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Combined androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer: a systematic review
B Schmitt1, T J Wilt, P F Schellhammer
1Veterans Administration Chicago Healthcare System/Lakeside Division, Chicago, Illinois, USA.
Objectives:
Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen for metastatic prostate cancer has been the subject of 20 randomized trials. The findings range from no expected increase in survival in 17 studies to an estimated 3.7 to 7 months' survival improvement noted in 3 studies. Most recently, a 1999 evidence report from the Agency for Healthcare Research and Quality and a 2000 overview from the Prostate Cancer Trialists Collaborative Group indicated that combined androgen blockade was associated with an approximately 3% to 5% increase in 5-year survival. We report herein a systematic review on combined androgen blockade performed by the Cochrane Collaborative Review Group on Prostate Diseases.
Methods:
Controlled trials that included a randomization of immediate nonsteroidal antiandrogens with castration versus castration alone for metastatic prostate cancer and provided information on survival were reviewed. Information on overall survival, toxicity, progression-free survival, cancer-specific survival, and type of nonsteroidal antiandrogen and castration therapies was abstracted by two independent reviewers.
Results:
Twenty trials (n = 6320 patients) were included. The pooled odds ratio (OR) for overall survival with combined androgen blockade was 1.03 (95% confidence interval [CI] 0.85 to 1.25; n = 4970 from 13 trials), 1.16 (95% CI 1.00 to 1.33; n = 5286 from 14 trials), and 1.29 (95% CI 1.11 to 1.50; n = 3550 from 7 trials) at 1, 2, and 5 years, respectively. Progression-free survival was improved at 1 year (OR = 1.38; 95% CI 1.15 to 1.67; n = 2278 from 7 trials). Cancer-specific survival was improved at 5 years (OR = 1.58; 95% CI 1.05 to 2.37; n = 781 from 2 trials). When analysis was limited to studies identified as being of high quality, the pooled OR for overall survival progressively increased but was not significant at any follow-up interval.
Conclusions:
We find that there is a 5% improvement in the percentage of men surviving at 5 years (30% vs. 25%) with combined androgen blockade with nonsteroidal antiandrogens as well as improvements in progression-free survival at 1 year. Appropriate patients with metastatic prostate cancer should be informed of the potential benefits, toxicities, and out-of-pocket expenditures.
Insights
Combined androgen blockade significantly improves 5-year survival rates for men with metastatic prostate cancer, offering a 5% survival benefit. This treatment also enhances progression-free survival at one year, providing crucial options for patients.
Area of Science:
- Oncology
- Clinical Trials
- Evidence-Based Medicine
Background:
- Metastatic prostate cancer treatment often involves combined androgen blockade (CAB) using castration and nonsteroidal antiandrogens.
- Previous reviews have shown mixed results regarding the survival benefits of CAB.
- A systematic review by the Cochrane Collaborative Review Group on Prostate Diseases aimed to clarify these benefits.
Purpose of the Study:
- To systematically review randomized controlled trials comparing CAB with castration alone for metastatic prostate cancer.
- To evaluate the impact of CAB on overall survival, progression-free survival, and cancer-specific survival.
- To assess the influence of study quality on the observed survival outcomes.
Main Methods:
- A systematic review of 20 randomized controlled trials (n=6320 patients) was conducted.
- Data on overall survival, toxicity, progression-free survival, and cancer-specific survival were extracted by independent reviewers.
- Pooled odds ratios (OR) and confidence intervals (CI) were calculated for various time points.
Main Results:
- CAB showed a trend towards improved overall survival at 1, 2, and 5 years (ORs ranging from 1.03 to 1.29).
- Progression-free survival was significantly improved at 1 year (OR=1.38).
- Cancer-specific survival was improved at 5 years (OR=1.58), though based on limited trials.
Conclusions:
- Combined androgen blockade with nonsteroidal antiandrogens offers a 5% improvement in 5-year survival for metastatic prostate cancer patients (30% vs. 25%).
- Improvements in progression-free survival at 1 year were also noted.
- Patients should be informed about the benefits, toxicities, and costs associated with CAB.