Random Biopsies Essential for Endoscopic Surveillance of Patients with Hereditary Diffuse Gastric Cancer

Random biopsy sampling was found to substantially enhance early detection of signet ring cell carcinoma when using endoscopic surveillance for patients with hereditary diffuse gastric cancer.

For patients who meet the clinical criteria of hereditary diffuse gastric cancer but do not carry the CDH1 pathological variant, or for patients who are carriers but wish to delay gastrectomy, endoscopic surveillance is recommended to determine the timing of prophylactic total gastrectomy. However, there is limited evidence on which sampling technique for surveillance is optimal.

This prospective longitudinal cohort study included 145 patients recruited from a prospective registry, 63% of which were carriers of the CDH1 pathogenic variant. The primary outcome was detection of intramucosal signet ring cell carcinoma foci in systemic random or targeted biopsies.

Over a median follow-up time of 51 months, 40% of the patients were diagnosed with invasive signet ring cell carcinoma. The first diagnosis was made by random biopsies in 50% of those patients, compared to 26% of patients first diagnosed via targeted biopsies alone. There were also 10% with positive signet ring cell carcinoma findings on both random and targeted biopsies, 9% with macroscopic advanced tumors directly visualized at index endoscopy, and 5% diagnosed after undergoing prophylactic total gastrectomy with no previous positive endoscopic findings.

The signet ring cell carcinoma foci diagnosed via random biopsies also had an anatomic distribution that more accurately reflected those identified in prophylactic total gastrectomy specimens, compared with foci diagnosed via targeted biopsies. Study authors determined had there been no use of random biopsies, the under-diagnosis rate of this cohort would have been 42%.

Limitations of the study include retrospective assessment of suspicion based on endoscopic reports, a study period of 16 years over which endoscopic technology and operator experience improved, and a targeted sequencing that included only CDH1 germline variants.

Study authors concluded, “we provide definitive evidence to support the use of non-targeted systemic biopsies as an essential component of endoscopic surveillance, which allows comprehensive assessment of early cancer distribution and complementary information to targeted biopsies.”

Source:

Lee CYC, Olivier A, Honing J, et al. Endoscopic surveillance with systemic random biopsy for the early diagnosis of hereditary diffuse gastric cancer: A prospective 16-year longitudinal cohort study. Lancet Oncol. Published online December