Napoli Niccolò, Ripolli Allegra, Kauffmann Emanuele F, Ginesini Michael, Casadei Riccardo, Coppola Roberto, Egorov Vyacheslav, Nagakawa Yuichi, Rangelova Elena, Vicente Emilio, Boggi Ugo
Division of General and Transplant Surgery, University of Pisa, Pisa, Italy.
Alma Mater Studiorum, University of Bologna, IRCCS, AOUBO, Bologna, Italy.
Ann Surg Oncol. 2025 Sep 15. doi: 10.1245/s10434-025-18212-w.
Modern chemotherapy has redefined resectability of pancreatic ductal adenocarcinoma (PDAC), prioritizing tumor biology over anatomy. However, comparative outcomes of surgery versus continued oncologic therapy (COT) in borderline resectable (BR) or locally advanced (LA) PDAC remain unclear. This study addresses this gap.
This retrospective, international, multicenter cohort study included patients with BR/LA-PDAC treated with neoadjuvant or primary chemotherapy between 2012 and 2024. All met guideline-based criteria for potential resection on the basis of anatomy, biology, and performance status. Treatment allocation (surgery versus COT) was based on institutional practice or surgeon preference, reflecting real-world decision-making. The primary endpoint was overall survival (OS), analyzed using unadjusted comparison, propensity score matching (PSM), and entropy balancing.
A total of 312 patients were included: 158 underwent resection and 154 received COT. Median OS was 39.0 months (IQR 14.3-42.6 months) with resection versus 16.7 months (IQR 8.8-22.5 months) with COT (p < 0.0001). After PSM (75 pairs), OS remained significantly longer with resection (42.6 months, IQR 12.9-42.1 months) versus COT (18.6 months, IQR 9.4-23.9 months; p < 0.0001). In the LA-PDAC subgroup, OS was 42.6 months (IQR 23.2-NA months) with resection versus 18.6 months (IQR 11.8-25.6 months; p < 0.0001) with COT. On multivariable analysis, resection (HR 0.34, 95% CI 0.21-0.54; p < 0.0001) and CA 19-9 (HR 1.0001; p = 0.0297) were independently associated with OS. Entropy-weighted models confirmed these findings. The survival benefit persisted when postoperative deaths were included.
In patients with BR/LA-PDAC with favorable response to chemotherapy, surgical resection significantly improves survival compared with COT.
现代化疗重新定义了胰腺导管腺癌（PDAC）的可切除性，将肿瘤生物学置于解剖学之上。然而，在临界可切除（BR）或局部晚期（LA）的PDAC中，手术与持续肿瘤治疗（COT）的比较结果仍不明确。本研究填补了这一空白。
这项回顾性、国际性、多中心队列研究纳入了2012年至2024年间接受新辅助化疗或一线化疗的BR/LA-PDAC患者。所有患者均符合基于解剖学、生物学和体能状态的潜在切除指南标准。治疗分配（手术与COT）基于机构实践或外科医生的偏好，反映了现实世界中的决策。主要终点是总生存期（OS），采用未调整比较、倾向评分匹配（PSM）和熵平衡分析。
共纳入312例患者：158例行切除术，154例接受COT。切除术后的中位OS为39.0个月（IQR 14.3 - 42.6个月），而COT组为16.7个月（IQR 8.8 - 22.5个月）（p < 0.0001）。PSM（75对）后，切除术的OS仍显著长于COT（42.6个月，IQR 12.9 - 42.1个月）对比COT（18.6个月，IQR 9.4 - 23.9个月；p < 0.0001）。在LA-PDAC亚组中，切除术后的OS为42.6个月（IQR 23.2 - NA个月），而COT组为18.6个月（IQR 11.8 - 25.6个月；p < 0.0001）。多变量分析显示，切除术（HR 0.34，95%CI 0.21 - 0.54；p < 0.0001）和CA 19-9（HR 1.0001；p = 0.0297）与OS独立相关。熵加权模型证实了这些发现。纳入术后死亡病例后，生存获益依然存在。
在对化疗反应良好的BR/LA-PDAC患者中，与COT相比，手术切除显著提高了生存率。
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