Role of proliferative activity estimated by bromodeoxyuridine labeling index in determining predictive factors of recurrence in superficial intermediately malignant bladder tumors

Purpose: Previous studies have shown that factors predictive of tumor recurrence include a history of the disease, multiple tumors at diagnosis, and high tumor grade and stage. Additional biological markers for predicting tumor recurrence could potentially be used in the decision making process and could alter the frequency of clinical cystoscopy. We attempted to clarify whether the tumor proliferative activity estimated by bromodeoxyuridine, which is believed to be a thymidine analogue, and deoxyribonucleic acid (DNA) ploidy status correlates well with tumor recurrence as an objective parameter. Materials and Methods: We evaluated 103 patients with superficial grade 2 transitional cell carcinoma of the bladder treated with transurethral resection. Mean followup plus or minus standard deviation was 49.5 +/- 11.3 months (minimum 36). Tumor specimens were obtained by transurethral cold-cup biopsy, with bromodeoxyuridine in vitro pulse labeling then performed under hyperbaric oxygen. The flow cytometric determination of the bromodeoxyuridine labeled cell index and DNA ploidy were estimated. Results: When the tumor was classified according to the bromodeoxyuridine labeled cell index the 5-year no recurrence rates were 82.0 and 27.1% for an index of less than 5.3 and more than 5.3%, respectively. Furthermore, the 5-year no recurrence rates were 75.1% for DNA diploid compared to 29.3% for DNA aneuploid tumors, respectively. Multivariate analysis using Cox's proportional hazards model showed that the most important risk factor for tumor recurrence was a bromodeoxyuridine labeled cell index of more than 5.3% (risk ratio 5.31, p < 0.001), followed by DNA ploidy (risk ratio 2.61, p < 0.05). Tumor stage, initial lesion versus recurrence and single versus multiple tumors did not influence the risk factor for tumor recurrence. Conclusions: These data indicate that bromodeoxyuridine labeling status can be used as an objective risk factor for bladder cancer recurrence.