Urinary Biomarkers in Childhood Cancer Survivors With Lower Urinary Tract Dysfunction

To evaluate urinary biomarkers in childhood cancer survivors (CCS) as a screening mechanism for therapy-related lower urinary tract dysfunction (LUTD) resulting from either prior pelvic external beam radiation therapy (EBRT) or chemotherapy exposures.

First morning urine samples were collected from CCS enrolled in a prospective cohort study and analyzed for adenosine triphosphate (ATP), nerve growth factor (NGF), proNGF, brain-derived neurotrophic factor (BDNF), and creatinine. Each patient completed one non-invasive urodynamic study (niUDS). Biomarkers were compared according to radiation exposure and niUDS outcomes. Conditional logistic regression and receiver operating characteristic (ROC) analyses were used to evaluate associations with abnormal uroflow and diagnostic performance.

Biomarker levels demonstrated minimal differences between survivors with and without pelvic EBRT. Although creatinine-normalized proNGF levels were higher among irradiated participants, no biomarker was significantly associated with abnormal uroflow. In the multivariable analyses, pelvic EBRT was associated with increased odds of abnormal uroflow, but no biomarker demonstrated meaningful associations with LUTD. ROC analysis demonstrated poor discriminatory performance for all biomarkers.

The urinary biomarkers evaluated in this exploratory study did not reliably identify LUTD in CCS; neither were any biomarkers associated with prior pelvic EBRT. Given the increased risk of LUTD in CCS, particularly in those who received pelvic EBRT, and the limitations of symptom-based screening, additional objective biomarkers and screening approaches are needed to improve detection of LUTD in survivors of pediatric cancer.