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Background The current AJCC staging system for gastric cancer (AJCC7) incorporated several major revisions to the previous edition. The T and N categories and the stage groups were newly defined, and adenocarcinoma of the esophagogastric junction (EGJ) was reclassified and staged according to the esophageal system. Studies to validate these changes showed inconsistent results. The International Gastric Cancer Association (IGCA) launched a project to support evidence-based revisions to the next edition of the AJCC staging system. Methods Clinical and pathological data on patients who underwent curative gastrectomy at 59 institutions in 15 countries between 2000 and 2004 were retrospectively collected. Patients lost to follow-up within 5 years of surgery were excluded. Patients treated with neoadjuvant therapy were excluded. The data were analyzed in total, and separately by region of treatment. Results Of 25,411 eligible cases, 84.8 % were submitted from 24 institutions of Japan and Korea, 6.4 % from other Asian countries, and 8.8 % from 29 Western institutions. The T and N categories of AJCC7 clearly stratified the patient survival. Patients with pN3a and pN3b showed distinct prognosis in all regions, and by introducing pN3a and pN3b into a cluster analysis, we established a new stage grouping with better stratification than AJCC7, especially among stage III subgroups. Survival of Siewert type 2 and 3 EGJ tumors was better stratified by this IGCA stage grouping than by either esophageal or gastric scheme of AJCC7. Conclusions For the next revision of AJCC classification, we propose a new stage grouping based on a large, worldwide data collection.

Background The “watch-and-wait” approach is a common treatment option amongst patients with locally advanced rectal cancer (LARC). However, the diagnostic sensitivity of clinical modalities, such as colonoscopy and magnetic resonance imaging to determine pathological response, is not high. We analysed the clinical utility of circulating tumour DNA (ctDNA) of patients with LARC to predict response to preoperative therapy and postoperative recurrence. Methods A serial ctDNA analysis of 222 plasma samples from 85 patients with LARC was performed using amplicon-based deep sequencing on a cell-free DNA panel covering 14 genes with over 240 hotspots. Results ctDNA was detected in 57.6% and 22.3% of samples at baseline and after preoperative treatment, respectively, which was significantly different ( P  = 0.0003). Change in ctDNA was an independent predictor of complete response to preoperative therapy ( P  = 0.0276). In addition, postoperative ctDNA and carcinoembryonic antigen (CEA) were independent prognostic markers for risk of recurrence after surgery (ctDNA, P  = 0.0127 and CEA, P  = 0.0105), with a combined analysis having cumulative effects on recurrence-free survival ( P  = 1.0 × 10 –16 ). Conclusions Serial ctDNA analysis may offer clinically useful predictive and prognostic markers for response to preoperative therapy and postoperative recurrence in patients with LARC.

BackgroundThe long-term outcomes of type 4 and large type 3 gastric cancer patients with positive peritoneal lavage cytology (CY1) remain unsatisfying. We evaluated our treatment strategy of conversion therapy for CY1 patients without peritoneal dissemination (P0).MethodsDiagnostic staging laparoscopy (DSL) was performed before treatment. Chemotherapy was applied for DSL-diagnosed P0CY1. The re-evaluation of peritoneal metastasis by staging laparoscopy (re-SL) was performed when a response to chemotherapy was identified by gastroscopy and/or CT. Gastrectomy with radical lymphadenectomy was applied as conversion therapy when peritoneal lavage cytology-negative (CY0) and P0 were diagnosed with re-SL, with the aim of achieving R0 resection. Chemotherapy was continued as palliative treatment in patients for whom re-SL was not applicable or when re-SL did not confirm P0CY0. The long-term outcomes were retrospectively evaluated.ResultsBetween 2009 and 2015, 214 patients with type 4 and large type 3 gastric cancer underwent DSL in the Cancer Institute Hospital. Thirty-nine patients were initially diagnosed with P0CY1. Seven patients received palliative gastrectomy first due to outlet obstruction or other reasons. Thirty-two patients received chemotherapy first. Among them, 13 patients underwent gastrectomy as conversion therapy and 19 were treated with palliative chemotherapy. The 3-year survival rate of patients who underwent conversion therapy, palliative chemotherapy and palliative gastrectomy was 76.9% [95% confidence interval (CI) 47.8–92.4%], 10.5% (95% CI 1.9–42.3%), and 0%, respectively.ConclusionConversion therapy might be a promising treatment for P0CY1 type 4 and large type 3 gastric cancer patients. Re-SL was useful for selecting candidates for R0 resection.

Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC. In metastatic urothelial carcinoma, it has not been established whether circulating tumor DNA (ctDNA) can replace archival primary tissue to assess mutations and biomarkers. Here, the authors show high mutation concordance between ctDNA and tumour tissue, with high consistency in serial samples.

