Neoadjuvant hormone therapy for patients with high-risk prostate cancer: a systematic review and meta-analysis

Abstract

This study aimed to identify the pathological outcomes and survival benefits of neoadjuvant hormone therapy (NHT) combined with radical prostatectomy (RP) and radiotherapy (RT) administered to patients with high-risk prostate cancer (HRPCa). We searched PubMed, Embase, and the Cochrane Library for studies comparing NHT plus RP or RT with RP or RT alone, administered to patients with HRPCa. We used a random-effects model to compute risk estimates with 95% confidence intervals (CIs) and quantified heterogeneity using the I "2" statistic. Subgroup and sensitivity analyses were performed to identify potential sources of heterogeneity. We selected 16 studies. NHT before RP significantly decreased lymph node involvement (risk ratio [RR] = 0.69, 95% CI: 0.56-0.87) and increased the rates of pathological downstaging (RR = 2.62, 95% CI: 1.22-5.61) and organ-confinement (RR = 2.24, 95% CI: 1.54-3.25), but did not improve overall survival and biochemical progression-free survival (bPFS). The administration of NHT before RT to patients with HRPCa was associated with significant benefits for cancer-specific survival (hazard ratio [HR] = 0.51, 95% CI: 0.39-0.68), disease-free survival (HR = 0.51, 95% CI: 0.44-0.60), and bPFS (HR = 0.54, 95% CI: 0.46-0.64). Short-term NHT combined with RT administered to patients with HRPCa conferred significant improvements. Although the advantage of local control was observed when NHT was administered before RP, there was no significant survival benefit associated with HRPCa. Therefore, short-term NHT combined with RT is recommended for implementation in standard clinical practice but not for patients who undergo RP.

Keywords: high-risk diseases; meta-analysis; neoadjuvant hormone therapy; prostate cancer; prostatectomy; radiotherapy.

Figure 1

Selection of relevant articles. NHT: neoadjuvant hormone therapy; RP: radical prostatectomy; RT: radiotherapy.

Figure 2

Meta-analyses of the survival outcomes of patients with HRPCa administered NHT plus RP or RT versus RP or RT alone (hazard ratios). (a) Overall survival and (b) biochemical progression-free survival associated with RP. (c) Overall survival, (d) cancer-specific survival, (e) disease-free survival, and (f) biochemical progression-free survival associated with RT. HRPCa: high-risk prostate cancer; NHT: neoadjuvant hormone therapy; RP: radical prostatectomy; RT: radiotherapy; TE: estimate of treatment effect; seTE: standard error of TE; CI: confidence interval.

Figure 3

Meta-analyses of the pathological outcomes of patients with HRPCa administered NHT plus RP versus RP alone (risk ratios). (a) Lymph node involvement. (b) pT staging: downstaging. (c) pT staging: organ confined. (d) Positive surgical margins. (e) Seminal vesicle involvement. HRPCa: high-risk prostate cancer; NHT: neoadjuvant hormone therapy; RP: radical prostatectomy; RT: radiotherapy; CI: confidence interval; pT: pathological tumor.

Figure 4

Subgroup analyses of pathological and survival outcomes according to study design. HRPCa: high-risk prostate cancer; NHT: neoadjuvant hormone therapy; RT: radiotherapy; RP: radical prostatectomy; RCT: randomized controlled trial; HR: hazard ratio; RR: risk ratio; pT: pathological tumor; CI: confidence interval; - : minus.