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Ruchika Talwar: Hi, everyone. Welcome back to UroToday's Health Policy Center of Excellence. My name is Ruchika Talwar, and today I'm really excited to be joined by Dr. Marshall Strother, who's an assistant professor of urology at Oregon Health and Science University. Dr. Strother, we're super excited to have you here today. Please kick off your presentation talking about the symptomatic and functional recovery after TURBT for bladder cancer.

Marshall Strother: Alright. Thanks so much for having me, and thanks so much for the opportunity to present my work. The purpose of this project was to answer a very simple question that we get in clinic all the time, which is, "How long is the recovery from this procedure going to be?" We chose to address transurethral resection of bladder tumors specifically because it's just a super common procedure that we do in urologic oncology. Of course, there are a lot of sub-questions that are hidden within this larger question of how long the recovery is, and we all do our best to answer these questions based on our own clinical knowledge and experience. But when it comes to having real data to answer these questions in a scientific and granular way, the fact is that we have absolutely no idea because there's no data published in the literature that gives really detailed answers to these questions.

In order to do this, we used a method called ecological momentary assessment, which is really a very fancy-sounding term for a very simple concept. The idea is that instead of giving patients a survey at the end of a month, say, after surgery, that asks them to recall their experience of recovery from surgery, we ask them on a day-by-day basis very short questionnaires that are designed to interrupt their day as little as possible, and we ask them questions about what they're experiencing at that moment or within the last 24 hours.

The way we did that is with a text message-based system. On fixed days after the surgery, the patients would receive text messages that look like this. Each text message contains a personalized link for that patient, and it took them to a very simple, very patient-friendly questionnaire, which asked them questions like this about how they're feeling, the color of their urine, things like that. We asked these questions seven days before surgery to establish a baseline and then on fixed postoperative days, going out to about two weeks after the procedure.

From all this data, we were able to generate a bunch of graphs that look like this with regards to different symptoms. This is specifically the patient's level of agreement with the prompt "It burns when I urinate." You can see on the X-axis here we have the postoperative day; postoperative day negative seven represents our baseline, and then going forward in time out to about two weeks. The dotted line here just carries forward that baseline to make comparison with the patient's baseline a little bit easier. The Y-axis here shows the level of agreement with the statement, ranging from not at all to very much, and the blue line shows patients that underwent larger tumor resections, and the orange line shows the level of agreement for patients who underwent smaller resections for tumors less than two centimeters.

The nice thing about this sort of visualization is it gives us both an idea of the magnitude of the patient's symptoms as well as their duration. You can see that this is a pretty unsurprising result here. Patients unsurprisingly have a little bit more dysuria on postoperative day one after a TURBT relative to their baseline. But an interesting point that we can see here is that the magnitude of that dysuria is actually pretty mild. Even on postoperative day one, the level of agreement with the statement is ranging from a little bit to somewhat, and then that drops off pretty quickly after the procedure.

Perhaps more surprisingly, continuing a little bit in that vein, is the degree to which none of the symptoms really budge very much from the baseline even on postoperative day one. If you look at quality of life, frequency of urination, ability to empty the bladder, urinary control/continence, and overall levels of pain, you can see that there are small differences on postoperative day one relative to pre-op, but they're really quite small, and again, they return to baseline relatively quickly.

This is looking at the patient's level of agreement with the statement, "I feel recovered from surgery overall," and so based on what you saw previously, it's maybe not so surprising that patients are reporting relatively high levels of feeling recovered from surgery as early as postoperative day one or two. Looking at this data a different way, you can plot the cumulative incidence of return to baseline. You compare the patients' baseline responses to their response on any given postoperative day. When the patient responds that they're feeling as good on the postoperative day as they did preoperatively, then you could consider them returned to baseline, and then you get this sort of upside-down Kaplan-Meier plot here. Specifically, with a very important question that I get from my patients, "How quickly can I get back to work?", you can see that, again, as early as postoperative day two, about 75% of patients, including those who underwent larger resections, are feeling like they're able to get back to work as well as they were prior to surgery.

