Clinical understaging in early gastric cancer: A common and significant problem.

333 Background: A portion of clinical stage I gastric cancer (GC) patients who undergo upfront surgery are understaged preoperatively and found to be higher stage based on final pathology, which can affect the treatment algorithm and GC outcomes. We sought to identify the incidence of understaging in this cohort and variables associated with increased risk of being understaged. Methods: Patients with clinical stage I (T1/2 N0) GC undergoing oncologic resection without neoadjuvant therapy from 2013-2020 were identified in the National Cancer Database (NCDB). Clinicopathologic predictors of understaging were identified using multivariable logistic regression. The relationship between identified variables and understaging was then modeled using logistic regression with natural cubic splines to allow for a flexible, nonlinear analysis. Cox proportional hazards analysis and Kaplan-Meier curves evaluated survival outcomes. Results: 4,370 clinical stage I GC patients were identified, of which 36.0% were initially understaged on clinical staging. Tumor size (per millimeter increase OR: 1.05, 95% CI 1.04-1.05, p<0.001), higher grade (moderate: OR 2.76, 95% CI 1.99-3.84; poor/anaplastic OR: 5.99, 95% CI 1.99-3.84, p<0.001), and non-academic treatment facilities (OR 1.19, 95% CI 1.03-1.38, p=0.017) were associated with increased risk of understaging. Spline analysis showed increased risk of understaging based on tumor size. This was compounded when tumor differentiation was considered, such that a tumor measuring 2.5cm was associated with 16.9%, 31.8%, or 51.6% likelihood of clinical understaging if the tumor was well, moderate, or poorly differentiated, respectively. Understaging was associated with increased mortality (OR 2.31, 95% CI 2.10-2.95, p<0.001). Conclusions: More than a third of patients with clinical stage I GC are understaged and found to have higher stage on final pathology. Early GC with higher grade and larger size are at risk of being understaged using existing components (T-tumor depth, N-lymph node, M-metastasis) to determine clinical stage. Tumor grade and size should be considered on pre-operative evaluation of early GC to improve identification of patients at risk for understaging. Predicted probability of understaging by tumor size and tumor grade differentiation. Tumor Size (cm) Well-differentiated Moderately-differentiated Poorly-differentiated 1.0 4.0% 8.7% 17.9% 2.0 12.7% 25.1% 43.4% 3.0 20.3% 36.8% 57.1% 4.0 25.5% 43.9% 64.2% 5.0 30.7% 50.4% 69.9% 6.0 36.3% 56.6% 74.9% 7.0 42.4% 62.7% 79.4% 8.0 48.5% 68.3% 83.2% 9.0 54.5% 73.3% 86.3% 10.0 60.2% 77.6% 88.8%