Listen to the Clinical Chemistry Podcast
Andrew J. Vickers. Redesigning Prostate Cancer Screening Strategies to Reduce Overdiagnosis. Clin Chem 2019;65:39-41.
Dr. Andrew Vickers is a researcher at the Memorial Sloan Kettering Cancer Center in New York City.
This is a podcast from Clinical Chemistry, sponsored by the Department of Laboratory Medicine at Boston Children’s Hospital. I am Bob Barrett.
The January 2019 issue of Clinical Chemistry is devoted to the area of men’s health. Aside from non-melanoma skin cancer, prostate cancer is the most common cancer among men in the United States. It is remarkable that even though the introduction of prostate specific antigen, or PSA, into U.S. clinical practice occurred over three decades ago, researchers and clinicians are still debating its value for prostate cancer screening.
In that special issue, Dr. Andrew Vickers published an Opinion article titled, “Redesigning Prostate Cancer Screening Strategies to Reduce Overdiagnosis.” Dr. Vickers is a researcher at the Memorial Sloan Kettering Cancer Center in New York City and he’s our guest in this podcast. So, Dr. Vickers, randomized trials have shown that PSA screening just doesn’t work. Why should we even still consider using it?
Yeah. What you said is a very common misconception, actually. There's been several randomized trials and as is common in many fields of medicine, some show it works, some show that it doesn’t work. And there's a tendency to say, “Well, we don’t really know” or “Well, the American trial, the large American trial, the PLCO, showed it didn’t work, so we should believe that more.” My view is that you have to look a little bit more carefully at the data. So, there have been three large trials that were well done. One in the UK, one throughout Europe, one in the U.S. The U.S. trial was “negative,” it did not see a difference between patients in the PSA arm and the control arm. But if you actually dig down, what you find is that most of the men in the control arm got a PSA test because they were just older Americans going about their business and many older Americans going about their business end up at doctors and end up getting PSA tests.
So, if you actually read the paper carefully, the authors of that paper do not say, “This is a trial of screening versus no screening.” They say, “This is a trial of organized screening
versus opportunistic screening.” So, to say that the PLCO
trial, the big U.S. trial, to imply that that says PSA screening
does not work, is not true because that was not the question
that was addressed by the authors.
So, that leaves the two other trials. The big European trial
clearly shows a reduction in mortality from PSA screening.
It was modest, but it was there. The UK trial was a little
unusual for two reasons. One is that the follow up, how
long the trial has been followed, it’s relatively immature.
So, it's going to be interesting to see what happens as data
The other important thing about it is that it was a one-off
PSA test. So, in the trial you are randomized either not to
get a PSA test or just to get one PSA and leave it at that. I
don’t know anybody who works in the field who says the
way we should screen for prostate cancer is to give men
somewhere between 50 and 70 one PSA test and leave it at
So, many would argue, and I'm very sympathetic to that
argument, that the UK trial, which is called the Cap Trial, is
testing an intervention that no one would actually want to
implement in practice, which is all to say that we should talk
about the PSA screening because there has been one large
well done trial that did actually address the question of the
value of screening compared to no screening, and it did
show an effect on prostate cancer mortality.
Fair enough. We've been screening men with PSA in the
U.S. for over 30 years, has that been good or bad for
Yeah, that’s a great question and people disagree. I
personally, probably would—I'm on the fence. I'm
probably leaning over towards the people that say that it's
done more harm than good. The key thing to realize about
PSA screenings is not one thing, right? We could have a
debate. Should we be giving 80 milligrams of aspirin to
men and perhaps women also once they hit 65 for heart
disease prevention? And we would be talking about 80
milligrams of aspirin daily, and you either give 80 milligrams
of aspirin or you don’t. It's just one thing.
