Signet ring gastric cancer: neoadjuvant chemotherapy showed no survival edge, but guidelines stand

Design

Systematic review and meta-analysis of randomised and observational studies

Population

5,388 patients with signet ring cell-containing gastric adenocarcinoma in 6 studies

Primary outcome

Overall survival, neoadjuvant chemotherapy vs upfront surgery

Effect

HR 0.96 (95% CI 0.68–1.34); I² 83%

Signet ring cell-containing gastric cancer is thought to be less chemosensitive than other gastric adenocarcinomas, and some clinicians have questioned whether neoadjuvant chemotherapy is worthwhile. This meta-analysis pooled six studies — seven cohorts, 5,388 patients — comparing neoadjuvant chemotherapy followed by surgery with upfront gastrectomy.

Overall survival did not differ significantly (HR 0.96, 95% CI 0.68–1.34), with very high heterogeneity (I² 83%). Results were similar in Western (HR 0.85) and Eastern studies (HR 1.12), and in randomised (HR 1.16, 95% CI 0.81–1.67) and observational studies (HR 0.92).

The authors stress that perioperative chemotherapy remains the recommended approach, and that contemporary chemotherapy regimens need studying in this subtype. The finding is a reason to discuss signet ring histology at the tumour board and to enrol patients in trials, not to drop perioperative chemotherapy on histology alone. Guidelines have not changed.

• Keep perioperative chemotherapy as standard for locally advanced signet ring gastric cancer, per current guidelines.
• Discuss signet ring histology specifically at the multidisciplinary meeting.
• Assess response after neoadjuvant cycles; poor responders need early surgical review.
• Offer clinical trials where available, as contemporary regimens are under-studied in this subtype.
• Do not cite this analysis as grounds to skip neoadjuvant treatment.

Why it matters

The survival benefit of neoadjuvant chemotherapy in this subtype remains unproven, which keeps the question open rather than closed.

Don't overread it

With I² above 80% and few contemporary regimens, this pooled estimate cannot show that chemotherapy is ineffective.

The statistics, in plain English

A hazard ratio of 0.96 with an interval from 0.68 to 1.34 is compatible with a 32% benefit or a 34% harm. Very high heterogeneity means the studies disagreed substantially, so a single pooled number hides wide variation.

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