234 CHAPTER 6 Urological neoplasia

Management of advanced prostate cancer: hormone therapy II

Mechanisms of androgen deprivation

•Surgical castration: bilateral orchiectomy

•Medical castration: LHRH agonists, LHRH antagonists, estrogens

•Antiandrogens (steroidal or nonsteroidal): androgen receptor blockade at target cell

•Maximal androgen blockade (MAB): medical or surgical castration plus antiandrogen

Both forms of castration (androgen ablation or deprivation are the preferred terms today) have equivalent efficacy, so patients should be given the choice. Estrogens are no longer first-line agents because of the significant cardiovascular morbidity. Antiandrogens alone are less effective in treating metastatic disease, but equivalent for nonmetastatic disease.

MAB has a theoretical advantage over castration in blocking the effects of the adrenal androgens, but significant clinical advantages have not been demonstrated in trial meta-analyses.

5AR inhibitors such as finasteride or dutasteride are not used in the treatment of prostate cancer but appear to have a role in prevention.

Bilateral orchiectomy

This is a simple procedure usually carried out under general anesthesia. Through a midline scrotal incision, both testes may be accessed. The testes are entirely removed or some prefer to incise the tunica albuginea of each testis and the soft tissue content is removed, after which the capsule is closed.

The epidiymes and testicular appendages are preserved; this allows some fullness to remain in the scrotal sac and may psychologically benefit the patient.

Postoperative complications include scrotal hematoma or infection (both rare). Serum testosterone falls within 8 hours to <0.2 nmol/L.

LHRH agonists

Developed in the 1980s, LHRH agonists give patients an alternative to bilateral orchiectomy, with which they are clinically equivalent. They are given by subcutaneous (SC) or intramuscular (IM) injection, as monthly or 3-, 6-, or 12-month depots. Some examples of these peptides include goserelin, triptorelin, histrelin, and leuprolide (see Table 6.6). Nasal forms are available outside the U.S.

If the anterior pituitary is desensitized to the pulsatile release of natural LHRH by the analogue of LHRH, it switches off LH production, although serum testosterone rises in the first 14 days because of a surge of LH. This can result in “tumor flare,” manifest in 20% patients with increased symptoms, including catastrophic spinal cord compression. To prevent this, cover with antiandrogens is recommended for a week before and 2 weeks after the first dose of LHRH agonist.

An injectable LHRH antagonist (degarelix) (Table 6.6) rapidly reduces serum testosterone by blockade of the LHRH receptors.

Copyright © MedReviews®, LLC. Reprinted with permission of MedReviews®, LLC. Gomella LG (2009). Effective testosterone suppression for prostate cancer: is there a best castration therapy?. Rev Urol. 11(2):52–60. Reviews in Urology is a copyrighted publication of MedReviews®, LLC. All rights reserved.

236 CHAPTER 6 Urological neoplasia

Side effects of bilateral orchiectomy and LHRH agonists/antagonists

•Loss of sexual interest (libido) and ED

•Hot flushes and sweats can be frequent and troublesome during work or social activity

•Weight gain and obesity

•Gynecomastia

•Anemia

•Cognitive (mood) changes

•Metabolic syndrome (increased blood glucose and lipid profile)

•Osteoporosis and pathological fracture secondary to osteoporosis may occur in patients on long-term treatment.

Antiandrogens

These are administered as tablets. Examples include the nonsteroidal antiandrogens such as bicalutamide (50 mg daily for MAB, in combination with LHRH analogues or orchiectomy; 150 mg daily as monotherapy [not FDA approved in the U.S.]), flutamide, nilutamide, and the steroidal antiandrogen cyproterone acetate.

Bicalutamide monotherapy raises the serum testosterone slightly, so sexual interest and performance are often maintained.

Side effects include frequent gynecomastia, breast tenderness, and occasional liver dysfunction; flutamide can cause GI upset.

At its full dose, cyproterone acetate may cause reversible dyspnea; it may be used at 50 mg bid for treatment of castration-induced hot flushes.

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