B Mohandessi | PubMed Health

PubMed2000

[Early detection of prostate carcinoma. What diagnosis is of value when?].

Early detection of carcinoma of the prostate is based on digital rectal examination of the gland (DRE), transrectal ultrasonic exploration of the gland (TRUS) and determination of the prostate specific antigen (PSA) in the serum. The sensitivity of DRE along, but also in conjunction with TRUS is inadequate for early detection. Furthermore, two-thirds of all palpable prostate carcinomas have already breached the organ (T3), and are no longer curable by such local measures as radical prostatectomy or radio-therapy. Nevertheless, DRE is mandatory, since, when an induration is palpable, a prostate biopsy should be obtained even when the PSA is normal (< 4 ng/ml). Imaging procedures, such as TRUS or endorectal NMR have only a secondary role in early detection, while TRUS is indispensable for a controlled biopsy of the prostate. The most important early detection measure is the annual determination of PSA (syn. traditional or total PSA), during which both bound and free PSA is determined using an immunoassay. A chronic problem with the evaluation of serum levels of this organ marker - which is not an antigen specific for prostate carcinoma - is the fact that although it has an acceptable sensitivity (> 90%),its specificity is low (40% false positive findings). Attempts have been made to reduce the rate of unnecessary biopsies by measuring free PSA, PSA-density, age-corrected PSA or bound PSA. However, such attempts have failed to improve the efficacy of traditional PSA measurement in the individual case. In the guidelines relating to the diagnosis of prostate carcinoma established by the German urologists, the present recommendation requires PSA measurement once a year from the age of 45 onwards.

Adult↗

PubMed2000

[Maximal androgen blockade].

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.

Androgen Antagonists↗