Sophia Kamran, MD

Sophia Kamran, MD, a radiation oncologist at Massachusetts General Hospital and assistant professor of radiation oncology at Harvard Medical School, discusses future roles that radiation oncology will play in combination with resection and targeted therapy in urothelial carcinoma.

While radiation oncology is currently used in nonmetastatic muscle-invasive bladder cancer (MIBC), Kamran anticipates it may be used in oligometastatic bladder cancer. Data from ongoing clinical trials suggest that combined with immune checkpoint inhibitors, it can improve outcomes compared with chemoimmunotherapy.

Kamran says that the current treatment regimen in MIBC will be optimized by incorporating novel multimodal therapies and using hypofractionated radiation to shorten the duration of radiotherapy. Adaptive planning of radiotherapy can also help radiation oncologists deliver the optimal level of treatment on a daily basis. Even physicians treating non­–MIBC may be able to employ radiotherapy, based on data from a small trial showing efficacy of chemoradiation in patients who were Bacillus Calmette-Guérin (BCG) refractory.

Additionally, as drug-eluting devices that provide more local targeting of the bladder are introduced, patients may also benefit from combination with radiation therapy based on the established efficacy of chemoradiation. Kamran says more research into these areas could confirm the importance of combining radiation with other modalities of therapy, improving efficacy and quality of life for patients.

 I also foresee radiation oncology moving into different areas of urothelial carcinoma. Right now, we have the muscle-invasive stage that we play a big role in, but I do foresee radiation oncology moving more into the metastatic role. There [are] a lot of exciting data on oligometastatic disease, particularly in combination with immune checkpoint inhibitors. I do think that's an area of great need, where we actually see patients do extremely well if you combine it just right, and it's a right amount of metastases, and things like that.

I do foresee us playing a bigger role, probably in the metastatic setting. I think we're going to further improve upon muscle-invasive disease, improve upon the current treatment regimen, either by incorporating more of these novel therapies, and figuring out the sequencing using hypofractionation. We have adaptive planning coming down the pipeline, which is where we can adapt the radiation plan on a daily basis. I think that's great for bladder cancer. Even in earlier disease, so in T1 disease, typically non–muscle-invasive disease, we don't really think about radiation oncology, but there was a recent small trial that was presented at the [American Society for Radiation Oncology Annual Meeting] this past year that did show good outcomes in patients that were BCG refractory. I think that was where they were going to go on to radical cystectomy. But when we did chemoradiation, the doses were a little bit different. When we did the bladder-sparing therapy, patients did very well. It was a very early trial, a very small trial, but I think that needs to be further investigated.

Then there are novel therapies where there are drug-eluting devices that you can put into the bladder, and they can elute drugs locally. Perhaps combining that with radiation might be very effective. I think that there are a lot more roles and a lot more areas that radiation can get involved in. I think it's very exciting to be in radiation oncology, particularly in the bladder space.

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Sophia Kamran, MD, discusses future roles that radiation oncology will play in combination with resection and targeted therapy in urothelial carcinoma.

Anticipating Expanded Uses of Radiotherapy in Urothelial Carcinoma

Sophia Kamran, MD, a radiation oncologist at Massachusetts General Hospital and assistant professor of radiation oncology at Harvard Medical School, discusses the research supporting the use of trimodality therapy with immunotherapy for patients with urothelial cancer.

 using resection, radiotherapy, and chemotherapy has been shown in retrospective studies to be as effective as radical cystectomy while preserving the bladder. According to Kamran, clinical studies are now investigating the use of immune checkpoint inhibitors as part of trimodality therapy in localized muscle-invasive bladder cancer. Several immunotherapies are currently used in the metastatic setting.

Phase 1 trials of radiotherapy plus immunotherapy showed that it had low toxicity and could be used safely. Kamran says that one of the largest trials of trimodality therapy, the phase 3 NRG SWOG1806 trial (NCT03775265), is randomizing patients with localized muscle-invasive bladder cancer 1:1 to receive either standard trimodality therapy (transurethral resection, up to 7 weeks of radiotherapy, and chemotherapy with cisplatin, gemcitabine, fluorouracil, and mitomycin) versus trimodality therapy plus atezolizumab (Tecentriq) every 21 days for 9 cycles.

The trial is recruiting approximately 475 participants, and 250 have already been enrolled nationwide, according to Kamran. The primary end point is bladder-intact event-free survival for up to 5 years.

 Immune checkpoint inhibitors are effective in the metastatic setting of bladder cancer. And so our thought is, what happens if we move it earlier in localized disease where it's not metastatic, and then see if we can safely combine it with radiation therapy in the trimodality treatment combination. That’s actually being explored right now. There were some phase 1 trials looking at the combination of just radiation plus immune checkpoint inhibitors upfront, just to see if it's safe and not toxic and is well tolerated. It was shown that it was safe, and they weren't looking at efficacy, they just wanted to make sure that it was safe and had low associated toxicity.

From those early phase 1 trials, because it was determined to be safe, we have moved forward, and now we're designing larger trials, and some larger trials have opened and are ongoing. Probably the largest trial of bladder-sparing therapy to date is currently open and ongoing. This is the NRG SWOG1806 trial, which is a phase 3 randomized trial, and it’s randomizing patients to either standard trimodality therapy, or trimodality therapy plus atezolizumab, which is an immune checkpoint inhibitor. [They’re] going to be 50/50 randomized. The goal is for 475 patients, I believe, and when I gave the talk on Saturday, we had almost 250 patients enrolled nationwide.

Sophia Kamran, MD, discusses the research supporting the use of trimodality therapy with immunotherapy for patients with urothelial cancer.

Sophia Kamran, MD | Authors

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Anticipating Expanded Uses of Radiotherapy in Urothelial Carcinoma

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