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Sam Chang: Hi, my name is Sam Chang. I’m a urologist in Nashville, Tennessee, at Vanderbilt University, and we have the honor of having Dr. Jen-Jane Liu here. Dr. Liu is the director of urologic oncology at the Knight Cancer Institute at Oregon Health Sciences University. She is also an associate professor in the Department of Urology there. And most importantly for our session today, she basically led a session in the SUO 2024 meeting in Dallas, Texas, focusing on muscle invasive bladder cancer and looking at actually the long-term implications of therapeutic interventions, as well as follow-up, as well as overall success of disease management.

And so we’re quite fortunate to have Dr. Liu give us the highlights of that session. So Dr. Liu, you’ve given me the permission to call you Jen. Please call me Sam. We look forward to you hitting the highlights of that session that you led, which was truly one of the highlights of the meeting.

Jen-Jane Liu: Well, thank you so much. And I really appreciate the opportunity to share our talks and also to UroToday. So I’ll just jump right in. So our first talk was from Dr. Mamta Parikh at the University of California at Davis. She gave a really great talk looking at the changing landscape in muscle invasive disease for perioperative systemic therapy. So the big buzz was about the NIAGARA study, which was the addition of durvalumab to a cisplatin-based regimen for patients with muscle invasive bladder cancer, which did demonstrate an improved event-free survival.

What I thought was particularly interesting, however, was the highlighting of several other studies looking at the platinum-ineligible population, which traditionally we don’t have a lot to offer. She highlighted the use of ADCs, so the enfortumab-pembrolizumab data is hotly anticipated given its success in the metastatic setting. But other ADCs, for example sacituzumab, are undergoing study in combination with immunotherapy.

Other forms of chemotherapy for this population, as well as the use of targeted therapies based on mutational status—FGFR and HER2, for example. Particularly interesting is the addition of intravesical therapy to this space, which has traditionally been in the non-muscle invasive space. And I think that there will be several studies such as that will change this paradigm for us moving forward. And it’s nice to see lots of options for patients.

Next, we looked at some of the technical complications associated with radical cystectomy, and I have to admit that I suffer from these just like others that do the surgery. Ureteroenteric strictures are an unfortunately common problem, and Dr. Hadley Wyre from the University of Kansas really highlighted some interesting and important aspects to preventing these. So here, he’s demonstrating the blood supply to the ureter and showed some interesting data about how ureteral resection length correlates with ureteral strictures, and also highlighted the importance of ureteral rest when managing these. And as you can see, when we do these surgeries, we basically devascularize this distal part of the ureter, so it makes sense why resecting more could help reduce stricture rates.

The other complication he addressed was parastomal hernias. He discussed the data demonstrating the benefits of prophylactic non-absorbable mesh, but I thought his algorithm for management of these hernias was particularly interesting once they occur, particularly highlighting the use of the retro-rectus space in this population to help treat these hernias, and how having a longer conduit to work with is particularly beneficial for reconstructive urologists.

Trinity Bivalacqua from the University of Pennsylvania also gave an excellent talk about long-term survivorship complications related to sexual dysfunction. He highlighted some of this data from the Cleveland Clinic showing that in the male population post-cystectomy, there is a very high rate of sexual dysfunction. And he also demonstrated that despite advancements in radical prostatectomy, where there’s a high rate of nerve sparing, that’s really not as commonly done in cystectomy bladder cancer patients. And in fact, pharmaceutical data demonstrates that prescription of these drugs post-cystectomy happens at low rates in male patients.

And there is a disparity in female patients, so the top graph highlights counseling in patients prior to radical cystectomy. The yellow bars represent female patients, so they have a high rate of baseline sexual dysfunction, which then also translates to a higher rate of sexual problems post-cystectomy. And despite this, in a survey study of the Society of Urologic Oncology members, many people do not routinely counsel female patients regarding sexual function after cystectomy.

Things that we can do to help reduce sexual dysfunction include reproductive organ sparing and nerve sparing, both of which are oncologically safe and appropriate. However, the majority of urologic oncologists surveyed do not actually perform these endeavors in these patients.

So take-home messages, the landscape in muscle invasive bladder cancer: systemic therapy is changing rapidly. Hopefully, that will translate to lots of different options to meaningfully improve survival in our patients. Radical cystectomy will continue to be a mainstay of treatment, and so we need to, as surgeons, continue to evolve to improve our techniques, to decrease the morbidity and prevent long-term complications.

And survivorship as it relates to sexual dysfunction is an underrecognized problem that we can do better in terms of counseling our patients. And also, there are surgical techniques that we can use, particularly in female patients, to help reduce the risk of sexual dysfunction post-cystectomy.

Thank you so much for this opportunity to present the wonderful speakers and their talks from the SUO meeting.

Sam Chang: Jen, that was a great overview. I think your conclusion slide really hit the key points. And so I’m going to go actually from the last talk and then move up. When you look at sexual dysfunction, I think the very first point that was emphasized is we don’t ask about it, we don’t talk about it. And honestly, as urologic oncologists, we probably really don’t know much about it.

We focus on it so much for nerve sparing radical prostatectomy. But when it comes to cystectomy, both in male and female patients, I think we really do a disservice in terms of under counseling and underappreciating. Now, after that talk and probably even before that, tell me how you counsel and what you do for your female patients as they are about to undergo cystectomy.

Jen-Jane Liu: A big part of my counseling has to do with if they’re sexually active, their menopausal status, which in many bladder cancer patients they are postmenopausal. And I routinely perform reproductive organ sparing unless there’s an oncologic contraindication, such as significant urethral or bladder neck involvement. And we discuss the benefits of doing so as well as performing nerve sparing.

