2024晚期胃癌诊疗指南更新对比与梳理：CSCO、NCCN和ESMO

doi:10.19401/j.cnki.1007-3639.2025.02.009

摘要/Abstract

摘要：

胃癌是全球范围内高发恶性肿瘤，具有高度侵袭性，总体预后不佳等特点。东西方胃癌人群在流行病学、临床病理学特征、治疗模式及药物选择等方面存在差异。近年来，随着靶向治疗和免疫治疗的快速推进，精准治疗理念的成熟和多学科治疗的推广等，临床研究成果不断更新，胃癌指南每年持续更新，以适应不断变化的诊疗需求。本文就全球范围内三大权威胃癌指南最新版[包括美国国家综合癌症网络（National Comprehensive Cancer Network，NCCN）胃癌临床实践指南2024年V5版（2024年12月发布）、欧洲肿瘤内科学会（European Society for Medical Oncology，ESMO）胃癌在线指南2024版（2024年9月发布）和中国临床肿瘤协会（Chinese Society of Clinical Oncology，CSCO）胃癌诊疗指南（2024年4月发布）]更新内容的异同点进行对比与梳理，聚焦不可手术切除的局部晚期或转移性食管胃结合部和胃腺癌的临床治疗策略，关注基于靶点如人表皮生长因子受体2（human epidermal growth factor receptor 2，HER2）、程序性死亡受体配体1（programmed death-ligand 1，PD-L1）表达、错配修复蛋白（mismatch repair，MMR）状态和新靶点如Claudin 18.2（CLDN18.2）等为导向的抗肿瘤药物的精准实施和全程管理。其中，HER2阳性晚期胃癌进入全线抗HER2治疗时代，抗HER2的抗体药物偶联物（antibody-drug conjugate，ADC）成为一线曲妥珠单抗治疗耐药之后的新选择。除此之外，免疫治疗联合化疗成为晚期胃癌一线治疗新标准，基于MMR状态和PD-L1表达指导的诊疗模式将免疫治疗推向精准化，然而目前PD-L1表达检测在临床推广和执行的过程中仍存在一定困难。2024年发表的三大指南融合了最新的临床研究结果、药物适应证的获批情况和医疗保健系统的实情等内容，尤其是CSCO胃癌指南基于中国自主研发药物的快速发展和针对中国人群研究适应证的成功获批进行了更新。三大指南在靶向治疗、免疫疗法等新疗法的推荐和采用等方面存在差异，本文基于不同指南内容展现出不同的视角与侧重，以丰富临床决策的维度，增强循证医学指南的临床适应性，进而指导临床实践。

关键词: 胃癌, 诊疗指南, 中国临床肿瘤协会, 美国国家综合癌症网络, 欧洲肿瘤内科学会

Abstract:

Gastric cancer is a highly prevalent and aggressive malignancy worldwide, with generally poor prognosis. There are differences in epidemiology, clinicopathological characteristics, treatment modalities, and drug selection for gastric cancer between Eastern and Western populations. Recent advancements in targeted therapy and immunotherapy, the maturation of precision treatment concepts, and the promotion of multidisciplinary therapy have led to continuous updates in clinical research outcomes. Gastric cancer guidelines are annually updated to meet evolving diagnostic and therapeutic needs. This article compared the latest versions of three authoritative global gastric cancer guidelines [National Comprehensive Cancer Network (NCCN) clinical practice guidelines for gastric cancer 2024 version 5, European Society for Medical Oncology (ESMO) online guidelines for gastric cancer 2024, and Chinese Society of Clinical Oncology (CSCO) guidelines for gastric cancer diagnosis and treatment 2024], focusing on clinical treatment strategies for unresectable locally advanced or metastatic esophagogastric junction/gastric adenocarcinoma, and on the whole-process management and precise implementation guided by targets such as human epidermal growth factor receptor 2 (HER2) expression, programmed cell death ligand 1 (PD-L1) expression, mismatch repair (MMR) status,, and novel targets such as Claudin 18.2. Meanwhile, HER2-positive advanced gastric cancer has entered the era of full-line anti-HER2 treatment. Anti-HER2 antibody-drug conjugates (ADCs) has become a new option after first-line trastuzumab resistance. Immunotherapy combined with chemotherapy is regarded as a new standard for the first-line treatment of advanced gastric cancer. The diagnosis and treatment mode based on MMR status and PD-L1 expression promote the precision of immunotherapy. However, the detection of PD-L1 expression has difficulties in clinical promotion and implementation. The three guidelines in 2024 integrate the latest clinical study results, the new indication approval and the updated health care system. In particular, the CSCO gastric cancer guidelines are rewritten based on the rapid development of independently developed drugs in China and the approval of new indications. The three guidelines differ in the recommendation and adoption of targeted therapy and immunotherapy. This article showed different perspectives and focuses based on different guidelines, enriched the dimensions of clinical decision-making, helped the clinical adaptability of evidence-based guidelines to better enlightens clinical practice.

