Vivarelli Marco, Mocchegiani Federico, Nicolini Daniele, Vecchi Andrea, Conte Grazia, Dalla Bona Enrico, Rossi Roberta, Benedetti Cacciaguerra Andrea
Hepato-Pancreato-Biliary and Transplant Surgery, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, Ancona, Italy.
Front Oncol. 2022 May 30;12:914203. doi: 10.3389/fonc.2022.914203. eCollection 2022.
Pancreatic resection still represents the only curative option for patients affected by pancreatic ductal adenocarcinoma (PDAC). However, the association with modern chemotherapy regimens is a key factor in improving the inauspicious oncological outcome. The benefit of neoadjuvant treatment (NAT) for borderline resectable/locally advanced PDAC has been demonstrated; this evidence raises the question of whether even resectable PDAC should undergo NAT rather than upfront surgery. NAT may avoid futile surgery because of undetected distant metastases or aggressive tumor biology, providing more effective systemic control of the disease, which is hampered when adjuvant chemotherapy is delayed or precluded. However, recent data show controversial results regarding the efficacy and safety of NAT in resectable PDAC compared to upfront surgery. Although several prospective studies and meta-analyses indicate better oncologic outcomes after NAT, there are some biases, such as the methodological approaches used to capture the events of interest, which could make these results hardly reproducible. For instance, per-protocol studies, considering only the postoperative outcomes, tend to overestimate the performance of NAT by excluding patients who will never be suitable for surgery due to the development of chemotoxicity or tumor progression. To draw reliable conclusions, the studies should capture the events of interest of both strategies (NAT/upfront surgery) from the time of allocation to a specific treatment in an intention-to-treat fashion. This critical review highlights the current literature data concerning the use of NAT in resectable PDAC, summarizing the results of high-quality studies and focusing on the methodological issues of the most recent pieces of evidence.
胰腺切除术仍然是胰腺导管腺癌（PDAC）患者唯一的治愈选择。然而，与现代化疗方案联合是改善不良肿瘤学结局的关键因素。新辅助治疗（NAT）对可切除边缘/局部晚期PDAC的益处已得到证实；这一证据引发了一个问题，即即使是可切除的PDAC是否也应接受NAT而非直接手术。NAT可能避免因未检测到远处转移或侵袭性肿瘤生物学特性而进行的无效手术，提供更有效的疾病全身控制，而辅助化疗延迟或无法进行时，这种控制会受到阻碍。然而，最近的数据显示，与直接手术相比，NAT在可切除PDAC中的疗效和安全性存在争议。尽管一些前瞻性研究和荟萃分析表明NAT后肿瘤学结局更好，但存在一些偏差，如用于捕捉感兴趣事件的方法学途径，这可能使这些结果难以重现。例如，仅考虑术后结局的符合方案研究，往往会通过排除因发生化学毒性或肿瘤进展而永远不适合手术的患者来高估NAT的效果。为得出可靠结论，研究应采用意向性分析方法，从分配到特定治疗之时起，捕捉两种策略（NAT/直接手术）的感兴趣事件。这篇批判性综述强调了关于在可切除PDAC中使用NAT的当前文献数据，总结了高质量研究的结果，并关注最新证据的方法学问题。
