Department of Surgery, University of Arkansas for Medical Sciences, Little Rock.
Department of Surgery, Duke University Medical Center, Durham, North Carolina.
JAMA Surg. 2021 Jul 1;156(7):663-672. doi: 10.1001/jamasurg.2021.0149.
Adjuvant chemotherapy is the standard of care for resected pancreatic ductal adenocarcinoma (PDAC) based on level 1 evidence, but some studies suggest that a neoadjuvant approach (which is standard for borderline resectable PDAC) may be preferable for upfront resectable PDAC. An in-depth review was conducted of all randomized clinical trials that investigated neoadjuvant and adjuvant treatment of patients with resectable or resected PDAC, focusing on trial design, characteristics of enrolled population, and long-term outcomes.
The existing resectable PDAC trials have good internal validity but variable applicability because of their restrictive eligibility criteria. In these trials, overall survival is the criterion standard end point, but disease-free survival is more feasible, proximate, and specific to the assigned intervention (at the cost of subjective outcome assessment) and thus an acceptable end point in certain contexts. The prolonged survival in the PRODIGE 24 trial highlights both the success of mFOLFIRINOX (modified fluorouracil, leucovorin, irinotecan, and oxaliplatin) and the importance of patient selection. Neoadjuvant and perioperative trials have shown promising preliminary results; however, the number of patients who are not subsequently eligible for surgery reflects the limitations of this approach. Head-to-head comparisons of neoadjuvant and adjuvant treatments are limited to date in Western countries. Precision oncology with genomic and somatic testing for actionable mutations has promising preliminary results and may refine the management of PDAC, although the implications for early-stage disease and neoadjuvant therapy are unknown.
This review found that adjuvant chemotherapy with mFOLFIRINOX is currently the standard of care in fit patients with resected PDAC; however, the role of neoadjuvant treatment is expanding. Precision oncology may help individualize the treatment regimen and sequence and improve outcomes. Enrollment of patients with resectable PDAC in clinical trials is strongly encouraged.
辅助化疗是基于 1 级证据的可切除胰腺导管腺癌（PDAC）的标准治疗方法，但一些研究表明，新辅助方法（适用于临界可切除 PDAC）可能更适合可切除的 PDAC。对所有研究可切除或已切除 PDAC 患者新辅助和辅助治疗的随机临床试验进行了深入审查，重点关注试验设计、入组人群特征和长期结果。
现有的可切除 PDAC 试验具有良好的内部有效性，但由于其严格的入选标准，适用性不同。在这些试验中，总生存是标准的终点标准，但无病生存更可行、更接近和更具体于指定的干预措施（以主观结局评估为代价），因此在某些情况下是可以接受的终点。PRODIGE 24 试验中观察到的生存时间延长，突出了 mFOLFIRINOX（改良氟尿嘧啶、亚叶酸钙、伊立替康和奥沙利铂）的成功和患者选择的重要性。新辅助和围手术期试验显示出有希望的初步结果；然而，随后不符合手术条件的患者数量反映了这种方法的局限性。目前，在西方国家，新辅助和辅助治疗的头对头比较仅限于少数。基于基因组和体细胞检测可操作突变的精准肿瘤学具有有希望的初步结果，可能会改善 PDAC 的治疗，但尚不清楚其对早期疾病和新辅助治疗的影响。
本综述发现，对于身体状况良好的可切除 PDAC 患者，目前 mFOLFIRINOX 辅助化疗是标准治疗方法；然而，新辅助治疗的作用正在扩大。精准肿瘤学可能有助于实现治疗方案和治疗顺序的个体化，并改善治疗结果。强烈鼓励将可切除 PDAC 患者纳入临床试验。
