Inadequacy of the Eighth Edition of the American Joint Committee on Cancer Staging System for Invasive Carcinoma Associated with Premalignant Lesions in the Pancreas: Analysis Using the National Cancer Database

Abstract

Introduction: Invasive carcinomas (IC) arising from premalignant pancreatic lesions are staged according to the eighth edition of the American Joint Committee on Cancer staging system. The aim was to investigate the validity of the staging system. Method: The National Cancer Database was queried for patients who underwent surgery for IC associated with intraductal papillary mucinous neoplasm or mucinous cystic neoplasm between 2006 and 2016. Patients undergoing neoadjuvant treatment or with metastasis at surgery were excluded. Results: Among 723 patients, median survival was 72.1 months and the 5-year survival rate was 53.7%. The median survival of patients with T1, T2, and T3 lesions were 101, 60, and 62.6 months, respectively, and demonstrated poor stratification (T1 vs. T2: p=0.122, T2 vs. T3: p=0.957, T1 vs. T3: p=0.114). Patients with extrapancreatic extension (EPEx) had worse survival throughout all T-categories (p<0.001). There were no survival differences among T1, T2, and T3 in EPEx-negative group, nor for the EPEx-positive group (Fig.1a). EPEx was shown to be the dominant pathology predictor of survival. Further, subcategorization was not different between T1a vs. T1b or T1b vs. T1c (Fig.1b). Multivariate analysis found age ≥67, R1/R2 status, and EPEx to be independent prognostic factors, whereas size and prognostic groups were not (Table). Conclusions: These findings suggest that the current T-staging system is inadequate for IC associated with premalignant lesions. While re-categorization should be considered, further study with standardized size measurements would overcome the potential confounding of inconsistent reporting on size measuring either the cyst or invasive portion.EP02C-080VariableUnivariateHazard ratio95% CIP-valueMultivariateHazard ratio95% CIP-valueAge (years) <67 ≥671.6261.305-2.027<0.0011.5041.196-1.891<0.001Sex Male Female0.7970.644-0.9880.0390.8410.670-1.0560.135Operation0.621 PD1.0740.836-1.3790.578 DPRef TP0.9890.693-1.4110.952 Local excision--- Unspecified0.6890.334-1.4220.314R status<0.0010.010 R0 R1/R22.6051.987-3.413<0.0011.5851.175-2.1400.003 Unknown1.0740.443-2.6030.8740.9040.360-2.2730.083Extrapancreatic ext<0.0010.002 No Yes2.5152.021-3.131<0.0011.5981.209-2.1130.001 Unknown5.4952.244-13.454<0.0016.5210.821-51.7700.076Size (cm)0.0110.145 ≤2 2< ≤41.2500.938-1.6650.1270.8320.514-1.3450.453 >41.2550.954-1.6510.1050.6290.373-1.0590.081 T44.2371.712-10.4880.002--N<0.0010.145 N0 N13.4832.712-4.473<0.0013.0390.394-23.4160.286 N26.7774.865-9.439<0.00112.0040.988-145.8210.051Stage<0.0010.092 IA IB0.8710.590-1.2840.4850.8760.471-1.6300.677 IIA1.2310.880-1.7220.2241.7910.964-3.3260.065 IIB3.6562.620-5.100<0.0011.1670.142-9.6000.886 III7.0154.762-10.335<0.0010.4790.037-6.1550.572Grade<0.0010.496 Well Mod1.4621.084-1.9720.0131.2130.883-1.6660.234 Poor2.6041.832-3.701<0.0011.3580.912-2.0220.131 Undifferentiated1.0840.436-2.6950.8621.3810.528-3.6080.510 Unknown0.8990.643-1.2560.5321.0210.725-1.4380.904LV invasion<0.0010.998 No Yes2.5941.886-3.567<0.0010.9950.681-1.4540.978 Unknown1.0940.857-1.3950.4701.0060.780-1.2990.961Adj CTx No Yes1.4311.154-1.7750.0010.3150.113-0.8810.028Adj RT No Yes1.4231.110-1.825<0.0011.0470.758-1.4470.781Adj Tx No Yes1.4711.186-1.825<0.0012.3000.798-6.6250.123Charlson-Deyo Score0.0230.132 0 11.1640.917-1.4770.2111.0080.787-1.2910.948 21.6711.142-2.4440.0081.3370.902-1.9810.148 31.7290.941-3.1760.0781.8740.995-3.5270.052 Open table in a new tab