Impact of histologically poorly cohesive phenotype as a prognostic factor in patients with pStage II/III gastric cancer undergoing adjuvant chemotherapy

Gastric Cancer. 2025 May;28(3):478-492. doi: 10.1007/s10120-025-01599-6. Epub 2025 Feb 28.

Abstract

Background: Few studies have focussed on using histological phenotype to evaluate prognostic factors after adjuvant chemotherapy (AC) in patients with pStage II/III gastric cancer. We evaluated the impact of histological type based on the World Health Organization classification.

Methods: Overall, 348 patients with pStage II/III advanced gastric cancer undergoing R0 gastrectomy without neoadjuvant chemotherapy were included. Of these, 143 underwent AC. Univariate and multivariate analyses for prognostic factors of relapse-free survival (RFS) and overall survival (OS) were performed in all patients and patients receiving AC. Moreover, long-term survivals were compared by histological phenotype between patients with and without AC.

Results: Multivariate analysis in all patients revealed that histologically poorly cohesive carcinoma with not otherwise specified and signet ring cell subtype (PCC-NOS/SRC) and pN 2/3 independently and adversely affected RFS. Alternatively, male sex, poor PS and pN 2/3 adversely affected OS. In multivariate analysis of patients receiving AC, longer tumour size (≥ 80 mm), histologically PCC-NOS/SRC phenotype and pN 3 independently influenced RFS. Multivariate analysis in this population for OS revealed that pN 3 and poor postoperative immune-nutritional status significantly induced worse OS. Comparison of RFS and OS by histological phenotype between patients with and without AC showed that AC had no efficacy for improving long-term survivals in histologically PCC phenotype.

Conclusions: Histologically PCC phenotype by WHO classification, particularly PCC-NOS/SRC phenotypes, showed poor long-term RFS even after AC in patients with pStage II and III gastric cancer. An effective chemotherapeutic regimen needs to be developed for this specific subtype of gastric cancer.

Keywords: Adjuvant chemotherapy; Advanced gastric carcinoma; Histological phenotype; Poorly cohesive gastric carcinoma; Prognosis.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Carcinoma, Signet Ring Cell* / drug therapy
  • Carcinoma, Signet Ring Cell* / mortality
  • Carcinoma, Signet Ring Cell* / pathology
  • Chemotherapy, Adjuvant
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Phenotype
  • Prognosis
  • Retrospective Studies
  • Stomach Neoplasms* / drug therapy
  • Stomach Neoplasms* / mortality
  • Stomach Neoplasms* / pathology
  • Survival Rate