should actually do a little background on prostate cancer itself, yeah. So prostate cancer is exceptionally common. It is by far the most common cancer diagnosed among men in the US and one of the most common worldwide. It is the second leading cause of cancer death among men in the US. But the problem is that we use the term prostate cancer for an exceptionally broad spectrum of things that can happen to a prostate as a man gets older.

We can find cells that look like cancer under the microscope in half of all men. This is obviously not cancer the way we think about cancer. This is a pathologic anomaly, something that looks strange under the microscope. That is not what we are seeking to diagnose. Prostate cancer that we intend to screen is the more aggressive version, the more aggressive subtypes of cancer. And we are much better able today than we were 20 years ago to distinguish the aggressive and non-aggressive.

There are those of us that are starting to say we shouldn’t even call it a low grade one’s cancer, because it has basically no capacity to spread. And the controversy around PSA testing over the years has related to the fact that in the course of trying to find the aggressive ones, we also find a lot of non-aggressive prostate tumors.

And those, historically, have been treated aggressively with surgery and radiation therapy, and the side effects of those treatments are a large part of what led to the recommendations in 2012 that men should stop screening. This was from the US Preventive Services Task Force, which is the national guidelines panel, which is the one that has the most influence with primary care providers.

IRA FLATOW: So that was a mistake, then.

MATTHEW COOPERBERG: A lot of us would say that was a mistake. And that came from, on the one hand, a desire to reduce the harms of overdetection and overtreatment. On the other hand, it also came from a misinterpretation of the evidence base in several very important ways.

IRA FLATOW: So Dr. Vickers, can you give us some overview of the current screening guidelines for prostate cancer?

ANDREW VICKERS: Yeah. Matt made a very important point, which is for many decades, we were doing PSA screening wrong. And when a lot of these guideline bodies said, stop PSA screening, what they really meant is stop doing it wrong. And many of us would say, yeah, you should stop doing it wrong, but you should start doing it right. And in the past five to 10 years, there has been quite remarkable consensus amongst academics who study prostate cancer on the right ways to screen.

And like so many things, it’s easier to say what you shouldn’t do than exactly what you should do, or to start with that. If we’re going to screen, we shouldn’t be screening older men. In most countries of the world, the most common decade that men get a PSA test is in their 80s. Even 70s is often. For most men, they should not be getting PSA tests in their 70s. The key years to be screened is 45 to 70.

IRA FLATOW: Let me stop you right there and ask you why that is. Why should these older people not be screened?

ANDREW VICKERS: Because prostate cancer is a very slow growing disease, and so a man in their 40s or 50s or 60s is diagnosed with prostate cancer through a PSA test. There is a good chance that that is going to eventually grow to threaten his health or his life.

But if you find prostate cancer through a PSA test in a man in the 80s, the chances are that he will live out the course of his natural life and never, ever know that he had prostate cancer absent the PSA test. Or even if he does become aware, it would be discovered at a time where treatment would not be appropriate for him due to his age.

IRA FLATOW: So was Joe Biden’s diagnosis– and discovery, I should say– a rarity at his age?

ANDREW VICKERS: Let’s be very clear about what we do and what we don’t know about Joe Biden’s diagnosis. What we’ve heard is that he had a PSA in his early 70s. We haven’t heard what the level of the PSA was. Now, there is a nuance here. Most of the recommendations– including the ones that my hospital, MSK uses– say stop screening at the age of 70.

But stop screening does not mean stop taking a PSA test. If your PSA is elevated when you’re 70, that should continue to be monitored. We don’t consider that screening. We consider that follow up of an abnormal test. Now, it’s quite possible. And it just happens routinely, actually, is that doctors here stop screening at 70, and they interpret that as, stop taking a PSA.

IRA FLATOW: Yeah, that’s the confusing point. There’s a difference between getting the test and screening, you’re saying.

