Pathological complete response in microsatellite- stable gastric cancer with liver and bulky lymph node metastases after nivolumab-based chemotherapy and surgery: a case report.

BACKGROUND: Gastric cancer with liver metastases is generally associated with poor prognosis, and curative treatment is rarely achieved. Recently, the combination of cytotoxic chemotherapy and immune checkpoint inhibitors (ICIs) has shown promise. However, the efficacy of ICIs in treating microsatellite-stable (MSS) gastric cancer remains controversial. Herein, we present a case of advanced MSS gastric cancer with liver and bulky lymph node metastases, in which combination therapy with S-1 plus oxaliplatin (SOX) and nivolumab led to a pathological complete response.

CASE PRESENTATION: A 64-year-old man was diagnosed with gastric adenocarcinoma with a solitary liver metastasis (S6) and bulky regional lymph node metastasis. Four cycles of SOX and nivolumab (360 mg every 3 weeks) were administered. Imaging revealed marked tumor regression, and surgery was performed. The patient underwent distal gastrectomy with D2 lymphadenectomy and partial hepatectomy. Pathological evaluation revealed complete tumor regression in the primary lesion, lymph nodes, and liver. The tumor was MSS, Epstein-Barr virus-negative and had a low tumor mutational burden (TMB). Immunohistochemistry showed a mean CD8+ tumor-infiltrating lymphocyte density of 59.5 ± 14.3 cells per high-power field, a programmed death-ligand 1 (PD-L1) combined positive score (CPS) of ≥ 70% (clone 28-8), and a germline TP53 p.R106C mutation.

CONCLUSION: This case illustrates that even in MSS gastric cancer with low TMB levels, exceptionally high PD-L1 expression may predict a profound response to ICI-based therapy. The PD-L1 CPS may serve as a critical biomarker independent of TMB or microsatellite-instability status.