Study identifies markers for presurgical staging system in cholangiocarcinoma

A Japanese study identifies markers for a presurgical staging system in intrahepatic cholangiocarcinoma, with results comparable to those of an existing postsurgical staging system.

Intrahepatic cholangiocarcinoma (ICC), or bile duct cancer that arises in the liver, remains difficult to treat with 5-year survival rates of less than 10% if diagnosed after the localized stage. Surgery remains the only option for a cure, but even that option presents challenges.

Clinicians have lacked noninvasive biomarkers to predict CHF prognosis before surgery. The staging available is based on the Japan Liver Cancer Study Group system, which relies on postoperative findings. Today, however, with some clinical trials examining neoadjuvant treatment of CHF before surgery, pre-surgical biomarkers that could guide treatment are desired.

A recent article in Cancer discusses the development of a presurgical staging system, called PRE-Stage, developed primarily by Hisashi Kosaka and colleagues at Kansai Medical University, Hirakata, Japan. The researchers looked at several different indices that assess a patient’s nutrition, immunity, and inflammatory status, then combined those results with categorizations of ICC tumor location to create a predictive model.

This retrospective analysis used clinical and histopathological data of 227 consecutive patients treated for CHF after hepatectomy at 5 hospitals in Kansai region, Japan, from January 2009 to December 2020. The mean patient age was 72 years and 69% were men. Investigators had a number of data points, including a measurement of indocyanine green (ICG), which is a dye that binds to necrotic cell membranes and can be used as a biomarker.

First, the researchers looked at available indices, including neutrophil to lymphocyte ratio (NLR), prognostic nutritional index (PNI), platelet to lymphocyte ratio (PLR), C-reactive protein ratio (CRP) /albumin (CAR) and CRP-albumin-lymphocyte index (CALLY). Each clue, taken on its own, is “unsuitable for use in treatment-taking and patient life planning,” they wrote.

Each of these indices was evaluated on their ability to predict disease-free survival (DSS) and disease-free survival (DFS). In this analysis, NLR, PNI and PLR “did not demonstrate significant prognostic value”. The CALLY index offered the best predictive value, followed by CAR.

The team hypothesized that a prognostic model combining CALLY index results, central tumor location, and whether CA19-9 levels were above 40.05 U/mL, as all were more predictive of SSM than other factors, such as age, years with hepatitis, and ICG

The PRE-Stage was then developed using the 3 prognostic factors, and researchers reported that it was able to significantly predict DSS and DFS when patients were stratified into 4 stages, with those at higher stages having a darker prognosis.

“When DSS was stratified by PRE-Stage, the median DSS of patients with PRE-Stage 4 was 13.9 months,” they wrote. Given that the median survival time for patients with unresectable CHF treated with gemcitabine plus cisplatin was 11.7 months in a pivotal trial, “indications for surgery should be carefully determined for patients with PRE-stage 4” .

And, when DFS was stratified using the PRE-Stage, most patients with PRE-Stage 3 or 4 had their cancer return within a year (the median DFS of PRE-Stage 3 vs 4 was 10.3 months vs 7.4 months).

“These patients with poor prognoses may be candidates for neoadjuvant chemotherapy in future clinical trials, whereas few retrospective studies have evaluated neoadjuvant chemotherapy for patients with locally advanced CHF,” the researchers wrote.

Additionally, the PRE-Stage produced risk ratios (HRs) similar to those of the Liver Cancer Study Group of Japan (LCSGJ). The HRs for DSS for PRE-Stage and the LCSGJ were 1.923 and 1.985, respectively, both with P

“The PRE-Stage demonstrated similar accuracy in predicting the prognosis of CHF as that of the LCSGJ stage, which is based on postoperative outcomes. The PRE-Stage may aid in appropriate treatment decision-making,” have they concluded.


Kosaka H, ​​Ueno M, Komeda K, et al. The impact of a preoperative staging system on the accurate prediction of prognosis in intrahepatic cholangiocarcinoma. Cancer. 2022;14(5):1107. Published February 22, 2022.

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