Pioneering Advances in Bladder Cancer: New Drug Classes, Biomarkers, and Treatment Models

A virtual roundtable, hosted by Dr. Petros Grivas of Fred Hutchinson Cancer Center, contextualized the latest bladder cancer research updates and trials of relevancy to come out of the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium. Dr. Grivas was joined by Drs. Guru Sonpavde, Elizabeth Plimack, Christopher Wallis, Terence Friedlander, and Matthew Galsky.

In the final segment of the roundtable, the panel elaborates on what excites them most about the future of bladder cancer research, highlighting promising advancements, including personalized mRNA vaccines, novel radioligand therapies, T-cell engagers, biomarker-driven treatment strategies, and a shift toward individualized care paradigms, reflecting a rapidly evolving field focused on improving patient outcomes.

View previous segments of this roundtable.

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Dr. Grivas: I suggest that we go around the virtual room. I will ask each of you to share what excites you most regarding ongoing research trials, biomarkers, or anything else that comes to mind. Let us close with a discussion of future directions. Dr. Plimack, I will start with you.

Dr. Plimack: There is a lot to be excited about, but I will choose one in the interest of time. I am particularly excited about the V-940 personalized neoantigen therapy, which is essentially an mRNA vaccine tailored to a patient’s tumor. We have this therapy in trials at Fox Chase for adjuvant renal and bladder cancer. The melanoma data were compelling, and I am glad to see this approach expanding to genitourinary cancers. It is still very early, but it holds a lot of promise.

Dr. Grivas: Personalized immunotherapy using neoantigens is an important area of research, and it will be fascinating to see the results of these trials.

Dr. Sonpavde: There are many exciting developments, including the use of circulating tumor DNA to select patients for minimal residual disease detection. However, I believe the most promising advancements are the emergence of radioligand therapeutics and T-cell engagers. These represent a new class of agents that could drive the next wave of progress in treatment and significantly improve patient outcomes.

Dr. Grivas: Modern imaging techniques for bladder cancer may also evolve alongside radioligand approaches, which is very exciting.

Dr. Friedlander: We now have a new standard of care in the frontline metastatic setting, and it is crucial to build upon that. The key question is what we can add to this regimen to enhance its efficacy while minimizing toxicity. I agree that biomarkers will play a significant role. For instance, exploring Nectin-4 PET or Trope-2 PET could help us better classify patients and move away from a one-size-fits-all approach to metastatic disease.

Beyond biomarkers, there are several promising novel therapies. One example is TGF-beta inhibitors, including an investigational agent from AbbVie, which we are about to open a trial for. This therapy may resensitize tumor cells to immunotherapy. Additionally, there are other small-molecule approaches, such as a bispecific antibody-drug conjugate targeting HER3 and EGFR, which showed encouraging early data at ESMO. Of course, we need larger studies to confirm these findings. While we have achieved a significant milestone with EV/pembro in the frontline setting, this is only the beginning. Five or ten years from now, we will hopefully look back and see how far we have come.

Dr. Grivas: It is incredible to witness this progress and to contribute to these advancements.

Dr. Galsky: As a field, I am excited that we are shifting from simply developing new drugs to rethinking treatment paradigms. While academia does contribute to drug development, much of our focus is on optimizing how we use existing tools. Instead of relying on treatment strategies that have remained unchanged for decades, we are now using emerging therapies in a way that allows us to treat patients in a more individualized and effective manner.

Dr. Grivas: The concept of refining treatment paradigms is just as important as identifying therapeutic targets and biomarkers.

Dr. Wallis: I have the advantage of hearing five brilliant responses before me, but I would echo Dr. Galsky’s point. One of the most exciting developments is the move away from standardized, one-size-fits-all treatment approaches toward truly personalized, patient-specific strategies. This applies across all stages of disease and represents a major step forward.

As a urologist, I make a point to attend medical oncology meetings because they offer insight into where the field is headed. Treatments that start in the second- or third-line metastatic setting often move to first-line use and, eventually, into earlier stages of disease and localized treatment. The opportunity to use therapies that have demonstrated substantial benefit in metastatic patients to potentially cure those with localized disease is incredibly exciting. Achieving this goal requires a deeper understanding of disease biology through imaging and biomarker research. By improving how we classify and target disease, we can develop rational, evidence-based treatments that will ultimately lead to better patient outcomes.