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

• Published in: Prostate cancer and prostatic diseases Vol. 9; no. 3; pp. 279 - 283
• Main Authors: Augustin, H, Freibauer, C, Bayer, L, Lunglmayr, G, Tschurlovich, F, Kuber, W, Pummer, K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.09.2006
• Subjects: Aged; Aged, 80 and over; Androgen Antagonists - therapeutic use; Androgens; Anilides - administration & dosage; Anilides - therapeutic use; Antigens; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bcl-2 protein; Biomarkers, Tumor - analysis; Biopsy; Carcinoma - diagnosis; Carcinoma - drug therapy; Carcinoma - pathology; Cell Proliferation; Deprivation; Gene Expression Regulation, Neoplastic; Goserelin - administration & dosage; Goserelin - therapeutic use; Humans; Male; Markers; Middle Aged; Multivariate analysis; Neoplasm Staging; Nitriles; Parameters; Patients; Prognosis; Prostate cancer; Prostate-specific antigen; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - pathology; Recovery time; Regression analysis; Testosterone; Testosterone - blood; Tosyl Compounds; Tumors; Withholding Treatment
• ISSN: 1365-7852; 1476-5608
• DOI: 10.1038/sj.pcan.4500883

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