Preoperative risk score for prediction of long-term outcomes after hepatectomy for intrahepatic cholangiocarcinoma: Report of a collaborative, international-based, external validation study

Abstract

A preoperative risk score (PRS) to predict outcome of patients with intrahepatic cholangiocarcinoma treated by liver surgery could be clinically relevant. To assess accuracy for broadly adoption, external validation of predictive models on independent datasets is crucial. The objective of this study was to externally validate the score for prediction of long-term outcomes after liver surgery for intrahepatic cholangiocarcinoma proposed by Sasaki et al. and based on preoperative albumin, neutrophil-to-lymphocytes-ratio, CA19-9 and tumor size. METHODS Patients treated by liver surgery for intrahepatic cholangiocarcinoma at 11 international HPB centers from 2001 to 2018 were included in the external validation cohort. Harrell's c-index and Hosmer-Lemeshow analyses were used to test PRS discrimination and calibration. Kaplan-Meier curve for risk groups as described in the original study were displayed. RESULTS A total of 355 patients with 174 deaths during the follow-up period (median=41.7 months, IQR 32.8-50.6) were included. The median PRS value was 14.7 (IQR 10.7-20.6), with normal distribution across the cohort. A Cox regression on PRS covariates found coefficients similar to those of the derivation cohort, except for tumor size. Measures of discrimination estimated by Harrell's c-index was 0.61(95%CI:0.56-0.67) and Hosmer-Lemeshow p=0.175. The Kaplan-Meyer estimation showed reasonable discrimination across risk groups, with 5years survival rate ranging from 20.1% to 0%. CONCLUSION In this external validation cohort, the PRS had mild discrimination and poor calibration performance, similarly to the original publication. Nevertheless, its ability to identify different classes of risk is clinically useful, for a better tailoring of a therapeutic strategy.

Modification of the AJCC/UICC 8th edition staging system for intrahepatic cholangiocarcinoma: proposal for an alternative staging system from cholangiocarcinoma-prevalent Northeast Thailand

“…Combining the PRS score and the 8th AJCC staging can correct the problem of overlapping overall survival in T2, T3, and T4 categories and classify ICC patients with sufficient prognostic difference. 37 Cancer biomarkers, such as cancer stem cell markers (CD44v6, 8-10, CD133, EpCAM, and ALDH1A1), are also favored to enhance capacity for prognostication of CCA and have been used as additional factors for prediction of recurrence in early-stage disease. 35 Similarly, our study showed that the 8th edition did not satisfactorily classify the prognosis of iCCA in the Thai OV.-associated CCA cohort.…”

Proposed modification of the eighth edition of the AJCC staging system for intrahepatic cholangiocarcinoma

“…The inclusion of tumor size in ICC staging has also been debated. [25][26][27] In fact, tumor size was not included in the first ICC staging system in the 7th edition manual, only being added to the 8th edition. 6 Currently, a single tumor 5 cm and a solitary lesion >5 cm with no vascular invasion are classified as T1a and T1b disease, respectively, in the 8th edition of AJCC staging.…”

Preoperative leukocytosis and the resection severity index are independent risk factors for survival in patients with intrahepatic cholangiocarcinoma

“…Prognostic stratification scores for survival after resection of different malignancies, including ICC, have been published in recent years to optimize perioperative decision making [29][30][31][32]. We have recently introduced the RSI, estimating the future functional liver remnant with respect to the preoperative liver function and the expected or actual extent of hepatic surgery, as an independent risk factor for survival after resection of hepatocellular carcinoma and colorectal liver metastases [11,12].…”