Treatment Options for BCG-Unresponsive NMIBC: Balancing Efficacy, Logistics, and Patient Preferences

In the second segment of this roundtable, Roger Li, MD, Vitaly Margulis, MD, Kyle Rose, MD, and Paul Crispen, MD, explore the evolving landscape of treatments for BCG-unresponsive bladder cancer. The conversation covers the challenges of balancing efficacy, toxicity, and patient preferences while addressing innovative therapies like gem/doce, adstiladrin, and pembrolizumab. Practical insights into clinical trials, patient-specific considerations, and the role of cystectomy as the gold standard are highlighted, offering valuable guidance for practitioners in this complex therapeutic space.

Watch the third segment of this roundtable: TAR-200 Monotherapy for NMIBC Durability and Dwell Time

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Dr. Li:
So BCG refractory or unresponsive disease has really been a challenge for all of us. And we’ve been at this for a long time now, developing effective bladder sparing therapy agents. So obviously, we can just go through some of the approved agents. But given all of the agents and the logistics that comes with it, efficacy, toxicity, what are some of the agents that you go to once you have a patient who recur with high grade disease after adequate BCG?

Dr. Crispen:
So really guidelines-based right out of the box. Discuss cystectomy with them. Then you’ve got patients that aren’t going to be candidates or refuse. For those patients, discuss clinical trials when they’re available. Outside of clinical trials, then that’s when I go to my other list of what’s available if it’s FDA approved or non-FDA approved such as gem/doce, adstiladrin, pembrolizumab. And you could go down the agents and what you have available at your own center is going to largely dictate what you offer your patients. I’m not sure what Kyle’s doing currently.

Dr. Rose:
Absolutely. No, absolutely the same thing. I think we have to have the cystectomy conversation once they meet criteria. We have that with every patient, but we really adhere to the NCCN guidelines that the best place for our patient is on a clinical trial. So we try to prioritize our BCG unresponsive trials as much as possible. And then afterwards, we do have to become more selective, and it can be tricky. You had mentioned about payers, about what’s available at what institution and what the burden will be on the patient and the institution. Some of that hasn’t been hashed out.

Dr. Margulis:
Yeah, I don’t have much to add to that. These are excellent points. I think we are sort of… It’s good to be in this space where you have options, which we didn’t before.

Dr. Li:
So in my experience, even though a lot of these agents have been approved, either due to availability issues or due to the cost issues for the patients, for me, gem/doce still seems to be the go-to because of our familiarity with it. And also just because of the lack of toxicity. Is that more or less your experience as well?

Dr. Crispen:
Well, when I talk about those non-cystectomy options, I talk to the patients about potential side effects, efficacy and dosing schedule. And then with that discussion, we come up with what’s going to be best for them. For efficacy, single-agent pembrolizumab, at around 20% complete response rate at a year. With all of the potential for systemic toxicities. Most patients aren’t all that interested in my experience. For adstiladrin, if those patients are coming from a distance and they only have to come once every three months, they’re much happier with that plan. And so, it all depends upon where the patient’s coming from, what efficacy they’re looking for and other factors.

Dr. Rose:
No, I would just add to that, patient satisfaction and the financial burden to the patient as well as the time invested is something that clinical trials have really, I think, looked into and nailed moving forward. Something that we need to take into account for every patient, because they’re not all from our hometowns that we’re treating.

Dr. Li:
For sure.

Dr. Margulis:
Yeah. A lot of important points. You look at each individual patient. For example, you have a lot of patients whose bladders are so beat up that they cannot hold anything for any certain period of time in which some of the newer options of know TAR-200, for example, or pembro. I’ve had patients who cannot retain any treatment agent inside of their bladder. You have to refuse cystectomy.

But I think the key point here, and we forget, and I see this all the time in my referral practice, is that patients go through 3, 4, 5 lines of therapy and then there never offered cystectomy. And I think we keep forgetting that right now that is the front-line option.