Two-tier architecture-based grading for pancreatic cancer outperforms traditional grading

Abstract Objectives A novel architecture-based grading system for pancreatic ductal adenocarcinoma (PDAC) is tested against traditional grading. Methods A total of 103 PDAC resections were graded by College of American Pathologists/American Joint Committee on Cancer (CAP/AJCC) guidelines and by a system using an architectural pattern (dispersed larger duct = low grade vs dense smaller duct = high grade). Survival analyses and interobserver variability were assessed. In total, 114 cases from a public data set were used for validation. Results Median overall survivals were 15 and 36 months for architectural high-grade and low-grade cases, respectively (P < .001). Conversely, CAP/AJCC grading showed no survival difference between well-differentiated and moderately differentiated tumors (P = .545). Architecture-based grading remained prognostically significant for recurrence-free survival (P = .004), but CAP/AJCC grading was not (P = .226). Adjusted for stage and margin status, architectural high-grade PDACs showed a hazard ratio of 2.69 relative to low grade (P < .001) for survival. The validation cohort confirmed prognostic differences in overall (P < .001) and recurrence-free survival (P = .027) for the architecture-based system, outperforming CAP/AJCC grading. Architecture-based grading exhibited a Cohen’s ĸ value of 0.710 (substantial agreement), superior to traditional grading (0.488, moderate agreement). Conclusions Grading PDAC based on architectural pattern results in superior prognostication and reproducibility vs CAP/AJCC grading.