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

Int J Radiat Oncol Biol Phys. 2000 Mar 15;46(5):1213-21. doi: 10.1016/s0360-3016(99)00544-1.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Apoptosis*
  • Biomarkers, Tumor / analysis*
  • Combined Modality Therapy
  • Female
  • Humans
  • Ki-67 Antigen / analysis*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Survival Rate
  • Tumor Suppressor Protein p53 / analysis*
  • Urinary Bladder
  • Urinary Bladder Neoplasms / chemistry*
  • Urinary Bladder Neoplasms / drug therapy
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / radiotherapy


  • Biomarkers, Tumor
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53