Stewart, take it away, and thank you so much for being with us.
Stewart Whalen: Many thanks to you, Dr. Wein, and for UroToday for inviting me on here. I'm just going to briefly talk about this paper that we published looking at the urodynamic findings in patients with DU before and during a trial of sacral neuromodulation.
This will be very familiar to most of the listeners here, but SNM is an established treatment for DU and non-obstructive retention. The mechanism in DU remains unclear, and, unlike in DO where we have very strict criteria to denote a successful SNM trial, we really don't have that in DU. It's still a bit of a mystery as to who does well here. Our objective was to investigate the effects of SNM on DU patients during a staged SNM trial.
We did a retrospective chart review on patients who had been diagnosed with detrusor underactivity on urodynamics and identified patients that had their urodynamics repeated 10 to 14 days after their first-stage tined lead placement. We excluded patients with obstructed voiding, previous Botox in nine months, and insufficient data for analysis. And then we divided the patients into responders and non-responders. And the definition for a responder we came up with was improvement in baseline voiding efficiency of greater than 50% after the stage one procedure or improvement in detrusor contractility index of greater than 50% after the stage one procedure in those patients who are already fully emptying their bladder. And we did a statistical analysis using the Wilcoxon signed-rank test.
We identified 17 patients. The median age was 72 years. About equal male and female patients. The majority of these patients had detrusor overactivity as well as detrusor underactivity with the smaller number having pure detrusor underactivity. And at the end of the trial, 11 in the DO-DU group and two in the DU group had a battery implanted.
In terms of risk factors for detrusor underactivity in this cohort, the most common risk factor was non-traumatic lumbar disc disease followed by pelvic surgery, diabetes, pelvic radiation, stroke, and we had one patient who had a neurogenic bladder secondary to hereditary spastic paraparesis.
With respect to our main findings in our cohort as a whole, we observed an improvement in the PdetQmax pre and post stage one as well as an improvement, unsurprisingly, in the detrusor contractility index. Responders had improvement in Qmax, PVR, voiding efficiency, and detrusor contractility index without a statistically significant improvement in PdetQmax, and non-responders had an improvement in PdetQmax alone.
This is just a graphic from our paper that I think hits the main points here home. Again, in all participants, there is an improvement in PdetQmax observed without an improvement in Qmax. In those patients we denoted as having had a successful trial or had responded to the SNM trial for the DU component, they had a PdetQmax that approached statistical significance but was not statistically significant and an improvement in their Qmax. And then in the non-responders, they had an improvement in PdetQmax without improvement in Qmax.
This is obviously a small retrospective study, but based on this data, we suggest that the possible mechanisms of action of SNM and DU based on this dataset are inhibition of the guarding reflex and relaxation of the urethra. That would be seen with the improvement in Qmax in those who responded as well as direct strengthening of bladder contractility which we saw in the group as a whole as well as in the non-responders. Obviously, bigger prospective studies would be required to further elucidate these findings, but as a kind of exploratory study, this is what we found and certainly very interesting.
Again, I really appreciate the opportunity to present here and have this chat with you, Dr. Wein.
Alan Wein: Thank you so much. For the mechanism and detrusor underactivity, is the ... First of all, it's one of the few places where I've actually ever seen somebody postulate a mechanism, so that's good. And for inhibiting detrusor overactivity, I gather that it's something different than. It's something that has to do with, obviously, it's sensory blockade, but it occurs somewhere else. In other words, if you have an individual that has DO and DU, and you're applying sacral neuromodulation, and you expect it to work as it does in many of these people, what's the different mechanism for inhibiting DO?
Stewart Whalen: That's a great question, Dr. Wein, and, to me, it's one of the big mysteries of SNM is how can it work for overactivity and underactivity. I think the answer to that question is a bit beyond the scope of this investigation and this paper, but presumably that afferent activity that's being interfered with during the DO process is different than what's happening in DU. And for some reason, it does seem to work for both. And again, that's not something that I can totally explain and something that would be kind of beyond the scope of this paper.
Alan Wein: Are there any predictors? Can you do a pre-procedure urodynamic study and look for a particular phenotype, let's say, in somebody that has detrusor underactivity in which you think SNM is going to be successful?
Stewart Whalen: Absolutely. That's something that my fellowship director, Dr. Ghani, has published previously, and the main thing to look for on urodynamics, if you're considering SNM in someone with DU, is going to be their pre-procedure contractility. If you have an acontractile bladder, the likelihood of a successful SNM trial is going to decrease very significantly. The most important aspect for counseling and kind of predicting a successful trial is going to be that pre-operative bladder function and really looking for some degree of contractility on the pre-op urodynamics.
Alan Wein: Yes. For these patients where you're trying to define bladder outlet obstruction on the basis ... Let's say men because in women it's different. There are no norms that everybody agrees on. But in men, if you're trying to exclude ones that have bladder outlet obstruction, how do you do that when a patient doesn't have very good detrusor contractions? In other words, let's say they have a low bladder contractility index, a low P detrusor at maximum flow. How do you exclude obstruction in those people?
Stewart Whalen: That's an excellent question. It's something that for sure I struggle with. Obviously, you have an underactive bladder. You're never going on the plot, right?
Alan Wein: Exactly.
Stewart Whalen: I think that's where it becomes important to correlate your urodynamic findings with your cystoscopic findings as well. If you have a patient who has seemingly underactive bladder in the urodynamics but with a very large obstructive-looking prostate, I think in those instances I would certainly advocate for doing an outlet procedure as a first step and seeing where you get with that before moving on to a trial of sacral neuromodulation.
Alan Wein: Because I think that that situation arises. In those patients, if you did an outlet-reducing procedure, and let's say you made a big hole, let's say with a HoLEP, enucleation, and it didn't work, then would you try sacral neuromodulation in those patients?
Stewart Whalen: I think I would. Absolutely. I think we've seen now recently in a lot of studies showing patients having good outcomes with HoLEP or outlet procedures who have very poor preoperative contractility. Presumably, those patients are just able to strain, and the reduced outlet resistance is allowing them to empty reasonably well, but that's not going to do anything for the contractility in the bladder.
Again, I think this is very small study, but this and several other studies that have looked at SNM and DO have actually shown that it improves the contractility. I think if you do have a patient that's had an outlet procedure and is still not voiding well, that there's very little to lose with a trial of SNM.
Alan Wein: Are there any other types of neuromodulation, any other nerve that you could stimulate, that works for detrusor underactivity?
Stewart Whalen: Not that I'm aware of. I know peripheral nerve or PTNS has been suggested, but I'm not really aware of any data. You may know a bit more about that-
Alan Wein: I don't.
Stewart Whalen: Fair enough. But I'm not aware of any other type of stimulation that's been proven to be efficacious in DU.
Alan Wein: Super. Well, listen, thank you so much for your time. We appreciate the information. I know it'll be very interesting to folks who watch this because the patient who's in supposed non-obstructive urinary retention is a real problem. Listen, thanks so much for your time, and we appreciate your appearance on UroToday.
Stewart Whalen: Thanks so much. I really appreciate the opportunity.