The interesting thing about PSA screening, it's a complex
intervention. There’s lots of different ways that it can be
done and what we've been doing in the U.S. over the past
30 years or so, is a lot of the wrong thing. We've been
screening older men but not younger men, so that the age
group with the highest incidence at screening are men in
their late 70s and we’re almost—we’re pretty sure PSA screening is ineffective for those men. We’re also pretty
sure it's most effective for men in their 50s which have very
low rates of screening.
Something else we've been doing in the U.S. is having very
liberal criteria for biopsy. The best evidence suggests, “Oh,
you’ve got a high PSA. Well, that’s interesting but we have
got to jump through a number of other hoops before we
biopsy you, you probably don’t have the kind of aggressive
cancer, we’re interested in identifying” and for many years
we would biopsy men at a drop of the hat. I mean, we've
often joked that you kind of—you really need to be a
special guy to get out of the urologist’s office without having
a biopsy because there are so many different criteria to
Perhaps the biggest problem is that we were treating the
wrong cancers. So, for many years, the low-risk prostate
cancers would be treated because we could cure them and
we would not treat aggressively the higher risk prostate
cancers on the grounds that we felt that those probably
couldn’t be cured. But the point was that those low-risk
cancers were unlikely ever to kill a man and it was the high-risk
cancers that were more likely to cause cancer-related
mobility and mortality.
So, over the past 30 years we've been screening the wrong
men, we've been biopsying the wrong men, we've been
treating the wrong men. And there's some ballpark
estimates that we've maybe treated a million Americans
that didn’t need treatment. And remember, these
treatments for prostate cancer are not a walk in the park.
They cause long term side effects including loss of sexual
function, loss of urinary function, and bowel problems.
Doctor, what are the key points for making sure that PSA
screening does more good than harm for patients?
I think there’s a simple answer to that question, which is to
look at everything we've been doing wrong and make sure
we don’t do it.
Make sure that we do what's right instead of what's wrong.
So, we've been screening the wrong people with the PSA
test. So, lets screen the right people, but the men who
have most to benefit from PSA screening are those in the
age of—between about 50 and 70, really very problematic
screening men over 70, and certainly men over 75 have
little, if anything, to benefit. So, make sure we focus on the
younger men, not the older men.
Now the second thing is, only biopsy men who are at an
importantly elevated risk of having aggressive prostate
cancer. It’s often said that the purpose of PSA screening is
to identify prostate cancer. That’s not a useful way of
thinking about PSA screening. It turns out that almost
every man will get prostate cancer if he lives long enough.
There’s been studies of men who had strokes or heart
attacks or died in a motor vehicle collision. And if you take
the prostate out and look at it under the microscope, you
will find cancer very often. So, we can actually do these
studies where we can estimate your risk of having prostate
cancer given your age.
It’s pretty much a ubiquitous disease. We shouldn’t be
running around trying to find prostate cancers. We should
be trying to find only the aggressive prostate cancers. So, it
means we have to much more selective about the men we
One of the big developments over the past 10 years is now
we have both markers, and some imaging approaches, that
help us determine that a man who’s got mildly elevated PSA—we often say a PSA above three is worrisome for prostate
cancer—so, you have a man with a PSA of about six, it’s not
explained by a benign disease, should we biopsy him or not?
Well, why don’t we run one of these markers, do some more
imaging, and then make a decision? So, we need to be
much more selective about who we biopsy.
Probably the biggest change we can make to the general
approach to PSA screening, to make that it does more good
than harm, is not to treat the low-risk cancers. About half
of the cancers we find with PSA screening are low-risk and
would never cause a man any morbidity during the course of
his natural life. And those cancers can be managed
conservatively using programs, what’s called active
So, a man has a biopsy. The cancer is found to be low-risk,
he’s followed every year with a PSA, every few years he
gets another biopsy, and he only goes and gets something
like surgery or radiation therapy if the cancer is found to
progress to a more aggressive phenotype. And finally, we
can make sure that when we do have a man with an
aggressive cancer that does need treatment, we can make
sure that he is treated appropriately, that he gets a good
Now, there’s tons of evidence in the literature, and this isn’t
just in prostate cancer surgery, it’s throughout surgery, that
you get better results if you go to an experienced surgeon
or a high-volume surgeon.
