Bilateral Orchiectomy with or without Flutamide for Metastatic Prostate Cancer

Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson, IM Jr,
Abramson Cancer Center of the University of Pennsylvania
Last Modified: November 1, 2001

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Reviewers: Kenneth Blank, MD
Source: New England Journal of Medicine 339 (15):1036

Background

The treatment of metastatic prostate cancer is controversial. Radiotherapy plays a critical role in palliating bone pain and preventing local symptoms;hormonal therapy palliates pain and can increase survival and chemotherapy remains investigational when hormonal therapy fails. Controversyexists over when to initiate these treatments and what type of hormonal therapy to use.

Prostate cancer is a hormone sensitive tumor in that prostate cancer cells need the hormone testosterone to grow and divide. When testosterone isremoved the majority of cells die. However, a few prostate cancer cells remain and these can grow without the stimulation provided bytestosterone (these are termed hormone insensitive). With time these few cells grow into a large tumor and eventually metastasize (spread to otherplaces in the body) leading to the patients decline.

The testis produces ninety percent of the body's testosterone and the other 10% is secreted by the adrenal glands. Several strategies have beendevised to rid the body of testosterone and therefore slow down the growth of prostate cancer. These include surgical removal of the testes(orchiectomy) and prescribing oral medications called leutenizing hormone releasing hormone (LHRH) agonists. One potential problem with thesetherapies are that they only effect testosterone made by the testis not the adrenal gland. Another class of medications called anti-androgensfunction to block uptake of testosterone into the cell. The use of LHRH agonists or orchiectomy in combination with an anti-estrogen is calledcombined androgen (androgen is the generic term for testosterone) blockage as both adrenal and testicular testosterone are removed from thecancer cell.

Materials and Methods

One controversy in the treatment of metastatic prostate cancer is whether or not the addition of an anti-androgen provides additional benefit to justorchiectomy or just LHRH therapy. Theoretically, combined androgen blockage makes good sense but clinical testing is always warranted todetermine the efficacy of a treatment.

The October 8, 1998 issue of the New England Journal of Medicine reports on a trial examining this issue. 1387 men underwent surgical removalof their testes and were then randomly assigned to either receive a placebo or an anti-androgen (flutamide).

Results

There were no differences in major toxicities in either arm but there was more anemia and diarrhea with the flutamide. Unfortunately, the additionof flutamide had no effect on survival or progression free survival. This finding was surprising in light of a prior study by the same group ofphysicians demonstrating a significant survival advantage to flutamide when dosed with LHRH agonist versus LHRH agonist alone. The authorsprovide an explanation for the discrepancy in that it is possible that patients were not compliant with the LHRH agonist.

Conclusion

The controversy remains as to what constitutes the best therapy for patents with metastatic prostate cancer. The results of this study suggest that the useof combined androgen blockade provides no benefit over orchiectomy alone.



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