BackgroundSpecific treatment strategies are sorely needed for scirrhous-type gastric cancer still, which has poor prognosis. Based on the promising results of our previous phase II study (JCOG0210), we initiated a phase III study to confirm the efficacy of neoadjuvant chemotherapy (NAC) in type 4 or large type 3 gastric cancer.MethodsPatients aged 20–75 years without a macroscopic unresectable factor as confirmed via staging laparoscopy were randomly assigned to surgery followed by adjuvant chemotherapy with S-1 (Arm A) or NAC (S-1plus cisplatin) followed by D2 gastrectomy plus adjuvant chemotherapy with S-1 (Arm B). The primary endpoint was overall survival (OS).ResultsBetween October 2005 and July 2013, 316 patients were enrolled, allocating 158 patients to each arm. In Arm B, in which NAC was completed in 88% of patients. Significant downstaging based on tumor depth, lymph node metastasis, and peritoneal cytology was observed using NAC. Excluding the initial 16 patients randomized before the first revision of the protocol, 149 and 151 patients in arms A and B, respectively, were included in the primary analysis. The 3-year OS rates were 62.4% [95% confidence interval (CI)  54.1–69.6] in Arm A and 60.9% (95% CI  52.7–68.2) in Arm B. The hazard ratio of Arm B against Arm A was 0.916 (95% CI  0.679–1.236).ConclusionsFor type 4 or large type 3 gastric cancer, NAC with S-1 plus cisplatin failed to demonstrate a survival benefit. D2 surgery followed by adjuvant chemotherapy remains the standard treatment.

Background Esophagogastric junction (EGJ) carcinoma has attracted considerable attention because of the marked increase in its incidence globally. However, the optimal extent of esophagogastric resection for this tumor entity remains highly controversial. Methods This was a questionnaire-based national retrospective study undertaken in an attempt to define the optimal extent of lymph node dissection for EGJ cancer. Data from patients with EGJ carcinoma, less than 40 mm in diameter, who underwent R0 resection between January 2001 and December 2010 were reviewed. Results Clinical records of 2807 patients without preoperative therapy were included in the analysis. There are distinct disparities in terms of the nodal dissection rate according to histology and the predominant tumor location. Nodal metastases frequently involved the abdominal nodes, especially those at the right and left cardia, lesser curvature and along the left gastric artery. Nodes along the distal portion of the stomach were much less often metastatic, and their dissection seemed unlikely to be beneficial. Lower mediastinal node dissection might contribute to improving survival for patients with esophagus-predominant EGJ cancer. However, due to low dissection rates for nodes of the middle and upper mediastinum, no conclusive result was obtained regarding the optimal extent of nodal dissection in this region. Conclusions Complete nodal clearance along the distal portion of the stomach offers marginal survival benefits for patients with EGJ cancers less than 4 cm in diameter. The optimal extent of esophageal resection and the benefits of mediastinal node dissection remain issues to be addressed in managing patients with esophagus-predominant EGJ cancers.

BackgroundDouble-flap technique (DFT) has received increased attention as an anastomotic procedure preventing reflux esophagitis after laparoscopic proximal gastrectomy (LPG) for upper-third gastric cancer. However, incidence of anastomotic stricture still remains high. This study was a retrospective review aimed to demonstrate details of surgical outcomes and to assess risk factors for anastomotic complications using pre-operative CT image after LPG with DFT (LPG–DFT).MethodsPatient background data, surgical outcomes, post-operative courses, and complications for patients who underwent LPG–DFT from January 2013 to June 2017 were collected. In addition to the details of short-term outcomes, risk factors for anastomotic stricture and gastroesophageal reflux were analyzed.ResultsThe study sample was 147 patients, including 139 patients with upper-third gastric cancer and 8 patients with submucosal tumor of the upper-third stomach. The overall morbidity rate was 12.2% (18/147), and 97.3% (143/147) of the patients achieved R0 resection. Twelve (8.3%) patients required endoscopic balloon dilatation for anastomotic stenosis, and six (4.2%) suffered regurgitation grade ≥ B in the Los Angeles classification. Multivariate analysis revealed that diameter of the esophagus < 18 mm on pre-operative CT image and the presence of short-term complications were found to be independent risk factors for post-operative anastomotic stenosis. No specific risk for gastroesophageal reflux was identified.ConclusionsThe incidence rate of anastomotic complications after LPG–DFT was far lower than that reported after conventional esophagogastrostomy. Alternative anastomotic method may be considered for patients with diameter of the esophagus < 18 mm on pre-operative CT image. Prevention of short-term complications may lessen post-operative stricture.

Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.

PurposeThe second planned interim analysis (median follow-up 12.5 months) in a phase III trial of postoperative adjuvant chemotherapy for stage III gastric cancer revealed significant improvement in relapse-free survival (RFS) for S-1 plus docetaxel over S-1 alone. Although enrollment was terminated on the recommendation of the independent data and safety monitoring committee, we continued follow-up and herein report on 3-year RFS, the primary endpoint.Patients and methodsPatients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive adjuvant chemotherapy with either S-1 plus docetaxel or S-1 alone. In the S-1 plus docetaxel group, S-1 was given orally for 2 weeks followed by 1 week of rest for seven courses, and docetaxel was given intravenously on day 1 of the second to seventh courses. The combination therapy was followed by S-1 monotherapy for up to 1 year.ResultsThe 3-year RFS rate of the S-1 plus docetaxel group was 67.7%. This was significantly superior to that of 57.4% in the S-1 group (hazard ratio [HR] 0.715, 95% CI 0.587–0.871, P = 0.0008). This translated into a significant benefit in the 3-year overall survival (OS) rate in the S-1 plus docetaxel group (77.7% versus 71.2%, HR 0.742, 95% CI 0.596–0.925, P = 0.0076).ConclusionOn 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel was confirmed to improve both RFS and OS and can be recommended as a standard of care for patients with stage III gastric cancer treated by D2 dissection.