Intravesical Bacillus Calmette‑Guérin (BCG) following transurethral resection of bladder tumour (TURBT) remains the primary treatment strategy for intermediate‑ and high‑risk non‑muscle‑invasive bladder cancer (NMIBC). Nevertheless, around four in ten patients experience cancer recurrence despite BCG induction, which warrants further investigation as to why this might be.
A newly published study in the World Journal of Urology* (April 2025) by Hoyoung Ryu et al. might shed some light on this issue, as they may have exposed a link between treatment outcomes and the pH value of a patient’s urine. If this is the case, then this could serve as a highly useful prognostic biomarker for recurrence risk after TURBT plus BCG induction.
Study Design & Patient Cohort
The study retrospectively assessed 578 patients with intermediate‑ to high‑risk NMIBC, treated with TURBT followed by intravesical BCG induction, between May 2003 and April 2021.
The participants were stratified by urine pH at baseline:
- Acidic urine: pH ≤ 5.5
- Non‑acidic (higher) urine: pH > 5.5
Baseline Characteristics & Biochemical Correlates
Patients with acidic urine displayed several notable laboratory differences compared to the higher‑pH group:
- Elevated fasting plasma glucose (p = 0.017)
- Increased serum uric acid (p = 0.011)
- Lower estimated glomerular filtration rate (eGFR) (p = 0.022)
- Higher rates of abnormal urinary cytology (p = 0.021)
Most importantly, there were no significant differences in adverse clinicopathological features – such as tumour grade, stage, multifocality, or size – between the two groups.
Recurrence Outcomes
Over a median follow‑up of 56 months, significantly higher rates of recurrence were found in patients with acid urine (pH > 5.5) compared to those with non-acid urine (pH ≤ 5.5) – 42.2% vs 33.8%.
As for disease progression to muscle‑invasive or metastatic disease, no significant difference was noted between urine‑pH groups.
Independent Prognostic Value
Multivariate analysis demonstrated that acidic urine independently predicted higher recurrence risk – even after adjusting for established prognostic variables such as age, smoking history, tumour size, and other clinicopathologic factors – indicating a recurrence risk of around 45% for patients with acidic urine.
Mechanistic Considerations
The authors propose that an acidic urinary microenvironment may impair BCG‑mediated immune responses. BCG relies on immune cell activation (notably macrophages and T cells) within the bladder to work effectively – so an acidic pH may suppress this activity and compromise therapeutic efficacy.
On top of this, prior research suggests that acidic urine may favour carcinogenic processes, particularly by enhancing the activation of aromatic amines from cigarette smoke, leading to DNA damage in urothelial cells – potentially promoting recurrence.
What Are The Clinical Implications?
Testing urine pH before treatment could now be a useful way of identifying patients at higher recurrence risk despite BCG induction.
Then, for patients found to have acidic urine, therapeutic strategies could include urine alkalinisation (via dietary measures or buffering agents), along with frequent monitoring.
Further research is warranted to provide further validity, and to explore mechanisms (in vitro and in vivo immunologic studies) to determine whether or not pH modulation does actually improve BCG response.
Potential Limitations of the Study
Due to its retrospective, single-institution nature (or limited institution base), the study introduces potential selection and measurement biases.
Also, the typical dipstick-based method for measuring urine pH
may be less accurate than pH electrode analysis.
The study did not evaluate whether interventions to modify urine pH could alter cancer recurrence risk – meriting future interventional studies, as previously mentioned.
In Conclusion
Ryu et al. provide compelling evidence that acidic urine (pH ≤ 5.5) is an independent risk factor for recurrence after TURBT plus BCG in intermediate- and high-risk NMIBC – raising the intriguing potential of urine pH as a simple, cost-effective biomarker. It opens exciting doors for enhancing personalised care: from evaluating prognostics to developing novel interventions targeting the bladder microenvironment.
We would like to see further prospective studies to see whether, in fact, modulating urine pH can improve clinical outcomes for NMIBC patients – which is a rather appealing concept given the relative ease of measuring and potentially manipulating urinary acidity.
*Acidic urine as a prognostic factor after intravesical Bacillus Calmette-Guérin induction therapy for nonmuscle-invasive bladder cancer
Hoyoung Ryu et al.
