All right. And for our presentation today for grand rounds, we have Dr. Andy Wolf, an associate professor in the Department of Medicine by way of brief introduction, which Dr. Wolf asked me to give. He's been at UVA since 1993, is well-loved by the health staff. 

His one innumerable Outpatient Attending of the Year Awards has been recognized in 2018 as the ACP Teacher of the Year and also has won a GMA Master Educator Award-- well-loved, and well-respected. So if you could join me in welcoming Dr. Wolf. 

[CHEERS AND APPLAUSE] 

Thank you very much, Sumner, although I do realize, now, why I was asked to speak today. I think the PGY3s are gone. PGY1s are psychologically checked out. PGY2's are running up on the wards taking care of everybody. So this was a perfect day to have me here. So very good. Seriously, I'm very happy to be here. 

And [COUGHS] I have prepared this, hopefully, probing presentation on prostate cancer screening-- a paradigm for promoting patient preferences. No disclosures. So let's start with a case. This is a 62-year-old white man without significant medical history. He comes in for his annual preventive visit. 

No family history of prostate cancer, mild urinary hesitancy. Prostate is mildly enlarged, no nodules. His PSA has been gradually rising. And there you have it to three, up to 4.51 at your visit today. So the question I've got is, where do we go from here? And we will come back to this case at the end of the presentation and see where we might go from here. 

So the key questions that I hope you'll be able to answer at the end of our presentation are, do we have any new evidence for or against screening? Do we have anything better than the PSA? What about the good old DRE? Is that still a useful tool? Are we doing any better identifying who needs to be treated among those we do diagnose with prostate cancer? And finally, what are the experts recommend? 

So first, a little bit about epidemiology. This is a figure of incidents and mortality. On the left are white men. On the right are black men. And this is over time over the last 40 years. The red lines are incidents-- black mortality. Two main points here-- you can see that in the late 1980s, there was a huge surge in the incidence of prostate cancer. That was the widespread dissemination of the PSA. 

You can also see that for both incidence and mortality in any given year, African-American men much higher risk than white men. So independent and strong risk factor for developing and for dying for prostate cancer. Other points here-- you can see that the mortality from prostate cancer began to decline in the early 1990s. 

Proponents of screening said that this was due to screening. Opponents of screening said that this was too early after the advent of PSA to have seen a mortality decline so still a debate. They would ascribe this to environmental factors and better treatment. Also of note was this relatively sharp decline in incidents that you see in the 2010, 2015 era. 

And that coincides with when the US Preventive Services Task Force gave prostate cancer screening a D recommendation. Up until then, they had not issued a recommendation. Their first recommendation was a B recommendation, meaning, do not screen for prostate cancer. 

And in the year following that decision, the drop off in incidence was about 30,000 men in this country. And there was a commensurate rise in diagnosis metastatic disease. So and that was a controversial decision and was against what other organizations recommended at the time, which we'll discuss. 

So prostate cancer in 2019, and this is the ACS Statistics is the number one diagnosed cancer in the United States, nonskin cancer with 175,000 cases. It is the number two cause of death among men with 31,000 cases expected in 2019, not right behind, but behind lung cancer. Lung cancer-- a lot more deaths. So again, significant morbidity and mortality from prostate cancer. 

So let's address the first question. Do we have any new evidence for or against prostate cancer screening? And the answer is yes. We do have evidence for and against prostate cancer screening. So from that standpoint, things haven't changed too much. This was a study from 2017 that pooled two large randomized trials. 

It didn't kill them. It looked at them in a new way statistically. And it was published in 2017. I'll go over that in a few minutes. And then this study came out last year. It was a large randomized trial from Great Britain that suggested that prostate cancer screening doesn't work. So we'll review this. 

10 years ago, roughly today, two back-to-back studies were published in the New England Journal-- one from the US, one from Europe. This was the US study. It was 75,000 men were randomized to prostate cancer screening with the PSA and digital rectal exam versus usual care. And it showed no impact of prostate cancer screening on mortality. You can see the lines over a 10-year period are roughly comparable. 

Problem with this study was that the patients in the control group also got screened-- about half of them got screened. So the contamination issue in this study was huge. Also, in this study, men who did have elevated PSAs often didn't get biopsies and, hence, didn't get treated. So follow-through in the study was a major issue. 

