PROGNOSTIC FACTORS IN PROSTATE-CANCER

The clinical course of prostate cancer (PCa), the most common cancer i n Swedish men, is highly variable and difficult to predict. Consequent ly, there is an urgent need to distinguish tumours with a high risk of progression from those with a low risk. To investigate the prognostic implications of proliferation and apoptosis, two important processes in tumour biology, immunoreactivity for biomarkers associated with the se processes was assessed, quantified in indexes, and related to cause -specific survival (CSS). A consecutive series of 186 men presenting w ith voiding symptoms and PCa were treated with transurethral resection and deferred endocrine therapy. After 13-21 years follow-up, 43% of t hese men had died of prostate cancer. In a subgroup of men with locali sed disease at the time of diagnosis, 27% succumbed to the disease. Im munoreactivity for p53 protein, indicative of a defective p53 function , predicted shorter CSS in univariate (52 vs 123 months, p<0.0001), bu t not in multivariate analysis. Mean index for the apoptosis blocking bcl-2 protein was higher in foci of prostatic intraepithelial neoplasi a, a putative precursor to PCa, than in manifest cancer areas (79 vs 1 2, p<0.0001). This indicates that bcl-2 may be involved in early tumou rigenesis. No prognostic value was found for the bcl-2 index. A high i ndex for the proliferation marker Ki-67 predicted shorter CSS in univa riate (53 vs 132 months p<0.0001) and in multivariate analysis. To tes t if p53 is predictive for clinical radioresistance, as suggested by e xperimental models, p53 immunoreactivity was investigated in biopsies obtained before radical radiotherapy in an unrelated series of 60 PCa patients. Patients with p53 reactive tumours had longer CSS, indicatin g that p53 is not treatment-predictive for radiotherapy in Pca. Core b iopsies were obtained before and a week after castration therapy in pa tients with advanced PCa. According to the serum prostate specific ant igen (PSA) level 3 months after therapy, 15 responding tumours and 13 non-responding tumours were selected. Regressive morphology was seen i n 14/15 responders after castration therapy, compared with 4/13 non-re sponders. Median apoptotic index increased significantly after castrat ion therapy for responders (from 2.6 to 3.5, p<0.05) whereas it was 2. 8 before and after therapy in non-responders. This indicates that subs equent clinical response can be predicted by the induction of regressi ve morphology and an increase in apoptotic index. In conclusion, immun oreactivity for Ki-67 appeared to be a putative prognostic factor in P Ca, whereas the prognostic value of p53 and bcl-2 was dubious. p53 imm unoreactivity did not appear to be predictive of radioresistance in PC a. Cellular response in biopsies shortly after castration therapy migh t be treatment-predictive.