Synchronous metastatic gastric cancer-molecular background and clinical implications with special attention to mismatch repair deficiency

Eur J Surg Oncol. 2018 May;44(5):626-631. doi: 10.1016/j.ejso.2018.02.208. Epub 2018 Mar 2.

Abstract

Background: Current guidelines recommend that metastatic gastric cancer should not be treated with surgery unless this is required for symptom control. We hypothesized that patients with mismatch repair deficiency (MMRd) gastric cancer and metastatic disease detected at the timepoint of surgical resection would have superior survival compared to patients with MMRd cancers in the same setting.

Methods: Clinicopathological details and survival data were collected from prospective databases at two large European centers on patients who had undergone surgery and were diagnosed with synchronous stage IV gastric cancer (distant lymph nodes, positive peritoneal cytology, peritoneal, and distant metastases) at the timepoint of surgery. Resection specimens were tested for the presence of microsatellite instability using a standard 5 mononucleotide repeat panel.

Results: One hundred and seventy six patients with resected stage IV gastric cancer were identified. 14/176 (8.0%) had MSI-H (high) disease. There was no significant difference between the clinical and pathological characteristics of MSI and microsatellite stable (MSS) patients. No differences in the type of metastases were observed between MSI and MSS groups. Patients who were MSI-H had superior OS compared to MSS patients (median OS 15.9 vs. 8 months, p = 0.023). However, in Cox regression multivariate analysis only liver and peritoneal metastases were independent predictors of survival.

Conclusions: Surgically treated patients with MSI-H stage IV gastric cancer have a better survival than patients with MSS gastric cancer. Further analysis of the role of surgery in MSI stage IV GC is required.

Keywords: Metastasis; Microsatellite instability; Molecular; Prognosis; Stomach cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Brain Neoplasms
  • Carcinoma / genetics
  • Carcinoma / secondary
  • Carcinoma / surgery*
  • Colorectal Neoplasms
  • DNA Mismatch Repair / genetics*
  • Female
  • Gastrectomy*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / secondary*
  • Male
  • Microsatellite Instability
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplastic Syndromes, Hereditary
  • Peritoneal Neoplasms / genetics
  • Peritoneal Neoplasms / secondary*
  • Proportional Hazards Models
  • Retrospective Studies
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / surgery*
  • Survival Rate

Supplementary concepts

  • Turcot syndrome