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Maximal androgen blockade for advanced prostate cancer
B Schmitt1, C Bennett, J Seidenfeld
1Health Services Research & Development Program, VA Chicago Health Care System-Lakeside Division, 333 E. Huron Street, Chicago, Illinois 60611, USA. Cbenne@nwu.edu
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 Strategy:
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 1, 2, and 5 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 6,320 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 5 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 6 months).
Reviewer'S Conclusions:
MAB produces a modest overall and cancer-specific survival at 5 years but is associated with increased adverse events and reduced quality of life.