#388 — Prostate cancer screening: why current PSA guidelines are failing men and how modern tools improve early detection and save lives

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1:04Peter Attia:Welcome to a special episode of The Drive. In this episode, I'm going to walk through a single topic in depth, and this is prostate cancer screening, something that I'm very passionate about. And because we consider this a really important PSA, no pun intended, the full episode and the detailed show notes for this discussion will be available to everyone, regardless of whether or not you're a premium subscriber. In this episode, I discuss why advanced and metastatic prostate cancer diagnoses are rising despite the availability of screening tools, what PSA actually measures and why it's more useful when interpreted over time than it is in a single one-off number, how MRI, PSA density, PSA velocity, and improved biopsy techniques can reduce unnecessary procedures while improving the detection of aggressive cancers, how active surveillance helps avoid overtreatment in men with low-risk cancers, why the evidence used to argue against PSA screening was deeply flawed, how drugs like finasteride, which are commonly used to prevent hair loss, can suppress PSA and lead to missed warning signs if clinicians and patients are not vigilant, and why I think regular PSA testing is so important if one of our objectives in life would be to eliminate prostate cancer mortality.

2:30Peter Attia:So without further delay, I hope you enjoy this special episode of The Drive.

2:40Peter Attia:Well, today I want to dig into something that I feel quite strongly about and something that I think we're getting wrong at the population level in a way that is measurably costing lives. We're going to talk about prostate cancer screening, specifically PSA testing, and why I believe the current guidelines have failed men and obviously what I think a more modern an approach to screening should look like in 2026 and beyond. And this is really a discussion that I think is relevant for anybody listening to this as a potential patient, someone who cares about a patient, or whether you're a clinician.

3:18Peter Attia:I'm going to spend some time towards the end of this discussion on something that I also think is dangerously underappreciated, which is the interaction between a drug called finasteride. This is a drug that literally millions of men are taking for hair loss prevention and how that drug interacts with our ability to interpret PSA correctly. Because if you're on finasteride and your doctor doesn't understand the implications of that and how that impacts your PSA values, you could be sitting on a ticking time bomb without anybody knowing it. Let me set the stage. Prostate cancer is the second leading cause of cancer death in men, with only lung cancer claiming more lives.

4:00Peter Attia:About one in eight men will receive a prostate cancer diagnosis at some point in their lives, and this year alone, roughly 36 ,000 American men will die from it. So what makes this disease both uniquely hopeful and uniquely frustrating is that when you catch it early, the prognosis is outstanding. So we're talking about a 15-year survival rate approaching 97 % from first diagnosis. And we have detection tools that are simple, widely available, and getting more sophisticated every year. And yet here we are watching the rates of advanced stage prostate cancer climb. That's right. So the rates at which advanced prostate cancers are showing up is higher today than it was 15 years ago.

4:52Peter Attia:Recent data out of both the United States and Canada confirm what many urologists have been warning about for years. We're catching more and more of these cancers only after they have already metastasized or spread. And that's what we call stage four disease. And once you're at stage four, the picture changes dramatically. Five-year survival falls to 38 percent, and the median time from diagnosis to death is about two and a half years. So the question that I think demands an answer is quite straightforward. How did we get here? We have the screening tools. We have effective therapies for early cancers.

5:31Peter Attia:Why are outcomes getting worse instead of better? And of course, most critically, then what do we need to do about this? Now, to answer any of that, you need to start with the basics of what the PSA actually is, because it's the linchpin of this entire conversation. And quite frankly, if we had the PSA equivalent for every other cancer, the world could look a heck of a lot different than it does today with respect to cancer mortality. So PSA, which stands for prostate-specific antigen, has been available as a blood test since the early 90s. It's a protein made by the prostate gland. Its biological function is to help keep seminal fluid in a liquid state.

6:11Peter Attia:So a tiny amount of PSA naturally leaks from the prostate into the bloodstream, and that's what we measure when we draw a person's blood. So here's the kind of important physiologic point. As the prostate grows, which happens in virtually all men as they age, the amount of PSA in the blood tends to rise proportionally. So when the PSA test was first deployed, the logic was simple. if your PSA is unusually high, your prostate is unusually large, and that could mean trouble. An elevated PSA would prompt an ultrasound, an abnormal ultrasound would trigger a biopsy, and cancer on a biopsy would lead to treatment.

