In one of the largest prospective efforts of its kind, Japanese researchers have delivered the first long-term survival figures for locally advanced gastric cancer based on clinical staging determined before any treatment begins, offering oncologists worldwide a new benchmark for deciding who truly needs intensive chemotherapy around surgery. The study, a follow-up analysis of the Japan Clinical Oncology Group trial JCOG1302A published in Annals of Gastroenterological Surgery, tracked more than 1,100 patients for a median of six years and found that five-year overall survival ranged dramatically, from above 83 percent in the most favorable clinical subgroup to below 58 percent in the highest-risk category. The results arrive at a pivotal moment, as the field shifts from surgery-first strategies toward perioperative chemotherapy and, increasingly, chemo-immunotherapy, making the accuracy of preoperative staging more consequential than ever before.
The central challenge the researchers set out to address is deceptively simple: when a patient is diagnosed with gastric cancer that appears advanced on scans, how reliable is that initial assessment, and what does it actually predict for survival? In Japan, where many tumors that look advanced on imaging turn out to be early-stage disease obscured by inflammatory changes, clinicians have long struggled to identify which patients genuinely benefit from neoadjuvant chemotherapy, or chemotherapy given before surgery. Traditionally, decisions about postoperative chemotherapy have rested on pathological staging, the detailed examination of the removed tumor and lymph nodes. But that approach requires surgery first, leaving no opportunity to shrink the tumor beforehand. With evidence accumulating that perioperative chemotherapy improves survival in resectable advanced disease, the need for trustworthy clinical staging, performed entirely before the operating room, has become urgent.
JCOG1302A was designed as a prospective, multicenter observational study to test exactly how well endoscopy and computed tomography could classify tumor depth and nodal spread. Between July 2013 and November 2014, 1,275 patients were enrolled across 53 specialized Japanese institutions. Each underwent staging with multidetector-row CT using prespecified imaging criteria: localized wall thickening with a smooth serosal surface indicated T2 disease, diffuse thickening with a smooth surface indicated T3, and irregular or nodular serosal change or invasion of surrounding fat signaled T4a, while loss of the fat plane between tumor and adjacent organs defined T4b. Lymph nodes with a short axis of at least 8 millimeters or a long axis of at least 10 millimeters were called metastatic. The earlier analysis found that a striking share of patients clinically labeled T2 or T3 without nodal involvement actually harbored pathologically Stage I disease, contamination that ranged from 50.4 percent in cT2N0 down to just 3.0 percent in cT4aN(+).
That earlier work led the investigators to conclude that patients with clinical T3 disease plus detectable nodes, and those with any T4 disease, were the optimal candidates for preoperative chemotherapy, a conclusion that directly shaped the ongoing Phase III trial JCOG1509. But a critical piece was missing: no study had ever described long-term survival stratified by prospectively determined clinical stage. The new follow-up analysis, JCOG1302A2, collected additional survival data on the original cohort. After excluding patients who did not undergo surgery, those found ineligible, and 83 patients lost to follow-up, 1,176 patients formed the analytical population. The group was overwhelmingly treated with the Japanese standard of gastrectomy plus D2 lymph node dissection, performed in 98 percent of patients, and roughly half received adjuvant chemotherapy, most commonly the oral agent S-1 alone.
The survival data revealed a clean, stepwise gradient across both clinical dimensions. Five-year overall survival was 82.1 percent for clinical T2 tumors, 72.7 percent for T3, 60.0 percent for T4a, and 40.0 percent for the small T4b group. Nodal status told a parallel story: 78.0 percent for node-negative disease, 70.6 percent for cN1, 59.1 percent for cN2, and 28.4 percent for cN3. In statistical models measuring the risk of death over time, clinical T4a carried nearly two and a half times the mortality hazard of T2, while cN3 disease carried almost five times the hazard of cN0. When both dimensions were combined, the picture sharpened further. The most favorable group, comprising cT2N0, cT2N(+), and cT3N0, all achieved five-year survival near or above 77 percent, with cT2N0 topping the chart at 83.5 percent.
Perhaps the most consequential finding concerns the middle of the distribution. Patients with cT3N(+) disease and those with cT4aN0 disease showed nearly identical, intermediate survival, around 68.0 and 66.8 percent at five years respectively, and both carried roughly double the mortality risk of the cT2N0 reference group. Meanwhile, cT4aN(+) patients fared worst among the sizable subgroups, at 57.7 percent. Notably, cT3N0 disease did not show a statistically significant increase in risk compared with cT2N0, suggesting that node-negative T3 tumors, at least when staged by rigorous CT criteria, behave more like earlier disease than like truly advanced cancer. This three-tier risk architecture, favorable, intermediate, and poor, gives clinicians a practical framework for matching treatment intensity to genuine baseline risk.
