《胰腺导管腺癌系统治疗亚洲专家共识》解读

doi:10.16139/j.1007-9610.2025.06.01

摘要/Abstract

摘要：

胰腺导管腺癌（PDAC）因早期诊断困难，多数病人确诊时已进展至局部晚期或转移阶段，系统性治疗成为改善生存的关键。为弥合亚洲各国指南差异并回应区域临床实践需求，亚太地区14位权威专家基于德尔菲法形成《胰腺导管腺癌系统治疗亚洲专家共识》。共识围绕14条核心推荐（R1-R14），按疾病分期提出分层管理策略。对于可切除PDAC，辅助治疗首选改良FOLFIRINOX（mFOLFIRINOX），体力状况较差者可选用吉西他滨联合卡培他滨、S-1单药等方案。临界可切除PDAC病人推荐新辅助治疗，首选GnP或FOLFIRINOX。局部进展期PDAC病人根据体力状况选择联合或单药化疗。转移性PDAC病人一线推荐GnP、NALIRIFOX或mFOLFIRINOX，二线强调交叉使用吉西他滨与5-FU为基础方案。该共识首次为亚洲PDAC系统治疗提供综合、标准化管理框架，旨在提升区域诊疗同质化与病人结局。本文对共识内容进行解读，以期指导临床实践。

关键词: 胰腺癌, 胰腺导管腺癌, 系统治疗, 专家共识, 亚洲

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is difficult to diagnose in its early stages. Most patients are diagnosed at a locally advanced or metastatic stage. Systemic therapy has become the key to improve survival. To bridge the differences in guidelines across Asian countries and address regional clinical practice needs, 14 leading experts in the Asia-Pacific region developed the “Asian Consensus on systemic therapy for pancreatic ductal adenocarcinoma” on the Delphi method. The consensus centers on 14 core recommendations (R1-R14) and proposes stratified management strategies based on disease stage. For resectable PDAC, adjuvant modified FOLFIRINOX (mFOLFIRINOX) is the preferred option, while for the patients with poor performance status gemcitabine plus capecitabine, S-1 monotherapy, and other regimens can be selected. For borderline resectable PDAC, neoadjuvant therapy is recommended, with GnP or FOLFIRINOX as the preferred regimens. For locally advanced PDAC, combination or monochemotherapy is selected based on their performance status. For metastatic PDAC, first-line options include GnP, NALIRIFOX, or mFOLFIRINOX, with second-line therapy the cross-use of gemcitabine-based and 5-FU-based regimens are emphasized. This consensus provides for the first time a comprehensive and standardized management framework for systemic therapy of PDAC in Asia, aiming to enhance regional homogeneity in clinical practice and improve patient outcomes. This article interpreted the consensus content with the goal of guiding clinical practice.

Key words: Pancreatic cancer, Pancreatic ductal adenocarcinoma(PDAC), Systemic therapy, Expert consensus, Asia

中图分类号:

R735.9

温晨磊, 邹思奕, 李凡露, 詹茜, 沈柏用. 《胰腺导管腺癌系统治疗亚洲专家共识》解读[J]. 外科理论与实践, 2025, 30(06): 461-468.

WEN Chenlei, ZOU Siyi, LI Fanlu, ZHAN Qian, SHEN Baiyong. Interpretation of the Asian Consensus on systemic therapy for pancreatic ductal adenocarcinoma[J]. Journal of Surgery Concepts & Practice, 2025, 30(06): 461-468.

