# The Impact of Neoadjuvant Chemotherapy on Survival Outcomes in Gastric Signet-Ring Cell Carcinoma: An International Multicenter Study

## TL;DR

This study found that neoadjuvant chemotherapy had limited overall benefit for gastric signet-ring cell carcinoma but improved survival in specific subgroups.

## Contribution

The study identifies subgroups of GSRCC patients who may benefit from neoadjuvant chemotherapy.

## Key findings

- NAC did not improve overall survival in unselected GSRCC patients.
- NAC showed significant survival benefits in mid/distal and cTNM II/III stage tumors.
- Tumor stage and size were key predictors of survival in GSRCC patients.

## Abstract

This retrospective study analyzed 1773 SEER and 1289 NCC patients with gastric signet-ring cell carcinoma (GSRCC) undergoing radical surgery (2011–2018) to assess neoadjuvant chemotherapy (NAC) efficacy. NAC utilization was low (24.6% SEER, 22.6% NCC), with a median 30-month follow-up. Multivariate analyses identified tumor stage/size as survival predictors (p < 0.05), but NAC showed no overall survival benefit (SEER p = 0.653; NCC p = 0.139). Subgroup analysis revealed significant survival improvement with NAC in mid/distal tumors and cTNM II/III stages (all p < 0.001). While NAC demonstrated limited efficacy in unselected GSRCC, tailored use for locally advanced or anatomically specific cases may enhance outcomes. Further studies are warranted to optimize NAC strategies for this aggressive malignancy.

Background: Gastric signet-ring cell carcinoma (GSRCC) is associated with a poor prognosis, and the effectiveness of neoadjuvant chemotherapy (NAC) in improving survival outcomes remains inconclusive. This study aimed to evaluate the impact of NAC on survival in patients with GSRCC. Methods: This retrospective cohort study included GSRCC patients from two databases: the National Cancer Center (n = 1289) and SEER (n = 1773), all of whom underwent radical surgery between January 2011 and January 2018. The primary endpoint was overall survival (OS) after surgery. Kaplan–Meier survival curves were generated, and multivariate Cox regression analyses were performed to adjust for confounding factors. Additionally, subgroup analyses were conducted to assess the potential survival benefits of NAC in specific patient subsets. Results: NAC use was limited, with 24.6% (436/1773) of patients in the SEER cohort and 22.6% (292/1289) of patients in the NCC cohort receiving NAC. The median follow-up duration was 30 months (range: 8–131 months; IQR: 24–70 months). In the SEER cohort, the 3-year and 5-year survival rates were 47.4% and 41.3%, respectively, whereas in the NCC cohort, they were 82.4% and 73.9%. Multivariate analysis identified race, tumor size, cTNM stage, pT stage, and pN stage as independent predictors of survival in the SEER cohort (all p < 0.05). In the NCC cohort, age, tumor size, and cTNM stage were significant predictors (p < 0.05). NAC did not demonstrate a significant OS benefit in either cohort (SEER: p = 0.653; NCC: p = 0.139). Subgroup analyses focusing on mid/distal tumor locations and cTNM stages II/III indicated a significant trend towards improved survival with NAC (all p < 0.001). Conclusions: NAC showed limited efficacy in unselected GSRCC patients. However, its selective application in patients with mid/distal tumors or locally advanced tumors (cTNM II/III) may offer potential survival benefits. Further studies are needed to explore tailored NAC strategies as a means to improve outcomes in this highly aggressive cancer.