Overview of Intravesical vs Systemic vs Combo vs Surgery: Benefits, Concerns in NMIBC

In the first part of this six-part roundtable series, Sam Chang, MD, MBA, Vanderbilt University Medical Center begins the discussion on non-muscle invasive bladder cancer by asking each participant what considerations they have when deciding between systemic therapy versus surgery versus intravesical, and so on.

Qian Janie Qin, MD, UT Southwestern Medical Center; Gautam Jayram, MD, Urology Associates of Nashville; and María Teresa Bourlon, MD, MS, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán share how each of their institutions clinically evaluate different disease states and approach the decision-making process.

—

Sam Chang, MD, MBA:
Hello everyone. My name is Sam Chang. I am very honored and privileged to be joined with three real experts as we talk a little bit about non-muscle invasive bladder cancer. And so we have to my left Dr. Qin from Dallas, Texas, Dr. Tom Jayram from Nashville, Tennessee, obviously close to my heart, the city of great vim and vigor. And we have Professor Bourlon from Mexico City. I’ll ask each of them to introduce themselves as we start this panel and as we start discussing non-muscle invasive bladder cancer because we’ll have the perspective of not only the urologic surgeon, but the medical oncologist because this field in non-muscle invasive bladder cancer has really changed quite a bit. We’ll start off with the overview of non-muscle invasive bladder cancer, how you evaluate patients as they may show up in your practice. Professor Bourlon in Mexico City, tell us a little bit about your institution and your practice, and then tell us how you initially evaluate those patients that see you with non-muscle invasive bladder cancer.

Maria Teresa Bourlon, MD, MS:
I work at the National Institute of Medical Science and Nutrition Salvador Zubiran, and we have a urologic oncology clinic. Oftentimes we get to see non-muscle invasive bladder cancer patients. And you always see these patients struggling between going to surgery or not. They’re really aware of the change that surgery might give to their life, the quality of life, and they’re also looking for new options for their treatment. And it might be hard to offer them options that have a benefit in overall survival, but we always talk about delaying surgery that’s in a safe way. We always talk about clinical trials and standard of care options in order for them to make a decision of their treatment.

Dr. Chang:
Dr. Qin, tell us more about yourself in Dallas, Texas, your practice, and who walks into your clinic then with non-muscle invasive bladder cancer, and what do you initially evaluate?

Qian Janie Qin, MD:
Yeah. I am at UT Southwestern in Dallas, Texas. I’m one of the geomedical oncologists with a focus on these patients bladder cancer. And then my research interest is in clinical trials. And so most of the time I’m seeing these patients when they’re more high-grade BCG refractory, right? There’s considerations for pembrolizumab, and that’s what I tend to see them in our clinic. It’s a handful of patients that might come to me. And it’s really a decision, right? Because we’re talking about systemic therapy now. And systemic therapy always comes with its set of side effects, right? And for non-muscle invasive bladder cancer patients, we really have to weigh the risk-benefit of those side effects, right? Particularly with immunotherapy, we know overall it’s well tolerated, but when the side effects come, they can be dangerous and they can be long-lasting, right? If you get any of the cytosis in your heart or lungs, it can be very dangerous.

And then some of the endocrinopathies can be lifelong. And so usually when I see these patients, I really talk about those potential systemic side effects. In the context of moderate response rate that we saw in the keynote study of pembrolizumab in this setting where the three-month CR was about 40, 41%, but if we look at the twelve-month CR, it was less than 20%. That duration of response is of concern and maybe not concern, but I think that probably contributes in addition to the potential systemic side effect to the moderate uptake of using pembrolizumab in this space.

Dr. Chang:
Yeah. I think that that concept of systemic therapy for non-muscle invasive bladder cancer really was unknown to someone as old as me when I went through training. Dr. Jayram is much, much younger. He may have learned early on about the possibility of systemic therapy. Tom, tell us a little bit about your practice and the types of non-muscular invasive bladder cancer. As a surgeon, obviously you see a range.

Gautam Jayram, MD:
Yeah. Thanks for having me. I’m a urologic oncologist in the community in a big private practice, about 30 urologists. And I’m fortunate to have a good infrastructure to have a really busy clinical trials program. We have over 15 active trials in bladder cancer spanning phase one to phase three. And it’s been really exciting to see what’s happened and you’ve been really involved in that as well over the last 10 years with emerging both intravestigal options, systemic options, and then these combinations. And so really, I echo what the group has said about for me, the end point is not really CR, it’s cystectomy-free survival. How can we get these patients to keep their bladders intact for as long as possible? And so the variety of non-muscle invasive bladder cancer spans from low-grade disease, highly recurrent. We call that intermediate risk. And there’s a plethora of interesting trials in that space too.

And then once you get to high-grade disease, you see superficial disease, T-1CIS. We know each of those has different risks of progression. And a lot of the efforts here interestingly have been focused on CIS, which as we know we see quite a bit, but we probably see more papillary disease. And there are some logistical issues with designing trials to try to address papillary disease. You have to control for the TURBT, which is really, and we’ve talked about this still, and I talk to our community colleagues about this all the time. Still, the best thing we can do for these patients is a really good TURBT and really good surgery, and that can really alter their course in a positive way. I agree that the main goal here is to have a personalized discussion with patients and their families. And in the community, we have a little bit different purview is that we see these patients for years and years and years.

They’re families we know. We’ve seen them go through the gamut of a lot of these things. And so quality of life has almost been overemphasized in the community. I like to joke around about, we have patients who we’ve overutilized BCG, overutilized intravascular therapy, but it’s for a reason. We all know the morbidity of radical cystectomy and we want to keep patients away from that. It’s really nice to have other options aside from BCG. I agree systemic therapy is going to be an important component of this. We’re trying to piece that together. But the intravascular piece, especially as a urologist, is familiar and we would love to defer to a good intravascular option if we could.

Dr. Chang:
We’ve touched on a lot of concepts here, quality of life, obviously patient-reported outcomes have become very, very important. The idea of preservation of the bladder, I don’t like the term bladder sparing. I like the term bladder preservation myself in an attempt to avoid cystectomy. We’ve talked about systemic therapy, integration of that in patients at an earlier and earlier stage within the disease progression. This will focus on non-muscle invasive bladder cancer, but obviously the systemic options for advanced disease, for invasive disease have actually just come in waves and waves.