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Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a Urologic Oncologist at the Georgia Cancer Center. I'm delighted to be joined on your show today by Dr. Trinity Bivalacqua, a Urologic Oncologist from the University of Pennsylvania. Trinity, thanks so much for joining us on UroToday.

Trinity Bivalacqua: Thanks, Zach. Happy to be here.

Zachary Klaassen: We're going to discuss your SUO 2024 presentation, a really important topic looking at sexual dysfunction after radical cystectomy. So maybe walk us through a few of the key highlights from your presentation at SUO.

Trinity Bivalacqua: Sure, I'm going to talk a little bit about the incidence of sexual dysfunction following cystectomy in both men and women first, because I think it's important to note that, especially bladder cancer patients, they are a different patient population than our typical prostate cancer patient. They're usually older, they have more systemic comorbidities that predispose them prior to surgery to the development of sexual dysfunction. And this is in both men and women.

This is actually a study out of Europe. Jim Catto looked at a large group of patients from multiple trials—bladder cancer patients that had undergone different treatments for bladder cancer, as in TURBT for non-invasive disease, cystectomy for muscle invasive disease, as well as radiation therapy. And what he found, if you look at the boxes there towards the left, you've got male sexual problems and female sexual problems.

You can see after cystectomy, highly prevalent. The higher the number, the more problems with sexual function. And in women, there was also a high incidence of sexual function problems. But it was different. It was mostly related to sexual intimacy, enjoyment, and actually problems with penetrative intercourse and dyspareunia, which I think we'll talk about a little bit more later. So what this study told us, in a quantitative way, is that it is highly prevalent after bladder cancer treatment.

So next, I'd like to talk about just what we know about sexual dysfunction following a radical cystoprostatectomy in men. And this is just a study that was done about 20 years ago, which was really the first one to use validated questionnaires to quantify erectile dysfunction in men that underwent a cystoprostatectomy. And this is a retrospective cohort. But it's a cohort of men that were young.

So as you can see, the average age in this group was actually 57 years of age, so much lower than the average age of someone undergoing a cystectomy in their early to mid-70s. And these were all sexually active men. And it was striking to me when you look at actually the breakdown: the surgeons only performed one out of three patients, or 33% of the patients that were sexually active, with a nerve sparing operation.

Now, could you imagine if you had a prostate cancer patient with localized disease and you told that patient that is sexually active, "We're not going to do nerve sparing"? So that highlights one of the problems with what we do today and looking at quality of life outcomes in bladder cancer patients. But the reason why I've chosen the article is really because they used the Sexual Health Inventory for Men or SHIM to look at and quantify sexual or erectile function recovery.

And if you look at the bottom, the total IIEF score—so remember that the highest number is 25. If you've got a number of 21 to 25, it's normal erections. And you can see preoperatively all patients had IIEF scores or SHIM scores of 22, so normal function. But looking postoperatively, and this was greater than two years, so these are patients that should have, if they're going to regain function, they would be. And actually all of them were impotent or had problems with erections.

And then the other thing that was striking is that only two out of the 24 patients that they were looking at actually were responding to PDE5 inhibitors, suggesting that really nerve sparing was not performed, or if it was, not done well. Now, this is a study that one of my previous students, Meera Chappidi, who's actually a fellow at the University of Washington, SUO fellow, did. What she did was, actually we hypothesized that patients that undergo cystectomy are actually not being treated for ED postoperatively.

So we looked at the national insurance claims database, and we purposely looked at men that were less than 65 years of age to enrich for patients that were sexually active and looked at all ED pharmacotherapy postoperatively. And actually, what we found was that less than 20% of male patients that underwent a cystectomy were actually being prescribed PDE5 inhibitors or getting intracavernous injection therapy, and less than 5% were getting an IPP at some point.

And then in multivariate analysis, predictors of ED treatment—so those that were going to get ED treatment—were those that were younger than 50 years of age, which makes sense. These are patients that you would want to help with erection recovery, had baseline erectile dysfunction, so they were already prescribed ED meds, so they just continued, those that got neoadjuvant chemotherapy or neobladder diversion.

What this suggests to me is that these are probably smart patients. These are patients that are motivated and really are looking for that. So what these studies demonstrate is that sexual dysfunction is highly prevalent, and we're not actually doing our job as urologic oncologists in treating it.

I'd like to shift gears now to female sexual dysfunction, post-mastectomy. And this is just a schematic. This is actually from Mayo Clinic, which describes an approach to a cystectomy in women, which is a reproductive organ sparing radical cystectomy in which we only remove the bladder and urethra. We do not remove the anterior vagina. We leave the cervix, the uterus, as well as the ovaries in place, in an effort to preserve the reproductive organs and the pelvic floor, as well as doing a nerve sparing operation.

