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Declan Murphy: This is a very important topic, as David set up very nicely for us this morning. There was a very nice piece written in the British Journal of General Practice recently. Is this one supposed to go forward? British Journal of General Practice recently, which reports a survey from Prostate Cancer UK of about 2,000 men addressing the fear of digital rectal examination. And look at this, 60% of this group of men are concerned about DRE, a third of whom are so concerned that it's the reason that they're not going to go and see the GP. And Black men within that survey were significantly more concerned due to cultural issues despite them being at higher risk of mortality. So I think that's the background to a discussion about the role of DRE—it is preventing many men from going to seek advice from their doctors about prostate issues. While there are lots of memes and videos and so on, that's not really helping. I think what we need to do as clinicians is have more nuanced advice towards the role of DRE.

This is the obvious question: do we need to do DRE in an era when we have MRI? And that's the whole backdrop, I think, to a conversation about DRE in 2024. It hinges on MRI, but it also hinges on which world you live in. If you live in the idyllic APCCC world—which, by the way, what's written here is what Silke and Aurelius write on the top of the panel questions every year: "Assume that everything's available and free." So that's the only way in which MRI makes a difference for DRE. But of course, in the real world, MRI is actually usually not available for very many of you and your patients, even in high-income countries like the U.S., which has probably the greatest of all health disparity. MRI is not available for huge swathes of the uninsured, at-risk population. So that's the backdrop as we discuss the role of DRE.

I have three different scenarios that I'll discuss. First is primary care, where I suppose imaging doesn't really come into it. Well, let's presume that we're talking about the at-risk, asymptomatic screening-type population and presume that MRI is not really available for most of these regions around the world. And of course, DRE in this setting has poor sensitivity. There are concerns about the experience general practitioners have with DRE. And as I've pointed out, the patient perception. And yes, yes, before you all tell the stories of that rock-hard prostate with a PSA of 1.1 that we've all seen, remember to balance that off against the huge deterrent that DRE is in primary care; we need to have a view that's not just about the rare patient who has a low PSA and a nasty cancer who usually will develop some symptoms. So it's not that we're really concerned about.

There are two recent papers, two papers I'll quickly show to you that really kill off the role of DRE in this GP setting. This is a nice systematic review in European Urology Oncology led by Shahrokh Shariat and team. What they conclude in brief is when looking at both positive predictive value for significant cancer and cancer detection rates, DRE is the same as just PSA on its own and even worse for cancer detection rates. And Shahrokh sent out a triumphant tweet in January when the paper was published saying finally, he's proven that DRE has no role in the early detection GP screening setting, and hopefully this will begin to appear in guidelines.

That systematic review did not even include this nice paper from Peter Albers's group in Germany published a few months ago in European Urology Oncology as well, the PROBASE trial, a prospective screening trial starting from men aged 45. In this paper, Peter's group were asking, what is the utility of DRE in the screening population? The answer: really useless. DRE has poor diagnostic performance. That's the main headline coming out of this study, which I think will feed into guideline recommendations going forward and really question the role of DRE.

So that's my sense of this. I don't think there's a real role for DRE. Little caveat and a shout-out to Scott Eggener, a urologist in Chicago who has a summary tweet here from last year about the role of DRE. He comments that he finds it useful for determining PSA density. So he must be quite good at estimating prostate volume with his finger. I'm no good at doing that. From one day to the next, the same patient could have a gigantic difference in what I think the size of his thing is. But I think the key message here is in primary care, there's no real role, even notwithstanding those patients with low PSA and nasty cancer.

This is the really interesting area. What about urologists? Those of us who diagnose men with prostate cancer? And let's first of all consider the idyllic APCCC world where MRI is available. And we've all got very used, of course, to novel imaging showing—and this is just a patient of mine from last Friday. I'm only going to show you a beautiful case, of course, but it happens to be one from last week. The MRI is very convincing. The PSMA PET is very convincing, the final pathology confirms it. But I want you to look at the T2 image in the top left where this actually feels just like a clinical T2. You can just about feel it. But on MRI, it looks like it is T3, it is extracapsular extension, and the final pathology, that yellow line, is all extracapsular extension. So I think Martin's question about the futility and lack of reproducibility of CT examination, clinical examination, needs to be questioned in the era of novel imaging and grade volume, as he says, core volume.