So this study was really troubled from the start. The other issue with this study was that many of the men had been screened prior to study entry. So it was already enriched with the population at low risk for prostate cancer. So not a great study to help answer the question, at least, initially. This study published the same time as the European study. 

Actually a lot larger was 180,000 men in seven European countries were randomized to PSA screening versus usual care. And fortunately in Europe at that time, usual care meant no prostate cancer screening. So it was more of a pure experiment. And in Europe, men did what they were told and got their PSAs if they were in the study. 

So in this study, which had less contamination, it was also updated in 2014. And these are the results I'm presenting after 13 years of follow up, in fact, did show 27% lower risk of dying from prostate cancer over a 13-year follow-up period. And you can see that the arms began to separate at around 10 years. The number needed to invite to screening to save one life-- about 781. 

The number needed to invite to screened to prevent one case of metastatic cancer got 350. So that number of 781-- sounds like a lot of men to screen to save one life. However, it's actually fairly comparable to other screens we do, like, colorectal cancer screening and mammography, in say, a 60-year-old woman. 

So it's not that dissimilar from other commonly employed screens. The number needed to diagnose with prostate cancer to save one life from prostate cancer was 27 over that 13-year period. And that gets to the major issue of overdiagnosis and overtreatment that we'll get to in a few minutes. 

So in two years ago in 2017, the results of these studies were re-analyzed by a group of investigators and well-respected epidemiologists. And to be honest, their techniques were very sophisticated. And I'm not going to go through them. And I don't understand a lot of them. 

However, they control for differences in study design and adjusted for lead time and looked at screening versus no screening in both of these studies and found that, actually, in both studies, the US and the European study-- there was about a 25 to 32% reduction in prostate cancer mortality when men were screened versus no screening. 

It looks like we're getting some evidence that screening actually works. But then comes the cluster randomized trial of PSA testing for prostate cancer, which somehow becomes the cap trial. I don't know how you get that tortured acronym from that particular title of the study. But that's typical of acronyms for studies. 

In any event, this is a very large trial. 415,000 men randomized-- middle-aged men randomized to a single offer of screening versus usual care. And usual care was an information sheet about PSA testing was available on request. This was a one-time screened. Men were followed for a decade. 

If they were diagnosed with prostate cancer, they were then randomized to treatment with radiation or surgery versus active surveillance. That was a separate study called the ProtecT Trial, which we'll talk about in a few minutes. So single offer of screen, usual care was generally not to be screened. 

About a third of the men who were offered screening actually got screened. About 10% of the men who got the information sheet if they asked for it got screened. So relatively few men got screened in the study in the intervention arm and even fewer in the usual care arm. So that was a significant issue. 

And not surprisingly, you can see in the bottom graph here that there were more men diagnosed with prostate cancer in the orange intervention arm than in the control arm. But this is prostate cancer specific mortality up here. You can see there was really no difference. This difference towards the end of the follow-up period was not statistically significant in very small numbers up there. 

So not a positive study, a negative study. Problems-- again, this wasn't a study of screening effectiveness. It was really examining the impact of offering screening to English men, who, I guess are not very interested in prostate cancer screening. I think in England, people tend to be less interventional than they are here. If we have a new test, Americans want it. 

And so over there, not so much. A third of them took them up on it-- 10% to 15% controls. The likelihood of seeing a difference from the control group was low to start with. 10-year follow-up relatively short for prostate cancer. It's about the earliest time from the prior studies that you would see a mortality benefit. 

No, I don't expect to see a difference emerge in this study, given the low percent that were actually screened. Another issue is that men who are diagnosed with prostate cancer in Great Britain are not treated as aggressively as in the US. That could have affected outcomes. 

So again, designed to study the impact of a single screen not really generalizable to what we do here, which are serial screens over time. Hard to extrapolate too far from this study. But I would say, is putting all the evidence together is, there really is sufficient evidence to say that prostate cancer screening probably does save lives. And it probably does lower the likelihood of metastatic disease. 

So having said that, we're going to move on to the second question. Do we have anything better than the PSA? Or, at least, do we have anything that can augment the PSA's value as a screening test? And first, we'll talk a little bit about the PSA. PSA is not a bad test. It's not a great test, but it's not a bad test. 

