Bladder cancer is a biologically heterogeneous disease, and its classification plays a critical role in guiding treatment. However, current bladder cancer classification remains based primarily on clinical-pathological features or staging, with molecular subtyping yet to be standardized. At the 2025 European Association of Urology (EAU) Congress, Dr. Jeffrey S. Damrauer from the UNC Lineberger Comprehensive Cancer Center shared key insights on the response of different bladder cancer types to treatment, the role of neoadjuvant therapy, and the growing possibilities of bladder-sparing strategies.

UroStream: Are there different kinds of bladder cancers and if so, how does the type affect the treatment?

Dr. Jeffrey S. Damrauer: That’s a great question. There are a few different classifications of bladder cancer.The first is kind of what it looks like under a microscope. Although there are several different so-called histologic subtypes, the main one is urothelial cancer, and that makes up about 90% of all tumors.

The next—and probably most clinically impactful—is whether or not it’s non-muscle-invasive or muscle-invasive. That really dictates a few things: first, whether the tumor grows into the bladder lumen or through the muscle.If it grows into the muscle, it’s a much more serious disease and is usually treated with neoadjuvant therapy, followed by surgery to remove the bladder.Non-muscle-invasive disease, although it can recur fairly frequently, can often just be scooped out in a less invasive manner, with the ability to retain your bladder.

UroStream: What is the purpose of neoadjuvant therapy?

Dr. Jeffrey S. Damrauer: So, neoadjuvant therapy—or therapy given prior to radical cystectomy (removing the bladder)—is mainly about trying to kill off any small cells that have broken away from the tumor and could be throughout the body.This way, we can reduce the main tumor size but also eliminate cells that may lead to metastases or growths in other organs following surgery.

UroStream: Do all patients with MIBC need their bladder removed?

Dr. Jeffrey S. Damrauer: There’s a lot of focus now on being able to retain the bladder.One of the main factors in deciding whether or not you can avoid cystectomy is the success of neoadjuvant therapy.If, after chemotherapy, the tumor is completely gone, there’s growing research to suggest that—with close monitoring or follow-up radiation therapy—patients may be able to safely retain their bladder.

UroStream: What are the different factors that can affect the efficacy of bladder cancer therapy?

Dr. Jeffrey S. Damrauer: There’s a lot of research going on right now to understand what factors influence the success of therapy.Different mutations that occur within the tumors can affect how sensitive they are to treatment.Also, the amount of immune cells that are within or around the tumor—its so-called microenvironment—are thought to be important markers. Now, with many new therapies coming online, a lot depends on the properties of the tumor—what genes or proteins are being expressed, and whether we can target those specifically.

UroStream: What are the promising new therapies?

Dr. Jeffrey S. Damrauer: As I said, there are a lot of new therapies now that fall under precision medicine—they target the individual nature of each tumor. These include antibody-drug conjugates, which have shown to be very successful in the metastatic setting or in advanced bladder cancer. They target specific markers on the tumor and deliver drugs directly to it. There are also viral therapies being developed for non-muscle-invasive cancer. Many of these approaches focus on patient- or tumor-specific properties—really aiming to kill only bladder cancer cells while producing the least amount of side effects.