ANDREW VICKERS: Right. Exactly. Yes. What we don’t know in Joe Biden’s case is whether his doctor followed the recommendations of most academic societies, which was to continue to get PSA screening because his PSA was elevated, or in fact, his PSA was not elevated in his early 70s, and he unfortunately had a very rapidly growing cancer, the sort that really can’t be detected by screening.

We do have these cases where men have cancers that become very aggressive very quickly, and no screening test is ever going to detect them. And that’s true of all cancers. It’s true of breast cancer. A woman has a mammogram, and then a few months later turns up with a very aggressive breast cancer.

IRA FLATOW: Dr. Cooperberg, there are different types of prostate cancer. And as you’ve said before, you’ve advocated to not call the less aggressive form of prostate cancer cancer at all. I want you to explain that a little bit more, please.

MATTHEW COOPERBERG: Sure. And this gets philosophical, but it’s an important philosophical question. The reality is we have to step back and recognize that the word cancer literally goes back to Hippocrates in ancient Greece. For literally millennia, a cancer was something that you found because you either saw it on the surface of the body, or it caused terrible symptoms, and it was almost invariably incurable.

And it was only in the last 150 years that we started looking under the microscope and defining things that happened to the body according to what they looked like at the microscopic level. It’s only in the last couple of decades that we are now in this screening era where, because somebody has an elevated PSA, that we give tissue to a pathologist from somebody who had absolutely no symptoms, and the pathologist says, well, this looks like the same cancer that we diagnosed a few decades ago when somebody took an organ out of the body.

So we’ve completely changed the nature of the cancer diagnosis in medical circles. We’ve gone from a diagnosis which is primarily made clinically, to a diagnosis which is primarily made by a pathologist. And society has in no way caught up with that trend. So many of us have been advocating for literally decades now that we should not be overtreating low risk prostate cancer, that we should be doing active surveillance, and trying to educate the public in terms of what the word cancer means and doesn’t mean.

But the reality is that word still has this incredibly deep resonance. If somebody hears prostate cancer– and even though we spend the next 20 minutes talking about how this is low grade and non-threatening– they’re thinking about their neighbor that they just saw die of pancreatic cancer or their cousin that just died of a bad prostate cancer. So the word has a lot of implications. People have to pay more for life insurance, for health insurance.

We do a lot of potential harm with that diagnosis when we know that the low grade prostate cancers have absolutely no capacity to spread if it’s a pure– what we call– grade group 1. Now, some of them can get worse over time. And in some cases, where we find a grade group one, there is also higher grade cancer somewhere else in the prostate.

So all of us that are discussing this changing the name question, everybody would say we absolutely still need to follow this, meaning we follow the PSA over time, meaning we do serial imaging, we repeat biopsies, et cetera, so that if and when we find evidence that the cancer is getting worse, we are still well within the window of opportunity to cure it. And that window, we measure in years or even in decades.

IRA FLATOW: And that’s very interesting. I’m glad you’ve talked about this and made that distinction. I want to talk a bit about racial disparities in prostate cancer. Black men are much more likely to develop than men of any other race. Do we know why exactly that is?

ANDREW VICKERS: So we have to be very careful about the use of the word disparity, because let’s start talking about differences. We know that there is a difference in the incidence of prostate cancer. For every 100 white Americans that get prostate cancer, about 170 Black Americans will get prostate cancer. And for every 100 white Americans who die of prostate cancer, over 200, about 210 Black Americans will die of prostate cancer.

Now, the best evidence is that the difference in incidence, the fact that more Black men get prostate cancer than white men, is due to genetic changes that are common in men from West Africa, which is where most Black Americans come from because of the slave trade. But because there’s a difference between 1.7 and 2.1, once you are diagnosed with prostate cancer are more likely to die of it if you are a Black man.

And it’s very well known that is due to differences in care. When white and Black men receive care at the same institutions in the same setting, they have very similar outcomes. But across the country, they receive care in different settings. Black men get poorer care, and they die as a result. So the disparity is in care. The cause of the difference in incidence is predominantly due to genetics.

