ROLE OF PROLIFERATIVE ACTIVITY ESTIMATED BY BROMODEOXYURIDINE LABELING INDEX IN DETERMINING PREDICTIVE FACTORS OF RECURRENCE IN SUPERFICIALINTERMEDIATELY MALIGNANT BLADDER-TUMORS

Purpose: Previous studies have shown that factors predictive of tumor recurrence include a history of the disease, multiple tumors at diagno sis, 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 estim ated by bromodeoxyuridine, which is believed to be a thymidine analogu e, 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 carc inoma of the bladder treated with transurethral resection. Mean follow up plus or minus standard deviation was 49.5 +/- 11.3 months (minimum 36). Tumor specimens were obtained by transurethral cold-cup biopsy, w ith bromodeoxyuridine in vitro pulse labeling then performed under hyp erbaric oxygen. The flow cytometric determination of the bromodeoxyuri dine labeled cell index and DNA ploidy were estimated. Results: When t he tumor was classified according to the bromodeoxyuridine labeled cel l index the 5-year no recurrence rates were 82.0 and 27.1% for an inde x 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 f actor 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 recur rence and single versus multiple tumors did not influence the risk fac tor for tumor recurrence. Conclusions: These data indicate that bromod eoxyuridine labeling status can be used as an objective risk factor fo r bladder cancer recurrence.