A  joint research team from Seoul National University Bundang Hospital (SNUBH) and other hospitals has identified urine acidity as a potential biomarker to predict treatment outcomes in patients with non-muscle invasive bladder cancer (NMIBC).

A joint research team has identified urinary acidity as a predictive biomarker for bladder cancer recurrence following BCG therapy. From left are, Professors Lee Sang-chul of Seoul National University Bundang Hospital, Ryu Ho-young of Ewha Womans University Mokdong Hospital, and Song Byeong-do of Hanyang University Guri Hospital. (Credit: SNUBH)
A joint research team has identified urinary acidity as a predictive biomarker for bladder cancer recurrence following BCG therapy. From left are, Professors Lee Sang-chul of Seoul National University Bundang Hospital, Ryu Ho-young of Ewha Womans University Mokdong Hospital, and Song Byeong-do of Hanyang University Guri Hospital. (Credit: SNUBH)

NMIBC is an early-stage form of bladder cancer that has not penetrated the bladder muscle wall and accounts for approximately 70 percent of all bladder cancer cases.

While surgery can remove the tumor, the disease carries a high risk of recurrence. Patients typically undergo intravesical immunotherapy with bacillus Calmette–Guérin (BCG), a treatment derived from tuberculosis bacteria, to reduce this risk. However, around 40 percent of patients experience recurrence even after BCG therapy, highlighting the need for reliable predictors of treatment response.

Previous studies have suggested that an acidic microenvironment can suppress immune cell activity and diminish the effectiveness of immunotherapy.

Building on this, the team, led by Professors Lee Sang-chul of the Department of Urology at SNUBH, Ryu Ho-young of the Department of Urology at Ewha Womans University Mokdong Hospital, and Song Byeong-do of the Department of Urology at Hanyang University Guri Hospital, investigated whether the acidity of the bladder environment, reflected in urinary pH, influences the efficacy of BCG therapy.

The researchers analyzed data from 578 NMIBC patients who underwent tumor resection followed by BCG treatment between 2003 and 2021. Patients were divided into two groups based on pre-treatment urine pH -- an acidic urine group with pH below 5.5 and a non-acidic urine group with pH at or above 5.5.

The study revealed a significant difference in recurrence rates -- 42.4 percent in the acidic urine group versus 33.8 percent in the non-acidic group. Multivariate analysis factoring in age, smoking history, tumor size and number confirmed that acidic urine independently increased the risk of bladder cancer recurrence by approximately 45 percent.

“This research demonstrates that urinary acidity can influence BCG treatment response and could serve as a predictive biomarker for prognosis,” Professor Lee said. “A simple urine test performed before treatment could help predict patient outcomes, reduce uncertainty, and support the development of personalized treatment strategies.”

Professor Song also stressed the need for future studies that will examine whether modulating bladder acidity can enhance BCG efficacy.

“We aim to establish clinical evidence to support therapeutic approaches that improve outcomes by addressing urinary acidity,” Song said.

The findings were published in the SCIE-indexed international journal World Journal of Urology.

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