Yanagisawa Takafumi, Rajwa Pawel, Quhal Fahad, Kawada Tatsushi, Bekku Kensuke, Laukhtina Ekaterina, Deimling Markus von, Chlosta Marcin, Karakiewicz Pierre I, Kimura Takahiro, Shariat Shahrokh F
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Wahringer Gurtel 43 18-20, 1090 Vienna, Austria.
Department of Urology, The Jikei University School of Medicine, Tokyo 105-8461, Japan.
J Pers Med. 2023 Apr 7;13(4):641. doi: 10.3390/jpm13040641.
(1) Background: Several phase II studies, including randomized controlled trials (RCTs), assessed the efficacy of adding androgen receptor signaling inhibitors (ARSIs) to androgen deprivation therapy (ADT) as a neoadjuvant treatment in patients treated with radical prostatectomy (RP) for prostate cancer (PCa). Summarizing the early results of these studies could help in designing phase III trials and patient counseling. (2) Methods: We queried three databases in January 2023 for studies that included PCa patients treated with neoadjuvant ARSI-based combination therapy before RP. The outcomes of interest were oncologic outcomes and pathologic responses, such as pathologic complete response (pCR) and minimal residual disease (MRD). (3) Results: Overall, twenty studies (eight RCTs) were included in this systematic review. Compared to ADT or ARSI alone, ARSI + ADT was associated with higher pCR and MRD rates; this effect was less evident when adding a second ARSI or chemotherapy. Nevertheless, ARSI + ADT resulted in relatively low pCR rates (0-13%) with a high proportion of ypT3 (48-90%) in the resected specimen. PTEN loss, ERG positive, or intraductal carcinoma seem to be associated with worse pathologic response. One study that adjusted for the effects of possible confounders reported that neoadjuvant ARSI + ADT improved time to biochemical recurrence and metastasis-free survival compared to RP alone. (4) Conclusions: Neoadjuvant ARSI + ADT combination therapy results in improved pathologic response compared to either alone or none in patients with non-metastatic advanced PCa. Ongoing phase III RCTs with long-term oncologic outcomes, as well as biomarker-guided studies, will clarify the indication, oncologic benefits, and adverse events of ARSI + ADT in patients with clinically and biologically aggressive PCa.
（1）背景：多项II期研究，包括随机对照试验（RCT），评估了在接受前列腺癌（PCa）根治性前列腺切除术（RP）的患者中，将雄激素受体信号抑制剂（ARSIs）添加到雄激素剥夺疗法（ADT）中作为新辅助治疗的疗效。总结这些研究的早期结果有助于设计III期试验并为患者提供咨询。（2）方法：我们于2023年1月查询了三个数据库，以获取在RP前接受基于ARSIs的新辅助联合治疗的PCa患者的研究。感兴趣的结局是肿瘤学结局和病理反应，如病理完全缓解（pCR）和微小残留病（MRD）。（3）结果：总体而言，本系统评价纳入了20项研究（8项RCT）。与单独使用ADT或ARSIs相比，ARSIs + ADT与更高的pCR和MRD率相关；添加第二种ARSIs或化疗时，这种效果不太明显。然而，ARSIs + ADT导致相对较低的pCR率（0 - 13%），切除标本中ypT3比例较高（48 - 90%）。PTEN缺失、ERG阳性或导管内癌似乎与较差的病理反应相关。一项对可能混杂因素的影响进行调整的研究报告称，与单纯RP相比，新辅助ARSIs + ADT改善了生化复发时间和无转移生存期。（4）结论：与单独使用或不使用相比，新辅助ARSIs + ADT联合治疗可改善非转移性晚期PCa患者的病理反应。正在进行的具有长期肿瘤学结局的III期RCT以及生物标志物指导研究，将阐明ARSIs + ADT在临床和生物学侵袭性PCa患者中的适应证、肿瘤学获益和不良事件。
