Do androgen-directed therapies improve outcomes in prostate cancer patients undergoing radical prostatectomy? A systematic review and meta-analysis

Abstract

Introduction: Approximately 50% of patients with non-metastatic prostate cancer are treated with radical prostatectomy. While some men will be cured with surgery alone, a substantial proportion will experience cancer recurrence. Androgen-directed therapy (ADT) is an effective adjuvant therapy for patients treated with prostate radiation. Comparatively, the efficacy of ADT in surgical patients has not been well studied. Methods: A systematic search of MEDLINE, Embase, and the Cochrane Library from inception to July 2020 was performed. Randomized trials comparing ADT with radical prostatectomy vs. prostatectomy alone in patients with clinically localized prostate cancer were included. Neoadjuvant ADT and adjuvant ADT interventions were assessed separately. The primary outcomes were cancer recurrence-free survival (RFS) and overall survival (OS). Pathologic outcomes following neoadjuvant ADT were also evaluated. Results: Fifteen randomized trials met eligibility criteria; 11 evaluated neoadjuvant ADT (n=2322) and four evaluated adjuvant ADT (n=5205). Neoadjuvant ADT (three months of treatment) did not improve RFS (hazard ratio [HR] 0.90, 95% confidence interval [CI] 0.74- 1.11) or OS (HR 1.22, 95% CI 0.62-2.41). Neoadjuvant ADT significantly decreased the risk of positive surgical margins (relative risk [RR] 0.48, 95% CI 0.41-0.56) and extraprostatic tumor extension (RR 0.75, 95% CI 0.64-0.89). Adjuvant ADT improved RFS (HR 0.65, 95% CI 0.45- 0.93) but did not improve OS (HR 1.02, 95% CI 0.84-1.24). Conclusions: Neoadjuvant ADT causes a pathologic downstaging of prostate tumors, but has not been found to delay cancer recurrence nor extend survival. Few studies evaluated adjuvant ADT. Trials are needed to determine the benefits and harms of intermediate or long-term adjuvant ADT for radical prostatectomy patients.