Large Unstained Cells: A Predictive Biomarker for Recurrence and Survival in Resected Gastric Cancer

Background and Objectives: Despite advances in surgery and perioperative chemotherapy, locally advanced gastric cancer continues to pose significant challenges, creating a pressing need for biomarkers capable of predicting therapeutic efficacy and survival outcomes. This study evaluates the prognostic and predictive significance of large unstained cells (LUCs), a morphologically distinct subset of white blood cells identified in peripheral blood that remain unstained by standard hematological dyes, as potential indicators of immune competence and treatment response. Materials and Methods: This retrospective analysis included patients diagnosed with locally advanced gastric cancer (cT2-4, N0-3) at Ankara Bilkent City Hospital between January 2018 and November 2024. Primary endpoints were overall survival (OS) and disease-free survival (DFS), stratified by LUC levels. The secondary endpoint was the association between LUC levels and pathological tumor response. Results: A total of 180 patients were analyzed, with a median age of 59 years; a total of 76% were male. The median follow-up period was 16.5 months, during which OS and DFS rates were 82% and 66%, respectively. Most patients were presented with advanced-stage disease, including T3-T4 tumors (91%) and nodal positivity (81%). Stratification by LUC levels revealed significantly shorter DFS (HR: 2.12; 95% CI: 1.12-4.01; p = 0.020) and OS (HR: 3.37; 95% CI: 1.26-9.03; p = 0.015) in the low-LUC group compared to the high-LUC group. Furthermore, the high-LUC group exhibited a significantly higher tumor shrinkage rate (ypN0: 60% vs. 44%; p = 0.020), although tumor regression scores were similar across groups. Advanced tumor stage and lack of pathological response were strongly associated with reduced DFS and OS, while poorly cohesive carcinoma histology emerged as a predictor of inferior OS. Conclusions: This study demonstrates that elevated LUC levels are significantly associated with improved DFS and OS, as well as enhanced tumor shrinkage, in patients with locally advanced gastric cancer. These findings show the potential of LUCs as a promising biomarker for prognostication and therapeutic stratification in this population, offering a novel avenue for refining clinical decision-making. Further validation through prospective investigations is warranted.