Marcus Drake: Well, thank you very much indeed, Alan. I would absolutely appreciate your contribution in functional urology as somebody that's really helped so many of us to get into the field. So for the urodynamics side of things, we did do a very large study in the United Kingdom, which we called UPSTREAM, which is Urodynamics for Prostate Surgery Treatment, the randomized evaluation of assessment methods. The key point about this randomized and, hence, level-one evidence is that we enabled the full set of evaluations what the guidelines expect us to do. So take the history and examination to measure a symptom score, to check the urine sample, flow rate, and do a bladder diary. Everybody got that. But then half the participants at random also underwent urodynamic test. Following that, the surgeon looked at the results that they had available to them and made a recommendation as to whether an operation might be appropriate or may not be appropriate.
The patient then chose which operation that they had. Now our assumption when we designed the study is that if the men had urodynamics, it would be possible to identify detrusor underactivity. If underactivity is present, we would expect the surgeon not to recommend urodynamics. So we'd expect a lower surgery rate in the men that had urodynamics. Now when it came to the results, what we found was that actually there was almost no difference between the two arms. Whether or not the men had urodynamics actually made no difference to the symptoms. So you can see that in this graph. Over the 18-month duration of the study, if the men had surgery, if they were treated conservatively, there was simply no difference in symptom outcome. Crucially, there was no difference in surgery rates. The result, therefore, has to be that urodynamics does not really improve outcome or reduce surgery rate and, therefore, it should not be used routinely on a population basis. A very clear outcome. Now I'd be very interested to know what your thoughts of that initial headline result from UPSTREAM was, Alan.
Alan Wein: Yeah. My initial uptake was that urodynamics was certainly less useful than some of the true, die-hard proponents of urodynamics made them out to be in terms of evaluating men with suspected bladder outlet obstruction due to BPH, and that it really didn't make any difference whether you did urodynamics or not. I liken this to the increasing number of papers that report good outcomes in patients that come in in urinary retention with a fair-sized bladder, which is supposed to be a bad prognostic feature, have apparent even acontractility on urodynamics studies, and yet have an inoculative procedure. Although the success rate is certainly ... Success meaning getting off of intermittent catheterization, the success rate is not what you would expect in a normal population, still, there's enough of a success rate justifying doing the procedure as long as the patient understands that the success rate's going to be less than it would in someone his age, sex, et cetera, et cetera, that maybe had what we would call a decent bladder.
Marcus Drake: That's a very fair point. But the next thing that comes out of the UPSTREAM study, a headline which their population use does not achieve much, is not at all the same as excluding benefit to individual patients.
Alan Wein: Right.
Marcus Drake: So we'll go on to what it is in the UPSTREAM study that says we absolutely support the use of urodynamics in the appropriate patient. So I'd very strongly say anybody that you hear mentioning, "Oh, UPSTREAM does not support urodynamics," has not understood the message.
Alan Wein: Right.
Marcus Drake: So here is point one. Now this is the plot of the IPSS score before and after treatment. The red arrow indicates no change in the IPSS after treatment. So what we are seeing here, there are quite a few people whose IPSS is at the red arrow or even above the red arrow, which means that their symptom got worse. Now when you look at the lower line, the surgery patients, to be honest, if you're giving a man surgery and they come back with worse symptoms, you're really not going to be able to convince them that that's been a successful operation. They did not come to your operating theater to have a deterioration in symptoms, and yet we absolutely, with our very high follow-up rate and independent assessment of outcome, have clearly identified that some men, having followed the surgeon's recommendation, had a deterioration in symptoms. I think this has to be a vital message from UPSTREAM is that let's not be complacent about offering surgery, because if somebody gets worse, it is a personal disaster for that man and does not look good for the surgeon either. So we then quickly moved on to do secondary analysis of the data, specifically to identify the factors which predict outcome from the baseline assessments, specifically the flow rate testing, the symptoms score, the bladder diary, and the general medical evaluation.
Two key papers here. Hiroki Ito's paper published in '24 and Grace Young's paper published before that. Those two together give us the positive and negative predictive outcomes, but Hiroki's paper is the one in which we've published this now quite famous algorithm where you absolutely can identify where a person has got a good prospect of outcome. That's the green parameters on the left, that the man is most bothered by his voiding LUTS, while relief of obstruction, there's a good chance of improving that. Slow stream specifically below 10 mls per second, severely bothered by their LUTS with a bad impact on quality of life, and not too many comorbidities. So these people will actually probably do well from surgery and really do not need urodynamics. Now on the other side, if anybody has got any of the red factors, you've really got to get the urodynamics, and that will be ... That is if you're considering surgery. That will be the men who aren't bothered by voiding LUTS or less effect on quality of life. The stream is above 13 mls per second.
You really need urodynamics then. Symptoms that may have a bad response rate such as nocturia or incontinence, or comorbidities where underactivity becomes more prevalent, they need urodynamics. But they may actually do quite well if the urodynamics identify that they truly do have quite significant bladder outlet obstruction, in other words an index above 48, as well as good contractility. If they're obstructed with a good bladder contractility, then actually surgery, they might do quite well, and they shift back towards the green side if the urodynamics identify that. If those aren't present, surgery has a high risk of deterioration in symptoms. So hopefully that's quite a clear and practical algorithm that people can then really focus on, the voiding symptoms, quality of life, and key predictive factors when thinking about whether to recommend surgery to a man. So the other vital aspect from the UPSTREAM study was to think about how well each individual unit is doing its urodynamic studies, and that actually includes flow rate testing.
