Presenter(s)
P. Chaudhary1, L. K. Ballas2, and X. Li1; 1Cedars-Sinai Medical Center, Los Angeles, CA, CA, 2Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): Bladder cancer exhibits high rates of recurrence and progression despite successful radical cystectomy and trimodal therapy (TMT). The underlying biological drivers of relapse are poorly defined. Blood urea nitrogen (BUN), widely used clinically as a marker of renal function, is one of the most abundant urinary metabolites. Epidemiologic associations between high urea and urothelial malignancy raise the possibility that urea itself contributes to bladder cancer–promoting effect. We investigated whether circulating BUN serves as a clinically relevant biomarker for prognosis, recurrence risk, and therapeutic response in bladder cancer, and explored the biological effects of urea on tumor growth and drug resistance.
Materials/Methods: BUN levels were retrospectively analyzed in 168 patients diagnosed with bladder cancer (121 males, 47 females; age range 30 to <95 years). Sex- and age-stratified distributions were assessed. Overall survival (OS) was evaluated in 153 patients with up to 10 years of follow-up, comparing normal BUN (6–24 mg/dL) versus high BUN (>24 mg/dL). OS was evaluated in 110 cystectomy patients and 43 TMT patients. Recurrence-free survival (RFS) was analyzed in 96 patients undergoing radical cystectomy using pre-operative BUN with up to 15 years of follow-up. Associations between BUN and pathological Tumor, Node, and Metastasis (TNM stage) were analyzed. Mechanistic relevance was assessed using in vitro studies in human bladder cancer T24 cells.
Results: BUN levels were significantly higher in male bladder cancer patients compared with females. Age-stratified analysis revealed an increased number of patients with elevated BUN in the 60–90-year age range, with BUN levels rising with advancing age. High BUN (>24 mg/dL) was associated with significantly reduced OS compared with normal BUN (Log-rank ?² = 9.518, df = 1, P = 0.0020). Among radial cystectomy patients, high preoperative BUN predicted worse RFS (Log-rank ?² = 4.176, df = 1, P = 0.041). In patients receiving , high BUN was strongly associated with inferior OS (Log-rank ?² = 11.25, df = 1, P = 0.0008). However, given the relatively small sample size, validation in larger, independent cohorts will be required to confirm these findings. Although BUN levels did not significantly correlate with pathological TNM stage, in vitro, urea treatment in T24 human bladder cancer cells increased cell proliferation and cisplatin resistance. Treatment with urea increases IC50 of Cisplatin from 6.79 µM to 13.83 µM.
Conclusion: Elevated BUN identifies bladder cancer patients with poorer survival and higher recurrence risk after cystectomy. These findings support BUN as a low-cost, widely available biomarker for risk stratification and suggest urea as a previously underappreciated metabolic driver of bladder cancer progression and therapy resistance. Further study is warranted to evaluate BUN effect on progression free survival in RC and TMT populations.