Molecular markers and their prognostic impact in patients with advanced prostate cancer undergoing intermittent androgen suppression.
OBJECTIVE
Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.


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.
Augustin
H
H
Department of Urology, LKH Graz, Medical University of Graz, Graz, Austria. herbert.augustin@meduni-graz.at
Freibauer
C
C
Bayer
L
L
Lunglmayr
G
G
Tschurlovich
F
F
Kuber
W
W
Pummer
K
K
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D002277:Carcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D017273:Goserelin / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009570:Nitriles; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology; D013739:Testosterone / Q000097:blood; D014105:Tosyl Compounds; D028761:Withholding Treatment
D000726:Androgen Antagonists; D000813:Anilides; D014408:Biomarkers, Tumor; D009570:Nitriles; D014105:Tosyl Compounds; D017273:Goserelin; D013739:Testosterone; C053541:bicalutamide