Tufan Tarcan: Alan, thank you so much. Thanks for having me. It's such a big pleasure for me to be here. Thanks for the opportunity, because I think this is a very important discussion now going on in functional urology. Before I go into the details of the FUTURE study, I would like to share with you the publication that we had recently about how to assess the value of the urodynamic studies. As you know, Alan, we have recently published in Neurourology and Urodynamics, how should prospective research be designed to legitimately assess the value of urodynamic studies in female urinary incontinence? The thing is, the Oxford University Centre for Evidence-Based Medicine does not consider the RCTs appropriate to assess the value of the diagnostic tests. Usually, if you look to the other parts of medicine, we see that diagnostic tests are usually judged by observational studies. But still, if someone wants to assess the value of the urodynamic studies with RCTs, then there should be some rules and principles on how to do that. First of all, the study population must reflect its real-world counterpart. This is especially important in stress urinary incontinence patients in women, where the index or so-called uncomplicated patients are actually the minority of the real-world counterparts. Then, the clinical endpoints should not only include urinary incontinence, but also other types of symptoms such as voiding difficulty, for example, or overactive bladder. The interventional arm must receive individualized management based on urodynamic findings.
But what many studies do is they allocate the patients from the beginning to a certain treatment arm and they do ignore the urodynamic findings. The patient ends up with allocated treatment whatever the urodynamic study says. This is against the philosophy of urodynamics, because urodynamics are not for populations, urodynamics are for individuals. Then, if you want to have a control arm, which is, of course, something good for RCTs, otherwise, they're not called RCTs, the control arm is ethically very problematic, because in the control arm, you have to ignore the urodynamic findings, which is not always possible. If there is a patient who certainly needs urodynamic findings and when you diagnose a problem in the urodynamic study, how are you going to ignore it or how can you continue with, for example, if it's an invasive treatment in this patient who certainly needs a urodynamic study? Establishing a control arm has always been problematic, and so far, no study in the literature succeeded in achieving an optimal control arm in the RCTs. Statistical power should be sufficient and this is certainly imperative for the findings of this study to be valid. And finally, we need a long-term follow-up in these studies. We know that when we talk about even the mid-term follow-up, we then should have at least a two-year follow-up after any type of treatment. Again, we are talking here about the diagnostic study, not about the treatment.
And, if we want to design an RCT on the diagnostic test, that is today a urodynamic study, we have to respect all these principles. Now, about the FUTURE study. The FUTURE study is a UK multicenter superiority RCT, which aimed to assess whether urodynamics is needed routinely in female refractory overactive bladder, and it was published in The Lancet in March 2025, with the principal author, Professor Abdel-Fattah, who is a good colleague and friend of mine. Women with refractory overactive bladder from 63 UK hospitals reaching a total number of 1099 were randomized into two groups. One arm was urodynamic study plus a comprehensive clinical assessment arm, whereas the other arm was clinical assessment alone. At 15 months, participants reported management success and cost-effectiveness were not superior in the urodynamics arm versus the clinical-assessment-only arm. The authors concluded that urodynamic studies were neither clinically superior to clinical assessment alone nor cost-effective in this patient cohort. They also stated that the FUTURE study will change clinical guidelines, and that, from now on, invasive treatment, for example, such as botulinum toxin, will be offered to this patient population on the basis of clinical assessment alone. There are some issues that we have to discuss from the beginning of the study. Some misjudgments, for example, the FUTURE study assumes women with refractory overactive bladder are essentially all the same, but we know that that is not the truth. It's not true for overactive bladder patients or refractory overactive bladder patients. This is a heterogeneous diagnosis with multifactorial pathophysiology, and there is no single recipe that will work for the whole group of overactive bladder patients. And, like unfortunately, other RCTs in this area that you have mentioned in your introduction, this study tries to judge the value of the diagnostic test using the outcomes of therapy.
This is, by itself, contradictory, and it views diagnostic insight as irrelevant and it doesn't use the findings of urodynamics to guide the treatment in their study. It's very interesting that the success rate, the overall success rate, was very low. We see the same in the ValUE study. In the ValUE study, for example, the dry rate was about 70%, and I remember that I read your editorial, Alan, about it, mentioning that no urologist will be happy with such a dry rate after a mid-urethral sling surgery in so-called index stress urinary incontinence patients. Here, we have a success rate in both arms that is less than 25%, and we do not know whether this is a result of a maybe unusual refractory population or this is a usual refractory population or maybe this is due to a poor treatment choice. Still, the authors conclude that urodynamics is useless in all women with refractory overactive bladder. Again, I'm trying here to show all the similarities with the ValUE study, because I see that there are principle errors shared by the two studies. We know, again, diagnostics don't fix problems themselves, so using treatment outcomes to judge them is always conceptually problematic. But still, if you want to do that, the treatment choice must clearly be concordant with the findings of the test, which is the urodynamic study. In the FUTURE study, we don't have very thorough information about the urodynamic findings, because urodynamic studies were used only to detect the presence or absence of detrusor overactivity. We don't see any information about other urodynamic parameters, such as, for example, bladder outflow obstruction or detrusor underactivity or compliance problems. We know the presence of detrusor overactivity or the absence of detrusor overactivity is not a very strong parameter for us to decide on our further treatment; however, the other urodynamic parameters are.
