Qiao Guoliang, Li Xiang, Mohamed Marwa, Bolm Louisa, Zhu Qian, Del-Castillo Carlos Fernandez, Zhang Qi, Chen Yiwen, Yang Zhiyong, Lillemoe Keith D, Bai Xueli, Qadan Motaz, Liang Tingbo
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Ann Surg. 2025 Apr 8. doi: 10.1097/SLA.0000000000006719.
This study evaluated the effect of neoadjuvant therapy (NAT) and the prognostic significance of carcinoembryonic antigen (CEA) levels in patients with non-elevated serum carbohydrate antigen (CA) 19-9 levels.
The impact of NAT followed by surgical resection on oncologic outcomes in patients with localized pancreatic ductal adenocarcinoma (PDAC) remains unclear.
This retrospective and propensity-score matched (PSM) study included primary and validation cohorts from four centers. Propensity scores were estimated using multivariable logistic regression and survival curves were generated using the Kaplan-Meier method and analyzed using the log-rank test. overall survival (OS) and recurrence-free survival (RFS) were compared and univariable and multivariable Cox proportional hazards regression model were applied.
Among 251 patients with PDAC with non-elevated CA 19-9 levels, 67 received NAT followed by surgical resection, and 184 underwent upfront surgery. Following PSM, NAT significantly improved OS (39.87 vs. 18.86 months, P=0.0175) and RFS (25.67 vs. 12.83 months, P=0.0197) compared to upfront surgery. These results validated in an independent external cohort. In the primary cohort after PSM, elevated CEA was associated with worse OS and RFS compared to non-elevated CEA (median OS: 18.86 months vs. 42.39 months, P=0.0014, and median RFS: 17.40 months vs. 28.60 months, P=0.0020). Furthermore, after adjusting for competing risk factors, elevated CEA was identified as an independent factor associated with both OS (hazard ratio (HR): 1.751, 95%CI: 1.087-2.821; P=0.021) and RFS (HR: 1.637, 95%CI: 1.046-2.561; P=0.031). These results were validated in an independent external cohort.
NAT followed by surgical resection improves outcomes in patients with PDAC with non-elevated CA 19-9 levels. Elevated CEA levels were associated with adverse prognostic effects on both OS and RFS. These findings support the need for further evaluation of patients with non-elevated CA 19-9 levels and serum CEA levels in prospective settings.
本研究评估了新辅助治疗（NAT）的效果以及血清糖类抗原（CA）19-9水平未升高的患者中癌胚抗原（CEA）水平的预后意义。
NAT后行手术切除对局限性胰腺导管腺癌（PDAC）患者肿瘤学结局的影响仍不明确。
这项回顾性倾向评分匹配（PSM）研究纳入了来自四个中心的原发性队列和验证队列。使用多变量逻辑回归估计倾向评分，采用Kaplan-Meier方法生成生存曲线并使用对数秩检验进行分析。比较总生存期（OS）和无复发生存期（RFS），并应用单变量和多变量Cox比例风险回归模型。
在251例CA 19-9水平未升高的PDAC患者中，67例接受了NAT后行手术切除，184例接受了直接手术。PSM后，与直接手术相比，NAT显著改善了OS（39.87个月对18.86个月，P=0.0175）和RFS（25.67个月对12.83个月，P=0.0197）。这些结果在独立的外部队列中得到验证。在PSM后的原发性队列中，与CEA未升高相比，CEA升高与更差的OS和RFS相关（中位OS：18.86个月对42.39个月，P=0.0014；中位RFS：17.40个月对28.60个月，P=0.0020）。此外，在调整竞争风险因素后，CEA升高被确定为与OS（风险比（HR）：1.751，95%CI：1.087-2.821；P=0.021）和RFS（HR：1.637，95%CI：1.046-2.561；P=0.031）均相关的独立因素。这些结果在独立的外部队列中得到验证。
NAT后行手术切除可改善CA 19-9水平未升高的PDAC患者的结局。CEA水平升高与OS和RFS的不良预后影响相关。这些发现支持在前瞻性研究中进一步评估CA 19-9水平和血清CEA水平未升高的患者。
