Klatskin Tumor in the Light of ICD-O-3: A Population-Based Clinical Outcome Study Involving 1,144 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (2001-2012).

Introduction Klatskin tumors (KTs) occur at the confluence of the right and left extrahepatic ducts and are classified based on their anatomical and histological codes in the International Classification of Diseases for Oncology (ICD-O). The second edition of the ICD-O (ICD-O-2) allocated a distinctive histological code to KT, which also included intrahepatic cholangiocarcinoma (CC). This unclear coding may result in ambiguous reporting of the demographic and clinical features of KT. The current study aimed to investigate the demographic, clinical, and pathological factors affecting the prognosis and survival of KT in the light of the updated third edition of ICD-O, Ninth Revision (ICD-O-3). Methods Data of 1,144 patients with KT from the Surveillance, Epidemiology, and End Result (SEER) database (2001-2012) were extracted. Patients with KT were analyzed for age, sex, race, stage, treatment, and long-term survival. The data were analyzed using chi-square tests, t-tests, and univariate and multivariate analyses. The Kaplan-Meier analysis was used to compare long-term survival between KT and subgroups of all biliary CCs. Results Of all biliary CCs, KT comprised 9.35%, with a mean age of diagnosis of 73±13 years, and was more common in men (54.8%) and Caucasian patients (69.5%). Histologically, moderately differentiated tumors were the most common (38.9%) followed by poorly differentiated (35.7%), well-differentiated (23.3%), and undifferentiated tumors (2.2%) (p<0.001). Most tumors in the KT group were 2-4 cm in size (41.5%), while fewer were >4 cm (29.7%) and <2 cm (28.8%) (0.001). ICD-O-3 defined most KTs in extrahepatic location (53.5%), while the remainder were in other biliary locations (46.5%) (p<0.001). Most KT patients received no treatment (73%), and for those who were treated, the most frequent modality was radiation (52.7%), followed by surgery (28.1%), and both surgery and radiation (19.2%) (0.001). Mean survival time for KT patients treated with surgery was inferior to all CCs of the biliary tree (1.72±2.61 vs. 1.87±2.18 years) (0.047). Multivariate analysis identified regional metastasis (OR=2.8; 95% CI=2.6-3.0), distant metastasis (OR=2.1; 95% CI=1.9-2.4), lymph node positivity (OR=1.6; 95% CI=1.4-1.8), Caucasian race (OR=2.0; 95% CI=1.8-2.2), and male sex (OR=1.2; 95% CI=1.1-1.3) were independently associated with increased mortality for KT (p<0.001). Conclusion The ICD-O-3 has permitted a greater understanding of KT. KT is a rare and lethal biliary malignancy that presents most often in Caucasian men in their seventh decade of life with moderately differentiated histology. Surgical resection does not provide any survival advantage compared to similarly treated biliary CCs. In addition, the combination of surgery and radiation appeared to provide no added survival benefits compared to other treatment modalities for KT.