Recent advances in urothelial carcinoma treatments may offer a path to curative care for more patients, including those with high-risk localized, muscle-invasive disease, according to an editorial published by Milowsky in The New England Journal of Medicine. The findings indicated that incorporating novel treatments and predictive biomarkers to more effectively select the most appropriate treatment options may improve the treatment of patients with urothelial carcinoma.
Background
Platinum-based chemotherapy has long been the standard treatment option for metastatic urothelial carcinoma and muscle-invasive urothelial carcinoma, where neoadjuvant chemotherapy is delivered prior to surgery. However, the landscape began to shift with the development of immune checkpoint inhibitors. When combined with chemotherapy and new drug formulations such as the antibody-drug conjugate enfortumab vedotin—which the U.S. Food and Drug Administration approved in 2019 for the treatment of advanced urothelial carcinoma—these treatments may be notably more effective than chemotherapy alone. Currently, these combination therapies are being explored to eliminate urothelial carcinoma in earlier stages, with the potential to increase survival and reduce the likelihood of recurrence.
Key Findings
Recent results from the NIAGARA trial, in which researchers evaluated the use of the immune checkpoint inhibitor durvalumab in combination with chemotherapy prior to and following cystectomy, demonstrated that patients treated with the combination therapy experienced a significantly higher 2-year survival rate than did those who received chemotherapy alone. The patients also experienced fewer cancer recurrences and a higher likelihood of disease-free progression.
The NIAGARA trial was one of the first randomized phase III trials to upend the current standard neoadjuvant approach for muscle-invasive urothelial carcinoma. However, the study had 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,” emphasized editorial author Matthew Milowsky, MD, FASCO, the George Gabriel and Frances Gable Villere Distinguished Professor of Bladder and Genitourinary Cancer Research and a bladder cancer expert at the University of North Carolina at Chapel Hill (UNC) School of Medicine as well as Co-Leader of the Clinical Research Program at the UNC Lineberger Comprehensive Cancer Center.
The use of predictive biomarkers is expected to further improve urothelial carcinoma care. These biomarkers may help to identify patients at high risk of recurrence, allowing physicians to tailor treatments more effectively. For instance, circulating tumor DNA may help to determine which patients will most likely benefit from perioperative therapies.
Conclusions
“The goal is to provide treatment only to those who need it,” underscored Dr. Milowsky. “By using predictive biomarkers, we can focus on patients most likely to benefit from additional therapy while sparing others from unnecessary side effects,” he concluded.
Disclosure: For full disclosures of the study authors, visit nejm.org.
