Pretreatment Proliferation and Local Control in Bladder Cancer after Radiotherapy with or without Concurrent Chemotherapy

Abstract

To investigate whether the addition of chemotherapy to radiotherapy (RT) is beneficial particularly in bladder tumors that possess the capacity for rapid proliferation. The Ki-67 index was evaluated by immunohistochemistry on pretreatment biopsies from 136 patients treated by transurethral tumor resection (TURBT) and RT (n=50) or platin-based radiochemotherapy (RCT; n=86). Ki-67 expression was correlated with response to RT/RCT and long-term local control rates. The median follow-up was 43 months. The percentage of Ki-67-positive cells ranged from 1.5% to 89%. Complete response (CR) was observed in 100/131 patients (76%, five without restaging TURBT). A statistically significant association between high Ki-67 index (>or= median) and CR was noted for patients receiving RCT (93% vs. 66% for Ki-67 < median; p=0.001), but not for patients treated with RT alone (p=0.12). Long-term local control was 39% for patients treated with RT, and 44% for patients after RCT (p=0.49). Patients with high Ki-67 index did significantly better when subjected to combined RCT (55% vs. 33% with low Ki-67 index; p=0.006), whereas no difference between high and low Ki-67 status was observed in the RT group (39% each; p=0.57). On multivariate analysis, Ki-67 status was an independent predictor for local failure in the RCT group (risk ratio, 0.43; p=0.007). Disease-specific survival was significantly better after RCT (62%) as compared with RT (42%; p=0.03), however, the Ki-67 index was not related to this endpoint. Rapid proliferation is associated with improved local control, if patients are treated with concurrent RCT. The cytostatic effect of concurrent chemotherapy may effectively inhibit repopulation during fractionated RT.