Using a PSA threshold of four, it has a sensitivity around 70%, specificity of around 93%, positive predictive value around 25%-- not too bad for a screening Test that means, however, that the 75% of abnormal PSAs are false positives. 

Also, the false negative issue is significant. Somewhere between 15% and 28% of men with a PSA under four have prostate cancer if we were to biopsy them which we don't. And of these, about 15% are actually high grade. So what that means is, up to 4% of men with, quote, "normal PSAs have high-grade prostate cancer." 

So again, we miss them. Whether or not we catch them by doing serial screens is not known. We hopefully do, but that hasn't been studied. False positives-- a significant issue. BPH is the biggie. Prostatitis often asymptomatic found on biopsy. Ejaculation can transiently raise the PSA a little bit. It's not a huge issue. 

Long bike rides-- studies show that biking-- think it was 80 kilometers in this study-- raises the PSA. So the take-home message from this is, advise your patients who are coming in for prostate cancer screening not to have sex and ride their bike to your office. That's the main point. 

The digital rectal exam probably doesn't raise the PSA significantly. There's debate about that but don't do a prostate massage and then do a PSA, because that probably would raise the PSA. So this is an older study. But it's an important study, because it talks about the impact-- the psychological impact of a false positive PSA. 

This was a study-- a six week survey. So six weeks out from PSA testing or from a biopsy where in the orange, these are the men who had a normal PSA. The blue are men who had an abnormally high PSA-- had a biopsy-- turned out to be a false positive. Surveyed six weeks later. 

What happened is you can see is, at six weeks, 40% of the men who had the false positive were still worried about prostate cancer. About over a third of them thought they were still at high risk for prostate cancer. And this is the most worrisome one. They thought life was better. A third of them thought life was better after having had a transrectal skewering of their prostate only to be told it was a false alarm. So that's concerning. 

Now, this is a transrectal prostate biopsy device, OK. And I have to ask you, does this look like dodging a bullet? Because that's what these people thought. They thought they were dodging a bullet. No, we gave them the bullet, but they didn't dodge it. All right, so false positives have consequences. 

What do we have beyond the PSA, at least, the PSA alone? We have PSA velocity. We have PSA density. We have something called percent free PSA. We have some newer tests-- the Prostate Health Index, 4K score. And newest-- the multi-parametric prostate MRI. I'm going to go over these. 

So PSA velocity is a concept has been around for a long time. This is the rate of rise of the PSA. Study done a number of years ago showed that a PSA velocity of greater than 0.35 per year associated with greater likelihood of death from prostate cancer. However, in a more recent study, it didn't really do any better than the absolute PSA level itself in predicting prostate cancer on biopsy. 

So as an independent predictor, not so useful. Its best role may be on people who have already had a biopsy. And then you're following their PSA after that. The rate of rise may be useful in terms of indicating when they need another biopsy, or if thing another biopsy. 

PSA density-- and this is just a PSA over the prostate volume, gives you a PSA density. You need a transrectal ultrasound to measure prostate volume. Men with BPH have lower PSA density than men with cancer. It could theoretically help differentiate the two. But it actually doesn't add much predictive value to the percent-free PSA, which I'm about to talk about, which is just a blood Test 

This requires a transrectal ultrasound. I think most men would appreciate a blood test over a transrectal ultrasound-- hasn't gained much traction, at least, in the initial evaluation of elevated PSAs. The percent-free PSA can be useful. PSA produced by cancer cells is more likely to be complex to a glycoprotein than PSA produced by non-cancerous cells. 

So the higher the percent-free or noncomplex PSA, the lower the risk of cancer. FDA has approved this for PSAs between four and 10 with normal digital rectal exams. Using a free PSA threshold of under 25%, meaning biopsing people with free PSAs of under 25% can detect 95% of cancers and reduce the biopsy rate by about 20%. 

So it can be useful. However, that means that 80% of men do have a free PSA with elevated PSAs have a free PSA below 25% and need a biopsy. So it has some discriminatory value. More recently has come the Prostate Health Index or PHI. This combines total PSA-- the free PSA which we just talked about and another isoform of the PSA called the pro-PSA. 