6:51Peter Attia:And the early data on this approach were generally reasonable. Two large trials, followed over 14 and 16 years respectively, showed that routine PSA screening cut prostate cancer mortality by 44 and 64 % respectively. That translates to preventing up to 3.1 cases of metastatic, which means fatal, disease for every 1 ,000 men who went through the screening process. And the test itself costs nothing, a standard blood draw fully covered by most insurance plans. So you would naturally ask, why wouldn't we screen everyone? Well, here's where the story takes a turn that I think had a devastating set of consequences.

7:39Peter Attia:Even though the people who made the decision were operating at least somewhat with reasonable logic at the time. The problem was that the straight line from elevated PSA to biopsy was generating too many false alarms. PSA can be elevated for many reasons that have nothing to do with cancer, including benign enlargement, transient inflammation, such as you might experience during a bout of prostatitis, recent sexual activity, and frankly, even just natural variation. But the biopsies that followed in elevated reading were hardly benign. The standard approach involved punching a needle through the rectal wall to sample prostatic tissue.

8:26Peter Attia:So now you're creating a contaminated pathway from a bacteria-rich environment into what should be a sterile organ. And even with things like prophylactic antibiotics and preparation, infection rates from these biopsies ran between 5 % and 7%, which of course, when you multiply that across the number of people that were having them, is an enormous amount of morbidity. And prostate infections, of course, are not a joke, especially if they reach into the bloodstream. They would frequently land men in the emergency room. They could lead to hospitalizations and take people away from work. So on top of that, there was the overtreatment issue.

9:02Peter Attia:So back in the 90s and early 2000s, finding cancer on a biopsy almost invariably led to treatment. And that treatment, surgical, carried real consequences. erectile dysfunction, urinary incontinence, bowel problems, especially if radiation was used. The psychological weight of a cancer diagnosis alone is enormous. And what we've come to understand since then is that a significant fraction of the cancers caught during the early PSA era were actually quite indolent. They were never going to progress to the point of threatening someone's life. These men were being subjected to the full burden of cancer treatment for a disease that if left alone would never have harmed them.

9:47Peter Attia:There's a saying in the urology world that says every man will get prostate cancer, but some will die of it. And the idea here is if you live long enough, you're always going to find prostate cancer inside some cells of the prostate. That's not the jugular question. The jugular question when you identify prostate cancer is how many of these cases are cases where, if left untreated, the cancer will spread from this organ to a distant organ, namely the bone, which is the most commonplace of spread. So in response to all of this, the United States Preventative Service Task Force, or USPSTF, made its move.

10:29Peter Attia:And in 2008, they stopped recommending PSA screening for men over 70. By 2012, they extended that recommendation against screening to men of all ages. The data they leaned most heavily on came from a large American trial called the Prostate Lung Colorectal and Ovarian Cancer Screening Trial, or PLCO. The prostate arm of this study randomized men to either undergo PSA screening or not, and it found essentially no difference in prostate cancer mortality between the two groups. The implication was that screening saved at best 1.3 lives per thousand men tested. And so the USPSTF's calculus went something like this.

11:18Peter Attia:If you're only saving one-tenth of one percent of men while causing serious complications, all the things we talked about, right? Infections, incontinence, erectile dysfunction, this stress that's associated with all of these things, in a meaningful proportion of the others, the math simply doesn't add up. The harms of over-diagnosis and over-treatment exceed the benefits. Now again, I can see how one could arrive at that conclusion. It's a little bit of a utilitarian argument, and there's a logic to it at the population level. But that logic only holds if the underlying data are sound, which we'll discuss, and it's been 15 years now.

12:00Peter Attia:If the USPSTF got it right, we should see at most a marginal uptick in late-stage disease, maybe a fraction of a percent. So the obvious next question is, what has actually happened over the past 15 years? Well, the data are now in, and they paint a very clear and very troubling picture. When you group together all prostate cancers caught at stages 1 through 3, so these are non-metastatic, five-year survival exceeds 99%. But at stage 4, which is metastatic disease, tumors that have spread beyond the prostate, survival plummets to 38%, with a median survival of about 30 months from diagnosis. So the timing of when you find the cancer is not a minor detail.