So the neurovascular bundle that innervates the anterior vagina and the clitoris are lateral to the bladder. So in theory, we should be able to perform a nerve sparing operation in women. And actually, the description of a nerve sparing operation in women was initially described in the late '90s, early 2000s. So this is something that has been described. But the question is, is it being adapted? But first, what are the sexual concerns of bladder cancer patients, or women bladder cancer patients?

So once again, a little bit different than males, where we're talking about a functional erection, a rigid erection. The extent of surgery in women can affect all of the woman's sexual response. If that patient undergoes an anterior pelvic exenteration with removal of the anterior vagina, they get loss of the vaginal introitus, they get a shortened vagina. And this can actually prohibit sexual or penetrative intercourse. If a patient undergoes a bilateral neurectomy, they go into a post-menopausal sexual response.

If the distal urethra is removed en bloc with the pelvic floor, the nerves that are innervating the clitoris can be resected, and this actually leads to problems with orgasm and lubrication due to lack of blood flow. And also obviously, just like in men, urinary diversion can affect body image and sexual confidence. So it's actually a lot more complicated in women than in men.

So what we also want to—one of my previous students, she's now a faculty member at NYU, Dr. Gupta, Natasha Gupta, actually asked the SUO, so members of the SUO, we asked urologic oncologists. We wanted to understand what our oncologists were doing in a cystectomy in women, in premenopausal women with localized disease. And we hypothesized that we weren't doing a very good job in counseling women. And we also included men in that survey.

Now, this was electronically administered to the SUO, and it really looked at, assessed sexual health counseling practices, barriers to counseling patients, and operative technique. And what we found in this survey is that 42% of providers do not routinely counsel sexually active female patients about the potential for a reproductive organ sparing operation. And actually, if you look in this top panel, in women is yellow, male is blue.

You can see that 61% of the respondents don't even ask women if they're sexually active or have sexual dysfunction. So we're not even counseling our women. And we are not talking about the risk of sexual dysfunction in women compared to men. So once again, the analogy: could you take a prostate cancer patient and not talk about erection recovery after prostatectomy? It just wouldn't happen. And then we looked at barriers.

So the barriers that our oncologists thought prevented us from counseling female patients as it related to sexual function were that they were older age and probably weren't sexually active. But if we're not asking the patients, how do we know that? Not enough time to discuss it in our clinics. And then the concern that the patient would be uncomfortable, and we don't have enough knowledge as it relates to female sexual function.

So in summary, providers, that's us, are less likely to perform their sparing operations in men, and then we're also less likely to prescribe ED pharmacotherapy post-op. Providers do not counsel female patients about sexual health, and current counseling is inadequate. And what I would say is I acknowledge that as a urologic oncologist—I just happen to also be a sexual medicine specialist—I'm talking to patients about this, but honestly, I don't expect you to do it.

But what you can do is actually refer to someone, either preoperatively or postoperatively, and have enough sense, I would say, to do that, because this is super important to both men and women. And then also, providers do not routinely perform reproductive organ sparing and nerve sparing operations in women. I didn't show you all the data for that, but that's also hard to believe. But it's the case. And I think it's dogma.

When I was training, we were taught you do an anterior pelvic exenteration, period. It wasn't until I became a senior resident and then junior faculty that I personally just started to rethink that process. And we as a community have to reduce barriers to counseling our patients. I personally believe that this is important. And I can tell you from our studies that patients really want it. So we need to be very cognizant of that. So I'll stop there, Zac, and answer any questions that you may have.

Zachary Klaassen: Trinity, phenomenal overview. So much to unpack there, both from the male and the female side. I'll start with the question specific to men. And it seems a little bit of a generic question, but I think it's important. Why are we less apt to discuss ED treatments in patients undergoing radical cystectomy for men versus radical prostatectomy? You mentioned several times. Could you imagine not discussing ED with a prostatectomy patient?

Is it because we think the disease is worse? What are your thoughts on why we're not even discussing it or treating these men?

Trinity Bivalacqua: Yeah. So actually, I've thought a lot about this, and I think because I see patients with prostate cancer and talk to them about surveillance, surgery, radiation. That conversation—it's not that it's less complex or it's not that it's less important than that of with a bladder cancer patient.

But that conversation is—oftentimes, we know the majority of the times that we're counseling prostate cancer patients, we're not talking about death, we're not talking about what you have is, yes, you may have lethal cancer, but we have wonderful treatments that are highly effective. So our conversations are very short as it relates to that outcome oncologically, and then it really shifts into that quality of life and functional outcomes and side effects.

Whereas with bladder cancer, oftentimes have muscle invasive disease. Listen, we're considering surgery, chemotherapy. Here's what your chemotherapeutic options are. What about radiation? Similar conversation in prostate cancer. And then the question about surgery is that a bulk of our conversation is about the complications associated with it. And that's such a laborious process. I think for most urologic oncologists, because we haven't educated them or us—both trainees as well as colleagues—it just falls to the wayside.