This does a better job at discriminating between high-grade cancer versus either low-grade cancer or no cancer. Higher the score, the higher the risk. A PHI cutoff score of 24 reduces biopsies by 36% at a cost of missing about 2.5% of high-grade cancers, meaning Gleason seven or higher. 

And a reminder-- Gleason score is a combined score of the two big largest areas in the prostate biopsy showing cancer on a score from one to five. But one and two aren't really considered cancer. So it's effectively three to five. So you add those two scores together. And you get a score between six, which is considered a low-grade cancer and seven or higher, which are now considered high-grade cancers. 

So again, a decent job, actually, discriminating, not perfect but also approved by the FDA for men with elevated PSAs between four and 10. They can be ordered an epic. I have this in your PDF version of this presentation for those who actually want to use that. It's a send out. 

The 4K score is fairly comparable. It's another combination test. It has the PSA-- the free PSA-- something called the human kallikrein 2 and then another isoform called the intact PSA. It also factors in some demographic and clinical factors-- age, digital rectal result, prior biopsy. 

It also discriminates between cancer and noncancer and low-grade cancer. The problem, thus far, for the 4K scores, there hasn't been a widely-accepted threshold for when to refer for biopsy versus no biopsy. So I haven't used this. But it is-- it is. There probably will be. And it's probably going to be comparable to the PHI. 

Perhaps, the most exciting development has been the development of the multi-parametric prostate MRI for evaluating abnormal PSAs or abnormal digital rectal exams. This was a large randomized trial published last year-- randomized men with elevated PSAs or abnormal digital rectal exams to either a targeted biopsy using the at prostate MRI or the traditional 12 core biopsy. 

And I'll take you through the results. Bottom line is, here at the top, you have 28% of the men in the multi-parametric MRI group didn't even get a biopsy because they had normal MRIs. So right off the top, you've cut out 28% of men who don't even need a biopsy. So that's big. 

The standard biopsy group are more likely to have negative biopsies, meaning the yield was more efficient in the MRI targeted biopsy group. On the other hand, clinically significant cancers were 12% more likely to be diagnosed in the MRI targeted group versus the standard 12-core biopsy. 

And conversely, 13% fewer men were found to have clinically insignificant cancer on the MRI targeted biopsy-- the ones we probably rather not know about. Not surprisingly, complication rates were significantly less in the MRI targeted biopsies, partly because or largely because there were only four biopsies done on average in the MRI targeted group versus 12 on the 12-core standard biopsy. 

And as you see, half the number of cases of hematuria, half the hematospermia-- post procedural pain was less. Rectal bleeding was less, again, because fewer biopsies were done. And this also points out, if you can look at the standard group, this is not a benign procedure-- a lot of hematuria, a lot of hematospermia, a lot of postprocedural pain and rectal bleeding. 

And about 3% of men get prostatatis-- some bad enough to get hospitalized. So not a benign procedure if we can reduce the number of biopsies we do, that's a good thing. Some caveats not yet routinely covered by insurance, except Medicare, is now covering it for elevated PSA evaluation. So that's big. 

And I think it will be covered by the others. Right now requires peer to peer-- more likely to get covered if they have a significantly elevated PSA if they have an abnormal Prostate Health Index or 4K test. Or if a subsequent biopsy confirms cancer. 

But the only way you'd know is to do the MRI targeted biopsy. And if it doesn't show cancer, they're saddled with a $3,000 bill. So still a work in progress, because we can't refer people, yet, routinely, unless we know they're going to get covered for this. 

I'm going to switch gears and talk about our old favorite-- the digital rectal exam. Does it still have a role in prostate cancer screening? So this was a meta-analysis that came out last year showing a sensitivity and specificity-- around 50%. So you can either do a digital rectal exam or flip a coin. And I would say flipping a coin is much more palatable to your patients. 

About half of medical school graduates in one survey had never performed a digital rectal exam, which is very sad for some of us old farts to hear. About half of us primary care doctors are confident in our ability to detect prostate cancer with a digital rectal exam. And those of us who are, are probably overconfident, because even urologists have poor correlation in terms of their ability to identify suspicious nodules. 