And I do try and prepare them with the expectation that sexual dysfunction is common, and that afterwards we don’t have a lot of very effective treatments for female patients. And so things like counseling, having healthy partner expectations, those are all important in terms of setting the expectations to maximize our outcomes.

Sam Chang: Yeah, I know, I think those are really important points. When it came to the complications talk, I smiled when you said that you were familiar with these. I think my middle name is complications associated with cystectomy. And one thing that we really focus on from strictures, I feel like, I think we do a fairly good job and we’re learning. When it comes to parastomal hernias, I still have no idea what to do and how to avoid them. And I think they’re really underreported.

And unfortunately, the trials looking at pre-placement of different things just hasn’t really panned out to be really, really helpful. But let’s talk about some of the key points you raised—some that totally make sense. The whole idea of ureteric stricture length. The more distal ureter you remove, the less likely you have a stricture. What was never really discussed, though, is the more you remove, the more difficult your anastomosis can be.

And so then the question is, do you struggle with anastomosis on tension, or perhaps not the best possible sutures, versus a little bit easier, a little bit better visualization, and the idea of using the fluorescein and different things to have an idea regarding vasculature? I think whatever we can do to decrease strictures makes sense. I know when we started with not only intracorporeal robotic cystectomy, making these small incisions, you saw those diagrams of the ureters coming out of these small incisions, and there’s no question. And we talked about how high our stricture rate was initially doing robotic cystectomies. So tell me your strategies when it comes to your ureteroenteric anastomosis.

Jen-Jane Liu: So disclaimer, I do have strictures also. [LAUGHS] I have not figured that out. And as I said, I just wish that I lived closer to Dr. Wyre, and that I could refer patients to him. But no, so I think that he made a lot of really great points. I do routinely remove more ureter now because I do an intracorporeal diversion, so I feel like that is a potential advantage. I also use ICG and the Firefly because I do my cystectomies robotically. Although there is some data that shows that that’s beneficial, there have also recently been some studies that question the added benefit. It’s low-risk. So I feel more comfortable if I have that information.

Sam Chang: Agree totally. Why not? It doesn’t detract from anything, so the fact that it may or may not be helpful, I agree with you totally with that point.

Jen-Jane Liu: I also think that there is some data about the learning curve with intracorporeal diversion, particularly in the retrospective data from Roswell Park where they showed that they really had more strictures early on. That’s a tough thing to overcome because everybody has one.

And I do also agree with the no-touch technique that Dr. Wyre mentioned. And I perform an interrupted anastomosis, which when you’re learning intracorporeal is pretty painful to watch yourself do. But I do think that allows more blood supply to get through, although I know that the randomized data in that setting from Dr. Steinberg’s group didn’t show a statistically significant difference. As I’ve become more facile with it, I don’t feel like it adds that much additional time.

And then the last concept that I’ve been toying with and thinking about is, how much do we need these ureteral stents? I’m not the bravest surgeon out there, but I do think there is more and more compelling data, both in the open and robotic setting, that suggests that shorter duration or no-stent placement may reduce stricture rate. And again, that’s a balance because you want to feel confident in your anastomosis, and that you don’t have a urine leak if you’re going to make that leap.

Sam Chang: We have really, really good points. It makes me think that with the ureteric anastomosis, so many different techniques, and that type of thing, it tells you that we still haven’t struck on the gold standard of what to do. And I think those are really, really good points.

Jen-Jane Liu: The last thing I’ll say is that if they have a stent from obstruction, I do try and get that out. Usually, many patients after receiving chemotherapy will have a relief of their obstruction, and you can get the stents out. And that gives a period of ureteral rest, just because the ureter is easier to work with intraoperatively then.

Sam Chang: I think that’s a really important point. Good point. So now with the changes with neoadjuvant chemotherapy and options, tell me how you integrate medical oncology into your practice as you diagnose these patients with muscle invasive bladder cancer.

Jen-Jane Liu: So we’re really fortunate at OHSU. We have a fantastic GU multidisciplinary clinic. And patients that have muscle invasive bladder cancer are automatically screened on referral into this clinic, where there’s a urologic oncologist, a medical oncologist, and a radiation oncologist. And that enables us to really give the patient the full view, and also optimally screen them for any clinical studies that they may be eligible for.

As the landscape gets more complicated, I think cooperation and multidisciplinary approaches are even more important because it’s hard for us. It will become harder and harder for us to just have a binary approach of chemo, no chemo. And so there’s going to become more and more different options, and particularly as some of them straddle the perioperative space—for example, in the NIAGARA study, part of the immunotherapy was given in an adjuvant fashion. And so I think that we really need to work closely with the medical oncologists to understand and optimize therapy for these patients.

Sam Chang: Yeah, hugely important as we integrate so many different therapies early in the disease process and later in the disease process—I think for all our... I mean, look at kidney cancer, look at prostate cancer. Now, bladder cancer has obviously exploded with different treatment options for non-invasive disease or invasive disease or metastatic disease. So I think your point is actually a really good one, and only to the benefit of our patients as they consider escalating, de-escalating treatment. Having all those different multidisciplinary inputs gives us a better idea of where we go next, and what we need to do next.

So Dr. Liu, thank you so much for spending some time with us. The session that you led helped surgeons, helped oncologists, helped all those caregivers as they contemplate different things in terms of the therapeutic interventions and the consequences of these treatments. And so we really appreciate the time you spent with us today, but also how you led that session of SUO.

Jen-Jane Liu: Thank you so much for the opportunity, and I really have to thank all of our fantastic speakers and of course, our wonderful members of the SUO who contributed to making it such a great session.