Frontiers and Challenges: Evolution Map of Standard Therapies for Gastric Cancer in China and the US from 2015-2025

Gastric cancer, as a globally high-incidence malignant tumor of the digestive tract, has undergone a profound transformation in its diagnostic and treatment models over the past decade, shifting from traditional empirical medicine to precise evidence-based medicine. With innovations in diagnostic technologies, the emergence of targeted and immunotherapeutic drugs, and the popularization of multidisciplinary team (MDT) concepts, both China and the US have continuously iterated and optimized standard therapies for gastric cancer, significantly improving patient quality of life and prognosis. DengyuePharma will systematically outline the developmental trajectory of gastric cancer diagnosis and treatment from 2015 to 2025, milestone events in China and the US, guideline differences, future trends, and prospects, providing a panoramic view of the evolutionary process in this field.

Development and Evolution of Gastric Cancer Diagnosis

Over the past decade, the core breakthrough in gastric cancer diagnosis has been the leap from "morphological diagnosis" to "molecular subtyping precision diagnosis," enriching diagnostic dimensions, significantly enhancing accuracy, and laying the foundation for individualized treatment.

In terms of screening and early diagnosis, the integrated application of serological testing and endoscopic technologies has improved the detection rate of early cancers. Traditional gastroscopy, as the "gold standard" for gastric cancer diagnosis, has gradually upgraded to high-definition endoscopy, magnifying endoscopy combined with narrow-band imaging (NBI) technology, which can clearly identify subtle mucosal lesions, glandular structures, and vascular morphology in the stomach, increasing the detection rate of early gastric cancer by more than 30%. It also accurately assesses lesion infiltration depth, providing a basis for endoscopic radical resection. In serological testing, beyond traditional tumor markers like carcinoembryonic antigen (CEA) and CA19-9, the combination of serum pepsinogen (PG), gastrin-17 (G17), and Helicobacter pylori (Hp) antibody testing has become a core method for gastric cancer screening in China. This allows risk stratification to prioritize endoscopic examinations and effectively identify populations with precancerous lesions such as atrophic gastritis.

In the field of molecular diagnosis, the popularization of precision subtyping technologies has reshaped the gastric cancer treatment pathway. A decade ago, molecular testing for gastric cancer was limited to a few centers, but now, detection of key biomarkers such as HER2, MSI-H/dMMR, Claudin18.2, and PD-L1 has been incorporated into routine clinical workflows. The 2025 edition of the CSCO gastric cancer guidelines explicitly recommends routine HER2 testing for all patients with locally advanced and metastatic gastric cancer, while MSI-H/dMMR subtyping has become a key predictive indicator for immunotherapy benefits. Additionally, the application of artificial intelligence (AI)-assisted diagnostic systems has achieved a leap in diagnostic efficiency, automatically identifying suspicious lesions in gastroscopic images and assisting in tumor staging. Currently, in China, the accuracy of AI-assisted T/N staging has improved to 60% and 75%, respectively, effectively reducing diagnostic disparities among different medical institutions. Pathological diagnosis has also become increasingly standardized, with the implementation of formatted pathology reports and specimen preprocessing standards ensuring the reliability of molecular testing results and providing core support for precision treatment.

Milestone Events in Standard Therapies for Gastric Cancer in China and the US Over the Past Decade

Over the past decade, relying on high-quality clinical research, China and the US have driven gastric cancer therapies from "chemotherapy-dominated" to a comprehensive upgrade of "chemotherapy + targeted + immunotherapy combinations," with a series of milestone events defining the standard treatment models at each stage.

Key breakthroughs in China have focused on building localized evidence-based medical evidence and optimizing regimens. Around 2015, long-term data from the ACTS-GC and CLASSIC studies further solidified the core position of D2 radical resection combined with postoperative adjuvant chemotherapy in locally advanced gastric cancer, establishing foundational regimens like S-1 and capecitabine combined with oxaliplatin. In 2021, the RESOLVE study, led by Professors Ji Jiafu and Shen Lin and published in The Lancet Oncology, was China's first phase III trial to head-to-head compare neoadjuvant chemotherapy with adjuvant chemotherapy. It confirmed that the perioperative SOX regimen (tegafur + oxaliplatin) could increase the 3-year disease-free survival rate to 59.4% in patients with locally advanced gastric cancer, significantly reducing recurrence risk. Tailored for Asian populations, this regimen was incorporated into the CSCO guidelines and gradually upgraded to a level I recommendation. In 2024, the DRAGON IV study achieved breakthrough progress, becoming the world's first phase III trial to confirm the benefits of a triple immunotherapy + targeted + chemotherapy regimen in the perioperative setting for resectable gastric cancer. The combination of camrelizumab with apatinib and SOX significantly improved the pathological complete response rate, ushering in a new era of perioperative triple therapy for gastric cancer. The 2025 CSCO guidelines further refined molecular subtyping-guided treatments, incorporating neoadjuvant immunotherapy for dMMR/MSI-H gastric cancer as a recommendation, perfecting the precision treatment system.