Kappa correlation of 0.22 not very good. So for these reasons, most guidelines do not recommend digital rectal exam as part of the standard exam. US Preventive Services-- it doesn't mention the digital or doesn't recommend it. The American Urological Association doesn't mention it. And the American Cancer Society says, optional. Does 

Still make sense to do it if there's an abnormal PSA or if a man has prosthetic symptoms. But otherwise, probably not. This says, it may be more inconvenient. But the reverse prostate exam is a lot less embarrassing for the both of us. And I think most of our patients will be happy to do away with a routine screening digital rectal exam, though I know we have some older patients who feel they're being gypped if we don't put our fingers in their rectums. So that may still be the case. 

Are we doing any better at identifying patients who need to be treated? Among those who we detect prostate cancer in, are we doing any better identifying the ones who need treatment versus those who don't need treatment? This gets to the issue of overdiagnosis and overtreatment. Overdiagnosis meaning the diagnosis of prostate cancers that would never have been diagnosed during the man's lifetime if screening had not occurred. 

The estimates of how frequent this is ranged from 23% to 42% of screen-detected cancers. So overdiagnosis is still a major issue. Overtreatment is just the logical consequence to the treatment of these screen-detected prostate cancers that never would have become apparent during a man's lifetime if we hadn't screened. 

So is overtreatment a big issue? After all, we overtreat a lot of conditions. We've have a lot of men and women on statins who were never going to benefit from being on that statin. High blood pressure medicines-- same deal. Maybe we're getting too excited about overtreatment. I would argue, no, we're not getting overly excited about the problem here. 

This was a survey of Medicare patients who had undergone either radical prostatectomy or radiation therapy, external beam for prostate cancer-- two years, five years, and 15 years out. I'm going to highlight a few things. 10% of men had significant urinary incontinence, either no control or very frequently two years out, one in 10. 

What is that? 78%, almost 80% of men had insufficient erections for intercourse two years out. And most of those men were bothered by it. Now, with external beam radiation, 61% of men two years out, inability to have intercourse. Bowel urgency-- about a third of men with radiation suffering from bowel urgency two years out. 

So overtreatment is a problem. If we can reduce overtreatment, we're doing something useful. Oh, how can we do that? The term, active surveillance, the practice of active surveillance is coming into vogue. And, well, it should be as a way to mitigate harm from overtreatment. 

The way this works is that men with low or intermediate grade cancers are offered the option to monitor their cancer with PSA and periodic biopsies rather than just treating and then treating those men if their prostate cancers progress. In the US, a Gleason 7 is generally offered treatment. And that's important, because in the UK, they often are not offered treatment. So that will become important in a minute. 

And this certainly can reduce the risk of overtreatment. Does it work? This trial, the ProtecT Trial, from Great Britain randomized 1,600 British men with screen detected prostate cancer to radical prostatectomy, radiation, or active surveillance-- what they called active monitoring. And you can see that over 10 years of follow-up, a lot fewer men got actively treated in the active surveillance group. 

Over time, over 10 years, about half the men ended up getting a switching over due to disease progression, presumably to active treatment. But still, that reduced the active treatment in half of men. So that's good. But did it work? This is the prostate cancer specific survival curve for the three groups. And you can see that people did extremely well. 

No one, very few men died from prostate cancer over 10 years. These are the three arms of the study. So that's good. This is not so good. This is freedom from disease progression over 10 years. And you can see that in the active surveillance group, there was a significant progression of disease compared to the active treatment groups. 

And this was any disease progression. So this may be cap extension beyond the capsule of the prostate. But it also included 6% of men who were diagnosed with metastatic prostate cancer, as opposed to 2% to 3% of men in the radiation surgery groups. So that led to a number needed to treat actively of about 30 to prevent one case of metastatic disease compared to active surveillance. 

And you'd have to say, well, it's number needed to treat of 30. Is that high enough to warrant to be OK with active surveillance? One thing I will say, is this is the British study. And there were a number of men in that active surveillance group who, at least, in seven cancers. And we treat those here. 

So I think this curve would look better in America than it did in Great Britain. Another price to pay with active surveillance. Are we creating a cohort of anxious men who are in cancer limbo? We diagnosed them with prostate cancer. But then we don't do anything about it. And, in fact, yes, we are creating anxiety. 