参考文献 33

[34]	SATOI S, YAMAMOTO T, YAMAKI S, et al. Surgical indication for and desirable outcomes of conversion surgery in patients with initially unresectable pancreatic ductal adenocarcinoma[J]. Ann Gastroenterol Surg, 2020, 4(1):6-13. doi: 10.1002/ags3.12295 pmid: 32021953
[35]	OBA A, DEL CHIARO M, FUJII T, et al. “Conversion surgery” for locally advanced pancreatic cancer: a position paper by the study group at the joint meeting of the International Association of Pancreatology (IAP) & Japan Pancreas Society (JPS) 2022[J]. Pancreatology, 2023, 23(6):712-720. doi: 10.1016/j.pan.2023.06.005 URL
[36]	SUKER M, BEUMER B R, SADOT E, et al. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis[J]. Lancet Oncol, 2016, 17(6):801-810. doi: S1470-2045(16)00172-8 pmid: 27160474
[37]	KIM Y J, LEE W J, WOO S M, et al. Comparison of capecitabine and 5-fluorouracil in chemoradiotherapy for locally advanced pancreatic cancer[J]. Radiat Oncol, 2013, 8:160. doi: 10.1186/1748-717X-8-160
[38]	BOECK S, WILKOWSKI R, BRUNS C J, et al. Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer[J]. Oncology, 2007, 73(3-4):221-227. doi: 10.1159/000127413 pmid: 18424886
[39]	BURRIS H A, MOORE M J, ANDERSEN J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial[J]. J Clin Oncol, 1997, 15(6):2403-2413. doi: 10.1200/JCO.1997.15.6.2403 pmid: 9196156
[40]	XIE D R, YANG Q, CHEN D L, et al. Gemcitabine-based cytotoxic doublets chemotherapy for advanced pancreatic cancer: updated subgroup meta-analyses of overall survival[J]. Jpn J Clin Oncol, 2010, 40(5):432-441. doi: 10.1093/jjco/hyp198 URL
[41]	VON HOFF D D, ERVIN T, ARENA F P, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine[J]. N Engl J Med, 2013, 369(18):1691-1703. doi: 10.1056/NEJMoa1304369 URL
[42]	VOGEL A, RÖMMLER-ZEHRER J, LI J S, et al. Efficacy and safety profile of nab-paclitaxel plus gemcitabine in patients with metastatic pancreatic cancer treated to disease progression: a subanalysis from a phase 3 trial (MPACT)[J]. BMC Cancer, 2016, 16(1):817. pmid: 27769210
[43]	WAINBERG Z A, MELISI D, MACARULLA T, et al. NALIRIFOX versus nabpaclitaxel and gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (NAPOLI 3): a randomised, open-label, phase 3 trial[J]. Lancet, 2023, 402(10409):1272-1281. doi: 10.1016/S0140-6736(23)01366-1 URL
[44]	WANG-GILLAM A, LI C P, BODOKY G, et al. Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial[J]. Lancet, 2016, 387(10018):545-557. doi: 10.1016/S0140-6736(15)00986-1 URL
[1]	Global Cancer Observatory. GLOBOCAN 2020[EB/OL]. [2025-3-31]. https://gco.iarc.fr.
[2]	TRUONG L H, PAUKLIN S. Pancreatic cancer microenvironment and cellular composition: current understandings and therapeutic approaches[J]. Cancers(Basel), 2021, 13(19):5028.
[3]	DUCREUX M, CUHNA A S, CARAMELLA C, et al. Cancer of the pancreas: ESMO clinical practice guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2015, 26(suppl 5):v56-v68.
[4]	National Comprehensive Cancer Network. NCCN pancreatic adenocarcinoma guidelines V1.2024[EB/OL]. [2025-03-31]. https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.
[5]	SOHAL D P, MANGU P B, KHORANA A A, et al. Metastatic pancreatic cancer: ASCO clinical practice guideline[J]. J Clin Oncol, 2016, 34(23):2784-2796. doi: 10.1200/JCO.2016.67.1412 URL
[6]	SOHAL D P S, KENNEDY E B, CINAR P, et al. Metastatic pancreatic cancer: ASCO guideline update[J]. J Clin Oncol, 2020, 38(27):3217-3230. doi: 10.1200/JCO.20.01364 URL
[7]	CONROY T, PFEIFFER P, VILGRAIN V, et al. Pancreatic cancer: ESMO clinical practice guideline for diagnosis, treatment and follow-up 2020[J]. Ann Oncol, 2023, 34(11):987-1002. doi: 10.1016/j.annonc.2023.08.009 pmid: 37678671
[8]	CUI J, JIAO F, LI Q, et al. Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of pancreatic cancer[J]. J Natl Cancer Cent, 2022, 2(4):205-215.
