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Prognostic Value of Serial Tissue Prostate-specific Antigen Measurements during Different Hormonal Treatments in Prostate Cancer Patients¹

Research Laboratory for Reproductive Health, Department of Woman and Child Health, Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm [M. G., Å. P.], and the Departments of Obstetrics and Gynecology [M. G., K. C.], Pathology [B. L. R.], Urology [R. S.], and Clinical Research Center [K. C.], Karolinska Institutet, Huddinge University Hospital, S-14186 Huddinge, Sweden

To reveal the effects of different hormonal treatments directly on the prostate during treatment, the concentration of prostate-specific antigen in the tissue (T-PSA) was studied in 63 patients with untreated newly diagnosed carcinoma of the prostate (CaP). T-PSA measurements were performed in fine-needle aspiration biopsies at the time of diagnosis and 6, 12, and 24 months after initiation of treatment. Treatments modalities were bilateral orchidectomy, gonadotropin-releasing hormone (GnRH) agonists, or parenteral estrogens. Thirty-one (49%) of the patients died of CaP and 18 (29%) of other diseases. Fourteen of the patients (22%) were still alive at the end of the observation period (median follow-up time, 111.5 months; range, 98–128 months). In all of the 31 patients who died of CaP, T-PSA values increased during treatment. This increase was observed long before clinical signs of progression appeared (median of interval, 14 months). Twenty of these 31 patients showed an increase in T-PSA from pretreatment values at 6 months. At 12 months this increase was observed in 30 of 31 patients. In contrast, in all of the patients who responded to the hormonal regimen, T-PSA values decreased and remained low during treatment. Furthermore, the patients who did not die of CaP and received estrogen treatment had significantly higher T-PSA values compared with those who were treated with bilateral orchidectomy or GnRH agonists. This indicates that estrogens may stimulate PSA synthesis in tumor tissue in vivo in the presence of castration levels of testosterone.

Statistical evaluation showed that the T-PSA ratio between month 12 and month 0 had the most significant prognostic value for predicting the clinical outcome. This ratio was superior to clinical classifications, e.g., tumor stage and cytological grade, and also was higher than T-PSA at the time of diagnosis. This study has shown that aspiration biopsy material can be used to reveal biochemical changes in the tissue during treatment and that one specific marker (T-PSA) can predict the clinical outcome of endocrine treatment of CaP patients better than previously used methods. We believe that selected tissue markers or the protein pattern can help us to characterize the tumors and predict the clinical outcome so an optimal treatment can be chosen for every patient.

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