Maximale Androgenblockade

Abstract

According to the representative data of the Tumor Registry Munich, 38.1 % of prostate cancer patients received a primary androgen deprivation, whereas 20.5 % had an adjuvant hormonal treatment. Following surgical castration being the most common form of androgen deprivation, 5 alpha-dihydrotestosterone is still present in prostate cancer tissue. Therefore, a maximal androgen blockade (MAB) consisting of a chemical or surgical castration plus a pure or antigonadotropic antiandrogen, has been proposed. Indeed, MAB lowers the dihydrotestosterone-androgen-receptor complex and suppresses the growth-factor dominated signal transduction. This leads to a measurable increase of apoptosis. New is the finding that LHRH as well as LH (for example following surgical castration) are bound by receptors located at the prostate cancer cell. In 30 phase-III trials, MAB has been tested against monotherapy and a cancer-specific survival advantage of 3 to 6 months and a approximately 6-month delay of progression was demonstrated. The most effective form of MAB is the combination of a LHRH agonist - in contrast to surgical castration - with a well-tolerated pure antiandrogen. The quality of life during MAB is low, if a pure antiandrogen such as flutamide is used which leads to rather serious side-effects. At the present time, special indications for MAB are patients with minimal metastases, bone pain at the time of diagnosis, a neoadjuvant or adjuvant application in combination with a radical prostatectomy or radiotherapy and particularly intermittent androgen deprivation which is tested at the present time in at least 5 international studies. An endocrine withdrawal syndrome is observed in approximately 30 % of patients, if, following a PSA-relapse, the antiandrogen is discontinued. Little notice has been given to the use of prognosticators for the decision, whether a MAB is useful or not. Patients with good prognostic factors as defined by Sylvester have a clear advantage, if MAB is compared to monotherapy, whereas patients with a pure prognosis did not benefit. In addition to these prognostic factors up-front, the PSA dynamics under an initial MAB may be employed for the decision, if this form of androgen deprivation is to be continued or not. In essence, in contrast to a general use of MAB a more differential application based on quality-of-life issues and prognosis should be preferred.

Prostate-Specific Antigen Dynamics Predict Risk of Progression in Advanced Prostate Cancer Treated with Bicalutamide plus Castration

“…Similarly, this study demonstrated a clear relationship between PSA levels at weeks 4 and 12 and the risk of progression, therefore failure of the PSA to fall to a low level within 12 weeks of starting CAB also indicates a poor prognosis. In this way, a differential approach to treatment with CAB may be employed, based on qualityof-life issues and prognosis [16].…”