How Multiline Therapies and Timely Surgery Achieved a Lasting Remission

A 73-year-old woman initially sought care for shortness of breath and fatigue. Investigations revealed anemia with hemoglobin at 6.5 g/dL and a type 3 gastric tumor located in the lower portion of the stomach body. Staging laparoscopy confirmed invasion into the pancreas and posterior transverse mesocolon, along with suspicious white nodules near the ligament of Treitz. Although intraoperative frozen sections were negative, the overall findings indicated peritoneal dissemination. This led to a final diagnosis of unresectable advanced gastric cancer (cT4bN3M1 Stage IVB).

First-line therapy commenced with S-1 plus cisplatin (SP), but severe neutropenia required dose adjustments. After four courses, imaging showed stable disease in the primary tumor, while the regional lymph nodes demonstrated shrinkage. However, worsening gastric stenosis necessitated a laparoscopic gastrojejunostomy for relief. To reduce renal and neurological risks, S-1 plus oxaliplatin (SOX) replaced cisplatin-based treatment. Disease progression in the lymph nodes then prompted a switch to weekly paclitaxel plus ramucirumab as second-line therapy.

When ascites and peritoneal dissemination worsened, nivolumab was introduced as a third-line option, supported by additional testing that revealed MSI-high status and a high PD-L1 combined positive score. Marked tumor regression was observed after several cycles, culminating in a clinical complete response on imaging at 24 cycles. Yet, regrowth of the primary lesion occurred after 36 cycles, prompting a distal gastrectomy and lymph node dissection. Final pathology confirmed ypT4bN0M0 Stage IIIA disease, with no evidence of distant metastases.

Given tumor growth during immunotherapy, a year of S-1 monotherapy was administered post-surgery. Remarkably, six years after the initial presentation and three years since the final operation, there has been no recurrence without further chemotherapy. This case underscores the potential of combination treatments—chemotherapy, immunotherapy, and surgery—to significantly alter the course of advanced gastric cancer.