And then we're also saying, well, maybe we're just not comfortable doing that. We're comfortable doing it with prostate cancer patients; why aren't we comfortable doing it with our bladder cancer patients? So I think it's a lot to discuss, and you oftentimes have multiple conversations with them. And I think, I personally think we just need to prioritize it because we now are treating bladder cancer more effectively.

So I think we just need to acknowledge that we haven't done a great job in the past. We just need to do better in the future.

Zachary Klaassen: That's a great answer. I think your point about—we look at our visits on a clinic day, the new patient bladder cancer patient always is the longest one. We're covering so much stuff. And you're right, we have to do better about bumping up in the priority list the side effects from a sexual standpoint.

Trinity Bivalacqua: Absolutely. Yeah. I mean, it's something that—and I'll say it again, and I said this both in Dallas and I'll say it here—if you're not comfortable doing it, absolutely no problem. But make it a priority to refer to someone to talk to them about that. And you could even say, "Listen, this is important, I'm going to do nerve sparing. Listen, you are 73 years old, you're sexually active, we're going to do nerve sparing, your chances of recovery are low, but we're going to do it. And then I'm going to get you to someone that can help you in the postoperative period."

Zachary Klaassen: Absolutely, and I want to touch on that point in one second. But I want to ask a question about women. I mean, certainly your data is phenomenal that we just need to do way better. I mean, the organ sparing aspect is huge. We've got great treatments in the non-muscle invasive disease space. At some point, if they fail enough, we may do a cystectomy. That's a great person to potentially do organ sparing. Somebody has a great response to neoadjuvant chemo.

So how do we educate us as SUO members, the majority of people doing cystectomies in this country, how do we get those numbers higher?

Trinity Bivalacqua: Yeah. I think what we've tried to do over the last five-ish years is do our best. And granted, I acknowledge our methods are retrospective, they're survey-based, we're doing things that are not the best level of evidence, but at least they're demonstrating that oncologically it's safe. We've shown in high-stage disease, variant histology, that it's safe. There's no increased positive margins. Overall survival, cancer-specific survival is similar.

What we have to be able to do, Zach—and I can't, and I've tried to quantify this—is intraoperatively, I wish that I and others would be able to say, you know what? These are the factors that we should not be performing reproductive organ sparing. You need to do an exenteration. I don't ever believe we need to take the ovaries out. Chances of metastasis to the ovaries is less than 2%. And I'm sure you've seen it. If it's there, it's there.

Zachary Klaassen: You know it's there, yeah.

Trinity Bivalacqua: You know it's there. So we should be doing a salpingectomy. But that's probably another whole conversation. But we preserve the ovaries, and then the question is, do we do an exenteration otherwise? And I think what we need to be able to do is identify factors that we are doing and that we should be doing in anterior pelvic exenteration, so we can educate. I have not been able to figure that out to date, looking at radiographically, looking intraoperatively.

But I will tell you that high-volume cystectomy surgeons, they know when they can do an exenteration and when you can do an organ sparing operation. And I think that's what the retrospective analyses have told us. So I think it's education. I think if you train your fellows, your trainees, how to do it, it just perpetuates. And then in 10 years, maybe things will be different.

Zachary Klaassen: For sure. And I think an important point to come back to this point about partnering with sexual medicine specialists. I've got a great one here, Dr. Sharita King at MCG. And I know across a lot of our big cancer centers, we have these partnerships. But talk about the people either at small cancer centers, or maybe in the community, or just don't have that access. What's your message to them in terms of getting patients to the appropriate people?

Trinity Bivalacqua: Yeah. I think nowadays, the solo practice groups are probably much less common. Lug pub groups, small community practices, I recognize that there's more generalists and there's more people that are maybe not as specialized, but erection recovery in men in particular, a general urologist can manage and can handle. So if you don't have a sexual medicine specialist, send them to the general urologist that's working in your practice.

For females, that's very different. That's hard. It's really hard. It's probably hard at academic centers to find someone that's doing that. And what I've learned over the years is that if you don't have someone that's a urologist in your group, urogynecologists are dealing with this as it relates to hysterectomy. So they're also a good resource to consider—might be able to partner with someone there.

Zachary Klaassen: Yeah. Great, great points. Trinity, phenomenal discussion. This is a really important topic. Maybe just a couple take-home messages for our UroToday listeners.

Trinity Bivalacqua: Yeah. I think right now we have now acknowledged that sexual dysfunction—erection recovery in both men and women—is important. And we need to be talking about it with our patients up front. And then we need to be either treating them ourselves or referring them to people that can. I think we now have surgical techniques that are safe and effective, and we need to implement that into our clinical practice.

And if we do that, I think we can improve the quality of life of both men and women after cystectomy. As I said earlier, we now have wonderful treatments. People are living longer. At least that's what I predict will happen, so we need to be concentrating on these quality of life indices.

Zachary Klaassen: Wonderful. Thanks so much, Trinity. Appreciate your time on UroToday.

Trinity Bivalacqua: Yeah. No problem, Zach. Thank you.