406 Background: Emerging evidence suggests that the preservation of certain lymph nodes adjacent to tumors can enhance the efficacy of immunotherapy. For patients demonstrating a favorable response to neoadjuvant chemotherapy combined with immune checkpoint inhibitors, proximal gastrectomy may offer a superior alternative to total gastrectomy. This approach not only minimizes the extent of surgical resection but also allows for the preservation of lymph nodes, potentially leading to improved long-term survival rates and postoperative quality of life. Methods: Patients diagnosed with locally advanced upper gastric cancer underwent 4 cycles of NCIT (SOX plus PD-1 antibody tislelizumab, every 3 weeks) . The partial response (PR) or clinical complete response (cCR) patients eligible for proximal radical gastric surgery were randomised 1:1 to either the proximal gastrectomy (PG) group or the total gastrectomy (TG) group. After surgery, patients received 4 cycles of SOX combined with Tislelizumab as adjuvant therapy, followed by one year of tislelizumab treatment. The primary endpoint was disease-free survival (DFS) at three years, requiring a total of enrollment of 404 patients. Secondary endpoints included pathological complete response (pCR) rate, major pathological response (MPR) rate, treatment-related adverse events (TRAEs), overall survival (OS), and R0 resection rate. The trial is registered with ClinicalTrials.gov (NCT06597227). Results: As of the cutoff date (September 7, 2025), 27 patients were enrolled, with 13 assigned to the PG group and 14 to the TG group. The median age of participants was 64.5 years (IQR, 58.0-68.0), and all patients presented with microsatellite stable (MSS). A total of 10 patients (37.0%) achieved pCR. In the PG group and TG group, there were 7 patients and 3 patients achieved pCR respectively (pCR rate: 53.8% and 21.4%). Grade 3 or higher TRAEs occurred in 13/27 (48.1%). There were no surgical-related deaths, although one patient in the TG group experienced an anastomotic leakage. Conclusions: The combination regimen of SOX and tislelizumab demonstrated a promising rate of pCR as perioperative treatment for locally advanced upper gastric cancer, with manageable safety profiles. The PG group markedly higher pCR rate underscores the imperative of biomarker exploration to clarify the underlying mechanisms. Our study is ongoing, and we anticipate that long-term outcomes for proximal gastrectomy may surpass those associated with total gastrectomy. Clinical trial information: NCT06597227 . PG group (n=13) TG group (n=14) Median age (range),years 62 (58-73.5) 65 (56.5-67.0) Sex, n (%) Male 12 (92.3%) 13 (92.9%) Female 1 (7.7%) 1 (7.1%) TRG 0-1, n (%) 8 (61.5%) 4 (28.6%) pCR, n (%) 7 (53.8%) 3 (21.4%) Grade ≥3 TEAE, n (%) 6 (46.2%) 7 (50.0%)
Guihua Wang (Sat,) studied this question.