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Jim Hu: Hi, I am Jim Hu, Professor of Urology at Weill Cornell Medicine. I'm delighted to have the opportunity today to share the Beyond the Abstract with you in UroToday. So let me get my PowerPoint up and running here to share the slides.

Okay, great. So this is a recent publication that we had about factors associated with the recovery of urinary continence. Specifically it's a multi-center comparison of radical prostatectomies performed here at Weill Cornell, with those performed at Georgetown with Dr. Kowalczyk as a key contributor and senior author. The reason for this, the study primarily is that we know that the likelihood of urinary incontinence after radical prostatectomy varies significantly depending on surgeon to surgeon, as well as the fact that it's one of the considerations for men who are considering getting PSA testing.

For example, this is an infographic from the United States Preventative Services Task Force. And cites that of the 80 men who have a positive biopsy that choose surgery or radiation therapy, starting out with a large number who get PSA testing, of those 80 men who have definitive treatment, 15 out of those 80 or 19% will experience urinary incontinence. So of course, that's a significant number of men who will suffer urinary incontinence, and it's estimated in the United States, at least 80,000 men have a radical prostatectomy on an annual basis. And so you can imagine that that affects a high number of men and that's permanent lifelong.

One of the techniques that's been introduced, and this was described by Dr. Kowalczyk and his team in European Urology, is the use of a posterior approach to pelvic fascia sparing. So in this figure, this is opening up the cul-de-sac in the peritoneum, and you see that the seminal vesicles being suspended by the sutures as well as the space being created behind the prostate on the rectum. And so with this approach, this posterior approach, we are getting behind the prostate, then dissecting circumferentially or around from posterior to anterior, and then in that fashion skiving under, dissecting underneath the pelvic fascia in order to spare the overlying endopelvic fascia.

Viewed differently, this is now a sagittal view of the dissection. So the traditional anterior approach with non-pelvic fascia sparing, of course, the bladder neck dissection is performed with my cursor showing that dissection plane, and then the apical dissection. So this overlying fascia and the dorsal vascular complex that comprises the structures, or that comprises some of the structures underneath and within the endopelvic fascia are taken along with the specimen. Whereas that posterior approach, or what's also known as retzius sparing because you're not entering the retropubic space, that approach goes behind the bladder as we saw, and then goes just hugging the anterior contour of the prostate to spare that overlying connective tissue. The downside of this approach is there is a learning curve associated, and it's a smaller working space, which may impact particularly the ability to dissect out larger prostates.

This is yet another view. So the traditional approach, again, typically at the base of the puboprostatic ligament, the apical dissection is performed. And so this is just showing that this fascia is dissected cleanly here as well as at the bladder neck. And it's left on top of the prostate and sent en bloc with the prostate. Whereas again, with the retcia sparing, we're coming down and we're dissecting underneath the endopelvic fascia, and therefore sending the prostate without that overlying fascia which is left in the patient.

So what do we know about the literature? Well, there was a master called The Master Study, which was a systematic review of meta-analysis. This was performed recently in 2022 in which studies were reviewed and essentially a meta-analysis was performed. And the meta-analysis essentially shows, and you can see these different diamond shapes that represent the odds ratios here, and so basically it shows that the likelihood of immediate continence is 1.8 relative risk versus the standard approach. And then at the other time points three months, six months and 12 months, there was no difference. That is the hazard ratio, the rest of the 95% confidence interval of the relative risk all crossed one, so therefore there was no statistical significance. And so the meta-analysis show that there's good immediate continence with catheter removal.

Further outcomes that were assessed and reviewed, there's no difference in immediate erectile function. However, with PT2 or pathologic T2 stage disease, there was a greater likelihood of positive surgical margins. And you can see that again based on that relative risk of 1.39 with the 95% confidence interval, again not crossing one. So finally, in terms of T3 disease, there was no significant difference in the likelihood of T3 disease when you use a post-year approach or a retzius sparing approach to dissect out the prostate versus the standard.