[9]	CHAN S L, CHIANG C L, CHOK K S H, et al. Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma[J]. Hong Kong Med J, 2024, 30(2):147-162. doi: 10.12809/hkmj2210476 pmid: 38590158
[10]	OKUSAKA T, NAKAMURA M, YOSHIDA M, et al. Clinical practice guidelines for pancreatic cancer 2022 from the Japan pancreas society: a synopsis[J]. Int J Clin Oncol, 2023, 28(4):493-511. doi: 10.1007/s10147-023-02317-x pmid: 36920680
[11]	OKUSAKA T, NAKAMURA M, YOSHIDA M, et al. Clinical practice guidelines for pancreatic cancer 2019 from the Japan pancreas society: a synopsis[J]. Pancreas, 2020, 49(3):326-335. doi: 10.1097/MPA.0000000000001513 URL
[12]	SATOI S, TAKAHARA N, FUJII T, et al. Synopsis of a clinical practice guideline for pancreatic ductal adenocarcinoma with peritoneal dissemination in Japan; Japan peritoneal malignancy study group[J]. J Hepatobiliary Pancreat Sci, 2022, 29(6):600-608. doi: 10.1002/jhbp.v29.6 URL
[13]	Committee of the Korean Clinical Practice Guideline for Pancreatic Cancer and National Cancer Center, Korea. Korean clinical practice guideline for pancreatic cancer 2021: a summary of evidence-based, multi-disciplinary diagnostic and therapeutic approaches[J]. Pancreatology, 2021, 21(7):1326-1341. doi: 10.1016/j.pan.2021.05.004 pmid: 34148794
[14]	Singapore Cancer Network (SCAN) Pancreatic Cancer Workgroup. Singapore Cancer Network (SCAN) guidelines for systemic therapy of pancreatic adenocarcinoma[J]. Ann Acad Med Singap, 2015, 44(10):388-396. pmid: 26763056
[15]	LEE S E, HAN S S, KANG C M, et al. Korean surgical practice guideline for pancreatic cancer 2022: a summary of evidence-based surgical approaches[J]. Ann Hepatobiliary Pancreat Surg, 2022, 26(1):1-16. doi: 10.14701/ahbps.22-009 URL
[16]	VERSTEIJNE E, VOGEL J A, BESSELINK M G, et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer[J]. Br J Surg, 2018, 105(8):946-958. doi: 10.1002/bjs.10870 pmid: 29708592
[17]	CHHETRI P, GIRI A, SHAKYA S, et al. Current deve-lopment of anti-cancer drug S-1[J]. J Clin Diagn Res, 2016, 10(11):XE01-XE05.
[18]	AMIN K, KHAN H, HEARLD L R, et al. Association between rural residence and processes of care in pancreatic cancer treatment[J]. J Gastrointest Surg, 2023, 27(10):2155-2165. doi: 10.1007/s11605-023-05764-z pmid: 37553515
[19]	BERTENS K A, MASSMAN J D 3RD, HELTON S, et al. Initiation of adjuvant therapy following surgical resection of pancreatic ductal adenocarcinoma (PDAC): are patients from rural, remote areas disadvantaged?[J]. J Surg Oncol, 2018, 117(8):1655-1663. doi: 10.1002/jso.25060 pmid: 29761510
[20]	CONROY T, HAMMEL P, HEBBAR M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer[J]. N Engl J Med, 2018, 379(25):2395-2406. doi: 10.1056/NEJMoa1809775 URL
[21]	UESAKA K, BOKU N, FUKUTOMI A, et al. Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01)[J]. Lancet, 2016, 388(10041):248-257. doi: 10.1016/S0140-6736(16)30583-9 URL
[22]	TEMPERO M A, PELZER U, O′REILLY E M, et al. Adjuvant nab-paclitaxel þgemcitabine in resected pancreatic ductal adenocarcinoma: results from a randomized, open-label, phase Ⅲ trial[J]. J Clin Oncol, 2023, 41(11):2007-2019.
[23]	NEOPTOLEMOS J P, PALMER D H, GHANEH P, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, openlabel, randomised, phase 3 trial[J]. Lancet, 2017, 389(10073):1011-1024. doi: 10.1016/S0140-6736(16)32409-6 URL
[45]	WANG-GILLAM A, HUBNER R A, SIVEKE J T, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: final overall survival analysis and characteristics of long-term survivors[J]. Eur J Cancer, 2019, 108:78-87. doi: 10.1016/j.ejca.2018.12.007 URL
[46]	CUI J, QIN S, ZHOU Y, et al. Irinotecan hydrochloride liposome HR070803 in combination with 5-fluorouracil and leucovorin in locally advanced or metastatic pancreatic ductal adenocarcinoma following prior gemcitabine-based therapy (PAN-HEROIC-1): a phase 3 trial[J]. Signal Transduct Target Ther, 2024, 9(1):248.