Key words: Gastric cancer, Diagnosis and treatment guidelines, CSCO, NCCN, EMSO

蓝煜, 王风华. 2024晚期胃癌诊疗指南更新对比与梳理：CSCO、NCCN和ESMO[J]. 中国癌症杂志, 2025, 35(2): 219-227.

LAN Yu, WANG Fenghua. Comparison and review of updated guidelines for advanced gastric cancer diagnosis and treatment in 2024: CSCO, NCCN and ESMO[J]. China Oncology, 2025, 35(2): 219-227.

图/表 2

表1

2024晚期胃癌诊疗指南更新对比：CSCO、NCCN和ESMO"

Patients types	The same recommendation	Different recommendation
First line treatment
HER2 overexpression (IHC3+ or 2+/ISH+)	Recommendations based on PD-L1 expressions: ① PD-L1 CPS≥1: chemotherapy+trastuzumab+pembrolizumab; ② PD-L1 CPS<1: chemotherapy+trastuzumab	-
HER2 overexpression (IHC3+ or 2+/ISH+)		-
HER2 negative	Recommendations based on PD-L1 expression levels in tumor tissues, should chemotherapy be further combined with immunotherapy and the selection of different ICIs ① PD-L1 CPS≥5: chemotherapy+nivolumab ② PD-L1 CPS≥1: chemotherapy+pembrolizumab	NCCN guideline ① PD-L1 CPS<5: consider chemotherapy+nivolumab in certain useful situations (Class 2B recommendation); ② PD-L1 CPS≥1 but<10: chemotherapy+pembrolizumab (Class 1 recommendation); ③ PD-L1 CPS 1-10: chemotherapy+pembrolizumab (Class 2B recommendation) ESMO guideline ① PD-L1 CPS 1-4: chemotherapy+nivolumab may be considered; ② PD-L1 CPS≥10: should receive chemotherapy+pembrolizumab; ③ PD-L1 CPS 1-9: chemotherapy+pembrolizumab may be considered CSCO guideline ① The selection of ICIs is more diverse. Including multiple PD-1 monoclonal antibodies (nivolumab, pembrolizumab, sintilimab, and tislelizumab), PD-L1 mAb (sugemalimab), and PD-1/CTL4 bispecific antibody (cadonilimab); ② Based on the different evaluation methods and expression levels of PD-L1 expression, the recommended immunotherapy regimen is more diversified; ③ For patients with lower PD-L1 expression or CPS-1<1 or whose testing is not accessible, first-line chemotherapy combined with immunotherapy may be considered as a Grade Ⅱ recommendation (Class 1B); ④ Consideration for inclusion in the population suitable for monotherapy immunotherapy: Grade Ⅲ recommendation for pembrolizumab monotherapy for those who have chemotherapy contraindications, refuse chemotherapy, or cannot tolerate chemotherapy (Class 2B)
dMMR/MSI-H	Immunotherapy is recommended regardless of PD-L1 or HER2 status	NCCN guideline Recommend pembrolizumab or dostarlimab, nivolumab combined with ipilimumab, nivolumab combined with chemotherapy, pembrolizumab combined with chemotherapy ESMO guideline Immunotherapy is recommended, but it is uncertain whether PD-1 mAb should be used alone or in combination with chemotherapy. If the patient with severe symptoms and metastases involving important organs, consider PD-1 mAb combination therapy CSCO guideline ① Recommended combination therapy of nivolumab and ipilimumab (Grade Ⅱ recommendation, Class 2B), pembrolizumab (Grade Ⅱ recommendation, Class 2B), nivolumab combined with chemotherapy (Grade Ⅲ recommendation, Class 2B), and pembrolizumab combined with chemotherapy (Grade Ⅲ recommendation, Class 2B); ② The use of ICIs alone is contraindicated or cannot be considered in a timely manner for chemotherapy alone
AFP-producing gastric cancer	-	CSCO guideline The CSCO guidelines focus for the first time on the treatment of subtypes of AFP producing gastric cancer and add a first-line treatment regimen of SOX+camrelizumab/apatinib (Grade Ⅱ recommendation)
