Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression

Prostate Cancer Prostatic Dis. 2006;9(3):279-83. doi: 10.1038/sj.pcan.4500883. Epub 2006 May 16.


Objective: Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.

Patients and methods: Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time.

Results: In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022).

Conclusions: During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use*
  • Anilides / administration & dosage
  • Anilides / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols
  • Biomarkers, Tumor / analysis*
  • Biopsy
  • Carcinoma / diagnosis
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Goserelin / administration & dosage
  • Goserelin / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Nitriles
  • Prognosis
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology
  • Testosterone / blood
  • Tosyl Compounds
  • Withholding Treatment


  • Androgen Antagonists
  • Anilides
  • Biomarkers, Tumor
  • Nitriles
  • Tosyl Compounds
  • Goserelin
  • Testosterone
  • bicalutamide