[47]	RIEDL J M, POSCH F, HORVATH L, et al. Gemcitabine/nab-paclitaxel versus FOLFIRINOX for palliative first-line treatment of advanced pancreatic cancer: a propensity score analysis[J]. Eur J Cancer, 2021, 151:3-13. doi: 10.1016/j.ejca.2021.03.040 URL
[48]	UENO M, NAKAMORI S, SUGIMORI K, et al. nal-IRIþ5-FU/LV versus 5-FU/LV in post-gemcitabine metastatic pancreatic cancer: randomized phase 2 trial in Japanese patients[J]. Cancer Med, 2020, 9(24):9396-9408. doi: 10.1002/cam4.v9.24 URL
[49]	PRAGER G W, OEHLER L, GERGER A, et al. Comparison of nab-paclitaxel plus gemcitabine in elderly versus younger patients with metastatic pancreatic cancer: analysis of a multicentre, prospective, noninterventional study[J]. Eur J Cancer. 2021, 143:101-112. doi: 10.1016/j.ejca.2020.11.003 URL
[50]	CONROY T, DESSEIGNE F, YCHOU M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer[J]. N Engl J Med, 2011, 364(19):1817-1825. doi: 10.1056/NEJMoa1011923 URL
[51]	MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase Ⅱ KEYNOTE-158 study[J]. J Clin Oncol, 2020, 38(1):1-10.
[52]	O’REILLY E M, LEE J W, ZALUPSKI M, et al. Randomized, multicenter, phase Ⅱ trial of gemcitabine and cisplatin with or without veliparib in patients with pancreas adenocarcinoma and a germline BRCA/PALB2 mutation[J]. J Clin Oncol, 2020, 38(13):1378-1388.
[53]	GOLAN T, HAMMEL P, RENI M, et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer[J]. N Engl J Med, 2019, 381(4):317-327. doi: 10.1056/NEJMoa1903387 URL
[24]	KANG S, YOO C, LEE S H, et al. Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma[J]. Ther Adv Med Oncol, 2022, 14:17588359221097190.
[25]	OETTLE H, NEUHAUS P, HOCHHAUS A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial[J]. JAMA, 2013, 310(14):1473-1481. doi: 10.1001/jama.2013.279201 pmid: 24104372
[26]	OETTLE H, POST S, NEUHAUS P, et al. Adjuvant chemotherapy with gemcitabine vs. observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial[J]. JAMA, 2007, 297(3):267-277. doi: 10.1001/jama.297.3.267 URL
[27]	VAN LAETHEM J L, HAMMEL P, MORNEX F, et al. Adjuvant gemcitabine alone versus gemcitabine-based chemoradiotherapy after curative resection for pancreatic cancer: a randomized EORTC-40013-22012/FFCD-9203/GERCOR phase Ⅱ study[J]. J Clin Oncol, 2010, 28(29):4450-4456. doi: 10.1200/JCO.2010.30.3446 URL
[28]	UENO H, IOKA T, IKEDA M, et al. Randomized phase Ⅲ study of gemcitabine plus S-1, S-1 alone, or gemcitabine alone in patients with locally advanced and metastatic pancreatic cancer in Japan and Taiwan: GEST study[J]. J Clin Oncol, 2013, 31(13):1640-1648.
[29]	SCHULTHEIS B, STRUMBERG D, BERGMANN L, et al. Results of a phase Ⅱ trial of S-1 as first-line treatment of metastatic pancreatic cancer (CESARstudy group)[J]. Invest New Drugs, 2012, 30(3):1184-1192. doi: 10.1007/s10637-011-9665-x URL
[30]	SATOI S, UNNO M, MOTOI F, et al. The effect of neoadjuvant chemotherapy with gemcitabine and S-1 for resectable pancreatic cancer (randomized phase Ⅱ/Ⅲ trial; Prep-02/JSAP-05)[J]. J Clin Oncol, 2019, 37(suppl 15):4126. doi: 10.1200/JCO.2019.37.15_suppl.4126 URL
[31]	CLOYD J M, HEH V, PAWLIK T M, et al. Neoadjuvant therapy for resectable and borderline resectable pancreatic cancer: a meta-analysis of randomized controlled trials[J]. J Clin Med, 2020, 9(4):1129. doi: 10.3390/jcm9041129 URL
[32]	MOTOI F, ISHIDA K, FUJISHIMA F, et al. Neoadjuvant chemotherapy with gemcitabine and S-1 for resectable and borderline pancreatic ductal adenocarcinoma: results from a prospective multi-institutional phase 2 trial[J]. Ann Surg Oncol, 2013, 20(12):3794-3801. doi: 10.1245/s10434-013-3129-9 pmid: 23838925
[33]	SATOI S, UNNO M, MOTOI F, et al. Randomized phase Ⅱ/Ⅲ trial of neoadjuvant chemotherapy with gemcitabine and S-1 versus upfront surgery for resectable pancreatic cancer (Prep-02/JSAP05)[J]. Jpn J Clin Oncol, 2019, 49(2):190-194. doi: 10.1093/jjco/hyy190 URL