In the US, global multicenter studies have been central to promoting the globalization of therapies and the implementation of innovative drugs. In 2017, the ATTRACTION-2 study confirmed the efficacy of nivolumab in third-line treatment for advanced gastric cancer, opening a new chapter in gastric cancer immunotherapy. In 2020, the KEYNOTE-811 study first confirmed that pembrolizumab combined with trastuzumab and chemotherapy could significantly improve the objective response rate in HER2-positive advanced gastric cancer, establishing the frontline status of immunotherapy + targeted + chemotherapy in this subtype. In 2024, the ASCO GI meeting announced results from the KEYNOTE-585 trial, showing that pembrolizumab combined with chemotherapy could increase the pCR rate to 12.9% in locally advanced gastric cancer, providing key evidence for perioperative immunotherapy. In 2025, positive results from the MATTERHORN study led to the approval of durvalumab combined with FLOT chemotherapy for perioperative treatment of resectable gastric cancer, becoming the world's first approved immunotherapy combination for this indication, listed as a category I preferred regimen in the 2026.V1 NCCN guidelines. In the same year, the FDA upgraded trastuzumab deruxtecan (T-DXd) to a category I recommendation for second-line treatment of HER2-positive gastric cancer, based on data from the DESTINY-Gastric04 study, which extended median overall survival to 14.7 months, significantly outperforming traditional regimens.

Comparison of Current Optimal Treatments in China-US Guidelines

Based on different disease spectra, population characteristics, and research evidence, the 2025 mainstream guidelines in China (CSCO) and the US (NCCN) exhibit "core consensus alongside regional differences" in optimal treatment regimens for gastric cancer, mainly in three dimensions: perioperative treatment, molecular subtyping-guided treatment, and advanced salvage treatment.

In perioperative treatment for resectable locally advanced gastric cancer, both China and the US recognize the intensification strategy of "chemotherapy combined with immunotherapy," but regimen choices differ. The US NCCN guidelines, based on studies in European and American populations, list FLOT chemotherapy (docetaxel + oxaliplatin + fluorouracil) combined with durvalumab as a category I preferred regimen, emphasizing its advantages in improving pCR rates and event-free survival. It also retains surgery combined with postoperative adjuvant chemoradiotherapy (based on the INT-0116 study) for patients unable to tolerate preoperative chemotherapy. The Chinese CSCO guidelines, more aligned with Asian pathological features and surgical models, list the SOX regimen for perioperative treatment as a level I recommendation, derived from clear benefits in Eastern populations from the RESOLVE study. For dMMR/MSI-H subtypes, it adds PD-1 monoclonal antibody combined with chemotherapy (level III recommendation) and PD-1 + CTLA-4 dual immunotherapy (level II recommendation), while recognizing the application of triple regimens supported by the DRAGON IV study in high-risk patients. It upholds D2 radical resection as the gold standard for surgical treatment, with postoperative adjuvant chemoradiotherapy only as a supplementary option for patients at extremely high risk of local recurrence.

In molecular subtyping-guided precision treatment, the recommendations for core targets in China-US guidelines are highly consistent, but differences exist in drug choices and evidence levels. For HER2-positive advanced gastric cancer, both countries list trastuzumab combined with chemotherapy as a frontline category I recommendation, with T-DXd prioritized for second-line; however, NCCN lists T-DXd as category 1, while CSCO, based on Chinese population data, lists it as level I, also retaining pyrotinib combined with chemotherapy as a second-line option. For MSI-H/dMMR subtypes, both recommend immunotherapy monotherapy or combinations for frontline and perioperative treatment; NCCN adds dostarlimab-gxly for neoadjuvant treatment, while CSCO focuses on PD-1 monoclonal antibody applications, better aligning with domestic drug accessibility. For Claudin18.2-positive patients, NCCN includes category II recommendations for ADC drugs and bispecific antibodies, while CSCO, based on domestic clinical trial data, lists relevant targeted drugs combined with chemotherapy as second-line and beyond recommendations for advanced patients.

In treatment for advanced unresectable or metastatic gastric cancer, both China and the US emphasize a "stratified treatment" philosophy, but differences exist in foundational chemotherapy regimens and later-line options. For frontline treatment, NCCN guidelines base on FLOT, combined with targeted/immunotherapy drugs; CSCO guidelines center on SOX and XELOX, prioritizing chemotherapy combined with immunotherapy (level I recommendation) for HER2-negative patients. In later-line treatments, NCCN covers more novel drugs like DKK1 inhibitors and TGFβ inhibitors, while CSCO emphasizes drug accessibility, focusing on domestic PD-1 monoclonal antibodies, apatinib, and other anti-angiogenic drugs, forming treatment paths suited to China's medical landscape.

