Apoptosis, p53, bcl-2, and Ki-67 in invasive bladder carcinoma: Possible predictors for response to radiochemotherapy and successful bladder preservation

Purpose: Several groups have reported the value of bladder preservation by a combined treatment protocol, including transurethral resection (TUR-B) and radiochemotherapy (RCT). As more experience is acquired with organ-sparing treatment, patient selection should be optimized. The purpose of this study was to investigate the role of several biologic markers that may predict response to RCT in muscle-invasive bladder carcinoma. Methods and Materials: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 70 patients treated for invasive bladder cancer by TUR-B and RCT. Expression of each marker was correlated with initial response, local control, and cancer-specific survival with preserved bladder. An exploratory multivariate analysis was also performed that included clinical and immunohistochemical variables.Results: A high AI (> median = 1.6%) and a high Ki-67 index (> median = 8.8%), but not the p53- and bcl-2 expression, were significantly related to initial complete response (CR) and local control with preserved bladder after 5 years. When the AI and Ki-67 expression were considered simultaneously, the association with initial CR (p < 0.001), local control (p = 0.0002), and cancer-specific survival with preserved bladder (p = 0.008) was highly significant. In an exploratory multivariate analysis (final model), only AI, Ki-67, and the combined AI/Ki-67 variable retained significance for local control with preserved bladder at 5 years. Conclusion: Patients with a high spontaneous AI and a high pretreatment Ki-67 index should be considered preferentially for treatment with RCT, whereas tumors with low proliferation and low levels of apoptosis are less likely to respond to RCT. Copyright (C) 2000 Elsevier Science Inc.