Bladder Preservation, Biomarkers for Detection, and BCG Predictors of Response in NMIBC

Sia Daneshmand, MD, of University of Southern California, highlights latest advancements in bladder preservation strategies for patients with non-muscle invasive bladder cancer (NMIBC), including how they compare to traditional approaches; some of the most promising biomarkers currently being researched for the early detection of NMIBC, and how these biomarkers might change the landscape of bladder cancer screening; and the key predictors of response to Bacillus Calmette-Guerin (BCG) in NMIBC, as well as how these predictors can be integrated into clinical practice to personalize treatment plans.

View his continued comments on Alternative Intravesical Therapy and Patient Preferences in NMIBC.

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What are the latest advancements in bladder preservation strategies for patients with NMIBC, and how do they compare to traditional approaches?

Dr. Daneshmand: Exciting times are ahead as we now have a range of new medications available for managing NMIBC, with more on the horizon. Traditionally, our options have been limited to treatments like BCG and pembrolizumab, but we have been working to expand these options through clinical trials. Now, we are starting to see the fruits of those efforts with the approval of several new drugs that are already on the market and being incorporated into our practice.

One example is nadofaragene firadenovec, which has been in use since November 2023. We are gaining experience with it, and it is proving to be a valuable addition to our treatment options. We also have the promising TAR-200 device in various clinical trials. Although it has not been approved yet, the ongoing SunRISe 1-4 studies are moving forward, with additional studies on the way. Another recent approval is nogapendekin alfa inbakicept-pmln, an IL-15 super agonist used in combination with BCG. The results were presented at the AUA in May, and shortly afterward, it became commercially available. It is exciting to have these additional options for our patients.

Can you highlight some of the most promising biomarkers currently being researched for the early detection of NMIBC, and how these biomarkers might change the landscape of bladder cancer screening?

Dr. Daneshmand: Another exciting avenue of research is the development of urinary biomarkers. We have had circulating tumor DNA (ctDNA) available in serum for some time, and now we are turning our focus to biomarkers in the urine. This includes urinary tumor DNA, which is similar to ctDNA. Several companies are working on these advancements, and while I will not single out any 1 in particular, they are being integrated into upcoming clinical trials. As these biomarkers are incorporated into trials, we will gather more data on their predictive value.

At my institution, we have also been working on this research, and I believe these biomarkers will significantly impact how we manage patients in the future. Traditionally, we have relied heavily on cytology, which has been around for a long time but suffers from a poor negative predictive value. I think the future lies in utilizing these urinary biomarkers to guide our decisions in patient management as we continue to accumulate more data.

What are the key predictors of response to BCG in NMIBC, and how can these predictors be integrated into clinical practice to personalize treatment plans?

Dr. Daneshmand: I think we are still lacking robust predictors for patient response. For example, we know that patients with carcinoma in situ (CIS) often respond well initially, and that performing a complete transurethral resection of the bladder tumor is crucial for the best response to BCG. However, beyond that, it is difficult to identify which patients will not respond. We know that up to 30% of patients with CIS will not respond to BCG, but predicting this from the outset remains a significant area of research.

There is ongoing exploration into whether adding a checkpoint inhibitor to BCG could improve outcomes, with the CREST trial results expected soon. We are also investigating whether starting with gemcitabine and docetaxel might be more effective for some patients, with another trial underway to compare intravesical chemotherapy with BCG. For now, intravesical BCG remains the standard of care worldwide, but we are gradually learning which patients might benefit more from alternative therapies.