New Approach May Reduce Recurrence in Muscle-Invasive Bladder Cancer

At the 2026 ASCO Genitourinary Cancers Symposium, the KEYNOTE-B15 trial revealed that combining Padcev (enfortumab vedotin) with Keytruda (pembrolizumab) alongside surgery may improve survival compared with traditional chemotherapy for patients with muscle-invasive bladder cancer (MIBC).

To break down the study and what it means for patients, Dr. Matthew Galsky, professor of medicine (hematology and medical oncology), deputy director of the Mount Sinai Tisch Cancer Center, director of Genitourinary Medical Oncology, and co-director of the Center of Excellence for Bladder Cancer, spoke with CURE about the results and their potential impact on care.

You can read the full findings from the KEYNOTE-B15 study here!

What should patients know about the KEYNOTE-B15 study?

The KEYNOTE-B15 study was a study testing a new regimen of medications given intravenously before and after surgery to remove the bladder. The reason that we give medications intravenously before and after surgery when patients have MIBC is because, with surgery alone, a subset of patients will have the cancer show up somewhere else months to years later. That is called metastatic disease.

When metastatic disease happens, it is because even before the bladder was removed, microscopic cancer cells disseminated from the original tumor to elsewhere in the body. These are too small to be seen, but over time, those cells can grow. We give this medication intravenously to try and eradicate those cells and to help the surgery that is taking care of the primary tumor.

Cisplatin-based chemotherapy given for about three months before surgery has been the standard of care for about 25 years, and it has been hard to beat that. There were a few attempts, but it remained the standard. Now, for patients with bladder cancer that has spread, we use a new regimen as of a few years ago that was shown to be much better than our older chemotherapy.

This new regimen is comprised of two drugs. One of them is called an antibody-drug conjugate, which is a protein designed to bind to cancer cells with chemotherapy attached to it. Some people have described it as a sort of "smart bomb" approach, as it tries to deliver chemotherapy more specifically to the intended target. It is given with a drug called Keytruda, which is an immune checkpoint inhibitor (loosely called immunotherapy) that tries to get the body’s immune system to fight cancer.

Since that combination has become our standard treatment for metastatic bladder cancer, it was logical to move this regimen earlier to the muscle-invasive setting to see if we could cure more patients by giving it with surgery compared to our older chemotherapy.

The study randomized 808 patients to this new regimen with surgery versus our older regimen with surgery. The primary end point of the study is something we call event-free survival, which is basically the amount of time before cancer comes back or worsens.

There was a substantial reduction in the likelihood of cancer progressing or coming back with the new regimen compared to the older one. There was also a significantly longer time that patients lived with the newer regimen, suggesting that, yes, we are curing more patients with MIBC with this new approach.

Transcript has been edited for clarity and conciseness.

References

1. “Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study,” by Dr. Matthew Galsky, et al. Journal of Clinical Oncology.

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