Impact of Integrated Pathologic Score on Treatment Outcomes for Borderline Resectable Pancreatic Cancer

Abstract Objective The Integrated Pathologic Score of the College of American Pathologists (IPSCAP) grading system independently predicts overall survival (OS) in patients with resected pancreatic adenocarcinoma after non-ablative neoadjuvant therapy. This study analyzes the impact of IPSCAP on the outcomes of patients with borderline resectable pancreatic cancer (BRPC) resected after neoadjuvant chemotherapy and 5-fraction stereotactic body radiation therapy (SBRT). Materials and Methods This Institutional Review Board-approved retrospective study queried patients with BRPC treated between 2013 and 2023 with either neoadjuvant FOLFIRINOX or gemcitabine-abraxane and SBRT, who underwent resection. SBRT was categorized at ablative dose thresholds of ≥40 or 45 Gy. The IPSCAP score was calculated by summing tumor regression grade, pathologic tumor stage, and nodal status for patients with more than 12 lymph nodes examined and was classified into 3 groups: group 1 (score 0-3), group 2 (score 4-6), and group 3 (score 7-8). The presence of actionable somatic and germline mutations was identified. OS was defined as the time from biopsy to death or last contact (in months). Statistical analyses were performed using R software. Results Overall, per-unit decrease of IPSCAP was significantly associated with increased median OS (hazard ratio [HR] = 0.770, 95% CI 0.670-0.886, P < .001). Kaplan-Meier survival analysis showed a significant difference between stratification of IPSCAP by group, with group 1 having significantly less risk of death than groups 2 and 3. Similar results were found when patients were stratified by their neoadjuvant chemotherapy: FOLFIRINOX (HR = 0.742, 95% CI 0.604-0.912, P < .01) and gemcitabine-abraxane (HR = 0.804, 95% CI 0.667-0.969, P = .022). Patients treated with ≥45 Gy were significantly more likely to have group 1 pathologic scores and had higher odds of achieving group 1 compared with those treated with <45 Gy (odds ratio, 2.458; 95% CI 1.060-5.783; P = .027, Fisher exact test). Conclusions This study suggests that IPSCAP incorporation is a reliable prognosticator in the setting of neoadjuvant chemotherapy and 5-fraction SBRT of OS in patients with resected pancreatic adenocarcinoma, warranting further studies with dose escalation in this population.