Bladder Cancer Awareness Month: Emerging therapies and evolving standards of care

In recognition of Bladder Cancer Awareness Month, Song Jiang, MD, PhD, a clinical assistant professor of urology at Northwestern University Feinberg School of Medicine, reflects on the rapid evolution of bladder cancer care and the translational science driving these changes. Over just a few years, the treatment landscape has shifted dramatically across both non–muscle invasive and muscle-invasive disease, with new intravesical therapies, immunotherapy combinations, and perioperative strategies redefining standards of care.

In the first installment of this 2-part Bladder Cancer Awareness month series, Jiang highlights how urologists are balancing innovation with practical challenges such as BCG shortages, access barriers, and treatment sequencing considerations. He also examines the growing role of combination regimens and emerging endpoints that may redefine success in clinical trials. Together, these changes underscore a broader transformation driven by the successful translation of laboratory discoveries into meaningful improvements in patient care.

Urology Times: In recognition of Bladder Cancer Awareness Month, what are some important recent advancements that have changed how urologists are approaching bladder cancer care across disease stages?

Jiang: Bladder Cancer Awareness Month [has felt like] “Bladder Cancer Awareness Decade.” It's a burgeoning field, and the standard of care is [rapidly changing]. I've been in practice for 3 years, and the standard of care has probably changed 3 or 4 times in terms of perioperative treatments for muscle-invasive bladder cancer and an explosion of new intravesical therapies [in non-muscle invasive bladder cancer]. There have been so many advances that are the result of translational research, and that bench-to-bedside ideal that we're all moving toward in the laboratory has really shown fruit on the clinic side.

Urology Times: How would you describe the current treatment landscape for BCG-naive patients, and where do you see the greatest unmet needs?

Jiang: Most of us continue to use a risk-stratified approach for NMIBC. Here at Northwestern, we take pride in an integrated system under the leadership of Dr. Joshua Meeks. It's integrated in the sense that we meet regularly; he puts out guidelines for us, and we allocate and share resources across the system. I think we're prudent and conscientious of using a risk-stratified approach. For example, for low-risk patients, our standard is to give a single dose of perioperative chemotherapy, and then [follow] institutional guideline-based surveillance protocol. For intermediate-risk patients, the typical recommendation is to give single agent induction chemotherapy and 1 year of maintenance. That serves to both adequately treat folks, but also to ensure that we're saving BCG for higher risk patients in light of BCG shortage. For patients who are high-risk, we do recommend and give induction BCG with the typical SWOG protocol-guided 3 years of maintenance and surveillance cystoscopy.

In terms of unmet needs, there's still a lack of regimented templates for those who can't tolerate BCG, for whom there's a contraindication to BCG, and certainly for those in which BCG has failed. All of that is in light of BCG shortage. In the community setting, if you can't get BCG, the alternative is to do combination chemotherapy with gemcitabine/docetaxel. That's probably going to be the most widely used, at least in the near future, but that is likely going to change.

Urology Times: Several studies are evaluating BCG/immune checkpoint inhibitor combinations in BCG-naïve NMIBC. What key end points are you watching most closely as these data mature?

Jiang: The most exciting aspect of the combination regimens is that they've been able to achieve benefit in event-free survival, and specifically high-grade recurrence, which is a very important clinical end point. I think the whole field is still waiting for a difference in progression-free survival, or another way to put it, cystectomy-free survival. That's the main goal of these therapies: to preserve the bladder. The other important thing as the data mature is the ability to preserve a functional bladder and to minimize [adverse] effects. The field has noticed with those trials that there is a high rate of immune-related toxicity, so that will certainly impact how we look at the data going forward.

Urology Times: With more therapies now available or in development for patients with BCG-unresponsive disease, how are you approaching treatment selection and sequencing in clinical practice?

Jiang: I think that's a great question, especially for me and my colleagues in the community setting. Unfortunately, the reality is that treatment options and sequencing are still based on operational, financial, and logistical limitations. It's hard to look past the element of the financial toxicity for some of these advanced therapies that are FDA-approved. It's been a bit of a challenge to get products to our patients. Ideally, I'd love to be able to sequence based on the highest complete response rates. The newer options such as the [gemcitabine intravesical system] and cretostimogene [grenadenorepvec] have phenomenal complete response rates that have not been seen before. Again, it's just a matter of getting these in front of our patients and into our clinics. Right now, in our system, it's centralized. It has to be done in infusion centers, so something that I look forward to is being able to offer it to a wider range of patients.

Urology Times: Looking beyond NMIBC, how are advances in perioperative and bladder preserving strategies changing care for patients with muscle invasive disease?

Jiang: There's been a lot of landmark studies that have been promulgated recently. [Enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda)] in combination in the neoadjuvant setting is FDA approved in the cisplatin-ineligible population based on level 1 evidence. What's even more exciting and not necessarily unexpected is that it's shown an excellent response in head-to-head comparison with gemcitabine plus cisplatin even in cisplatin-eligible patients. That's likely going to be the new standard of care. Talking with my medical oncologists here in the community, they're really excited about that. That's certainly an advancement that's impacting every one of our muscle-invasive bladder cancer patients.

In terms of adjuvant therapies, the data has shown a benefit in long-term disease-free survival. That's certainly a standard of care to give nivolumab [Opdivo] or pembrolizumab as an adjuvant therapy after surgery or definitive treatment. In those two spaces, it's been a huge change.