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. 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.