Matthew Milowsky, MD, FASCO, a bladder cancer expert at UNC School of Medicine and UNC Lineberger Comprehensive Cancer Center, wrote that the promise of incorporating new treatments and predictive biomarkers to select the right patient for the right treatment every time offers a bright future for bladder cancer patients.

Platinum-based chemotherapy has long been the standard treatment for metastatic bladder cancer and for muscle-invasive bladder cancer where neoadjuvant chemotherapy is delivered prior to surgery. However, the landscape began to shift with the development of immune checkpoint inhibitors, which release “the brakes” on immune cells, freeing them to attack cancer cells. When combined with chemotherapy and new drug formulations, like the antibody-drug conjugate enfortumab vedotin, which the FDA approved in 2019 for the treatment of advanced bladder cancer, these treatments are notably more effective than chemotherapy alone. Now, these combination therapies are being explored to fight bladder cancer in earlier stages, with the potential to save lives and reduce the likelihood of recurrence.

Recent results from the NIAGARA trial, which evaluated using the immune checkpoint inhibitor durvalumab in combination with chemotherapy before and after surgery to remove the bladder, showed that patients treated with the combination therapy experienced a significantly higher two-year survival rate than those who received chemotherapy alone. They also had fewer cancer recurrences and a higher likelihood of disease-free progression.

NIAGARA is the first randomized phase 3 trial to upend the current standard neoadjuvant approach for muscle-invasive bladder cancer, said Milowsky, the George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research at UNC School of Medicine and co-leader of the UNC Lineberger’s Clinical Research Program.

The NIAGARA trial had some significant shortcomings. Primarily, it was not designed to measure the respective contribution of the before and after surgery durvalumab components.

“Future trials must be designed to address this limitation because we have learned time and time again that more treatment is too often not better treatment, and it may lead to increased toxic effects and compromise quality of life,” Milowsky said.

Looking ahead, Milowsky said the use of predictive biomarkers is expected to further improve bladder cancer care. These biomarkers can help identify patients at high risk of recurrence, allowing doctors to tailor treatments more effectively. One promising tool is circulating tumor DNA, which can help determine which patients will most likely benefit from perioperative therapies.

“The goal is to provide treatment only to those who need it,” Milowsky said. “By using predictive biomarkers, we can focus on patients most likely to benefit from additional therapy while sparing others from unnecessary side effects.”