MATTHEW COOPERBERG: I would say I agree with a lot of that. I think it is more nuanced. But there are also structural and social determinants of health which have been pretty tightly associated not with prostate cancer mortality, but with diagnosis of high risk disease. So these are things like access to diet, proximity to areas of environmental contamination, chronic stressors, these sorts of things, which interact with genetic factors in ways that are really complicated.

Now, what we know is that the trajectory of prostate cancer is actually relatively similar between white and Black men from the point of diagnosis forward, but the whole thing appears to start about five years earlier. So the screening recommendations from everybody except the US Preventive Services Task Force now recommends starting to screen five years earlier for Black men or men with other risk factors, like family history, which means starting around age 40. And this is from the American Urological Association, from the American Cancer Society.

The point about outcomes after diagnosis– it actually depends a lot on which literature you look at. There are some high level social level studies suggesting worse outcomes after diagnosis. Black men are more likely to be diagnosed with a high grade, higher stage, higher PSA, prostate cancer. But once you adjust for all those things, and the more you know about the cancer, race tends to drop out of these models.

IRA FLATOW: We’ve covered a lot of ground here and very interesting stuff. I’m going to try to see if we can sum this up by asking if you have any final words of advice for men listening at home, in their car, or wherever they are, who feel overwhelmed by making these choices of when to screen and what the results might mean for their health. What is the general take home message here?

ANDREW VICKERS: So if a man is interested in PSA testing, there is just actually a very few things that you need to. One is that it can save your life. The second thing is it can do more harm than good if you don’t do it right, and there are a couple of things to think about. First off, if you are not comfortable hearing the word cancer and watching it– that means waking up every morning knowing you have cancer, and it hasn’t been treated– PSA screening is probably not for you. It’s probably going to cause more harm than good.

If you understand that many of the prostate cancers we’re going to find are low risk and probably shouldn’t even be called cancer, then you should think about getting a PSA test. PSA testing is for men between the ages of 45 to 75. If you’re older than 75 and haven’t had an elevated PSA test or any symptoms, do not get a PSA test.

IRA FLATOW: What would be considered an elevated test for, let’s say, somebody over 75?

ANDREW VICKERS: Typically above three. If you do have a PSA above three, do not get a biopsy without a very good reason, and that generally is going to be a secondary test, such as an MRI or a second blood or urine marker. And if you are diagnosed with cancer, do not get that treated aggressively with surgery or radiotherapy unless it is aggressive.

IRA FLATOW: All right. And I have one last question, which I thought about. Do the cutbacks in NIH funding for cancer research have any effect on your kinds of work?

MATTHEW COOPERBERG: The cuts that have been proposed, both in the last few months and are proposed in the upcoming budget, will be– catastrophic does not begin to define how severe this will be for health care across the country, around the world.

The reason President Biden has a very promising prognosis, frankly, is due directly to fundamental research funded by the NIH, funded by the DOD, by the CDC, by other federal agencies over the last 20 years. Every new treatment that we have for cancer, for Alzheimer’s disease– you name a condition where things are better now than they were 20 years ago, it is directly because of fundamental research conducted by NIH.

ANDREW VICKERS: Deaths from prostate cancer have fallen by about half. Half as many men are dying of prostate cancer now than they were dying 40 years ago, and that’s because of cancer research through the National Institutes of Health. If the current government doesn’t want cancer death rates to keep falling, then they’re doing the right thing by canceling the research. But I think most people in America who know people who’ve suffered from cancer actually want cancer death rates to keep falling and need to keep funding appropriate cancer research, which has a proven track record in improving cancer outcomes.

IRA FLATOW: Well, I want to thank both of you for taking time to speak with us about this really interesting and important topic. Dr. Matthew Cooperberg, urologic oncologist and professor at the University of California, San Francisco, and Dr. Andrew Vickers, a statistician who studies prostate cancer screening at Memorial Sloan Kettering Cancer Center based in New York. Thank you both.

MATTHEW COOPERBERG: Thank you.

ANDREW VICKERS: Thank you.

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