But I will remind you of the PRECISION study, the one key paper that has really changed practice for us when it was published in 2018. And by the way, only 15% of patients in this study have an abnormal DRE, a classic at-risk population. In the control arm, without MRI, we see 26% detection of clinically significant cancer and 22% detection of insignificant cancer. But when you bring the MRI triage pathway in, suddenly the really important thing is that the insignificant cancer drops to 9%. So by using an MRI pathway—forget about the DRE—what we're really doing is leading to much less overdiagnosis of prostate cancer. So I think the idea of the virtual DRE where MRI is replacing that as a tool for deciding who needs a biopsy or not is really, really important.

I'll give a shout to Nick who's speaking in the final session about the Lancet Commission in a very important session here today. His nice paper published in The Lancet recently addresses a whole load of stuff about prostate cancer. But in particular for high-income countries with MRI, he mentions—or the group mentions—that we must link MRI in the early detection pathway to reduce over-detection. But in the real world, what do we think about this for APCCC? Very little role. That's my conclusion. I rarely do a DRE if I'm planning to do an MRI. I sometimes do it at the time of a biopsy if it looks like it will be T1 disease just to make sure. And I don't do a DRE if the MRI is normal. If it's a telehealth consultation, the patient's had an MRI, it looks normal. And that's our key message, I think, is DRE has little role for urologists who use MRI.

But what about the real world? MRI is not widely available. That's the reality. And therefore, DRE still remains an essential tool for determining, will I recommend a biopsy for this patient or not? So if there is palpable disease, we clearly will because of the high positive predictive value for significant disease. And as Martin highlighted, it still is a key part of risk stratification. So I think if you don't have access to an MRI and your patient is referred in with a high PSA, yes, digital examination done by the urologist still has an important role if MRI is not available.

Final scenario, local staging. What's the role of DRE in local staging in the world where everybody has an MRI? Well, MRI is clearly the best tool for giving us local staging information, but I will still always do a DRE if it's been suggested this patient has extracapsular extension to see if it feels clinically T3, i.e., high-risk patient. Because that still determines, for example, if the patient's having radiation, at least in a conventional era without genomics, then they will have two years of ADT, for example, just based on the clinical T3. So I think the finger still remains important, but we would all love to hear Martin's wish for a revision of these systems to come through. And clearly for regional staging, PSMA PET CT will reign supreme. But in the real world, again, MRI is not available. CT is no good for local staging of the prostate itself. So DRE still has a key role for the urologist looking after a patient who's already been diagnosed with cancer and we're trying to plan the best treatment for that patient.

Now, I'm not showing the answer, but we will be looking at the answer to this question. So this is one of the questions this year. So I want you to think about this, Silke and Aurelius said, in the majority of patients that are clinically T2, so we can feel a little nodule, but the MRI clearly shows T3 disease, what do we recommend? Do we call it T2 or do we call it T3? So obviously, I voted T2 because it's clinically T2, but I'm interested to see what the vote says afterwards because it's quite a big difference in the planning.

Finally, PSMA PET CT—is there a role in early detection for these patients? Well, clearly when we started doing a PSMA PET for regional disease, we began to see examples like this where PSMA can tell us a lot about what's going on in the prostate, but clearly we're not going to do a PSMA PET for every man with a raised PSA if they've already had an MRI. In the primary study we did, though, to see what was the additive value of doing a PSMA PET CT, we did show that it increased the negative predictive value. But I think where that's really interesting is in the patients with a normal MRI or equivocal MRI—the ones we would traditionally biopsy, but maybe they don't need a biopsy. And you can see in the bottom left, yes, if we did a PSMA PET and it's negative, a lot of patients avoid a biopsy. So we followed that with a randomized trial, which is currently underway to determine what the role of PSMA is. These are my final thoughts on that. Silke, thank you very much.