Maintaining the postoperative quality of life (QOL) while ensuring curability without overtreatment is important in the treatment of early gastric cancer. Postoperative QOL is anticipated to be maintained through minimally invasive function-preserving gastrectomy in early gastric cancer. The concept of the sentinel lymph node (SN) basin is essential to maintain the curability of early gastric cancer using minimally invasive function-preserving gastrectomy. However, additional resection after surgery is difficult to perform in gastric cancer. Thus, the SN basin theory is important. Recently, a multicenter randomized phase III trial in South Korea (SENORITA trial) proved that laparoscopic sentinel node navigation surgery (LSNNS) for stomach preservation results in better postoperative QOL compared with standard gastrectomy in patients with early gastric cancer. LSNNS contributes to patients' QOL based on the concept that curability is not impaired. A multicenter nonrandomized phase III trial is ongoing in Japan, and oncologic safety is expected to be demonstrated. LSNNS has been established as a treatment option for selected patients with early gastric cancer, and its application will become widespread in the future.
Gastric cancer is one of the most common cancers in Korea and the world. Since 2004, this is the 4th gastric cancer guideline published in Korea which is the revised version of previous evidence-based approach in 2018. Current guideline is a collaborative work of the interdisciplinary working group including experts in the field of gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology and guideline development methodology. Total of 33 key questions were updated or proposed after a collaborative review by the working group and 40 statements were developed according to the systematic review using the MEDLINE, Embase, Cochrane Library and KoreaMed database. The level of evidence and the grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation proposition. Evidence level, benefit, harm, and clinical applicability was considered as the significant factors for recommendation. The working group reviewed recommendations and discussed for consensus. In the earlier part, general consideration discusses screening, diagnosis and staging of endoscopy, pathology, radiology, and nuclear medicine. Flowchart is depicted with statements which is supported by meta-analysis and references. Since clinical trial and systematic review was not suitable for postoperative oncologic and nutritional follow-up, working group agreed to conduct a nationwide survey investigating the clinical practice of all tertiary or general hospitals in Korea. The purpose of this survey was to provide baseline information on follow up. Herein we present a multidisciplinary-evidence based gastric cancer guideline.
Presently, surgery is the only treatment approach for gastric cancer and improving the prognosis of locally advanced gastric cancer is one of the key factors in promoting gastric cancer survival benefit. The MAGIC study was the first to demonstrate the efficacy of neoadjuvant chemotherapy (NAC) in European countries. In recent years, several clinical trials have provided evidence for the use of NAC in Asian patients with locally advanced gastric cancer. However, clinical practice guidelines vary between Asian and non-Asian populations. Optimal NAC regimens, proper target populations, and predictors of NAC outcomes in Asian patients are still under investigation. Herein, we summarized the current progress in the administration of NAC in Asian patients with gastric cancer.
Endoscopic resection (ER) is widely performed for early gastric cancer (EGC) with a negligible risk of lymph node metastasis (LNM) in Eastern Asian countries. In particular, endoscopic submucosal dissection (ESD) leads to a high en bloc resection rate, enabling accurate pathological evaluation. As undifferentiated EGC (UD-EGC) is known to result in a higher incidence of LNM and infiltrative growth than differentiated EGC (D-EGC), the indications for ER are limited compared with those for D-EGC. Previously, clinical staging as intramucosal UD-EGC ≤2 cm, without ulceration, was presented as 'weakly recommended' or 'expanded indications' for ER in the guidelines of the United States, Europe, Korea, and Japan. Based on promising long-term outcomes from a prospective multicenter study by the Japan Clinical Oncology Group (JCOG) 1009/1010, the status of this indication has expanded and is now considered 'absolute indications' in the latest Japanese guidelines published in 2021. In this study, which comprised 275 patients with UD-EGC (cT1a, ≤2 cm, without ulceration) treated with ESD, the 5-year overall survival (OS) was 99.3% (95% confidence interval, 97.1%-99.8%), which was higher than the threshold 5-year OS (89.9%). Currently, the levels of evidence grades and recommendations for ER of UD-EGC differ among Japan, Korea, and Western countries. Therefore, a further discussion is warranted to generalize the indications for ER of UD-EGC in countries besides Japan.
Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Under the standard of care, patients with advanced GC (AGC) have a median survival time of approximately 12-15 months. With the emergence of immunotherapy as a key therapeutic strategy in medical oncology, relevant changes are expected in the systemic treatment of GC. In the phase III ATTRACTION-2 trial, nivolumab, a monoclonal anti-programmed cell death 1 (PD-1) antibody, as a third- or later-line treatment improved overall survival (OS) compared with placebo in patients with AGC. Furthermore, nivolumab in combination with 5-fluorouracil and platinum as a first-line treatment improved OS in patients with human epidermal growth factor receptor-2 (HER2)-negative AGC in the global phase III CheckMate-649 study. Another anti-PD-1 antibody, pembrolizumab, in combination with trastuzumab and cytotoxic chemotherapy as a first-line treatment, significantly improved the overall response rate in patients with HER2-positive AGC. Therefore, immune checkpoint inhibitors (ICIs) are essential components of the current treatment of GC. Subsequent treatments after ICI combination therapy, such as ICI rechallenge or combination therapy with agents having other modes of action, are being actively investigated to date. On the basis of the success of immunotherapy in the treatment of AGC, various clinical trials are underway to apply this therapeutic strategy in the perioperative and postoperative settings for patients with early GC. This review describes recent progress in immunotherapy and potential immunotherapy biomarkers for GC.
Although continuous improvement in the treatment outcome of localized gastric cancer has been achieved through early screening, diagnosis, and treatment and the active application of surgery and adjuvant chemotherapy, the necessity of adjuvant radiotherapy (RT) remains controversial. In this review, based on the results of two recently published randomized phase III studies (Adjuvant Chemoradiation Therapy In Stomach Cancer 2 and ChemoRadiotherapy after Induction chemoTherapy of Cancer in the Stomach) and a meta-analysis of six randomized trials including these two studies, the role of adjuvant RT in gastric cancer was evaluated and discussed, especially in patients who underwent curative gastrectomy with D2 lymphadenectomy. This article also reported the possible indications for adjuvant RT in the current clinical situation and in future research to enable patient-specific treatments according to the risk of recurrence.
Currently, the prevalence of gastroesophageal junction adenocarcinoma (GEJAC) is increasing in both Asian and Western countries, although the increasing rate in Asian countries is much slower than in Western countries. With these current trends, concerns regarding the surgical treatment method are also increasing among gastrointestinal surgeons. However, the surgical treatment for GEJAC has been a controversial issue for a long time due to the relative scarcity of this tumor and its characteristics from its borderline location. Recently, a large-scale prospective study of this tumor has been conducted in Japan, and the results are now available. The results of this study will be helpful for understanding this tumor. In this article, the pattern of lymph node metastasis of GEJAC is reviewed, and the extent and method of lymph node dissection for this tumor are discussed and proposed based on the review.
The first edition of 'A Standardized Pathology Report for Gastric Cancer' was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.