This is the cumulative incidence of responding, saying that they feel at least quite a bit recovered from surgery, and you can see that this takes a little bit longer than feeling like they're ready to get back to work, but the majority of patients by the first week after surgery are really feeling mostly recovered. Take-home points from this sort of basic overview. To answer that key question, "How long is the recovery?", what I tell patients these days is that most people feel ready to get back to work within two to three days because I think that's really what they're getting at when they ask that question most of the time. But also, most people will feel mostly recovered about a week after the procedure.

That said, it's important to recognize that about 15% of patients will still feel like they haven't totally recovered even 10 to 14 days later. It's important to recognize that there's still a lot of variability in each patient's individual experience and not to discount that. I think, to me, it was fairly apparent that this was important, but given that it hasn't really been looked at in this kind of detail before, maybe it's worth just briefly mentioning. I feel it's important that we have this information because patients have a right to informed consent, and a big part of informed consent is knowing what you're signing up for.

Specifically with regards to TURBT, life planning is a really important aspect. It's true of any of our surgeries, but for TURBT, where patients are potentially going to have to undergo two, three, or more TURBTs throughout the course of their disease process, knowing whether they're going to have to take a week off of work each time or a month off of work each time can really make a big difference in their quality of life or their financial well-being, in addition to the very common questions that we get, like "Am I going to be able to make it to this wedding that I have coming up?", for example.

Then finally, as clinicians, being able to detect when our patients are experiencing a complication is really important. If a patient tells you on postoperative day one, "I'm having a little bit of dysuria," I think all of us would recognize that's probably not a problem. But it becomes a little bit more questionable if a patient says, "Oh, I'm a week out from surgery and I'm peeing every 15 minutes." Well, is that within the realm of normal? I think that based on this data, we can say pretty clearly not, because you shouldn't probably be having to pee every 15 minutes after a TURBT at all, but it definitely shouldn't be lasting a week after surgery, and I'm not sure that I would have been able to say that with the same degree of confidence.

Just a couple of exploratory things. I mean, this data, you can slice it a lot of different ways, and I've only really been able to scratch the surface just in this very brief talk. But one of the other things that we looked at that I think is a little bit provocative is the predictors of longer recovery, and we found two things that were fairly consistently associated with longer recovery. One is worse baseline symptoms. I find that personally fairly intuitive. I mean, patients who are really struggling going into surgery, it's not entirely surprising to me that they continue to struggle after surgery and feel like it's just harder for them to recover overall. But one thing that came up as well is perioperative gemcitabine. We had a very small number of patients in our cohort, so we really should not read too much into this data at all. We had only 20 patients, and we also did a lot of statistical tests, so saying that this is statistically significant really doesn't have a whole lot of meaning in the context of so much multiple testing.

But we did see that in the first week or so, those patients who did receive intravesical gemcitabine after the procedure did tend to take a little bit longer to feel like they were returning back to baseline. This is something that really hasn't been reported previously and it's not something that would have been caught in the clinical trials that led to the common use of gemcitabine in this setting because those trials, while they looked at complications, didn't really look at recovery in this sort of granular way. At least, this is something that I think needs to be looked into a little bit more. While again, I would really stress that we can't read too much into this very preliminary data, in my practice, it has given me a little bit more pause. Previously, I used intravesical gemcitabine as really a totally free move, and now I think just a little bit more about it before I go ahead and give it to most patients.

Ruchika Talwar: Thanks, Dr. Strother. I mean, I think this is just a really fascinating analysis. There's a lot to unpack here, but I first want to acknowledge one of the points you made, that this may seem like a simple study in that it's information that we probably already assumed when counseling our patients, but I just want to commend you for actually doing this sort of investigation so that we have the evidence to back up our counseling because that's obviously a really important point across the board. But as there's a policy focus to integrate things like patient-reported outcomes and the patient experience in healthcare, I think arming ourselves with this sort of data so we know what our baseline recovery is in general is important as we see different health systems, different payers, and different value-based care arrangements that actually may potentially reward or penalize a physician for, I should say, the data that comes out of these sorts of assessments. This is super important, and I hope that this is just an initial exploratory analysis in many to come for all common urologic issues because I think it's going to be really, really relevant.