So before we ran UPSTREAM, we joined forces with another study run by my colleague at the time, Hashim Hashim, who was looking at laser-style TURPs, and we analyzed the quality of urodynamic tests and flow rate tests from all the centers contributing to these two studies. We actually got quite a nasty shock, which led us to run a big education exercise for a urodynamics unit in the UK because there were very many issues identified. For example, the centers were not maintaining their equipment according to manufacturer guidelines, which could make the equipment inaccurate. They were not interpreting correctly and they weren't actually spotting major errors in their urodynamics test. So Martino Aiello's paper here where we published an example, where a supposedly expert center sent in this trace as an example of the quality of their work. I won't say which center because this is highly embarrassing, because this trace is absolutely riddled with major errors, which actually means that their conclusion that the patient has bladder outlet obstruction is completely unsupportable. So, in effect, the patient was told that they got obstruction when we literally have no idea from the quality of trace whether obstruction was present or not.
To be frank, it's a professional disgrace that centers can be this bad. So a core message has to be look at the ICS quality information. So here is a paper that we published quite recently about how to get the basics right in terms of urodynamics quality. Get each practitioner in the unit to read this, to understand how to produce good-quality traces, and make sure that everything is actually legitimate as opposed to just random lines on paper.
Alan Wein: So basically, I guess, the message is use your head. I found that diagram in the ETO article brilliant because it really does serve as a guide, it seems, as to who really should have urodynamics and basically who shouldn't in that male population with LUTS. So I think that those two articles together really represented distinct contribution to the literature. So these studies are urodynamics without video, correct?
Marcus Drake: Absolutely, yes.
Alan Wein: So do you see any value in video urodynamics for a patient like this as opposed to standard urodynamics?
Marcus Drake: Personally, I'd feel reasonably confident that a physical examination, a flow rate path, and a urodynamic without video is sufficient evaluation for an otherwise healthy man without neurological disease or previous surgery. I think then you are, of course, assuming that if bladder outlet obstruction is present, it's due to enlargement of the prostate into the urethral lumen. But on the whole, I think that that's a reasonable assumption. There aren't really other risk factors in that sort of situation to warrant video urodynamics. However, it would give additional information. So I would certainly not disagree with the use of video to give that little extra bit of information. No harm would result.
Alan Wein: What do you think about the continuing work and a totally intravesical monitor for bladder pressure and let's say they were able to develop a rectal sensor that you could do the same thing for physiologic bladder filling? Do you think that that's going to change at all if it's successful the way we do urodynamics?
Marcus Drake: Yeah, absolutely.
Alan Wein: In other words, the filling rate's normally like one to two mls per minute and we fill between 50 and 100 mls per minute.
Marcus Drake: I would be hopeful that that would reduce the risk of men being unable to pass urine when asked to pass urine in the setting of a conventional urodynamics test. So hopefully we'll get a higher proportion successfully undertaken. The data might be more reliable. A more natural filling rate does seem to make sense. It would need to be validated as being more reliable. Also not sure that it's going to be hugely more convenient compared with conventional urodynamics test because obviously you've got to place the components, you'll have to retrieve them after the test, and the timing all becomes a little bit unpredictable. So it's not necessarily convenient for appointments if natural filling is used. But I think the quality, there is a realistic prospect that that could be improved by those approaches.
Alan Wein: Well, I will leave it to you and your colleagues to do a very exacting study when it becomes absolutely, totally perfected and utilized frequently. But, listen, thanks so much for this discussion because I think it was great. I think that in a short period of time, you clarified how to look at the initial article based on the second article. I think that a lot of people haven't gotten that message yet because they're really not aware of what you put in the second article, which totally clarifies the first article.
Marcus Drake: Well, there is a consensus statement that we've just released from it as well, which is this one that just come out in European Urology Focus again, where we looked at all the information with a bunch of really hard to convince individuals they need proper conviction in order to really accept a statement. They challenge everything. But, nonetheless, we made a sequence of statements about the use of the urodynamics backing up the ETO conclusion and emphasizing the quality insurance being absolutely critical with 12 of the 13 points all agreed by that particularly demanding group. Then a little summary diagram just to back up the conclusions and the ETO statement as well. So it's not only me saying it now, it is actually a group of experts that are really taking this as a priority message for men potentially having urodynamics before the possibility of surgery.
Alan Wein: Well, I think that hopefully this will be helpful to a lot of people who I think got the wrong impression from the first article. Also, I think that hopefully it will be a message to people whose urodynamics studies are done not, let's say, with the best quality of study, which I think you and your folks have pointed out very clearly could be a significant source of error. So thanks so much. Sorry I won't see you at the EAU, but I will at the ICS. So, listen, take care and keep writing those very specific, very well-done articles because people like me really appreciate them. So thank you.
Marcus Drake: Thank you so much, Alan.
Alan Wein: Take care, my friend.
Marcus Drake: Brilliant.