Future Trend Predictions

Looking ahead to the next five years, gastric cancer diagnosis and treatment will evolve deeply toward "more precise, earlier, and more combined" directions, with molecular biology technologies, novel drug development, and innovative treatment models as core drivers, further breaking through existing efficacy bottlenecks.

Molecular diagnosis and subtyping will enter the era of "multi-omics integration." Single biomarker testing will gradually be replaced by whole exome sequencing (WES), spatial multi-omics, and other technologies, simultaneously capturing genetic mutations, gene expression, protein levels, and tumor microenvironment features to achieve ultra-precise subtyping of gastric cancer and tailor treatment regimens for patients. Minimal residual disease (MRD) monitoring technology will become fully popularized, using ctDNA dynamic detection to guide adjustments in perioperative treatment intensity and postoperative follow-up, achieving "precise de-escalation" and "timely escalation" to reduce recurrence risk. AI technology will deeply integrate into diagnosis and treatment decisions, upgrading from assisting lesion identification and staging to predicting treatment efficacy and adverse reactions, building an intelligent full-process diagnostic and treatment system.

Novel drug development will focus on "target expansion and therapeutic innovation." In targeted therapy, emerging targets like Claudin18.2, FGFR, and MET will see ADC drugs and bispecific antibodies gradually entering frontline treatment, combining with existing regimens to form "additive benefits"; drug development for HER2 low-expression populations will further breakthrough, filling current treatment gaps. In immunotherapy, the synergistic mechanisms of dual immunotherapy combinations and immunotherapy with anti-angiogenic drugs will be explored more deeply, potentially breaking through immunotherapy resistance in MSS-type gastric cancer. Additionally, novel therapies like CAR-T cell therapy and oncolytic viruses will show potential in later-line treatment for advanced gastric cancer, offering new survival hopes for refractory patients.

Treatment models will upgrade toward "full-cycle individualized management" and "deep multidisciplinary integration." Perioperative treatment will further refine stratification, based on molecular subtyping and MRD status, achieving "precise neoadjuvant + radical surgery + individualized adjuvant" full-process management, allowing some patients to preserve gastric function through de-escalation treatment and improve quality of life. For advanced gastric cancer, "chemotherapy-free regimens" will gradually become possible, replacing traditional chemotherapy with immunotherapy + targeted combinations to maintain efficacy while reducing adverse reactions. Multidisciplinary collaboration (MDT) will shift from "phased consultations" to "full-course management," integrating resources from surgery, internal medicine, radiotherapy, pathology, imaging, and other disciplines to provide full-cycle personalized regimens from diagnosis to follow-up. Furthermore, early cancer screening technologies will continue to optimize, with the combination of non-invasive screening methods (such as breath tests and fecal nucleic acid detection) and endoscopic technologies expected to achieve full coverage of "early screening, early diagnosis, early treatment" for gastric cancer, reducing mortality from the source.

Summary and Outlook

Over the past decade, the field of gastric cancer diagnosis and treatment has achieved leapfrog development, with diagnostic technologies shifting from morphological to molecular precision subtyping, and treatment models upgrading from chemotherapy-dominated to "chemotherapy + targeted + immunotherapy" multimodal combinations. Relying on their respective evidence-based medical evidence, China and the US have built standard treatment systems suited to local characteristics. Milestone studies like RESOLVE, MATTERHORN, and DRAGON IV have not only rewritten clinical guidelines but also granted countless gastric cancer patients longer survival and better quality of life, significantly enhancing China's international voice in gastric cancer diagnosis and treatment.

At the same time, we must face current challenges: China's early gastric cancer detection rate remains below 20%, with a significant gap compared to Japan and South Korea; accessibility to some novel drugs is insufficient, and the standardization of diagnosis and treatment in grassroots medical institutions needs improvement; efficacy for MSS-type gastric cancer and advanced metastatic gastric cancer still requires breakthroughs. In the future, we need to further strengthen the construction of early screening and diagnosis systems for gastric cancer, expand screening coverage for high-risk populations; accelerate the research, development, and transformation of domestic novel drugs to enhance the accessibility and inclusivity of innovative drugs; promote standardization and homogenization of diagnosis and treatment to narrow regional medical disparities.

With the continuous innovation of precision medicine technologies, the constant emergence of novel drugs, and the deep popularization of multidisciplinary collaboration models, gastric cancer diagnosis and treatment will gradually enter a "cure-oriented" new era. In the next decade, it is expected to achieve cure rates exceeding 90% for early gastric cancer, significantly extend median overall survival for advanced gastric cancer patients, and ultimately realize the shift from "disease treatment" to "health management," contributing Chinese wisdom and solutions to global gastric cancer prevention and control.