This was a survey of men 2 and 1/2 to 7 and 1/2 years out during active surveillance. And it was stratified by their self-perceived health risk. So these are men who consider their health to be fair to good. And you can see that over the ensuing years, about a third of them were significantly anxious, meaning they were anxious enough about prostate cancer to affect their mood and to affect their life planning. 

Men who were healthier, grading their overall health score of eight to 10, less anxiety. But still, that's quite a bit of anxiety that we're creating by not treating their prostate cancer. So something to be thinking about and making sure men know about. 

So what are the experts recommend? Putting all this together, we have three major organizations who've issued guidelines-- the US Preventive Services Task Force, the American Neurologic Association, USPSTF was last year. AUA was 2013. And American Cancer Society was 2010. 

They're updating their guideline next year. All three say, men should be informed about the pros and cons of prostate cancer and be allowed to make a decision whether or not they would like to be screened for it. You don't need to do this every year. But you do need to have the discussion with men. 

That's the recommendation of all three groups. Now, keep in mind this was an upgrade from a that's a C recommendation for US Preventive Services Task Force where the benefits and risks are too close to call, so have them engaged and informed decision making. The age range to offer screening or, at least, offer the discussion is 55 to 69. 

For the USPSTF-- same with the AUA-- that's based on the fact that the European randomized trial used those ages to screen men. ACS-- was less evidence based in their guideline of 50 to 74. However, they did base it on when prostate cancer incidence increases fairly exponentially after the age of 50. 

Interestingly, the US Preventive Services Task Force had no recommendation for men with a positive family history or African-American men. Keep in mind the significantly increased risk of prostate cancer in African-American men greater than even having one first-degree relative with prostate cancer. 

In fact, their own modeling showed that the benefit conferred by screening for an African-American man begins about five to eight years earlier than for a Caucasian. And yet, they didn't make a separate recommendation for when to begin the discussion. AUA says, individualize the decision from African-American men and men with a family history somewhere between 40 and 54. 

The ACS was much more practical and said, start at five years earlier at age 45-- start the discussion earlier. The screening tool I mentioned is the PSA without the digital rectal exam for both USPSTF and the AUA, PSA with or without the digital rectal exam-- your choice-- American Cancer Society. 

How often should you screen? Not defined by the USPSTF. The AUA says, every two years, which I think is very reasonable. Consider four years interval, PSA less than one. I actually think that's a very reasonable recommendation since the likelihood of developing cancer over 20 years for a PSA less than one is very low. 

So every four years is reasonable for low, low PSAs. The ACS says, two years for PSA under 2.5-- annual between 2.5 and four. And if you think about the false negative rate of the PSA in that range of PSA, that's not an unreasonable recommendation. So how do you do informed or shared decision-making in five minutes or less in a busy office practice? 

Well, you can provide the essential information they need to make the informed decision. You can for men who can't make a decision give them dichotomous values matching scenarios that we'll talk about in a moment. Or you can just assign them homework if you don't have time to do anything, or if they just can't decide. 

So what are the core elements of an informed decision? These would be reasonable core elements. PSA testing can find prostate cancer before you have symptoms. Early detection may and probably does reduce your chances of suffering from or dying from prostate cancer. 

There's a good chance that if we find prostate cancer, it would never have caused problems during your lifetime-- overdiagnosis. If we find a low-grade prostate cancer, you probably won't need treatment. But you will need to undergo yearly biopsies, which can be quite painful-- active surveillance. 

And treating prostate cancer that we find through screening frequently leads to erectile dysfunction, urinary leakage, and/or bowel problems. That's a key thing you got to get in there-- sexual problems, urinary problems, bowel problems could happen, cause a lot of men will say, hey, forget it. I've heard that. I don't even want to go there-- important to get that in. 

A lot of men will come back to you and say, I don't know. You're the doc. You decide. This is where you have to turn it back to them and say, this is based on your values. So it's a dichotomous decision. They're either going to screen or not screen. So give them a dichotomous values matching scenario. 

