Predicting futility of upfront surgery in perihilar cholangiocarcinoma: Machine learning analytics model to optimize treatment allocation

Abstract

Background: Whilst resection remains the only curative option for perihilar cholangiocarcinoma (PHC), it is well known that such surgery is associated with a high risk of morbidity and mortality. Nevertheless, beyond facing life-threatening complications, patients may also develop early disease recurrence, defining a “futile” outcome in PHC surgery. The aim of this study is to predict the high-risk category (futile group) where surgical benefits are reversed and alternative treatments may be considered. Methods: The study cohort included prospectively maintained data from 27 Western tertiary referral centers: the population was divided in a development and a validation cohort. The Framingham Heart Study methodology was used to develop a preoperative scoring system predicting the “futile” outcome. Results: A total of 2271 cases were analysed: among them, 309 were classified within the “futile group” (13.6%). ASA score ≥ 3 (OR 1.60; p = 0.005), bilirubin at diagnosis ≥ 50 mmol/L (OR 1.50; p = 0.025), Ca 19-9 ≥ 100 U/mL (OR 1.73; p = 0.013), preoperative cholangitis (OR 1.75; p = 0.002), portal vein involvement (OR 1.61; p = 0.020), tumor diameter ≥ 3 cm (OR 1.76; p < 0.001) and left sided resection (OR 2.00; p < 0.001) were identified as independent predictors of futility. The point system developed, defined three (i.e., low, intermediate, and high) risk classes, which showed good accuracy (AUC 0.755) when tested on the validation cohort. Conclusion: The possibility to accurately estimate, through a point system, the risk of severe postoperative morbidity and early recurrence, could be helpful in defining the best management strategy (surgery vs. non-surgical treatments) according to preoperative features.

The fibrosis-4 index is a prognostic factor for cholangiocarcinoma patients who received immunotherapy

“…In our study, bilirubin levels within a week before receiving immunotherapy were related to the total survival time of the patients (mOS: 1508 vs. 263 days), with higher levels indicating a worse prognosis. Bilirubin levels affect patients with cholangiocarcinoma's prognosis in several ways: Patients with hilar cholangiocarcinoma with higher bilirubin levels at diagnosis may not benefit from surgery (34); The albumin bilirubin (ALBI) grade, which combines bilirubin and albumin levels, is an independent prognostic factor for OS and PFS in intrahepatic cholangiocarcinoma (35,36). The analysis of FIB-4, SII, NLR, PLR, and PNI showed that FIB-4 is an independent risk factor for OS in patients with cholangiocarcinoma undergoing immunotherapy.…”

Letter to the Editor: How to define the futile outcome in patients undergoing surgery for perihilar cholangiocarcinoma?

“…To the editor, We read with great interest the paper by Dr. Ratti and colleagues. [1] The study included 2271 patients with perihilar cholangiocarcinoma (PHC) who underwent surgical resection at 27 institutions and developed a preoperative risk score for predicting futile outcomes following surgery for PHC. This risk score demonstrated simplicity and accuracy in predicting the risk of futile outcome and provided reliable guidance in avoiding unnecessary surgery for PHC patients.…”

“…We read with great interest the paper by Dr. Ratti and colleagues 1 . The study included 2271 patients with perihilar cholangiocarcinoma (PHC) who underwent surgical resection at 27 institutions and developed a preoperative risk score for predicting futile outcomes following surgery for PHC.…”

The utility of futility

“…Although these factors often are evaluated together in a clinical setting, they have most commonly been separated in outcomes/risk studies. The combination of poor outcomes both cancer-specific and from a complication standpoint is a unique and important contribution that Ratti et al 8 have defined as surgical “futility.”…”