Journal of Gastric Cancer最新文献

Gastric cancer (GC) is a highly heterogeneous disease that varies in both histological presentation and genetic characteristics. Recent advances in the treatment of metastatic and unresectable GC have made several biomarker tests essential for patient management. Predictive biomarkers such as human epidermal growth factor receptor 2 (HER2), programmed death-ligand 1 (PD-L1), mismatch-repair (MMR) proteins, claudin 18.2, and fibroblast growth factor receptor 2b (FGFR2b) are commonly evaluated using immunohistochemistry. However, the expression levels of these biomarkers may vary across different tumor areas, and the accuracy of biomarker diagnosis can be affected by sample quantity, sample location, and collection method. Therefore, tumor heterogeneity presents substantial challenges for accurate biomarker-based diagnosis and prediction of therapeutic responses. Tumor heterogeneity can be categorized into spatial heterogeneity, which refers to variations within the primary tumor (intra-tumoral) or between primary and metastatic sites, and temporal heterogeneity, which encompasses changes over time. This review addresses the tumor heterogeneity in predictive biomarker expression in GC, focusing on HER2, PD-L1, MMR, the Epstein-Barr virus, claudin 18.2, and FGFR2b.

Purpose: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023.

Materials and methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys.

Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023. Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014. The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023. However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively.

Conclusions: The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area. Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version. Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Differences in demographics, medical expertise, and patient healthcare resources across countries have led to significant variations in guidelines. In light of these differences, in this review, we aimed to explore and compare the most recent updates to gastric cancer treatment from five guidelines that are available in English. These English-version guidelines, which have been recently published and updated for journal publication, include those published in South Korea in 2024, Japan in 2021, China in 2023, the United States in 2024, and Europe in 2024. The South Korean and Japanese guidelines provide a higher proportion of content to endoscopic and surgical treatments, reflecting their focus on minimally invasive techniques, function-preserving surgeries, and systemic therapy. The Chinese guidelines provide recommendations addressing not only surgical approaches but also perioperative chemotherapy and palliative systemic therapy. Meanwhile, in the United States and European guidelines, a higher proportion of the content is dedicated to perioperative and palliative systemic therapy, aligning with their approaches to advanced-stage disease management. All guidelines address surgical and systemic chemotherapy treatments; however, the proportion and emphasis of content vary based on the patient distribution and treatment approaches specific to each country. With emerging research findings on gastric cancer treatment worldwide, the national guidelines are being progressively revised and updated. Understanding the commonalities and differences among national guidelines, along with the underlying evidence, can provide valuable insights into the treatment of gastric cancer.

Conversion therapy is a treatment strategy that shifts from palliative systemic therapy to curative surgical treatment for primary and/or metastatic stage IV gastric cancer (GC). To address its clinical statements, the Korean Gastric Cancer Association aims to present a consensus on conversion therapy among experts attending KINGCA WEEK 2024. The KINGCA Scientific Committee and Development Working Group for Korean Practice Guidelines prepared preformulated topics and 9 clinical statements for conversion therapy. The Delphi method was applied to a panel of 17 experts for consensus and opinions. The final comments were announced after the statement presentation and discussed during the consensus meeting session of KINGCA WEEK 2024. Most experts agreed that conversion therapy provides a survival benefit for selected patients who respond to systemic therapy and undergo R0 resection (88.3%). Patients with limited metastases were considered good candidates (94.2%). The optimal timing was based on the response to systemic therapy (70.6%). The regimen was recommended to be individualized (100%) and the duration to be at least 6 months (88.3%). A minimally invasive approach (82.3%) and D2 lymph node dissection (82.4%) were considered for surgery. However, resection for metastases with a complete clinical response after systemic therapy was not advocated (41.2%). All experts agreed on the need for large-scale randomized-controlled trials for further evidence (100%). Recent advancements in treatment may facilitate radical surgery for patients with stage IV GC. Further evidence is warranted to establish the safety and efficacy of conversion therapy.

