Prognostic Determinants of Overall Survival After Resection for Pancreatic Ductal Adenocarcinoma: A Consensus‐Based Conceptual Framework

Vollständiger Abstract

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ABSTRACT Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis despite surgical resection, yet the prognostic literature remains fragmented across hundreds of single‐institution studies that vary in design, covariates, and analytical approaches. A synthesis of this evidence is needed to identify which factors most consistently predict overall survival (OS) after curative‐intent resection and standardize covariate selection for future outcomes research and trial design. Following PRISMA guidelines, we systematically searched PubMed, Embase, Scopus, and CINAHL (1990–2023) for studies reporting on factors associated with OS following curative‐intent resection for PDAC. Prognostic variables from multivariable analyses were extracted and categorized into six conceptual domains: demographics and socioeconomic factors, clinical characteristics, laboratory parameters, molecular biomarkers, tumor characteristics, and treatment‐related factors. Strength of agreement across studies was classified as consensus (≥ 75% concordance), fair (> 50%–74%), or weak/none (≤ 50%). The protocol was pre‐registered in PROSPERO (CRD42021278699). Of 49 867 identified records, 947 studies encompassing 1 430 411 patients met inclusion criteria. A total of 650 prognostic factors were tested with OS across the literature; 58 were incorporated into the conceptual framework. Among tumor characteristics, pathological nodal status (pN; 82.1%, consensus) and tumor grade (75.0%, consensus) were the strongest and most consistent negative predictors of OS. Margin status, perineural invasion, and lymph node ratio reached fair‐level negative agreement. Receipt of adjuvant chemotherapy was the most robust positive predictor (80.4%, consensus), followed by treatment at an academic medical center (75.0%, consensus). Socioeconomic determinants—including private insurance and higher income—demonstrated consensus‐level positive associations with OS. Most comorbidities, laboratory parameters, and preoperative clinical characteristics showed fair‐to‐no association with OS in multivariable analyses. Tumor biology and receipt of adjuvant chemotherapy are the most consistent determinants of OS post‐PDAC resection. Socioeconomic and structural factors carry consistent prognostic weight and warrant routine inclusion in survival models. Our findings provide a framework for future prognostic modeling, clinical decision‐making, and trial design.