Alternative Intravesical Therapy and Patient Preferences in NMIBC

Sia Daneshmand, MD, of University of Southern California, shares his thoughts on alternative intravesical therapies showing the most promise in NMIBC and how they compare in terms of efficacy and safety. He also comments on how he envisions the integration of patient preferences and quality of life (QOL) considerations into the regular management NMIBC, particularly with regard to bladder preservation and alternative therapies.

View his previous thoughts on Bladder Preservation, Biomarkers for Detection, and BCG Predictors of Response in NMIBC.

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What alternative intravesical therapies are showing the most promise in NMIBC, and how do they compare in terms of efficacy and safety?

Dr. Daneshmand: I think that is an interesting question. We always say that we cannot compare across trials, but then we put up a table comparing all of them. So, I think we need that comparison. We need to have them side-by-side to see what the response rates are. As I said, these are exciting times. We have had a plethora of new drug treatments come online recently. But is one better than the other? We do not know. What we do know is that the target that used to be in the 20% to 30% range has now moved up to the 60% to 70% range. So, that is the new target for complete response at any time. The real question is the durability of the response. Are these going to be durable, and how are we going to sequence them? There is no question that we will be sequencing these in the future.

There are advantages and disadvantages to each of the treatments. For example, Adstiladrin is administered once a quarter with a single instillation. That is a huge advantage for patients who are traveling far, have difficulty coming in, or have transportation issues. On the other hand, the TAR-200 is placed once every 3 weeks, at least for the first quarter, and then once every quarter after that. So, there is the advantage of having the drug available to the patient with very high initial complete response rates, but the disadvantage of the in-and-out procedure. It is very well tolerated, though, and I think many patients on the trial are currently happy with this. Then, you have the traditional intravesical treatments, like the doublet gemcitabine-docetaxel, which works very well in patients. We have seen almost a 50% 2-year recurrence-free survival with these patients. It is a doublet, meaning it takes twice as long as BCG, but it is fairly well tolerated.

Each treatment is unique in its delivery, duration, and tolerability. In terms of side effects, I think we have raised the bar for complete response rates and lowered the floor for the tolerability of side effects because these new medications are, across the board, well tolerated. That is exciting too, because it means that in the future we can carefully think about and sequence them, depending on patient needs. However, in terms of deciding what to pick first, I do not think we have an answer yet. We may in the future know what is better, one or the other. There will be very few head-to-head trials with these drugs, as they are expensive and tough to conduct. But I think as we gain more experience in the real world, we will be able to make some sense of what we should do first.

We will have options, obviously, for what to do at the beginning and what makes sense for sequencing.

How do you envision the integration of patient preferences and QOL considerations into the regular management NMIBC, particularly with regard to bladder preservation and alternative therapies?

Dr. Daneshmand: I think that is present from the very beginning. Discussions about QOL and how treatments are administered are essential. Now, most patients in this space are going to be BCG-unresponsive, and they have likely experienced intravesical treatments, such as once-a-week catheterization and instillation. Some of these patients have had significant voiding symptoms, and those who had a terrible time with BCG—whose bladders look very inflamed—are the ones for whom we might consider one therapy over another. This is because some treatments cause less irritation or do not require as frequent procedures. For example, Adstiladrin might make more sense for a patient as a single instillation. Meanwhile, someone who cannot tolerate 2 separate chemotherapy agents or who cannot hold the medication for too long is not an ideal candidate for gemcitabine-docetaxel. If a patient has recently had gemcitabine, the addition of docetaxel might not make sense for them. So, there are these nuances that I think we are going to consider.

But back to your question; QOL is very, very important. I think our job in the future will be to describe these new, novel medications to patients and explain their schedules. I believe that the schedule is very important and directly impacts QOL. We should provide patients with all the information we have about complete response rates at 1 year, 2 years, and so on. For example, we might say, “This treatment works well, but this other one works better, although it has different side effects,” and allow them to make an informed choice. We are already doing a bit of this now with multiple clinical trials open for the same conditions, and patients are choosing to sign up for the trials that they find most suitable.

However, I think it is also our job to guide patients and not put too much responsibility on them. Many are overwhelmed by all this information and trying to determine what works better. The terms we use frequently, like complete response rates and durability of response, can be difficult for patients to understand. So, I think it is our role to guide them, and we will naturally have our own biases. We have many medications available for locally advanced and advanced diseases, so it is essential that we know everything we can about these drugs in order to guide patients effectively in the future.