Gautam Jayram, MD, on the top 5 things to know in bladder and kidney cancer

Gautam Jayram, MD

In this interview, Gautam Jayram, MD, shares takeaways from his 2024 LUGPA Annual Meeting presentation, “Five things urologists need to know now about bladder and kidney cancer in 2025.” Jayram is a urologic oncologist and director of the Advanced Therapeutics Center in Nashville, Tennesse.

This transcript was AI generated and edited by human editors for clarity.

You gave a presentation titled, "Five things urologists need to know about bladder and kidney cancer in 2025." Could you highlight some key takeaways from that session?

So much is happening; I tried to try to slow down and put some focus on some things that were most important. We talked a little bit about what's happening in intermediate-risk [bladder cancer]. A lot of the attention has been in high-risk disease, but intermediate-risk disease, I think, is kind of a more practical and a more popular disease state for a community urologist, because these are patients with lower grade disease. They come back fairly often. We're not really that threatened by them in terms of dying from their cancer, but it still is a big nuisance disease, and it's still a big quality-of-life issue. And so ultimately, there's so much happening with new drugs and new therapies coming in intermediate-risk disease, there's going to be a lot of questions of, "well, do we really need to treat all of these patients now with all of this stuff? Because I haven't been treating any patients with this stuff." So we tried to lay out a couple reasons why and who you should treat with intermediate-risk disease and what potentially those treatments could look like in the future.

We then talked a little bit about BCG-unresponsive disease, which is a really hot topic; a lot of trials and a lot of data are coming there. We outlined the 4 therapies that if we had to choose today for BCG-unresponsive carcinoma in situ that are available to urologists [as well as] the pros and cons of all of them.

I then talked a little bit about muscle-invasive disease, which is again aggressive disease, which usually requires major treatments. There have been a lot of advances in terms of new trials, new therapies that are coming out that potentially can change how we look at these patients, utilizing ctDNA as a marker for how to treat patients, how to prognosticate, how patients do on treatment.

And then we moved to kidney cancer. One really important thing that urologists need to know is that adjuvant treatment for high-risk renal cell carcinoma is now here to stay. It's cemented by overall survival data that we haven't had with any of the other treatments. So patients who have a nephrectomy for high-risk renal cell [carcinoma] should get consideration for immunotherapy either if the urologist is giving it, or a medical oncologist. But the bottom line is, they should be getting that.

And then the PET scan that that is now emerging for clear cell kidney cancer, which is called girentuximab or CAIX, is really exciting. It's kind of paralleling what we're seeing with PSMA in terms of its expression, its uptake, and its really high sensitivity and specificity for kidney cancer. That's something we really need in this space, because our imaging for kidney cancer is okay, but it leaves a lot of questions, and it causes a lot of follow-up procedures and visits to be done. And I think a tool like this could really, really change how we're thinking about kidney cancer.

There have been a lot of major advances in bladder cancer, specifically in the non–muscle-invasive space. Could you highlight some of the recently approved agents?

You have nadofaragene firadenovec [Adstiladrin], which has been out now for a year or 2. It's intravesical gene therapy with interferon. It's once every 3 month dosing. And now we're starting to get a good balance of data and information about it. A lot of urologists are using it and feel really comfortable with it, and it's really friendly to patients in terms of the dosing schedule, and it's easy to give in your practice. So that's something that I think has caught on and people are pretty happy with.

Pembrolizumab [Keytruda] was approved a few years ago. We've had some discussions about systemic therapy only in this space has limitations because of the side effects, and also the data aren't super strong, so most people are looking more at combination therapy for that, instead of just using pembrolizumab. And then we have an Anktiva [nogapendekin alfa inbakicept], which was just recently approved. It's an IL-15 agonist that stimulates natural killer cells to really mount an immune response, and I think that that's really exciting. We still are super early in the whole process, so there are a lot of things that need to be figured out, but a lot of groups that are giving some of these other therapies, of course, are going to look at that as well. There are some differences in terms of how these drugs are handled and stored. The economics of these drugs are a little bit different. All of that's going to be an important part of how we pick these therapies and how patients pick these therapies.

Are there any other agents that you're looking forward to seeing in the future?

There is a lot of trial activity going on with immunotherapy. Specifically with immunotherapy, we have BCG combination trials, BCG plus sasanlimab, BCG plus durvalumab, with a couple trials that are going to read out in the next 12 months. That's going to be really exciting to see if the BCG-naive population can benefit from combination treatment, and who would benefit the most, and then the other side of it are some of these other agents. Cretostimogene grenadenorepvac has a really robust trial platform, and that's intravesical gene therapy as well that has really good data and has a lot of interesting applications, I think, in patients with both intermediate-risk disease, BCG-unresponsive disease, and patients with carcinoma in situ. And so I think that that those trials are continuing to accrue or get more information. And then you have other players that are in a little bit earlier stages, Protara with [TARA-002], which is an intravesical agent. You have enGene, which is a non viral vector, intravesical agent that has a lot of promise and could be really easy to give for a community center. Those studies are still accruing. That data is still being accumulated. But there's a ton of activity in this space, and I think every 6 to 12 months, we're going to going to keep getting these boluses of information that's going to help us.

Are there any challenges or opportunities that come with all of these new agents being available?

Yes. People are going to ask, "how do I pick? What do I use? What what goes first? What comes second?" There's going to be an art to this, if you will. But the way I see it is, put everything in the toolbox and see what you can use, which is better than not having anything in the toolbox. But yes, there's going to be mechanism-of-action concerns. You're not going to want to give gene therapy multiple times to the same patient. There's cytotoxic therapy with gem-doce, or the pretzel. You're going to have a lot of of options. And there is going to be some concern about how to sequence them A to Z, and really, it's going to come down to ease of use and how your clinic can operationalize this, because what we've realized is that our centers are different than hospital systems. They're different than academic centers. We have different infrastructure; we have different legislation and state-specific regulations. And so at some point, you're going to have to just go with what's easiest for you to give and that's that's going to be a big part of all this.