12:48Peter Attia:It's arguably the determining factor in life and death. So what does the recent literature show? Well, data published within the last six months from both the American and Canadian registries, which builds on the earlier work from Ted Schaefer and his colleagues in 2016, is that we are finding more and more prostate cancers only after they've become metastatic. This is exactly what many urologists predicted would happen when we pulled back on screening. But what's even more alarming is that it's not just older men who are affected. The Canadian data show a 3.7 year-over-year increase in stage 4 diagnoses among men under 75 between 2010 and 2017.

13:34Peter Attia:And this is happening despite a declining total number of cancers detected in that same age group. So it's not that more men are getting cancer, it's that we're only finding it once it's too late to cure. The American data tell a similar story. Since the 2012 guideline shift, stage 2 cancer detection has been declining by about 0.1 % per year across all ages. Meanwhile, stage 3 has been climbing at 3.3 % per year and stage 4 at 6 % per year. Those increases in late stage detection far outpace the modest 0.8 % annual increase in total cases. So the interpretation here is not complicated and it is not ambiguous.

14:21Peter Attia:We stopped looking for early disease, so we started finding it late. Stage 4 cancer is what drives all prostate cancer mortality, or nearly all of it. And the trajectory we're on is the entirely predictable result of a policy that told doctors and patients that looking wasn't worth the trouble. I think the Canadian researchers summarized this paradox well, and I'm paraphrasing, but the gist was newer treatments have extended survival for men with metastatic disease, but overall survival across the population has actually worsened compared to when screening was recommended because we now have so many more men presenting with incurable cancer.

15:05Peter Attia:And it doesn't have to be the story. It just shouldn't be this way. So this is where I want to pivot, because I think this is actually the most important part of the conversation and honestly the most hopeful. The USPSTF built its guidance at a time when our tools were far cruder than they are today. The old pipeline, as I kind of talked about a few minutes ago, was essentially PSA goes up, you get an ultrasound, ultrasound looks somewhat concerning, you got a biopsy, if the biopsy finds any type of cancer, you get treated, and there was very little nuance in that algorithm. But the way we deploy PSA in 2026, and quite frankly over the last five years, looks poignantly different.

15:43Peter Attia:The single biggest conceptual shift is this. PSA is most value as a longitudinal trend, not a single snapshot. Any individual PSA reading is inherently noisy. Day-to-day values can fluctuate by as much as 15%. If a man has recently ejaculated, his PSA can spike by as much as 40%. And the person-to-person variability is staggering. A healthy man in his 60s might have a median PSA of 1.0 to 1.2, but the 95th percentile for that exact same demographic in men with no prostate cancer extends all the way up to 4.9. So in the show notes, we're going to leave a table that gives you all of this information.

16:25Peter Attia:We break it down by a decade of life. But the point here is that no single PSA value in isolation tells you very much. What does tell you something is the trajectory, and this is what we call PSA velocity, mapping a patient's baseline over time and tracking the rate of change of that PSA value. The prostate naturally enlarges with age, so some gradual PSA increase is expected, but rapid increases are cause for suspecting something pathological. Either the prostate is enlarging abnormally, a higher proportion of PSA is leaking into the blood relative to the amount of prostate, tissue, or both, and disrupted prostate architecture and vascular leakage are the hallmarks of malignant growth.

17:12Peter Attia:So in general, if we look at increases sustained over an 18-month window and use different cutoffs depending on the baseline value. So if we took a patient with a baseline PSA of less than 4 nanograms per milliliter, and in our practice, that's the norm. Most of our men are going to walk around with a baseline PSA less than 4. A sustained rise by more than about 0.35 nanogram per milliliter per year over 18 months is generally our red flag. In patients with a PSA value that starts above 4, we would let that increase to about a 0.75 nanogram per milliliter per year bump before we would flag that.

