Andel Paul C M, Campbell Brady A, Habib Joseph R, Molenaar I Quintus, Lafaro Kelly J, Burns William R, Daamen Lois A, Cameron John L, Wolfgang Christopher L, Burkhart Richard A, He Jin, Javed Ammar A
Department of Surgery, The NYU Grossman School of Medicine and NYU Langone Health, New York, NY, USA.
Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center and St Antonius Hospital Nieuwegein, Utrecht, The Netherlands.
Ann Surg Oncol. 2025 May 29. doi: 10.1245/s10434-025-17439-x.
Neoadjuvant therapy (NAT) for pancreatic ductal adenocarcinoma (PDAC) is increasingly being used. The aim of this study was to evaluate the association between type, duration, and sequencing of adjuvant therapy (AT) after NAT and overall survival (OS) in patients with resected PDAC.
Patients receiving NAT and resection for PDAC (2010-2019) at two high-volume pancreatic surgery centers were included and stratified into groups on the basis of NAT regimen: gemcitabine-based NAT, 5-fluorouracil (5FU)-based NAT, or switched NAT regimen. The maximally selected rank statistic was used to determine the optimal NAT duration. Univariate and multivariable Cox proportional hazards models were used to assess the association between NAT regimen and OS, and between AT and OS.
Of 651 patients, 200 (30.7%) received gemcitabine-based NAT, 362 (56%) received 5FU-based NAT, and 89 (13.7%) switched NAT regimen. Median OS in patients receiving gemcitabine-based NAT was 19 months (95% confidence interval (CI) 17-25 months), compared with 26 months (95% CI 24-31 months) in patients receiving 5FU-based NAT (hazard ratio (HR) 0.81, 95% CI 0.66-0.99, p = 0.04) and 21 months (95% CI 16-26 months) in patients who switched NAT regimen (HR 0.98, 95% CI 0.73-1.29, p = 0.86). Optimal NAT duration was 3.6 months in the complete cohort. Receiving AT was associated with improved survival (HR 0.61, 95% CI 0.43-0.86, p < 0.001), but its association was reduced after a NAT duration of ≥5 months (adjuvant chemotherapy × NAT duration ≥ 5 months: HR 1.50, 95% CI 1.00-2.24, p = 0.048).
Patients receiving 5FU-based NAT showed improved survival compared with patients receiving gemcitabine-based NAT before surgery for PDAC. Adjuvant therapy improved survival, particularly in patients with shorter NAT duration.
胰腺导管腺癌（PDAC）的新辅助治疗（NAT）应用越来越广泛。本研究旨在评估NAT后辅助治疗（AT）的类型、持续时间和顺序与接受手术切除的PDAC患者总生存期（OS）之间的关联。
纳入在两个大型胰腺手术中心接受NAT及PDAC切除术（2010 - 2019年）的患者，并根据NAT方案分层分组：吉西他滨为基础的NAT、5-氟尿嘧啶（5FU）为基础的NAT或转换的NAT方案。采用最大选择秩统计量确定最佳NAT持续时间。单因素和多因素Cox比例风险模型用于评估NAT方案与OS之间以及AT与OS之间的关联。
651例患者中，200例（30.7%）接受吉西他滨为基础的NAT，362例（56%）接受5FU为基础的NAT，89例（13.7%）采用转换的NAT方案。接受吉西他滨为基础的NAT患者的中位OS为19个月（95%置信区间（CI）17 - 25个月），而接受5FU为基础的NAT患者为26个月（95%CI 24 - 31个月）（风险比（HR）0.81，95%CI 0.66 - 0.99，p = 0.04），采用转换NAT方案的患者为21个月（95%CI 16 - 26个月）（HR 0.98，95%CI 0.73 - 1.29，p = 0.86）。整个队列的最佳NAT持续时间为3.6个月。接受AT与生存期改善相关（HR 0.61，95%CI 0.43 - 0.86，p < 0.001），但在NAT持续时间≥5个月后其相关性降低（辅助化疗×NAT持续时间≥5个月：HR 1.50，95%CI 1.00 - 2.24，p = 0.048）。
对于PDAC患者，术前接受5FU为基础的NAT的患者比接受吉西他滨为基础的NAT的患者生存期改善。辅助治疗改善了生存期，特别是在NAT持续时间较短的患者中。
