GU Cancers 2022 | Bladder-sparing trimodality therapy for muscle-invasive bladder cancer

So we know that bladder-sparing trimodality therapy is an effective treatment for muscle invasive bladder cancer. And so I’ll be talking about some of the novel therapeutics and I’m going to be highlighting some of the incorporation of those novel therapeutics with radiation therapy to try to improve upon our current outcomes. So essentially, we know that, again, trimodality therapy has excellent outcomes in comparison to a radical cystectomy in terms of clinical outcomes. And I’ll be presenting some data. There’s some data showing that functionally, and then from a quality of life perspective, patients do very well with trimodality therapy, which is excellent.

We want to improve upon those outcomes and so there’s been a lot of interest with combining immunotherapy with trimodality therapy, specifically with a radiation therapy. There’s a lot of data showing that if you combine immunotherapy with radiation, they actually work synergistically, and effectively, we can hopefully improve upon our clinical outcomes such as survival data, bladder intact survival data, disease specific survival data, et cetera.

So I’ll be talking a little bit about how there’s multiple trials, specifically the NRG/SWOG 1806 trial is one of the largest trials where we’re randomizing patients to plus or minus atezolizumab in addition with the standard of care, which is the trimodality therapy. And that’s going to be a very rich amount of data because we’ll really understand how immunotherapy may improve upon outcomes for patients with muscle invasive bladder cancer. And in addition, it’s going to provide us a wealth of data that we can look at. We’re looking at different biomarkers and we’re going to do lots of translational studies, see if we can identify patients that may benefit from bladder-sparing therapy with or without immunotherapy, things like that.

In terms of another area of interest for bladder-sparing therapy, there’s a lot of remaining questions with regards to it, especially with regards to field size, dose, fractionation size, things like that. And so there’s been a big movement towards hypofractionation radiation therapy, basically giving a larger dose of radiation per day to try to shorten the treatment duration. It’s been shown to be very effective in patients without the immunotherapy, but there’s been some early data that I’ll be to talking about that do show that there appears to be increased toxicities when we use hypofractionated radiation therapy in combination with immunotherapy.

This very early data so we need to kind of further understand and tease out what could be going on. In particular, in those early studies of just a small amount of patients, there was an increase, particularly, it looked like in GI toxicities when combining with the immunotherapy and using hypofractionated radiation. So in that NRG/SWOG 1806 trial, we don’t actually use hypofractionated radiation therapy. We use standard conventional fractionation for radiation therapy. But that’s an area of interest. There’s actually other trials that are opening up, trying to understand that question of if you combine immunotherapy with radiation, what is safe? What’s the appropriate dose? Can you do the hypofractionated? Who has these toxicities, et cetera. So that’s kind of an area of research that’s kind of coming down the pipeline so we need to kind of further understand that.

And then finally, I do touch a little bit upon adaptive radiation therapy. So that’s a big area in our field where we can actually adapt on a daily basis the radiation treatments using software and novel technology to actually change a patient’s plan. And this is important in bladder cancer because when you treat the bladder, there’s a lot of critical organs that are nearby and we want to reduce toxicity, reduce radiation dose to those nearby organs. So there’s a large study that’s actually evaluating that very question, using adaptive treatment for when you’re treating the bladder. So that’ll provide a lot more information. And that may actually be a key when wanting to hyperfractionate in combination with immunotherapy. They’re not doing that right now, but that is probably coming down the pipeline as well because that may be a novel way to really reduce the treatment field so we’re just treating the bladder tumor or boosting the bladder tumor that we absolutely need to treat and then safely reduce dose to some of those nearby organs, especially when in combination with immunotherapy, where we did see those side effects.