You may want to be tested. If you value finding cancer early-- you're willing to be diagnosed with cancer that you may not treat. And you're willing to risk the significant side effects you just talked about. You may not want to be screened if you place a higher value on avoiding the potential harms of screening, such as anxiety and all these injuries that we just talked about. 

And if they still say, I don't know, doc. You're the doc-- can say, well, I'll tell you what. I'm going to assign you some homework. And you can give them some literature. This is the CDC's literature-- printed literature. The CDC has a website that's pretty good. They have a little video there that talks about the pros and cons of PSA screening. 

You can go to what I would consider the gold standard informed decision making online guide which is from Georgetown. This goes through step by step-- every single element of it. It has a little video clips of men who've been screened and were happy about it. Men who were screened and unhappy about it. Men who've been through treatment. And what's that? 

It's got all the bells and whistles. It has them gauge where they are on their decision along the way. A great screening tool. But if you're more practical, you can use this little three-page pamphlet that I put together at about a seventh grade reading level. Should I be treated, tested for prostate cancer, courtesy of Dr. David Calendar Photography? Thank you, Dr. Calendar, though you should stick to your day job. 

[LAUGHTER] 

[LAUGHS] We're going to skip over this. We're going to come back to the case, because I want to have time for questions. So the case is our 62-year-old man with the rising PSA. Where do we go from here? Well, you could go to an online risk calculator, like this one. There's several available. 

Put in his information. Remember, he's Caucasian. He's Caucasian. He's 62. He's got a PSA of 4.51. No family history-- normal exam-- never had a biopsy. So this gives the patient and you a pictorial view of what we've got here in terms of risk. Got a 6% chance of a high-grade prostate cancer. Got an 18% chance of the cancer we probably don't want to know about. 

See these little thermometers? About 3% chance of getting an infection from the prostate biopsy. And so that may be useful to help the patient grade his risk and decide what he wants to do next. I would like you to see what happens, however. This man is an African-American man with exactly the same scenario. 

All of a sudden, we have a 15% chance of a high-grade cancer. So that may change your discussion. OK, and this risk calculator can be helpful to frame that. Not a perfect risk calculator. It probably, slightly underestimates the risk. But still better than going from the seat of your pants. So this may be helpful to you in terms of framing your discussion. 

But what are your options here for this man? You can repeat it. That would be reasonable to do. There's no urgency here. It probably won't change much. It's been consistent with the rate of rise. You could use one of these other tests. And I think it would be very appropriate here to use one of those. 

I would favor the PHI, because we have a nice cutoff score that would reduce the risk of needing a biopsy. The multi-parametric MRI-- certainly, if the PHI were elevated, that would be reasonable. It might be reasonable even without it. But you probably won't get it paid for quite yet, certainly not with Aetna, our insurance here. 

Or you could just send them over to urology for biopsy. Or you could send them to urology to have this discussion. But remember, when you go to Midas, you sometimes get a muffler, right? So it may be good for you to have this discussion first before sending them over. 

So some take home points. Then, we'll open it up for questions. Prostate cancer screening probably does save lives. But it definitely subjects men to unnecessary treatment or, at least, many men that can pose significant risk to urinary, sexual, and bowel health. We have a growing array of tools to refine our cancer probabilities and avoid unnecessary biopsy, including the free PSA, the PHI, and the multi-parametric MRI. 

Active surveillance is a powerful tool to reduce unnecessary treatment. But it does leave men with untreated cancer and its associated anxiety and annual biopsies, which are painful and uncomfortable. And most important, men need to know what they're getting into before they embark on the screening process or, at least, something about whether they're about to get into. 

Some resources for you. And I want to thank you very much. I want to point out in this picture, though. I had them put in that porta potty right there so those of us with PPH can stop between the medical school and the hospital. Thank you very much. It's now open for questions. 

[APPLAUSE] 

If you have any questions, we'll just wait for a microphone once we get to-- 

Andy, good talk. Do you want to comment on what happens if you put people that have slightly elevated PSAs on a five-alpha reductase and what changed it? 

Great question. So what happens is, that this is the [INAUDIBLE]. What happens is that PSAs drop by about half. And so they have to know that that's going to happen. So if we're going to be following PSAs, it's, again, not rocket science. But you basically have to double PSA that you're getting as a screening test to figure out where they really are. 

