Androgen deprivation therapy has long been prescribed for men with symptoms of metastatic prostate cancer, with current clinical practice leaning toward use of the therapy earlier in the disease.
A study by the Patient Outcomes Research Team for Prostatic Diseases, supported by the Agency for Healthcare Research and Quality (HS08397), concluded that radical prostatectomy patients who still have elevated prostate-specific antigen (PSA) levels after surgery (suggestive of cancer) and their doctors must weigh the reduced quality of life against the uncertain benefits of postoperative androgen deprivation therapy.
A second study by the Blue Cross-Blue Shield Association Technology Evaluation Center, an Evidence-based Practice Center supported by the Agency for Healthcare Research and Quality (contract 290-97-0015), found that combined androgen blockade (blocking testicular and adrenal androgens) did not significantly extend the lives of men with advanced prostate cancer over monotherapy (blocking testicular androgen only). Both studies are described here.
Fowler, F.J., Collins, M.M., Corkery, E.W., and others. (2002, July). "The impact of androgen deprivation on quality of life after radical prostatectomy for prostate carcinoma." Cancer 95, pp. 287-295.
These researchers used a 5 percent national sample of Medicare providers to identify men who had undergone radical prostatectomy between 1991 and 1992 and Medicare claims data from the date of discharge until the end of 1996 to identify those who received androgen deprivation therapy after the surgery. In 1999, they mailed a survey to men who had undergone only the surgery and those who had both the surgery and the androgen deprivation therapy. The survey addressed a range of prostate cancer-related and treatment-related issues, including health-related quality of life (HRQOL).
Men who received androgen deprivation therapy after surgery had significantly lower scores on all seven HRQOL measures: impact of cancer and treatment on their daily life, concern about body image, mental health, general health, activity, worries about cancer and dying, and energy.
Also, only 2 percent of men who received the therapy reported the ability to have sexual intercourse in the past month, and 69 percent reported no days of feeling sexual drive compared with 12 percent and 29 percent, respectively, of nonandrogen-deprived men. The researchers caution that lower HRQOL scores for the androgen-deprived group may have been due to the recurrence of the prostate cancer itself rather than the effects of androgen deprivation. Moreover, androgen deprivation therapy has been shown to provide a survival benefit to men with lymph node metastases at the time of surgery.
Recent data show a median time to metastasis of 8 years following PSA elevation after radical prostatectomy and another 5 years to death once metastases were documented. In this study, androgen deprivation was used solely for a rising PSA after prostatectomy. The potential advantages of monitoring PSA after prostatectomy include the early detection of patients with advanced disease, who then may benefit from treatment with radiation therapy or early androgen deprivation therapy (before painful bone metastases develop). However, given the negative impact on quality of life and the advanced age of men receiving the therapy (in this study, 65 percent of men were aged 75 or older), patients and doctors must carefully weigh the price patients pay with reduced quality of life against the uncertain benefits of androgen deprivation, conclude the researchers.
Samson, D.J., Seidenfeld, J., Schmitt, B., and others. (2002, July). "Systematic review and meta-analysis of monotherapy compared with combined androgen blockade for patients with advanced prostate carcinoma." Cancer 95, pp. 361-376.
Combined androgen blockade (blocking testicular and adrenal androgens) does not significantly extend the lives of men with advanced prostate cancer over monotherapy (blocking testicular androgens), concludes this meta-analysis of 27 studies of nearly 8,000 men. Monotherapy is the surgical removal of the testes or use of a luteinizing hormone-releasing hormone (LHRH) agonist to prevent testicular production of testosterone. Combination therapy uses surgical removal of the testes or an LHRH agonist plus a nonsteroidal or steroidal antiandrogen to block the action of adrenal androgens. Additional trials are unlikely to alter the balance of the evidence, conclude the researchers.
They searched the literature from 1996 through August 1998 to identify randomized trials comparing the two approaches. Twenty-one trials compared survival after monotherapy with survival after combined androgen blockade. The meta-analysis found no significant difference in men's survival at 2 years, even for men with minimally advanced disease. There was a significant difference in survival at 5 years that favored combined androgen blockade (10 trials, with a 13 percent less hazard of dying in 5 years).
However, adverse effects led more men to withdraw from the more costly combined therapy than the monotherapy. In addition, the one trial that compared the quality of life of men who underwent both types of treatment showed worse quality of life among men who received the combined therapy. The researchers conclude that the usefulness of combined androgen blockade must balance the modest increase in expected survival at 5 years against the increased risk of adverse effects and diminished quality of life compared with monotherapy.
Editor's Note: Copies of AHRQ Evidence Report/Technology Assessment No. 4, Relative Effectiveness and Cost-Effectiveness of Methods of Androgen Suppression in the Treatment of Advanced Prostatic Cancer (AHRQ Publication No. 99-E012) and a summary of the report (AHRQ Publication No. 99-E011) are available from the AHRQ.