And so this then leads to the background of conducting the study again with Georgetown. And we also included an anterior pelvic fascia sparing approach, which I'll show you, but basically it's just an anterior approach to dissecting that fascia off the prostate and leaving it in the anatomic position. And this was the most recently adopted approach. And so this explains why the sample size is smaller than the standard approach, which was began 10 years ago, and the posterior approach to pelvic fascia sparing. You can see the age of the patients ranged a bit in the sense that with the more recent patients with the anterior approach, these patients are older. On average four years older than the posterior approach, as well as the standard approach differed by two years.

There was also some differences, for example, in the prostate volume which has gotten smaller over time. There's some differences in ethnic variation or race variation from the two approaches.

Also, we can see that the anterior approach to pelvic fascia sparing was performed exclusively at Cornell, whereas in a small number of the pelvic fascia sparing with the posterior approach or the retzius sparing was performed here with the majority at Georgetown. And the biopsy grade group changed over time in the sense that with the standard approach, for example, 15% of these patients were grade group one or Gleason six. With the increased use of active surveillance, you can see progressively then the posterior pelvic fascia sparing approach was introduced. And then more recently, like I said, in the last two and a half, three years, the anterior pelvic fascia sparing approach came to be adopted, and so against the lower likelihood of operating on biopsy grade group one.

So in terms of the perioperative outcomes, really I think the key things worth highlighting is the anterior pelvic fascia sparing average time, median time rather was 146 minutes, 152 for the posterior pelvic fascia sparing, and 165 for the standard approach. We can see that we performed less non-sparing surgery over time as compared from standard to the posterior approach. Again, I pointed out the differences in operating on more aggressive disease, which is also reflected from the biopsy pathology to the radical prostatectomy pathology grade. In terms of surgical margin status, we noticed that there are, and it's focal positive margins and non-focal positive margins. When we look at least the posterior approach to pelvic fascia sparing, the 23% appears to be higher than the 14% for the anterior approach, and the 17% for the standard. The non-focal positive margins, and again this may be because of operating on more aggressive disease over time was slightly higher for the posterior approach as well as the anterior approach to pelvic fascia sparing.

And then when we look at our primary outcome, that is the recovery of urinary continence with continence defined as zero to one pads. You'll notice that the blue bar represents the posterior approach. The gray bar represents the anterior approach, the red bar is the standard. And so you can see that initially up front, the posterior approach has better continence, although I'll mention that and I'll come back to this when we talk about limitations, the Georgetown group assessed continence shortly after catheter removal one week later, whereas we assessed at Cornell, continence at the three to four month mark for the majority of our patients. And so that results in a little bit of a difference there.

But with that being said, you can also see that there are statistically significant differences when we compare the recovery course and trajectory of all these three different approaches with the standard being the slowest recovery. And then as we approach the 20-month mark, again, because of limited follow-up really for our anterior approach patients, we can see the gray line or the anterior line trajectory really capturing or catching up to the blue line, the posterior approach.

And then when we look at that for using a zero pad definition of urinary continence, again, you see similar things. That is beyond the one and a half year mark, the lines for continence are all the most overlapping. Similarly, there's a distance or there's a gap of roughly, what is that? A little over 15, over 15% difference as you compare it to the red line or the standard approach.

So this is the multivariable logistic regression. Now looking at factors associated with the zero to one pad continence definition in terms of recovery. And I'll just go through this very briefly because you can see here the highlighted areas that are significant, and this mirrors a lot of the findings when we look at the zero pad definition as well. But essentially, you see that older patients are less likely to recover urinary continence, again using the zero to one definition. Larger prostate or volume or higher prostate volume per 10 CCs was associated for every 10 CC increment that affected the odds ratio of recovery of urinary continence. Also, when we look at case experience or every 10 cases, that improves the likelihood of your recovery of zero to one pad continence. And when we specifically compare the surgical approaches, you can see that the odds ratios for the posterior pelvic fascia sparing range from 3.71 at three months, 3.57 at 12 months, and then at the 20-month mark, it's three times higher odds of recovery.

And then finally, with the anterior approach possibly being due to limited follow-up or smaller sample sizes, particularly at 20 months of follow-up, you can see there's only a trend there, 1.88 with a P value of 0.06. However, the odds ratios at three and 12 months aren't as high as the posterior approach, but certainly are significantly higher and better magnitudes better than the standard approach.

