Sindy Magnan1, Ryan Zarychanski2, Laurie Pilote1, Laurence Bernier1, Michèle Shemilt3, Eric Vigneault4, Vincent Fradet5, Alexis F Turgeon6. 1. Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada. 2. Department of Internal Medicine, Sections of Hematology/Medical Oncology and Critical Care, University of Manitoba, Winnipeg, Manitoba, Canada3Department of Haematology and Medical Oncology, Cancercare Manitoba, Winnipeg, Manitoba, Canada. 3. CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada. 4. Division of Radiation Oncology, Department of Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada4CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada. 5. CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada5Division of Urology, Department of Surgery, CHU de Québec, Université Laval, Québec City, Québec, Canada. 6. CHU de Québec Research Center, Université Laval, Québec City, Québec, Canada6Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, CHU de Québec, Université Laval, Québec City, Québec, Canada.
Abstract
IMPORTANCE: Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative. OBJECTIVE: To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA SOURCES: We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered. STUDY SELECTION: We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA EXTRACTION AND SYNTHESIS: Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index. MAIN OUTCOMES AND MEASURES: Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects. RESULTS: From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy. CONCLUSIONS AND RELEVANCE: Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.
IMPORTANCE: Androgen deprivation is the standard therapy for patients with advanced or recurrent prostate cancer. However, this treatment causes adverse effects, alters quality of life, and may lead to castration-resistant disease. Intermittent androgen deprivation has been studied as an alternative. OBJECTIVE: To conduct a systematic review and meta-analysis comparing the efficacy and tolerability of intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA SOURCES: We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar from inception of each database through March 2014. References from published guidelines, reviews, and other relevant articles were also considered. STUDY SELECTION: We selected randomized clinical trials comparing intermittent vs continuous androgen deprivation therapy in patients with prostate cancer. DATA EXTRACTION AND SYNTHESIS: Two reviewers performed study selection, data abstraction, and risk of bias assessment. We calculated hazard ratios (HRs) with the inverse variance method and risk ratios with the Mantel-Haenszel method, using random effect models. A noninferiority analysis was conducted for overall survival with a margin of 1.15 for the upper boundary of the HR. We assessed heterogeneity using the I2 index. MAIN OUTCOMES AND MEASURES: Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival, time to castration resistance, skeletal-related events, and adverse effects. RESULTS: From 10 510 references, we included 22 articles from 15 trials (6856 patients) published between 2000 and 2013. All but 1 study had an unclear or high risk of bias. We observed no significant difference between intermittent and continuous therapy for overall survival (HR, 1.02; 95% CI, 0.93-1.11; 8 trials, 5352 patients), cancer-specific survival (HR, 1.02; 95% CI, 0.87-1.19; 5 trials, 3613 patients), and progression-free survival (HR, 0.94; 95% CI, 0.84-1.05; 4 trials, 1774 patients). There was minimal difference in patients' self-reported quality of life between the 2 interventions. Most trials observed an improvement in physical and sexual functioning with intermittent therapy. CONCLUSIONS AND RELEVANCE: Intermittent androgen deprivation was not inferior to continuous therapy with respect to the overall survival. Some quality-of-life criteria seemed improved with intermittent therapy. Intermittent androgen deprivation can be considered as an alternative option in patients with recurrent or metastatic prostate cancer.
Authors: C Jin; Y Fan; Y Meng; C Shen; Y Wang; S Hu; C Cui; T Xu; W Yu; J Jin Journal: Prostate Cancer Prostatic Dis Date: 2016-09-06 Impact factor: 5.554
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