Neighborhood Deprivation and Circulating Tumor DNA Provide Distinct Prognostic Signals in Localized Pancreatic Cancer

Abstract Purpose: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US. Socioeconomic disadvantage, measured by Area Deprivation Index (ADI), may affect outcomes beyond tumor biology. We evaluate ADI and overall survival (OS) in localized PDAC, accounting for KRAS-mutant circulating tumor DNA (ctDNA).Methods: 165 patients with localized PDAC were prospectively enrolled (NCT04616131; Oct. 2020–Jan. 2026). ADI was dichotomized at the 50th national percentile. OS was compared by group and jointly with ctDNA using Kaplan-Meier analysis. Multivariable Cox assessed ADI and survival, adjusting for clinical covariates and ctDNA, and tested ADI/ctDNA interactions. C-index/likelihood ratio assessed added discriminatory value. Next-generation sequencing detected KRAS-mutant ctDNA.Results: High ADI was associated with shorter OS (26.7 vs 30.5 months, p=0.035; HR 1.79, 95% CI 1.09–2.92, p=0.020). Patients with both high ADI and detectable ctDNA had the poorest survival (9.8 vs 38.3 months, p=0.005). ADI and ctDNA each independently predicted shorter survival without significant interaction; combining both improved model discrimination beyond either alone.Conclusion: Greater area deprivation is associated with reduced survival in localized PDAC, independently of clinical and tumor biomarkers. ADI and ctDNA may have additive value for risk stratification, supporting interventions targeting social determinants alongside oncologic care.