And it's not perfect. But it's about 50% reduction. So good question. Also, there's the question, does that prevent prostate cancer? Because there was a big trial to see if an asteroid and the class of drugs that prevents prostate cancer is an asteroid they studied. 

And bottom line there is that it lowered the risk somewhat. But it lowered the risk, primarily in men with low-risk prostate cancers-- the ones we don't really care about preventing. So it didn't really do much for the high grade prostate cancers. It was originally felt that maybe they actually increased the risk of high-grade prostate cancer, but that's not the case. 

You open up an issue in all of physical examination of the issue of whether you expect to find something so that if people are doing screening of pre-surgery cases and not expecting to find anything, is their rate of detection of something in the prostate dramatically less? And has anyone actually assessed that? 

I've seen a couple of cases in this hospital where someone has clearly had a rectal exam and declared nothing. And yet, when something happened, i.e. they couldn't get up catheter. It was found that the prostate was grossly enlarged. And the original one was not expecting a result. 

Right. So I think it just speaks to the poor test characteristics of the digital rectal exam. And honestly, it's highly operator-dependent. It's a highly operator-dependent test. And that's the problem with it. I'm sure there are people who are very good at digital rectal exam. Most of us aren't. And plus, there's a lot of cancers that are not palpable on the digital rectal exam. 

So it's just not a very good test. But it ends up being an issue of case finding. Once we have symptoms or an elevated PSA, it's still recommended that you do a digital rectal exam. How much that refines your predictive capacity-- it can. And most of the studies that have shown that have been with urologist, not with primary care doctors. So again, the whole thing is very murky. And it's not a great test. Op, yes. 

Yeah. I was not sure on what do you actually see on MRI? And do you actually see a lesion? 

Yes. Yes, you see a focal abnormality. 

Yes. So if you see a lesion on MRI, why not just follow that lesion with repeated MRIs, rather than going through doing biopsies and all that? 

Well, the point, initially, is to determine, is that a high-grade cancer that warrants early intervention? Now-- 

Does the grade of cancer vary with the size of the lesion? 

Does the risk of cancer vary with the size of the lesion? 

Yeah, it-- 

Oh, yes. I'm sure it does. Yes. But you ask a good question. And we don't have an answer to that yet is, is there going to be a role for the prostate MRI in following men longitudinally after the initial negative MRI or for even for cancer recurrence which it does have a role. 

So Andy, thanks for the showing the risk calculator index, cause I think that's a very nice tool. And the visual impact can be very helpful for patients just as you showed with the African-American risk factor. With the family history, can you remind us, what is the category that qualifies for that positive family history, and the rough risk bump induced by a positive family history? 

Right. So we're talking about first-degree relatives, first of all. And that meaning father, brother. Obvious, there's no definite age cutoff where we consider that. Obviously most men do develop prostate cancer if you biopsy everybody over the age of 80, et cetera, and look hard enough. 

But as a lump variable of positive or negative, it increases the risk about 20% or 25%, not as much as Caucasian or nonblack versus black. That is a significant risk factor-- probably the most significant multiple family members. And there's certainly genetic syndromes that we didn't go over-- raise the risk significantly. 

Thanks, Andy. My question is, I find myself struggling with patients who have LUTS symptoms and wanting to send a diagnostic PSA. I have heard that there's basically you shouldn't. 

Well, the problem is that you can't differentiate by symptoms, like, who has prostate cancer and who just has BPH. And we know that BPH raises the PSA. And so this is where some of these other tests can be useful. It's the same discussion, whether they have BPH symptoms or not having BPH symptoms. 

Do you want to get into this or not? And it's fair. I mean, if I'm a patient with BPH symptoms who doesn't want to know whether they have cancer or not, then, I don't do a PSA. I just treat their symptoms-- sometimes not well, but I try to. 

And that my other question is, I use your pamphlet all the time. But I did notice that it's created in 2011. 

Oh, you're not using this pamphlet, then. This was created in 2019. 

Oh, no. You snuck one in there. 

The pamphlet you're using now is all of the old ones replaced. 

[INAUDIBLE]. 

[LAUGHTER] 

Dr. Wolf, thank you so much. 

Hey, you bet. 

[APPLAUSE]