Urinary concentration of human chorionic gonadotrophin and its fragments as a prognostic marker in bladder cancer

Objective
To examine the prognostic significance of elevated urinary beta human chorionic gonadotrophin (beta-hCG) in patients with bladder cancer.
Patients and methods
Total beta-hCG was measured in the urine of 142 patients referred for cystoscopic examination. Patients were followed for a minimum of 17 months and grouped according to stage of disease. Because the water output by individual patients varied, urinary creatinine levels were measured as an indicator of the concentration of the urine sample. Patient outcomes were correlated with urinary total beta-hCG levels both corrected and uncorrected for creatinine concentration. After correcting for urinary creatinine levels, 40 patients were excluded because the sample was too dilute (undetectable beta-hCG and a creatinine level of <4 mmol/L). A further four patients were excluded as they had concurrent malignancies not in the bladder and one patient was lost to follow up.
Results
None of the 52 patients with benign conditions, nine of the 27 with Ta–T1, and nine of the 25 with T2–T4 bladder disease had urinary total beta-hCG levels >3.74 IU/mmol/L creatinine. There was no significant association between urinary total beta-hCG concentrations and the rates of recurrence or progression for Ta–T1 disease at 17 months of follow-up. For patients with T2–T4 disease there was a significant association with widespread metastasis (P<0.01) and mortality (P<0.01) at 17 months of follow-up. These associations persisted when urinary total beta-hCG levels were not corrected for urinary creatinine concentration (metastasis, P<0.01; mortality, P=0.07; Kaplan–Meier survival time analysis, uncorrected for creatinine P=0.027, corrected for creatinine P<0.001). This association could not be accounted for by differences in age, histopathology or treatment.
Conclusion
Although sample concentration was a serious confounding factor, after correcting for dilution using the creatinine content, the elevated urinary levels of total beta-hCG indicated those T2–T4 lesions which were likely to metastasize and those patients likely to die early. If this test is to be used clinically, concentrated samples, i.e. early-morning urine, and a more sensitive beta-hCG assay are required. Nevertheless, for T2–T4 bladder tumours, an elevated pre-treatment level of urinary beta-hCG is a marker of poor prognosis and may prove useful in deciding appropriate therapy.