At MSK, we did some studies showing that you needed at
least 250 to 350 radical prostatectomies before your
recurrence rate started to plateau, so that you were getting
good results in terms of cancer control.
We then did a study to look at a population-based sample of
urologists to find out amongst those men doing surgery for
prostate cancer, what was the typical number of prostate
surgeries they were doing a year? Well, the median was
three per year. The mode was one. Twenty-seven percent
of urologists who did a radical prostatectomy only did one
per year. About 80% did 10 or fewer, which means they
would never get up the learning curve during the course of
their entire surgical career.
So, we have to make sure that the treatment that is
received by patients with prostate cancer is effective and
that we lower the chances of long-term side effects such as
those I’ve described, and that means treating them at
centers of excellence, regionalizing care to high-volume
That gives you something to think about, doesn’t it? Finally,
doctor, guideline groups have emphasized shared decision
making for PSA testing. Now, do you agree or disagree with
both agree and disagree with that. Really, we do need
shared decision making. There is something special about
PSA screening. That means that we shouldn’t do it to men
without explaining to them what’s going to happen and
getting their agreement. This isn’t like doing a blood
pressure test for a 50-year-old, which is something you do
as routine. You really do need to let men take a choice,
have a choice in that.
What I disagree with is that these guideline groups are sort
of abdicating their responsibility. They’re saying, “Well, it’s
a difficult issue. Let’s let the individual man make a choice.”
And I think what we’re going to get, or what we have gotten
for years is kind of chaos. There’s three things that can
happen right now. We can have no PSA screening at all.
We can have a systematic and organized program that is
specifically designed based on the best medical evidence to
reduce the harms of prostate cancer screening and make
sure that it has the largest impact on prostate cancer
mortality as possible, that would be the second option.
The third option is what we’re currently doing right now,
which is, well, whoever happens to ask for a PSA test will
get one, and then we’ll leave it to the doctor to decide who’s
biopsied and where they’re treated, and so on, and so forth.
That’s what we’re getting right now and it’s not good
practice and we know that.
There was an example recently in a European country which
shall, for the purposes of not wanting to point fingers at the
guilty, I won’t mention. But this country said “We’re not
going to have population-based screening, the evidence
doesn’t meet our criteria, et cetera, et cetera. If the
individual man is interested in it, he should consult with his
doctor and go through shared decision-making.”
Well, some colleagues of mine, and myself and some
urologists from that country, we actually did some back-of-the-
envelope calculations and we worked out, had that
country or were that country to implement population-based
PSA screening, they would do fewer PSA tests than they are
currently doing. Because what’s happening right now is in
that country, you're having many men in their 80s getting a
PSA test every single year for five or 10 years. And then
many of those men are having low-risk cancers discovered
and treated. It’s not only a waste of time, it’s actively
harmful to those men. And we worked out that if you
actually implement a systematic approach to screening, and
many of these screening programs, you need maybe three
PSA tests lifetime, you actually do fewer PSA tests. You
biopsy fewer men and would treat fewer men if you did it
properly rather than the current guideline approach, which
is to, “Let the people decide.”
So, I do understand why guideline groups say shared
decision making, that is important, but I don’t think
guideline groups can just abdicate their responsibility as to
how we should be doing PSA screening, and making sure
that the way in which we do PSA screening ensures that it
does more good than harm.
That was Dr. Andrew Vickers from the Memorial Sloan
Kettering Cancer Center in New York City. He’s been our
guest in this podcast about utilizing prostate specific antigen
in screening for prostate cancer. That article appears in the
January 2019 issue of Clinical Chemistry, a special issue
devoted to the area of men’s health. I’m Bob Barrett.
Thanks for listening!