Now, a couple of questions I have just about your data. The thing that we see in urological investigations that integrate these sorts of texting-based surveys or this sort of way that we reach out to patients, sometimes we see a bit of a response bias, particularly because our patients do tend to be of older age. I was just wondering if you saw any difference in response rates based on age or if that was a barrier for you in the study at all?

Marshall Strother: Yeah, so that's a great question. We definitely did. It was really at the enrollment stage of things that we saw a bias towards younger patients. In this particular study, we allowed a surrogate to respond for the patient. In a few cases, you had a child or caregiver who was responding on behalf of the patient, so absolutely there's going to be a bias towards younger patients here, but that was really more at the enrollment level than at the response level. There's definitely going to be a response bias overall, no question.

I think that one of the things that's interesting specifically with this study is that the response bias may actually be towards more negative outcomes. You imagine if you're suffering longer and you're continuing to get these text messages, you maybe are more likely to respond than if you feel great, you're ready to move on with your life on postoperative day two, and so it's interesting that our data shows, to me at least, that patients were recovering surprisingly quickly, and that is even with this bias probably towards patients responding more if they're not recovering as quickly. In some ways, that reinforces the main conclusions of the paper.

Ruchika Talwar: As physicians, again, when we counsel patients, we tend to draw upon our own experiences, and we are more likely to remember the patients who kept calling with dysuria and symptoms and all of that. I, too, was surprised by how fast the recovery was in your study and, again, just another reason why it's so important to do these assessments in common urological procedures because how accurate is our counseling, really, if we don't have the numbers to back up the data?

Marshall Strother: Yeah, absolutely. You mentioned before, at the beginning, you were like, "Well, I think we're probably all a little bit on the same page here," but when I was looking at handouts that are available online in the UK specifically, there's a lot of pre-packaged patient handouts for common procedures like this, and there was fairly wide variability in some of these handouts, telling patients that they should expect to take a month off of work or even saying that they shouldn't engage in any heavy lifting for a month or six weeks after TURBT. I mean, I think we might be a little bit surprised at just how high that variability is. I mean, as you know, setting these expectations can be really important. If you tell somebody that they're going to be suffering for three weeks, then they may be more likely to experience that.

Or if you tell them they should be lying in bed for a couple of weeks after surgery, then they may not be as willing or able to get back to their life. Not to mention, of course, the issue that I brought up before, which is like, "Do I need to cancel my plane tickets?" which I don't know if you experience this in your clinical practice, but I feel like I am getting this all the time, especially with patients undergoing TURBT where we're sort of working in their cysto schedule and working that around their travel plans and things like that.

Ruchika Talwar: I couldn't agree more with you on all fronts. I think those are all important points, and hopefully this can be an area of future quality improvement. Again, now that we have studies like this one, we know that there is a need to go back and improve our current literature because before we just didn't have the evidence. Again, I think that that goes to show the importance of your work and what a significant contribution this is.

As we wrap up, what are your final words to the urologic community? What are the main takeaways from this study, and how should that change the way we practice?

Marshall Strother: I think from this study specifically, the study is open access, so anyone, if you want, you can show these... if you have a patient who you think can benefit from actually seeing the graphs, if they ask you this question, you can actually show them this data very easily. I think it's really important that we have this data either in the way it is now or in a slightly simplified form for all urologic surgery patients, for all procedures. That's sort of my dream going forward. Then also, to think about this sort of granular assessment as we go forward in doing further clinical trials. We've gotten really good at doing minimally invasive surgery, so even for more major procedures like prostatectomy, for example, whereas in the past, knowing whether someone has a major complication or not, that's going to be the differentiator between two different surgical techniques, for example.

But now, as we've gotten better and better at things, we need to be looking closer and closer at patients' recovery. Maybe the next innovation is cutting down recovery time by just a couple of days, and these sorts of ecological momentary assessment techniques I'm hoping to see integrated more and more into clinical trials in the future.

Ruchika Talwar: I think that's super important, and I look forward to seeing your future work in this space. Thank you for spending time to chat with us today. This was such an important topic, and I know that our community really would benefit from both learning from your work and also sharing your work with our patients.

Marshall Strother: Thanks so much for having me. It was a pleasure.

Ruchika Talwar: To our audience, thanks for joining us. We'll see you next time.