Novel Treatment Strategies in Non-Muscle Invasive Bladder Cancer


A bird’s eye view of treatment modalities in urothelial carcinoma covering systemic, surgical, and bladder preserving strategies.


Shilpa Gupta, MD: We’ll switch gears to non–muscle-invasive bladder cancer, which we have started seeing. I first learned the definition of BCG-refractory disease during the KEYNOTE-057 [NCT02625961] study a few years ago. I would love to hear what Andrea has to share and what progress we have made for these patients where, historically, radical cystectomy was the only option for BCG-unresponsive disease.

Andrea B. Apolo, MD: Non–muscle-invasive bladder cancer is now an area that includes medical oncologists since the FDA [Food and Drug Administration] approved pembrolizumab in 2020 for this patient population, specifically patients with BCG-refractory carcinoma in situ who cannot undergo or refuse radical cystectomy. We do have pembrolizumab approved. That was based on the KEYNOTE-057 study data that were updated at GU ASCO [ASCO Genitourinary Cancers Symposium] this year with the papillary tumors, the T1 and high-grade Ta tumors showing as Petros had mentioned. Disease-free survival at 12 months was 43%, which is similar to what we had seen with the carcinoma in situ data.

We also have data for atezolizumab in the non–muscle-invasive setting. This was from a SWOG 1605 study [NCT02844816] that looked at monotherapy atezolizumab in this same setting, the BCG-unresponsive setting, showing very similar outcomes in carcinoma in situ and in papillary tumors that were BCG refractory. That’s for systemic therapy, but there are a lot of efforts right now in terms of intravesical therapy that are trying to develop larger trials for BCG-unresponsive disease and studies that include randomization.

Nadofaragene firadenovec, also known as Adstiladrin, is an adenovirus-mediated delivery system of the interferon alfa-2b gene that has also shown activity in BCG-unresponsive disease. Intravesical gemcitabine and docetaxel are probably being used in the community because it’s available for patients with BCG-unresponsive disease, and we’ve also seen data of N-803 plus BCG N-803 as an IL-15 superagonist. We have seen some nice CR [complete response] rates for this combination in patients who have BCG-refractory disease. There’s a lot of activity right now for patients with non–muscle-invasive bladder cancer that is BCG unresponsive.

Shilpa Gupta, MD: It’s an exciting field for this setting. Mamta, could you walk us through this abstract we saw at ASCO GU, which was really the phase 2 study of radiotherapy and tislelizumab for patients with high-risk, non–muscle-invasive disease refractory to BCG? This was an exciting novel abstract.

Mamta Parikh, MD, MS: This was an interesting approach to non–muscle-invasive bladder cancer. As Andrea mentioned, there’s a lot of really exciting stuff going on with intravesical therapies but because medical oncologists are invading non–muscle-invasive bladder cancer, we’re taking some of our more intensified approaches to non–muscle-invasive bladder cancer therapy. This study looked at tislelizumab in combination with radiotherapy in patients with high-risk, non–muscle-invasive bladder cancer that was BCG unresponsive, and they were treated with tislelizumab, which is a PD-1 antibody, for 8 cycles. They received radiation concomitantly over 7 weeks at 33 fractions. The primary end point of the study was disease-free survival at 12 months. The secondary end points were bladder preservation rate and overall survival [OS] as well as safety. This was a small study; 14 patients were enrolled and only 10 were valuable at the time that the data were released at ASCO GU. The disease-free rate at 1 year was 80%, which is exciting.

The disease-free rate at 2 years was 60%, so it still held up well. There were 2 patients who had recurrences that were high-grade Ta, and only 1 patient out of the 14 enrolled had developed metastatic disease. I think that’s an important thing in these trials that are looking at non–muscle-invasive bladder cancer, because these are patients who are declining cystectomy. We have to think about whether they go on to develop metastatic disease. This is a very small study, so we’re still waiting for a lot of data from this. The OS at 2 years was 100%, although this is in the non–muscle-invasive setting. So this may be one of the few areas where disease-free survival is the more compelling end point to keep an eye on.

Shilpa Gupta, MD: That’s really the key: not to do any harm and not to lose a curative option of cystectomy.

Transcript edited for clarity.

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