Improved Clinical Staging System for Localized Pancreatic Cancer Using the ABC Factors: A TAPS Consortium Study

Abstract

PURPOSE Previous studies suggest that besides anatomy (A: resectable, borderline resectable [BR], or locally advanced [LA]) also biologic (B: carbohydrate antigen 19-9 [CA 19-9]) and conditional (C: performance status) factors should be considered when staging patients with localized pancreatic ductal adenocarcinoma (PDAC). The prognostic value of the combined ABC factors has not been quantitatively validated. METHODS In this retrospective cohort study, we evaluated patients with localized PDAC treated with initial (modified) fluorouracil with leucovorin, irinotecan, and oxaliplatin ([m]FOLFIRINOX) at five high-volume pancreatic cancer centers in the United States and the Netherlands (2012-2019). Multivariable Cox proportional hazards analysis was used to investigate the impact of the ABC factors for overall survival (OS). RESULTS Overall, 1,835 patients with localized PDAC were included. Tumor stage at diagnosis was potentially resectable in 346 (18.9%), BR in 531 (28.9%), and LA in 958 (52.2%) patients. The baseline CA 19-9 was >500 U/mL in 559 patients (32.5%). Performance status was ≥1 in 1,110 patients (60.7%). Independent poor prognostic factors for OS were BR disease (hazard ratio [HR], 1.26 [95% CI, 1.06 to 1.50]), LA disease (HR, 1.71 [95% CI, 1.45 to 2.02]), CA 19-9 >500 U/mL (HR, 1.36 [95% CI, 1.21 to 1.52]), and WHO performance status ≥1 (HR, 1.31 [95% CI, 1.16 to 1.47]). Patients were assigned 1 point for each poor ABC factor and 2 points for LA disease. The median OS for patients with score 0-4 was 49.7, 29.9, 22.0, 19.1, and 14.9 months with corresponding 5-year OS rates of 47.0%, 28.9%, 19.2%, 9.3%, and 4.8%, respectively. CONCLUSION The ABC factors of tumor anatomy, CA 19-9, and performance status at diagnosis were independent prognostic factors for OS in patients with localized PDAC treated with initial (m)FOLFIRINOX. Staging of patients with localized PDAC at diagnosis should be based on anatomy, CA 19-9, and performance status.

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

“…Nevertheless, the interpretation of anatomical, biological, and conditional parameters for personalized restaging remains challenging, 4 , 5 , 6 illustrated by high early recurrence rates. 7 , 8 Histopathological residual tumor burden after resection following preoperative therapy is 1 of the biological parameters for disease response.…”

“…1 Preoperative therapy provides the chance for improved disease control while selecting patients with more favorable tumor biology for surgical resection, 2 leading to resection rates of 77%, 61%, and 22% among patients with primary resectable, borderline resectable, and locally advanced pancreatic cancer, respectively. 3 Nevertheless, the interpretation of anatomical, biological, and conditional parameters for personalized restaging remains challenging, [4][5][6] illustrated by high early recurrence rates. 7,8 Histopathological residual tumor burden after resection following preoperative therapy is 1 of the biological parameters for disease response.…”