New research from Duke Cancer Institute (DCI) is helping uncover why some bladder cancer patients are less likely to benefit from a common treatment and how a patient’s cancer history may help guide more personalized care decisions in the future.
For more than 50 years, Bacillus Calmette-Guérin (BCG) treatment has been the standard of care for patients with early-stage bladder cancer. It helps reduce the chances that cancer will come back after surgery, and it works well for many patients. But not all bladder cancers behave the same.
Bladder cancer is one form of a broader group known as urothelial cancers, which can develop anywhere along the urinary tract. Most cases begin in the bladder itself and are often caught early because patients develop symptoms, such as blood in the urine. These early-stage cancers are typically treated with surgery followed by BCG, which is delivered directly into the bladder to help prevent recurrence.
However, about 10 percent of urothelial cancers originate in the upper urinary tract—in the kidneys or ureters. Even after those tumors are treated, cancer can later reappear in the bladder.
“Historically, we’ve treated these bladder recurrences the same way we treat primary bladder cancer,” said Yu Guang Tan, MD, a urology fellow at Duke and a collaborator from Duke-NUS Medical School in Singapore. “But the question is, are they really the same disease?”
In a recent study published in Urologic Oncology, Tan worked with colleagues including Michael Abern, MD, co-chair of the DCI Center for Prostate and Urologic Cancers, to explore whether bladder cancers that arise after upper tract disease respond differently to BCG than cancers that originate in the bladder.
Across both a single-institution study and a larger systematic review and meta-analysis of more than 1,300 patients worldwide, the team found a consistent pattern: patients with a history of upper tract urothelial cancer were significantly more likely to experience recurrence or disease progression after BCG treatment.
“In some cases, nearly half of these patients did not respond well to BCG,” Tan said. “That’s a substantial number, and it suggests we may need to think differently about how we treat this group.”
BCG has long been the backbone of therapy for non-muscle invasive bladder cancer, but it is not without limitations. In addition to variable effectiveness, the treatment has also faced periodic shortages, particularly in smaller or rural care settings.
“This research gives us another piece of the puzzle,” Abern said. “If a patient has a history of upper tract disease, it may shape expectations about how well BCG will work and whether we should consider other options sooner, including clinical trials.”
Tan and Abern both emphasize that BCG remains an important and effective therapy for many patients. The goal is not to replace it, but to better match treatments to the patients most likely to benefit.
One of the most important implications of the study is its potential role in advancing precision medicine for bladder cancer. The team found that while these cancers may look similar under the microscope, they are likely biologically distinct. That difference may explain why they respond differently to treatment.
“We think this history of upper tract cancer may act as a clinical biomarker,” Tan said. “It helps us predict how a patient might respond, but we still need to understand the biology behind it.”
To answer that question, the researchers are now conducting whole genome sequencing studies to identify the genetic differences between these tumor types. They are also building a joint database between Duke and Duke-NUS to uncover additional factors that may influence treatment outcomes.
“It’s an exciting time in bladder cancer research,” Tan said. “We have many new therapies emerging, and the challenge now is figuring out which treatment is best for which patient.”
The research reflects a strong international partnership between Duke University and Duke-NUS Medical School in Singapore. By bringing together data from multiple countries and healthcare systems, the team was able to confirm that these findings are consistent across diverse patient populations.
“That global perspective is really important,” Abern said. “It shows that this trend holds true across different regions, which makes the findings more robust and meaningful.”
As new therapies, including immunotherapy and targeted treatments, continue to emerge, studies like this one will play a key role in shaping how patients are selected for different treatment approaches.
“By better understanding these differences, we can improve how we counsel patients, design clinical trials, and ultimately deliver more personalized care,” Abern said.