CLDN 18.2-positive	For patients with pMMR and HER2 negative and CLDN18.2 positive (≥75% tumor cells CLDN18.2 membrane staining, IHC≥2+), chemotherapy combined with zolbetuximab is recommended	NCCN and ESMO guideline CLDN18.2 as a first-line treatment stratification for HER2 negative patients, chemotherapy+zolbetuximab (Class Ⅰ recommendation) is recommended CSCO guideline ① As the indications for zolbetuximab have not been approved in China and there is no recommendation, positive research results are presented in the form of annotations; ② Emphasize the importance of the CLND18.2 target, and other novel drugs targeting CLND18.2 such as ADC, bispecific antibodies, CAR-T, etc. Phase Ⅰ-Ⅱ trials have shown good efficacy, with confirmatory studies underway. Encourage patients to participate in clinical trials
Second line and posterior line treatment
HER2 positive	① Cross line therapy with trastuzumab is not recommended; ② For HER2 overexpression patients (IHC 3+or 2+/ISH+), T-DXd is recommended as a third line treatment	NCCN and ESMO guideline For individuals with HER2 overexpression (IHC test results of 3+or 2+and ISH+), second-line T-DXd is recommended, and HER2 expression status should be evaluated by biopsy as much as possible before treatment CSCO guideline ① Patients who have failed first-line chemotherapy and have not received trastuzumab are recommended to trastuzumab+chemotherapy (Grade Ⅱ recommendation, 2A evidence); ② Second line treatment does not recommend anti-HER2 ADC, and patients are encouraged to participate in clinical trials; ③ For HER2 patients with IHC test results of 2+or 3+, first-line treatment with disitamab vedotin is recommended (Grade Ⅰ recommendation, Class 2A)
dMMR/MSI-H	① If the first-line treatment has not yet received immunotherapy for patients, it is recommended to choose immunotherapy as the preferred option; ② If the first-line treatment contains immunotherapy, it is recommended to choose second-line and second-line treatment plans based on HER2 status	NCCN guideline Pembrolizumab, dostarlimab, nivolumab combined with ipilimumab are recommended ESMO guideline Pembrolizumab is recommended CSCO guideline Recommendation: envafolimab, tislelizumab and serplulimab (Grade Ⅰ recommendation, Class 2A), pembrolizumab (Grade Ⅱ recommendation, Class 2B)
No specific target	Remdesizumab is recommended in combination with paclitaxel or monotherapy chemotherapy (paclitaxel or irinotecan)	NCCN and ESMO guideline For patients with contraindications to chemotherapy, monotherapy with ramucirumab is also recommended as an option CSCO guideline ① Add data on the second-line treatment of advanced gastric cancer with fruquintinib combined with paclitaxel in the form of annotations; ② Apatinib third line treatment (Grade Ⅰ recommendation, Grade ⅠA evidence)
Specific target and relative detection		NCCN guideline ① Patients with NTRK gene fusion mutations are recommended to receive entrectinib and larotrectinib; ② For BRAF V600E mutation patients, dabrafenib+trametinib is recommended; ③ Patients with RET gene fusion mutations are recommended to use selpercatinib; ④ Recommend NGS testing for newly diagnosed gastric cancer patients ESMO and CSCO guideline ① Currently, there is no treatment recommendation provided for the rare patient with the gene mutations mentioned above; ②NGS is not necessary according to ESMO, while CSCO guidelines recommend NGS testing for patients who have failed standard treatment to identify potential therapeutic targets

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