17:58Peter Attia:So let's make this tangible. So let's say I have a 55-year-old patient with a PSA of 1.3. So that's slightly above the median for his age. But I'm not alarmed, especially because, remember, I've got longitudinal data on him, and I realize that this is about where he settles out. So that one time he was 1.6, I didn't overreact because two months later or three months later, he was back to 1.3. Now, if he comes back a year later at 1.7, and then six months after that comes back at 1.9, that's an increase of 0.6 over an 18-month period of time, working out to a velocity of 0.4 per year. So now I'm paying attention.

18:40Peter Attia:That sustained acceleration is the signal I'm looking for, and it's personalized to him. This is actually what precision medicine is, and incredibly, it costs essentially nothing because this test is so cheap, like we're talking dollars, and it shows up in a routine blood test. So this is a great example of precision medicine, and incredibly, it costs essentially nothing beyond showing up for a routine blood draw. Again, the blood test itself costs dollars. But even with his velocity flagging a concern, we no longer would just jump to a biopsy here. The next step would now be an MRI, which serves as a much higher resolution test, and it's much less invasive than proceeding to a biopsy.

19:27Peter Attia:So the MRI gives us yet another metric, which is PSA density, which is simply the PSA concentration in the blood divided by the volume of the prostate provided by imaging. And by the way, you could do that with an ultrasound as well. But with the MRI, you're getting two for one because you're getting a better imaging study, and of course, you're getting volume. So here's the logic. A healthy prostate grows, PSA, and volume tend to increase in approximate proportionality. But when you have a malignancy, the tumor can disrupt the normal architecture of the prostate that normally contains PSA to the gland or alter the endothelia running through the prostate.

20:06Peter Attia:And in this situation, PSA starts escaping into the bloodstream at a rate that outpaces what you'd expect from the size of the gland alone. So if PSA is rising disproportionately to prostate volume, that's a strong indicator that something is wrong. And it gives us that signal before anybody needs to think about a needle. So when you put your PSA velocity from serial blood tests together with PSA density from MRI, the discriminating power of PSA screening today is dramatically better than what existed when the USPSTF made its call. Now, if we focus in on MRI for a moment, there's been a really significant development that I think is going to meaningfully change the accessibility equation.

20:50Peter Attia:Beyond PSA density, the main value of MRI in this algorithm is that it can identify suspicious lesions or regions in the prostate without invasive probing. It can credibly rule in or rule out the need for a biopsy, and if a biopsy is warranted, it guides the needle to the areas most likely to hand us a diagnosis. The obstacle historically was that the gold standard prostate MRI called a multi-parametric MRI requires a contrast called gadolinium. And that meant higher costs, the need for a medical professional to administer an IV injection, and significantly more time in the scanner. All of this, of course, limited patient throughput and made pre-biopsy MRI impractical in many scenarios.

21:37Peter Attia:But a trial in 2025 called the PRIME trial changed this. The study directly compared the full multi-parametric protocol, which is a T2-weighted image, a diffusion-weighted image, plus dynamic contrast-enhanced imaging, against a stripped-down contrast-free biparametric version that drops the contrast component altogether. The goal was to establish non-inferiority. In other words, the question asked was, does this stripped-down version perform at least as well as the gold standard. And the results were essentially a dead heat. The biparametric MRI identified clinically significant cancer in 143 out of 490 men who had been flagged by PSA screening, whereas the full multiparametric MRI complete with gadolinium caught 145 out of that same group of 490 study participants.

22:33Peter Attia:The difference between those detection rates was 0.4 percentage points, which was statistically indistinguishable. And the practical implications here are huge, obviously, right? Without contrast, the scan takes half the time, 15 to 20 minutes, instead of 30 to 40. You don't need a medical practitioner that's standing there giving you the contrast and overseeing you. And of course, the costs come down, speed goes up, etc. etc. Now, even with all of these improvements in non-invasive screening, some men are still going to need a biopsy. If the MRI flags something suspicious and you need tissue to know what you're dealing with, you've only got one place to get it.