Again, I mentioned earlier the zero pad continence definition. This is now the adjusted analysis, multivariable analysis. And you can see that again, age now across all recovery time points, older ages associated with lower odds of recovery of urinary continence, higher body mass index, also associated with lower odds of recovery. Again, parallel to what we saw before, larger prostate volume, less lower odds of recovery of continence, zero pads in this case again. And then a higher case number experience per 10 cases was associated with better recovery of continence at three months and 12 months. A trend at 20 months. And we may see that may reach statistical significance as we have more cases that attain that 20 month follow-up timeframe.

Here, nerve sparing, now again, at the zero pad definition, we see that complete nerve sparing has a higher odds of recovery across all three time points as compared to partial or non-nerve sparing. And again, the strongly significant recovery of urinary continence zero pads with the posterior pelvic fascia sparing approach, ranging from almost four times higher odds at three months to 2.25 higher odds at 20 months. And the anterior approach having almost two-fold higher odds of zero pad continence at three months. And so this again differs from the earlier meta-analyses that I showed you where there was only a significant improvement in continence shortly after catheter removal, as compared to our follow-ups here at three, 12 and 20 months.

So what are the limitations of the study? And I highlighted this earlier, that is the anterior pelvic fascia sparing approach has the shortest follow-up timeframe and therefore the smallest sample size. So that may limit our ability to detect significant differences, especially at the 20-month timeframe and beyond. I mentioned earlier Georgetown Group assessed urinary continence within a week of catheter removal, whereas for the majority of our patients here at Cornell, this assessment was first performed at three to four months postoperatively. And of course, this being a retrospective study design, there is the significant challenge of potential selection biases.

And that may be overcome only with randomized control trials. And I'll just briefly mention that we are in the midst of enrollment for the Pelvic fascia-spARing radical prostatectomy TrIAL or the PARTIAL trial, randomized trial that's funded by the National Cancer Institute. This just gives you a diagram of the primary outcome that we're assessing, which is surgical margin status, as well as looking at biochemical recurrence up until within a two-year timeframe. Secondary outcomes we're looking at patient reported outcomes such as health-related quality of life, as well as adverse events, surgical complications.

And then specifically number three is to look at differences in penile deformity. That is penile shortening or Peyronie's disease, as well as inguinal hernias as the posterior approach may have some advantages in, and as I showed earlier, preserving the dorsal vascular complex, and avoiding dissection into the retropubic space, which has that increased risk of inguinal hernias.

This is our inclusion and exclusion criteria. And finally, I'll just mention that this is a non-inferiority study designed to compare cancer control in terms of positive surgical margins, as well as to gather biochemical recurrence free survival and comparing this amongst the three approaches. That is the posterior pelvic fascia sparing which is performed largely at Georgetown. Other three centers that are actively enrolling include us as well as Johns Hopkins and Northwestern, which was depicted earlier on this schematic. So again, this just shows some of the instruments that we're using to measure urinary and sexual function, for example, the Memorial Sloan Kettering domain. To do that, we're also looking at decision regret and comparing that by surgical approach. As well as I mentioned earlier, the penile shortening or Peyronie's disease and inguinal hernias as well.

This is the milestones in terms of projected and enrollment and when study cessation would be. We anticipate 100% enrollment of our subjects with a sample size of 600 by October 2026. So thank you for your attention. Again, in summary, we found that using a multicenter retrospective study design that the posterior approach to pelvic fascia sparing, also known as reticence sparing and the anterior approach, which is also known as the hood technique, both improve the recovery of urinary continence as compared to the standard approach.

Also, finally, highlight that this is the largest study of urinary continence to date comparing pelvic fascia sparing approaches versus a standard approach. And it's also the first study really of this sample size and multicenter study design to compare anterior pelvic fascia sparing versus posterior pelvic fascia sparing. But we await the results of the randomized trial that will minimize some of these potential selection biases inherent in a retrospective study design. Thank you again for the opportunity to share Beyond the Abstract to the UroToday audience.