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 stu...

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Veröffentlicht in:International journal of radiation oncology, biology, physics biology, physics, 2000-03, Vol.46 (5), p.1213-1221
Hauptverfasser: Rödel, Claus, Grabenbauer, Gerhard G, Rödel, Franz, Birkenhake, Stefan, Kühn, Reinhard, Martus, Peter, Zörcher, Thomas, Fürsich, Dominik, Papadopoulos, Thomas, Dunst, Jürgen, Schrott, Karl M, Sauer, Rolf
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Sprache:eng
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Zusammenfassung: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.
ISSN:0360-3016
1879-355X
DOI:10.1016/S0360-3016(99)00544-1