The results also carry a pointed message about the TNM staging system itself. In the eighth edition of the TNM classification, clinical T3 and T4a tumors are grouped together, despite the acknowledged difficulty of distinguishing them on imaging. The Japanese data, with clearly separated survival curves between the two categories, suggest this merging may obscure clinically meaningful differences. The finding echoes the exploratory radiological sub-analysis of the PRODIGY trial, in which clinical T4 disease, with minimal contamination by pathological Stage I, was identified as the subgroup deriving the greatest benefit from neoadjuvant chemotherapy. Together, these results argue that T3 and T4a disease, when carefully distinguished by multidetector CT, warrant separate consideration in treatment planning and in the design of future clinical trials.
The study’s authors are careful to frame the work as prognostic rather than therapeutic. Because the analysis was observational, it did not directly test whether neoadjuvant chemotherapy improves survival in any subgroup, and the choice and regimen of postoperative chemotherapy were left to treating physicians, varying across patients and institutions. Most patients with Stage III disease received S-1 monotherapy, since the JACCRO GC-07 trial demonstrating the superiority of adding docetaxel had not yet reported when the cohort was treated. Adjuvant chemotherapy use also differed across clinical subgroups, from 34.5 percent in cT2N0 to 65.1 percent in cT4aN(+), a variation that may have influenced the observed outcomes. The cohort excluded scirrhous tumors, bulky nodal disease, and paraaortic metastases, so the findings cannot be generalized to those populations, and all patients were treated at specialized Japanese centers.
Even with those caveats, the timing of this evidence is significant. The Pan-Asian adapted ESMO Clinical Practice Guidelines now emphasize that perioperative chemotherapy should be considered only for selected patients with resectable locally advanced gastric cancer, and the recent MATTERHORN trial has shown that perioperative chemo-immunotherapy can improve outcomes, albeit with greater toxicity and cost. Against that backdrop, knowing which clinically defined groups face the highest baseline mortality risk, and which do well with surgery and standard adjuvant therapy alone, becomes essential for balancing benefit against burden. The data suggest that patients with cT2N0 and cT3N0 disease, who achieved roughly 80 percent five-year survival with upfront surgery, may have little to gain from intensified perioperative regimens, while those with cT3N(+), cT4aN0, cT4aN(+), and cT4b disease represent the higher-risk subgroups in whom such strategies deserve priority investigation.
For a disease that remains one of the world’s leading causes of cancer death, the study delivers something the field has lacked: a prospectively validated, clinically applicable survival map drawn entirely from information available before treatment. It validates the diagnostic criteria used in JCOG1302A, confirms that clinical T and N categories carry genuine prognostic weight, and provides the reference outcomes against which the ongoing JCOG1509 trial and the coming wave of perioperative chemo-immunotherapy studies will be judged. As treatment intensifies, the humble CT scan, applied with disciplined, standardized criteria, may prove to be the most important tool for ensuring that the right patients receive the right therapy at the right time.
Subject of Research: Long-term survival stratified by prospectively determined clinical staging in locally advanced gastric cancer
Article Title: Survival Results by the Prospectively Determined Clinical Staging for Locally Advanced Gastric Cancer: A Follow‐Up Study of JCOG1302A
Article References: Hayashi, T., Kato, R., Mitome, N., Ogawa, R., Fukagawa, T., Katai, H., Nunobe, S., Tokunaga, M., Bando, E., Ito, Y., Yamada, T., Nomura, T., Makino, S., Kinoshita, T., Hara, H., Aizawa, M., Boku, N., Kurokawa, Y., Terashima, M., & Yoshikawa, T. (2026). Survival Results by the Prospectively Determined Clinical Staging for Locally Advanced Gastric Cancer: A Follow‐Up Study of JCOG1302A. Annals of Gastroenterological Surgery, Article ags3.70293. https://doi.org/10.1002/ags3.70293
Image Credits: AI Generated
DOI: 10.1002/ags3.70293
Keywords: gastric cancer, clinical staging, neoadjuvant chemotherapy, JCOG1302A, overall survival, CT imaging, D2 lymphadenectomy, TNM classification, perioperative treatment, oncology, prognosis, Japan Clinical Oncology Group
