Repeated biopsies in evaluation of therapeutic effects in prostate carcinoma

Background. Apoptosis is one of the major events following total androgen b lockade (TAB). The aim of this study was to determine the predictive value of some histological parameters including apoptosis and gene products which influence apoptosis, based on repeated biopsies taken from the same patien ts. Methods. At the time of diagnosis by needle biopsy TNM stage, serum PSA, Gl eason's grade, apoptotic and mitotic index, Ki67, p53, and bC12 expression were investigated in 60 prostate carcinoma patients. Antiandrogen therapy s upplemented with surgical or chemical castration was administered. Serum PS A-test and needle biopsy were repeated 13-14 weeks after starting the thera py, simultaneously with determination of the apoptotic and mitotic index, K i67, p53, and bC12 expression. Results. Forty-seven patients were alive at the end of the study, 13 patien ts died. Decrease in mitotic, increase in apoptotic index predicted favoura ble long-term response to antiandrogen therapy. Lower Ki67 and (mutant) p53 expression in the first and also in the second biopsy pointed to favourabl e effect of antiandrogen treatment. Since the ratio between Ki67 and apopto tic index strongly decreased in the survivors upon therapy, changes in Ki67 /apoptosis ratio is recommended as a histologically detectable predictive f actor. bcl(2) expression did not show significant correlation with the outc ome of the disease. Conclusions. Histological evaluation of mitotic and apoptotic index, Ki67, and p53 expression in repeated biopsies contributes to predicting the value of the actual treatment and may be useful to institute alterations in ther apy. Prostate 49: 93-100, 2001. (C) 2001 Wiley-Liss, Inc.