Interestingly, the majority of patients in both arms ended with botulinum neurotoxin. This is basically a one-size-fits-all approach. This is opposite to the current trends in overactive bladder management. Now, we are always talking, especially in recent years, how can we increase our success in the treatment of overactive bladder patients, and I think everybody agrees here that an individual approach for overactive bladder treatment success is necessary. Here, we need to personalize the treatment. In order not to personalize the treatment, then you miss the whole point of urodynamics. And then, as I said in the beginning, urodynamics are not for populations, they're for individuals. If you want to assess the value, you have to respect the findings of the urodynamics, and you cannot do it if you ignore the findings of the urodynamics in this study. But still, despite all these, let's say, limitations, we see that in the FUTURE study, urodynamics still changed the diagnosis in 13% of patients from presumed overactive bladder to stress urinary incontinence, enabling management based on the real cause of their symptoms. Another interesting finding is the same level of success is achieved with less invasive therapy, because women in the urodynamics study arm achieved the same level of patient satisfaction with 59% use of botulinum neurotoxin versus 72% percent in the control arm. With urodynamics, the patients received the same success with less invasive interventions. However, there is no discussion going on on this important finding. When we look at the literature, what do our observational studies say? I've selected here two. One is from Verghese and Associates, the other is from Serati M and Associates.
They both have shown that, when you use urodynamic studies in overactive bladder populations, you achieve a greater satisfaction rate in patients who were treated according to the urodynamic study findings compared to patients who were treated empirically. Another interesting observation is, although the word routine is actually hidden in the FUTURE, the FUTURE stands for Female Urgency Trial of Urodynamics as Routine Evaluation, unfortunately, we don't see or read the word routine anymore in the text. In the publication, the text does not mention the word routine. I certainly agree that urodynamic studies are not routinely indicated in overactive bladder patients. No question about it. But not routine does not mean never. You can just compare it with cardiology, for example. Certainly, not every patient needs ECG, but it doesn't mean that no patient actually needs ECG at all. Especially, we have to remind ourselves that we are talking here about overactive bladder with not completely understood pathophysiology with heterogeneous background of etiology. Still, I think we should mention here that in overactive bladder patients, urodynamic studies should be needed selectively in this patient group. Again, talking, for example, about the UPSTREAM trial. The UPSTREAM trial mentions that we need urodynamic studies selectively. It doesn't claim that we don't need urodynamic studies in patients with male LUTS anymore, but it indicates urodynamic selectivity, so I think we need that kind of approach in our patients with OAB.
Unfortunately, I'm sorry that I have to say this, but this study appears to be designed not for science but more for payers. It looks like just an attempt to eliminate urodynamic studies in the treatment of refractory overactive bladder patients before proceeding with more invasive treatments. Although, in the FUTURE study, a considerable group ended up still with conservative treatments and with physical therapy. In summary, the FUTURE study claims that urodynamics can simply and safely be skipped in all women with refractory overactive bladder, and I find this is a very risky statement. In contrast to the title of the study, which is the FUTURE, this is actually a move back towards empiricism and that belongs to the past in the management of overactive bladder, but not to the future treatment of overactive bladder. Thank you.
Alan Wein: Wow, that was terrific. And I think for all students and all people who are aspiring to be reviewers and editors, this shows you what a careful review of an article by an expert can do in pointing out some of the inconsistencies in the primary argument. Whenever people are absolute, I mean Professor Tarcan is absolutely right, you have to wonder, is their absoluteness correct and why are they doing that? Now, there have been studies also about BPH and about stress urinary incontinence, and I'm assuming that if you read, if we had you back to discuss each one of those, that you would have similar problems accepting the primary conclusion that, "Hey, it's not of any value. Don't do it." Is that not correct?
Tufan Tarcan: Yeah, I completely agree with you, Alan. For example, I've mentioned the ValUE study. I can also add the VUSIS-II trial that assessed the value of urodynamic studies in the so-called index stress urinary incontinence female population. We had similar problems there. For example, in the ValUE study, actually the urodynamic studies changed the clinical diagnosis in more than half, namely in 56% of the cases. The study found voiding dysfunction in the so-called index group in 10% of the patients. This is such a paradox, because if you look at the guidelines, for example, AUA or EAU guidelines, they say, if you suspect voiding dysfunction, perform urodynamic studies prior to surgery for female stress urinary incontinence. I think it's very interesting to say that although there's 10% risk of voiding dysfunction, the urodynamics do not help you with the diagnosis. The problem is, in the ValUE study, the patient groups with and without voiding dysfunction, the statistical difference was very close. But because the study was not well-powered, it did not show a statistically significant difference. If we had a study well-powered, we certainly would find that patients with voiding dysfunction, unfortunately, do worse after female stress urinary incontinence surgery, and there are so many observational studies in the literature saying that. The other funny thing, for example, if you go into the detail.
Okay, urodynamic studies, it showed voiding dysfunction, let's say, detrusor underactivity. We see that in a certain group of patients, the urodynamic studies changed the type of mid-urethral synthetic slings. In some numbers, the TOT was changed to TVT, and in other groups, TVT was changed to TOT. Actually, it changed the surgical behavior of the surgeon. It depends on whether the surgeon thinks that the patient has an intrinsic sphincteric deficiency or detrusor underactivity, where the surgeon would choose maybe less obstructive surgical solutions compared, for example, in ISD patients, more obstructive patients, etc. Again, as I tried to elaborate in the beginning in this slide, how should your study be designed if you want to scientifically assess the value of the urodynamic studies? The control arm should be blinded, but that is not possible ethically here. Again, we should not forget that we are talking about a diagnostic test here. RCTs are very good options for our treatment options, but not for diagnostic tests.
Alan Wein: Well, that was a terrific discussion, and again, we thank you very much. I think, for everyone who watches this, you now know how to read an article about urodynamics critically, and I think that's one of the great things about your expertise, is that you and a very small group of people throughout the world can look at these articles and point out what's fact and what's fiction and what's opinion rather than fact. Listen, my friend, thank you so much. We really appreciate it.
Tufan Tarcan: Thank you, Alan, for this opportunity. It was great discussing with you all these issues and I've learned so much from you in my career and I appreciate it all. Thanks a lot.
Alan Wein: Thank you.