Systematic review of early vs deferred hormonal treatment of locally advanced prostate cancer: a meta-analysis of randomized controlled trials

Abstract

Objective: To compare the effectiveness of hormonal treatment (luteinizing hormone-releasing hormone agonists and/or antiandrogens) as an early or as a deferred intervention for patients with locally advanced prostate cancer (LAPC), as radiotherapy is currently the standard treatment for LAPC, with hormonal treatment considered a reserve option.

Methods: We systematically reviewed randomized controlled trials (RCTs) in patients with LAPC treated with standard care (radical prostatectomy, radiotherapy, and/or watchful waiting) or standard care plus hormonal treatment. Outcomes assessed were mortality and objective disease progression. The meta-analysis used a fixed-effects model.

Results: Of the 108 trials identified, seven met the inclusion criteria and were of sufficient quality to be included in the analysis. Early intervention with hormonal treatment significantly reduced all-cause mortality compared with deferred treatment (relative risk, RR, 0.86; 95% confidence interval, CI, 0.82-0.91; P < 0.001). Similarly, early vs deferred use of hormonal treatment significantly reduced: prostate cancer- specific mortality (RR 0.72; 95% CI 0.65-0.79); overall progression (RR 0.74; 0.69-0.78); local progression (RR 0.65; 0.57-0.73); and distant progression (RR 0.67; 0.61-0.74; all P < 0.001). Results were robust to changes in inclusion/exclusion criteria and use of a random-effects model for the meta-analyses. Heterogeneity and publication bias had no significant effect on the analyses.

Conclusions: Early intervention with hormonal treatment for patients with LAPC provides significantly lower mortality and objective disease progression than deferring their use until standard care has failed.