Matthew Milowsky, MD, FASCO, a bladder cancer expert at the UNC School of Medicine and the 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 given before surgery. However, the landscape began to change with the development of immune checkpoint inhibitors, which release the “brakes” on immune cells, leaving them free to attack cancer cells. When combined with chemotherapy and new drug formulations, such as 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 investigated to fight bladder cancer at earlier stages, with the potential to save lives and reduce the likelihood of recurrence.

Recent results from the NIAGARA trial, which evaluated the use of 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 improve upon the current standard approach to neoadjuvant for muscle-invasive bladder cancer, said Milowsky, the George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research at the UNC School of Medicine and co-director of the UNC Lineberger Clinical Research Program.

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

“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 can 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 the treatment of bladder cancer. These biomarkers can help identify patients at high risk of relapse, allowing doctors to tailor treatments more effectively. One promising tool is circulating tumor DNA, which may help determine which patients are most likely to 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.”