Comparison of short-term and long-term neoadjuvant hormone therapy prior to radical prostatectomy: a systematic review and meta-analysis

This study aimed to evaluate the efficacy of long-term neoadjuvant androgen-deprivation therapy (ADT) before radical prostatectomy (RP). We conducted meta-analyses and network meta-analyses, which included randomized controlled trials that assessed patients with prostate cancer (PC) who received either short-term ( Thirteen articles with 2778 patients were eligible for analysis. Short-term neoadjuvant ADT was neither associated with biochemical recurrence (OR 1.19, 95% CI, 0.93–1.51, p = 0.17), metastasis (OR 0.73, 95% CI, 0.45–1.19, p = 0.21), nor overall mortality (OR 0.72, 95% CI 0.43–1.21, p = 0.22); no study investigated survival outcomes in patients on long-term neoadjuvant ADT. In terms of pathologic outcomes, long-term neoadjuvant ADT was significantly associated with a reduced risk of positive surgical margin (SM) and an increased rate of organ-confined disease (OCD) compared to short-term neoadjuvant ADT (OR 0.56, 95% CI 0.39–0.80, p = 0.001, and OR 1.48, 95% CI 1.10–1.99, p = 0.009, respectively). These findings were confirmed in the network meta-analyses. Meanwhile, only a non-significant trend favoring long-term neoadjuvant ADT was observed for pathologic complete response (OR 1.98, 95% Crl 1.00–3.93). Long-term neoadjuvant ADT was associated with more favorable pathologic outcomes, but whether these findings translate into favorable survival outcomes still remains unproven due to very limited evidence. Since there are no reliable survival data, long-term neoadjuvant ADT before RP should not be used in clinical practice until more robust evidence arises from ongoing trials.本研究旨在评估根治性前列腺切除术（radical prostatectomy, RP）前长期新辅助雄激素剥夺治疗（neoadjuvant androgen-deprivation therapy, ADT）的疗效。我们开展了常规meta分析与网络meta分析，纳入了针对前列腺癌（prostate cancer, PC）患者的随机对照试验，这些试验对比了短期新辅助ADT与长期新辅助ADT。最终纳入13篇相关研究，共计2778例患者可供分析。短期新辅助ADT并未与生化复发（比值比OR=1.19，95%置信区间CI：0.93~1.51，p=0.17）、转移（OR=0.73，95%CI：0.45~1.19，p=0.21）或总死亡率（OR=0.72，95%CI：0.43~1.21，p=0.22）存在显著关联；目前尚无研究探讨长期新辅助ADT患者的生存结局。在病理结局方面，相较于短期新辅助ADT，长期新辅助ADT可显著降低手术切缘阳性（positive surgical margin, SM）风险，并提高器官局限性疾病（organ-confined disease, OCD）的发生率（分别对应OR=0.56，95%CI：0.39~0.80，p=0.001；OR=1.48，95%CI：1.10~1.99，p=0.009）。上述结论在网络meta分析中得到了验证。与此同时，仅观察到长期新辅助ADT在病理完全缓解方面存在非显著性的获益趋势（OR=1.98，95%可信区间CrI：1.00~3.93）。长期新辅助ADT可带来更优的病理结局，但由于相关证据极为有限，上述结果能否转化为生存获益仍未得到证实。鉴于目前尚无可靠的生存数据，在后续试验提供更充分的证据之前，临床实践中不应采用根治性前列腺切除术前的长期新辅助雄激素剥夺治疗方案。