Department of Urology, University Hospitals Leuven, Leuven, Belgium; Nuclear Medicine & Molecular Imaging, KU Leuven, Leuven, Belgium.
Division of Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy.
Eur Urol. 2019 Jan;75(1):44-60. doi: 10.1016/j.eururo.2018.07.027. Epub 2018 Oct 2.
Systemic therapies, combined with local treatment for high-risk prostate cancer, are recommended by the international guidelines for specific subgroups of patients; however, for many of the clinical scenarios, it remains a research field.
To perform a systematic review, and describe current evidence and perspectives about the multimodal treatment of high-risk prostate cancer.
We performed a systematic review of PubMED, Embase, Cochrane Library, European Society of Medical Oncology/American Society of Clinical Oncology Annual proceedings, and clinicalTrial.gov between January 2010 and February 2018 following the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement.
Seventy-seven prospective trials were identified. According to multiple randomized trials, combining androgen deprivation therapy (ADT) with external-beam radiotherapy (EBRT) outperforms EBRT alone for both relapse-free and overall survival. Neoadjuvant ADT did not show significant improvement compared with prostatectomy alone. The role of adjuvant ADT after prostatectomy in patients with high-risk disease is still debated, with lack of data from phase 3 trials in pN0 patients. Novel androgen pathway inhibitors have been tested only in early-phase trials in addition to primary treatment. GETUG 12, RTOG 0521, and nonmetastatic subgroup of the STAMPEDE trial showed improved relapse-free survival for docetaxel in patients treated with EBRT plus ADT, although mature metastasis-free survival data are still pending. Both the SPCG-12 and the VACSP#553 trial showed no improvement in relapse-free survival for adjuvant docetaxel after prostatectomy.
In contrast to the clearly demonstrated survival benefits of long-term adjuvant ADT when used with EBRT, its role after prostatectomy remains unclear especially in pN0 patients. Adding docetaxel to EBRT-ADT improves relapse-free survival, with immature results on overall survival. Novel androgen receptor pathway inhibitors are currently being tested in the neoadjuvant and adjuvant setting.
Treatment of high-risk prostate cancer is based on a multimodality approach that includes systemic treatments. The best treatment or therapy combination remains to be defined.
国际指南建议对高危前列腺癌的特定亚组患者采用联合局部治疗的系统治疗方法；然而，对于许多临床情况，这仍然是一个研究领域。
对高危前列腺癌的多模式治疗进行系统评价，并描述当前的证据和观点。
我们根据循证医学系统评价和荟萃分析报告的首选条目，对 2010 年 1 月至 2018 年 2 月期间的 Pubmed、Embase、 Cochrane 图书馆、欧洲肿瘤内科学会/美国临床肿瘤学会年会和 clinicalTrial.gov 进行了系统评价。
确定了 77 项前瞻性试验。根据多项随机试验，与单独使用外部束放射治疗（EBRT）相比，联合雄激素剥夺疗法（ADT）在无复发生存和总生存方面均表现出更好的效果。新辅助 ADT 与单独前列腺切除术相比并未显示出显著改善。在高危疾病患者中，前列腺切除术后辅助 ADT 的作用仍存在争议，缺乏 pN0 患者的 3 期试验数据。除了一线治疗外，新型雄激素通路抑制剂仅在早期试验中进行了测试。GETUG 12、RTOG 0521 和 STAMPEDE 试验的非转移性亚组显示，在接受 EBRT+ADT 治疗的患者中，多西他赛可改善无复发生存，但成熟的无转移生存数据仍有待确定。SPCG-12 和 VACSP#553 试验均未显示前列腺切除术后辅助多西他赛可改善无复发生存。
与长期辅助 ADT 与 EBRT 联合使用时明显显示出的生存获益形成对比，其在前列腺切除术后的作用仍不清楚，特别是在 pN0 患者中。在 EBRT-ADT 中加入多西他赛可改善无复发生存，但总体生存的结果尚不成熟。新型雄激素受体通路抑制剂目前正在新辅助和辅助治疗中进行测试。
高危前列腺癌的治疗基于多模式方法，包括系统治疗。最佳治疗或治疗联合方案仍有待确定。
