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Intermittent Versus Continuous Androgen Deprivation Therapy for Prostate Cancer: A Systematic Review and Meta-Analysis

      Purpose/Objective(s)

      To compare the effectiveness and tolerability of intermittent versus continuous androgen deprivation therapy for patients with prostate cancer.

      Materials/Methods

      Systematic review and meta-analysis of randomized controlled trials (RCTs). Data source: We searched Cochrane CENTRAL, Medline, Embase, Web of Science, Biosis, National Technical Information Service, OpenSIGLE, and Google Scholar. We also looked for ongoing trials at clinicaltrials.gov and controlled-trials.com. Referenced studies cited in published guidelines for prostate cancer as well as in reviews and other relevant articles identified in the search were also assessed for eligibility. The systematic review was conducted following a pre-established protocol. RCTs comparing intermittent (IAD) versus continuous (CAD) androgen deprivation therapy (any regimen) for patients with prostate cancer (any stage) were considered eligible. Primary outcomes were overall survival and quality of life. Secondary outcomes were cancer-specific survival, progression-free survival (biochemical and/or clinical), time to castration resistance, skeletal-related events and side effects. Duration of off-treatment intervals and testosterone levels were also considered for the IAD group. Two reviewers performed study selection, data abstraction and risk of bias assessment, independently. Hazard ratios using random effect models were conducted with generalized inverse variance method. Heterogeneity was assessed using I2 statistic.

      Results

      Among 8280 references, 14 studies were eligible. All studies presented an unclear or high risk of bias for the two primary outcomes. There was no significant difference between IAD and CAD in terms of overall survival (HR 1.02, 95% CI: 0.93-1.13; 5 studies, 4239 patients), cancer-specific survival (HR 1.00, 95% CI: 0.76-1.32; 3 studies, 1318 patients), and progression-free survival (HR 0.95, 95% CI: 0.78-1.14; 4 studies, 2704 patients). In 10 trials providing data on quality of life, 8 used different version of the EORTC QLQ-C30 questionnaire and 2 used other questionnaires. These studies observed variable results. No difference between the two interventions was observed for hot flashes, gynecomastia, depression, erectile dysfunction, decreased libido, and cardiovascular death.

      Conclusions

      In our systematic review, we did not observe a difference in overall survival between IAD and CAD. Although quality of life outcomes were evaluated in most studies, firm conclusions cannot be made due to differences in questionnaires used and inconsistent results.

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