Histological treatment response to neoadjuvant chemotherapy predicts the survival outcomes of patients with resectable pancreatic cancer: validation of the Japan Pancreas Society grading system

PURPOSE: To validate the prognostic value of histological treatment response, assessed using the Japan Pancreas Society (JPS) grading system, in patients with resectable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant chemotherapy (NAC) followed by surgical resection. METHODS: We analyzed, retrospectively, data from 117 consecutive patients who underwent NAC and curative-intent PDAC resection at Tohoku University Hospital between January 2010 and December 2022. Histological responses were graded using the JPS system. Survival analyses were conducted using Kaplan-Meier estimation and Cox proportional hazards modeling. RESULTS: Histological Grade 1a, 1b, 2, 3, and 4 responses were observed in 47 (40.2%), 42 (35.9%), 21 (17.9%), 6 (5.1%), and 1 (0.9%) patients, respectively. Patients with a Grade ≥ 2 response had significantly longer overall survival (OS) and significantly higher R0 resection rates than those with Grade 1a or 1b responses (median OS: 118.7 vs. 46.6 months, p = 0.037; 100% vs. 82.0%, p = 0.01). In a multivariable Cox regression model including RECIST progression status and baseline covariates, JPS Grade ≥ 2 remained significantly associated with better OS (adjusted HR 0.48; 95% CI 0.24-0.96; p = 0.039). CONCLUSION: Substantial histological response (JPS Grade ≥ 2) after NAC is strongly associated with improved OS and higher R0 resection rates in patients with resectable PDAC. The JPS grading system provides a basis for clinically meaningful prognostic stratification.