Androgens in Health and Disease.pdf - E Library

Chapter 9/Androgen Signaling in Prostatic Neoplasia and Hyperplasia 177
improvement of 3.5% (95% CI: 0–7) was not significant. Log rank time-to-death analyses
failed to detect significant heterogeneity between trials or significant differences
between the effects of various types of maximum androgen blockade. The authors concluded
that maximum androgen blockade did not result in longer survival than castration
alone. A more recent report provides a 10-yr follow-up comparing goesrelin acetate
alone with goesrelin plus flutamide (251). The study involved 589 patients, 55% of
whom had metastatic disease at the outset. The hazard ratio to survival was 0.88 (95%
CI: 0.68–1.25).
The side effects of androgen blockade are significant, and differences are noted in
cost-effectiveness. Bilateral orchiectomy may cause psychological trauma, and
antiandrogens may cause tumor flare, hot flashes, gynecomastia, and anemia (251).
Long-term, castration, and antiandrogen therapies may cause osteoporosis. Estrogen
administration may increase cardiovascular complications, but anemia and osteoporosis
are less problematic. Orchiectomy is the most cost-effective, and maximum androgen
blockade is the least cost-effective treatment (252).
It has been hypothesized that intermittent androgen blockade may prolong survival
and reduce symptoms associated with androgen deprivation (253). Forty-three patients
with M1b prostate cancer were treated for 12 mo in a nonrandomized study with androgen
deprivation (254). Treatment was stopped until the PSA exceeded 20 ng/mL or
when local failure or new bone metastases were detected. In the second treatment
period, seven patients experienced hormone-independent tumor growth and died with
a mean survival time of 27 mo. Thirty-five patients were responders. In another study,
androgen ablation was administered until PSA levels became undetectable or plateaued
(255). The time of therapy decreased as the number of treatment cycles increased. The
follow-up ranged from 7 to 60 mo (mean: 30 mo), and an average of 45% of the time
was spent not receiving androgen ablation. It should be recognized that T levels may
be suppressed for extended periods in older men after androgen suppression is stopped.
Serum T levels were prospectively measured at 3-mo intervals in 68 men after stopping
androgen-deprivation therapy (256). T levels >270 ng/dL were observed in 28%, 48%,
and 74% of men at 3, 6, and 12 mo, respectively. Thus, this approach may save money
and avoid some side effects; however, patients may not be hormonally normal between
treatment periods. Randomized trials are ongoing to determine if intermittent androgen
blockade has merit.
It has been hypothesized that antiandrogen treatment prior to radical prostatectomy
or prior to radiation treatment of localized disease may improve cure rates (257).
Neoadjuvant hormonal therapy decreased the rate of positive margins in six of seven
randomized prospective studies (258). Seminal vesicle invasion was not reduced in four
studies and only one of four showed a reduction in lymph node metastases. There also was
no difference in the time to a rise in PSA levels. Follow-up for these studies is limited to
48 mo, so long-term survival rates are not yet available. However, neoadjuvant therapy
does not seem to improve surgical outcomes. In these studies, antiandrogen treatment was
given for 3 mo prior to radical prostatectomy. A recent, nonrandomized study suggests that
longer (8 mo) antiandrogen treatment prior to surgery may be beneficial (259).
Management of patients who undergo radical prostatectomy and pelvic lymphadenectomy
and are found to have positive lymph nodes is a challenge. Timing of antiandrogen
therapy has been evaluated in a multicenter study (260). Ninety-eight patients were
randomized to observation or to androgen suppression. After a median follow-up of 7.1