Maximal androgen blockade for advanced prostate cancer

B. Schmitt, C. Bennett, J. Seidenfeld, D. Samson, T. Wilt

Research output: Contribution to journalReview articlepeer-review

107 Scopus citations

Abstract

Background: Prostate cancer is the second leading cause of cancer death in men. Long standing observations have found prostate cancer responsive to androgen suppression. The primary approach to androgen suppression for men with advanced disease (cancer that has spread outside the prostate gland) has been castration. However, medical or surgical castration eliminates only 90% to 95% of the daily testosterone production. The remainder is produced in the adrenal glands. In the 1980s Labrie hypothesized that counteracting adrenal androgens would further inhibit tumor growth and possibly improve symptoms and survival beyond the response achieved with monotherapy. In response to this hypothesis a number of anti-androgen agents were identified and used in combination with medical or surgical castration to obtain maximal androgen blockade (MAB). Despite multiple clinical trials and several meta-analyses the clinical efficacy and cost effectiveness of MAB compared with monotherapy has not been clearly established. Objectives: This systematic review assessed the effect of maximal androgen blockade (MAB) on survival when compared to castration (medical or surgical) alone for patients with advanced prostate cancer. Search methods: Randomized controlled trials were searched in general and specialized databases (MEDLINE, EMBASE, Cancerlit, Cochrane Library, VA Cochrane Prostate Disease register) and by reviewing bibliographies. Selection criteria: All published randomized trials were eligible for inclusion provided they (1) randomized men with advanced prostate cancer to receive a non-steroidal anti-androgen (NSAA) medication in addition to castration (medical or surgical) or to castration alone, and (2) reported overall survival, progression-free survival, cancer-specific survival, and/or adverse events. Eligibility was assessed by two independent reviewers. Data collection and analysis: Information on patients, interventions, and outcomes were extracted by two independent reviewers using a standardized form. The main outcome measure for comparing effectiveness was overall survival at one, two, and five years. Secondary outcome measures included progression-free survival and cancer-specific survival. The relationship of specific NSAA on outcome was evaluated. Additionally, the incidence of adverse effects was measured. Main results: Twenty trials enrolling 6320 patients were included. The pooled OR for overall survival was 1.03 (95% CI:0.85 to 1.25), 1.16 (95% CI:1.00 to 1.33), and 1.29 (95% CI:1.11 to 1.50) at 1, 2, and 5 years respectively. Overall survival was only significant at five years. The risk difference at 5 years was 0.048 (95% CI:0.02 to 0.077) and NNT at 5 years 20.8. Progression-free survival was improved only at 1-year follow up (OR = 1.38) and cancer-free survival was improved only at 5 years (OR = 1.22). Adverse events occurred more frequently in those assigned to MAB and resulted in withdrawal in 10%. Quality of life was measured in only one study favored orchiectomy alone (less diarrhea and better emotional functioning in the first six months). Authors' conclusions: MAB produces a modest overall and cancer-specific survival at five years but is associated with increased adverse events and reduced quality of life.

Original languageEnglish (US)
Article numberCD001526
JournalCochrane database of systematic reviews (Online)
Volume2011
Issue number5
DOIs
StatePublished - Apr 26 1999

Bibliographical note

Publisher Copyright:
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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