Neoadjuvant chemotherapy for Lauren diffuse-type gastric cancer: Is it necessary?

Lauren's diffuse-type adenocarcinoma is less sensitive to chemotherapy, whether neoadjuvant chemotherapy (NAC) benefits this subtype remains uncertain.

We retrospectively reviewed patients with Lauren's diffuse-type adenocarcinoma, clinical stage T3/N+ or T4/Nany, who underwent curative surgery. Patients were divided into a NAC group and an upfront surgery group, and propensity score matching (PSM) was applied to compare the treatment outcome.

274 patients (NAC 194/upfront surgery 80) were initially included. After PSM, 91 patients remained in the NAC group and 59 in the upfront surgery group. Both groups received a total of 8 chemotherapy cycles, with comparable dosage exposure. In the NAC group, only 1 patient achieved a pathological complete response (pCR), with a major pathological response (MPR) rate of 15.4% (14/91), while the upfront surgery group had a slightly higher R0 resection rate (93.8% vs. 85.6%). Post-surgery, the NAC group showed a higher incidence of complications above Clavien-Dindo grade II (NAC 22% vs Upfront surgery 6.8%, p = 0.02). Regarding survival, after PSM, the upfront surgery group demonstrated superior 3-year disease free survival (62.0% vs. 29.5%, p = 0.005) and overall survival (77.3% vs. 52.5%, p = 0.04) compared to the NAC group. Sensitivity analysis confirmed the robustness of the association between NAC and poorer survival outcomes, with increased risks of recurrence (HR = 2.5) and mortality (HR = 1.88) in the multivariate cox model.

Neoadjuvant chemotherapy was associated with inferior survival in this retrospective cohort. Its application for Lauren diffuse-type gastric cancer warrants careful re-evaluation.