Impact of Lauren’s subtype in locally-advanced gastric cancer (LAGC) prognosis: A call for change.
Authors: Felismino Tiago Cordeiro , Brito Angelo Borsarelli Carvalho , Garcia Larissa Rodrigues , Durant Lais Corsino , Senda Lais , Ribeiro Heber Salvador de Castro , Coimbra Felipe José Fernández 
Published: January 2025

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Background:
Patients with LAGC should undergo perioperative chemotherapy and surgery. Lauren’s diffuse subtype and signet-ring cell carcinoma have been linked to worse outcomes and chemoresistance in this setting. This study aimed to assess the impact of Lauren’s classification on response to neoadjuvant chemotherapy and prognosis in LAGC.
Methods:
This analysis involved adult patients from a prospectively collected gastric cancer database who had histologically confirmed LAGC and received curative-intent perioperative chemotherapy and surgery. Patients were classified into two groups according to Lauren’s classification: intestinal and non-intestinal subtypes (including diffuse, signet-ring cell carcinoma and mixed histologies). Clinicopathological and treatment characteristics (age, gender, primary site, HER-2 status, staging laparoscopy, neoadjuvant chemotherapy, surgery and pathological complete response) of the two groups were compared using chi-square tests. Survival curves were obtained using Kaplan-Meier, and log-rank and Cox proportional models used to compare survival between groups.
Results:
Between 2015 and 2022, 174 patients met the inclusion criteria, with a median follow-up of 62.2 months (95% CI: 57.9-66.9). The intestinal subtype comprised 72 patients (41.4%) and the non-intestinal subtype included 102 (58.6%). The median age of diagnosis was significantly higher for the intestinal subtype (63 years) compared to the non-intestinal subtype (56 years; p<0.001). Female patients represented 26.4% of the intestinal subtype and 46.1% of the non-intestinal subtype (p=0.013). The primary gastric site was more prevalent in the non-intestinal subtype (78.4%) compared to the intestinal subtype (51.4%; p<0.001). HER-2 positivity was observed in 12.5% of intestinal and 4.5% of non-intestinal subtypes (p=0.14). Staging laparoscopy was conducted in 67 out of 72 (93%) patients with the intestinal subtype and in 96 out of 102 (94.1%) patients with the non-intestinal subtype, p=1. FLOT and FOLFOX/CAPOX protocols were administered in 50% and 40.2% of intestinal subtype cases, and in 53.9% and 36.2% of non-intestinal subtype cases, respectively (p=0.14). Pathological complete response rates were 8.5% for intestinal and 11.5% for non-intestinal subtypes (p=0.46). Three-year recurrence-free survival rates were 67.1% for intestinal and 64.6% for non-intestinal subtypes (HR=0.99, 95% CI: 0.61-1.61, p=0.96), while five-year overall survival rates were 73.3% and 67.2%, respectively (HR=1.12, 95% CI: 0.63-1.97, p=0.70).
Conclusions:
Our findings demonstrate that the non-intestinal subtype is more common in younger, female patients with primary gastric sites. However, Lauren’s subtype did not significantly correlate with pathological staging post-neoadjuvant chemotherapy or prognosis in LAGC. Lauren’s subtype should not influence treatment decisions in LAGC.