Endoscopic submucosal dissection is performed in cases of early gastric cancer, where the risk of lymph node metastasis (LNM) is expected to be negligible, and 12%-21% of these patients are deemed to have undergone non-curative resections based on pathological criteria. In such cases, decisions regarding additional treatments must be made to maximize curability, depending on the anticipated LNM risk. Well-established risk factors for LNM include lymphatic invasion, vascular invasion, deep submucosal invasion, positive vertical margins, and larger tumor size. When pathological factors associated with a clear LNM risk, such as lymphatic or deep submucosal invasion, are present, additional gastrectomy with lymph node dissection should be considered. Conversely, in cases involving only a positive horizontal margin, additional endoscopic treatment may be an effective therapeutic option as opposed to gastrectomy because of the negligible risk of LNM despite the potential risk of residual tumors. Endoscopic resection is particularly advantageous for determining complete resection. In addition to pathological curability, patient-specific factors, such as age and comorbidities, must be considered. Several retrospective cohort studies have shown that the cause of mortality among patients placed only on observation without additional treatment after non-curative resection is generally related to underlying conditions irrelevant to gastric cancer. Thus, it is crucial to assess both GC-specific mortality and all-cause mortality to finalize treatment decisions that help minimize such mortality. Therefore, new treatment algorithms that integrate pathological curability with patient-specific factors must be developed.

Combining chemotherapy with immune checkpoint inhibitors (ICIs) that target the programmed death-1 (PD-1) protein has been shown to be a clinically effective first-line treatment for human epidermal growth factor receptor 2 (HER2)-negative and -positive advanced or metastatic gastric cancer (GC). Currently, PD-1 inhibitors combined with chemotherapy are the standard treatment for patients with HER2-negative/positive locally advanced or metastatic GC. Programmed death-ligand 1 (PD-L1) expression, as assessed using immunohistochemistry (IHC), is a crucial biomarker for predicting response to anti-PD-1/PD-L1 agents in various solid tumors, including GC. In GC, the PD-L1 IHC test serves as a companion or complementary diagnostic test for immunotherapy, and an accurate interpretation of PD-L1 status is essential for selecting patients who may benefit from immunotherapy. However, PD-L1 IHC testing presents several challenges that limit its reliability as a biomarker for immunotherapy. In this review, we provide an overview of the current practices of immunotherapy and PD-L1 testing in GC. In addition, we discuss the clinical challenges associated with PD-L1 testing and its future use as a biomarker for immunotherapy. Finally, we present prospective biomarkers currently under investigation as alternative predictors of immunotherapy response in GC.

Advances in gastric cancer screening have enabled earlier detection, shifting the focus of treatment toward preserving patients' quality of life (QoL). Function-preserving gastrectomy (FPG), including pylorus-preserving gastrectomy, proximal gastrectomy, and sentinel node navigation surgery, represents a paradigm shift in the surgical management of early gastric cancer. These techniques aim to balance oncological safety with the preservation of gastric function, mitigating postgastrectomy syndromes such as dumping syndrome, bile reflux, and nutritional deficiencies. QoL assessment tools, including EORTC QLQ-STO22, KOQUSS-40, and PGSAS-45, have become integral for evaluating patient-reported outcomes, providing insights into physical, emotional, and functional recovery. Although current evidence underscores the benefits of FPG, most studies are limited to East Asia, highlighting the need for multinational trials to validate these findings globally. FPG has demonstrated comparable short- and long-term oncological outcomes to conventional gastrectomy. Enhanced nutritional recovery and reduced gastrointestinal sequelae make FPG increasingly attractive. However, its widespread adoption is challenged by technical complexity, resource intensity, and the need for adequate surgical experience. The integration of advanced technologies, such as robotic surgery and artificial intelligence, coupled with personalized approaches, is expected to further optimize FPG outcomes. This review underscores the critical role of standardized QoL assessments, collaborative research, and technological innovations in advancing FPG as a cornerstone of patient-centered gastric cancer care.

Proximal gastrectomy (PG) has reemerged as a viable surgical option for managing proximal gastric cancer and gastroesophageal junction cancer, particularly for early-stage tumors, offering potential advantages over total gastrectomy (TG). This review examines the evolution of PG, emphasizing surgical techniques and outcomes. Although PG was initially abandoned due to postoperative complications such as reflux esophagitis, advances in reconstruction methods, such as the double-flap technique and double-tract reconstruction, have significantly improved patient quality of life and reduced complications. Modern techniques focus on preserving gastric function, enhancing postoperative nutritional status, and minimizing morbidity, especially compared to TG. However, debates persist regarding the optimal extent of lymphadenectomy, oncological safety, and the risk of metachronous gastric cancer after surgery. Various international guidelines support PG for specific cases, particularly where lymph node involvement is limited, and functional preservation is prioritized. Despite promising survival and quality-of-life outcomes, certain risks, such as anastomotic stenosis and metachronous cancer, remain. The role of PG in treating cancer of the gastroesophageal junction continues to be investigated, with ongoing studies further clarifying its effectiveness. The evolving techniques and increased focus on patient-centered outcomes suggest a renewed role of PG in the surgical management of gastric cancer.