63.01 A Modified Eighth AJCC Staging System For Intrahepatic Cholangiocarcinoma

X. Zhang¹, D. I. Tsilimigras², A. Guglielmi³, L. Aldrighetti⁴, M. Weiss⁵, T. W. Bauer⁶, S. Alexandrescu⁷, G. A. Poultsides⁸, S. K. Maithel⁹, H. P. Marques¹⁰, G. Martel¹¹, C. Pulitano¹², F. Shen¹³, O. Soubrane¹⁴, B. G. Koerkamp¹⁵, I. Endo¹⁶, T. M. Pawlik^{2 1}Department of Hepatobiliary Surgery and Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China,Xi’an, China ²Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center,Columbus, OHIO, USA ³Department of Surgery, University of Verona,Verona, ITALY, Italy ⁴Department of Surgery, Ospedale San Raffaele,Milano, ITALY, Italy ⁵Department of Surgery, Johns Hopkins Hospital,Baltimore, MARYLAND, USA ⁶Department of Surgery, University of Virginia,Charlottesville, VIRGINIA, USA ⁷Department of Surgery, Fundeni Clinical Institute,Bucharest, ROMANIA, Romania ⁸Department of Surgery, Stanford University,Palo Alto, CALIFORNIA, USA ⁹Department of Surgery, Emory University,Atlanta, GEORGIA, USA ¹⁰Department of Surgery, Curry Cabral Hospital,Lisbon, PORTUGAL, Portugal ¹¹Department of Surgery, University of Ottawa,Ottawa, CANADA, Canada ¹²Department of Surgery, Royal Prince Alfred Hospital, University of Sydney,Sydney, AUSTRALIA, Australia ¹³Department of Surgery, Eastern Hepatobiliary Surgery Hospital,Shanghai, CHINA, China ¹⁴Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital,Clichy, FRANCE, France ¹⁵Department of Surgery, Erasmus University Medical Centre,Rotterdam, NETHERLANDS, Netherlands ¹⁶Department of Gastroenterological Surgery, Yokohama City University School of Medicine,Yokohama, JAPAN, Japan

Introduction:  Validation of the updated 8th AJCC staging system for intrahepatic cholangiocarcinoma (ICC) has been limited and controversial. The objective of the current study was to improve the prognostic accuracy of the 8^thedition of the American Joint Committee on Cancer (AJCC) staging system for ICC with the establishment and validation of a new staging system. 

Methods:  Data from an international multi-institutional database (1999-2017)(n=643) and the SEER registry (1975-2016)(n=797) were used as development and validation cohorts, respectively. A modified TNM (mTNM) was proposed by redefining the 8^thAJCC T categories, and incorporating the recently proposed N status as N0 (no lymph node metastasis [LNM]), N1 (1-2 LNM) and N2 (>3 LNM), as well as adopting a new stage classification.

Results: The 8^thTNM staging system failed to stratify patients with stage II versus IIIA, stage IIIB versus IV, as well as overall stage III versus IV relative to long-term overall survival (OS) in both databases (multi-institutional database: median OS, stage II 37.8 vs. IIIA 50.8 months, p=0.314; IIIB 18.9 vs. IV 17.0 months, p=0.256; III 20.7 vs. IV 17.0 months, p=0.058; SEER registry: median OS, stage II 33.0 vs. IIIA 88.8 months, p=0.636; IIIB 18.0 vs. IV 15.5 months, p=0.858; III 18.9 vs. IV 15.5 months, p=0.779) (Figure).Based on multivariable analysis, perforation of visceral peritoneum (HR 1.2, 95% CI 0.9-1.6, p=0.219) was removed from the T definition, whereas multiple tumors (HR 1.6, 95% CI 1.3-2.1, p<0.001), tumors with periductal infiltration (HR 1.7, 95% CI 1.3-2.3, p<0.001), as well as tumors involving local extrahepatic structures by direct invasion (HR 1.7, 95% CI 1.1-2.6, p=0.012) were defined as T4 in the new staging system. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the multi-institutional (median OS, stage IA 101.4 months, IB 66.3 months vs. stage IIA 45.2 months, IIB 37.1 months vs. stage III 18.9 months vs. stage IV 16.4 months, all p<0.05) and SEER registry (median OS, stage IA 73.0 months, IB 85.1 months vs. stage IIA 46.0 months, IIB 24.5 months vs. stage III 17.7 months vs. stage IV 14.2 months, all p<0.05) datasets (Figure). On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the two cohorts.

Conclusion: The modified 8th AJCC TNM staging system for ICC using the new T and N definitions improved stratification of patients relative to long-term OS versus the original 8^thAJCC staging, and therefore should be considered for potential adoption in the next AJCC staging manual edition.