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

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.