23:11Peter Attia:So it's worth talking about the progress that's been made there as well, because the biopsy itself has gotten both safer and more accurate. Now, I mentioned earlier that the traditional approach was a transrectal approach, and that carries inherent risk of poking bacteria from the rectum into a sterile space. It also has its anatomical limitations. It biases your sampling towards the back of the prostate near the rectal wall, and this can miss the front and base of the gland. The alternative to this is called a transperineal approach, entering through the skin between the anus and the scrotum.

23:49Peter Attia:And this completely bypasses the rectum, which dramatically reduces infection risk, and it opens up much much better access to the anterior and apical portions of the prostate than the transrectal route does, which you tend to miss. So Ted Schaefer, who's been a guest on this podcast many times, is a very close friend of mine personally and is also the urologist that works with many of our patients when they are diagnosed with prostate cancer, was involved in a large multi-center phase three trial with over 1 ,700 patients that compared cancer detection rates and complication profiles between the two approaches head-to-head.

24:27Peter Attia:The transperineal biopsy detected more high-grade cancers and fewer low-grade ones, which tells you it's doing a better job of finding tumors that actually matter, generating fewer false negatives from indolent disease and obviously creating less emotional distress. And on the safety front, this is really the headline in my mind, not a single patient who underwent the transperineal biopsy in that study developed an infection, ZIP0. Compare that to the 5 % to 7 % infection rate widely reported in the transrectal approach. Importantly, the transperineal method doesn't require prophylactic antibiotics, which is a meaningful benefit both for the patient and for the antibiotic stewardship more broadly as we face an era of antibiotic resistance.

25:14Peter Attia:Now, adoption isn't universal yet. Only about 37 % of American urologists currently perform transperineal biopsies versus essentially all of them doing transrectal or being able to. So there's a gap between what the evidence supports and what's happening in practice, but the trajectory is encouraging. All right, so I've been building the case for more screening, for more MRI, and for better biopsies, but I haven't forgotten the other side of the original argument, which is the over-treatment problem. And I really take this seriously because with all of the advances in surgical care, this is not a benign operation.

25:52Peter Attia:Not every prostate cancer is going to kill you. Our treatments are effective, but they carry side effects that nobody wants to experience if they don't have to. So here's the critical point that I think changes the overtreatment calculus. We no longer treat every cancer we find. The decision tree has gotten much more sophisticated. Now, if you remember the podcast that we've covered in this topic in the past, we go through something called a Gleason scoring, but I'm just going to kind of reiterate it here a little bit because maybe not everybody's familiar with that previous content. So when a pathologist examines a biopsy specimen, they look at the cells under the microscope and they decide how abnormal the cells look relative to healthy cells.

26:40Peter Attia:And they use a grading scale called a Gleason score. Now you're getting two numbers in that score because they're looking in two places. So you might get a Gleason 3 plus 3 or 3 plus 4 or 4 plus 4. And the highest number there is 5. And the higher the number, the greater the malignant potential of the cell. Now, these numbers get compressed into a grade group, which is a scale that is graded 1 through 5. And again, it's similarly based on the abnormality of these cells. So a grade 1 or 2 is a relatively low-risk tumor. We know the natural history of grade one and grade two, which are the lower Gleason scores, behave very differently.

27:34Peter Attia:And these are cancers that may never spread. Now, we don't know that for a fact, but we know that if they're going to spread, they're going to do so by progressing into a higher grade Gleason score. And therefore, for these patients, we can continue to survey them or do other advanced forms of monitoring, which I'll talk about in a second. Conversely, if a patient presents with a higher grade group, like a grade 3, which would be a Gleason 4 plus 3, a grade 4, which would be a Gleason 4 plus 4, or a grade 5, which is anything higher, so a 4 plus 5, 5 plus 4, or any 5-5, these are very aggressive tumors, and treatment is immediately warranted.

28:21Peter Attia:So going back to what do you do with grade one and two? Well, again, these are patients that have prostate cancer, but our belief is that it is not an imminent threat to their life because it is not clear if these cancers will spread. And if they're going to turn into spreading cancers, they're going to do so by progressing. So we would, in this case, look at other blood markers like tests called the PHI or the 4K score. These are things that we talked about on previous podcasts. We'll link to some of that stuff in the show notes if you want to follow that in more detail. But the point is we now turn into an area called active surveillance.