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ImportanceClear indications on how to select retreatments for recurrent hepatocellular carcinoma (HCC) are still lacking.ObjectiveTo create a machine learning predictive model of survival after HCC recurrence to allocate patients to their best potential treatment.Design, Setting, and ParticipantsReal-life data were obtained from an Italian registry of hepatocellular carcinoma between January 2008 and December 2019 after a median (IQR) follow-up of 27 (12-51) months. External validation was made on data derived by another Italian cohort and a Japanese cohort. Patients who experienced a recurrent HCC after a first surgical approach were included. Patients were profiled, and factors predicting survival after recurrence under different treatments that acted also as treatment effect modifiers were assessed. The model was then fitted individually to identify the best potential treatment. Analysis took place between January and April 2021.ExposuresPatients were enrolled if treated by reoperative hepatectomy or thermoablation, chemoembolization, or sorafenib.Main Outcomes and MeasuresSurvival after recurrence was the end point.ResultsA total of 701 patients with recurrent HCC were enrolled (mean [SD] age, 71 [9] years; 151 [21.5%] female). Of those, 293 patients (41.8%) received reoperative hepatectomy or thermoablation, 188 (26.8%) received sorafenib, and 220 (31.4%) received chemoembolization. Treatment, age, cirrhosis, number, size, and lobar localization of the recurrent nodules, extrahepatic spread, and time to recurrence were all treatment effect modifiers and survival after recurrence predictors. The area under the receiver operating characteristic curve of the predictive model was 78.5% (95% CI, 71.7%-85.3%) at 5 years after recurrence. According to the model, 611 patients (87.2%) would have benefited from reoperative hepatectomy or thermoablation, 37 (5.2%) from sorafenib, and 53 (7.6%) from chemoembolization in terms of potential survival after recurrence. Compared with patients for which the best potential treatment was reoperative hepatectomy or thermoablation, sorafenib and chemoembolization would be the best potential treatment for older patients (median [IQR] age, 78.5 [75.2-83.4] years, 77.02 [73.89-80.46] years, and 71.59 [64.76-76.06] years for sorafenib, chemoembolization, and reoperative hepatectomy or thermoablation, respectively), with a lower median (IQR) number of multiple recurrent nodules (1.00 [1.00-2.00] for sorafenib, 1.00 [1.00-2.00] for chemoembolization, and 2.00 [1.00-3.00] for reoperative hepatectomy or thermoablation). Extrahepatic recurrence was observed in 43.2% (n = 16) for sorafenib as the best potential treatment vs 14.6% (n = 89) for reoperative hepatectomy or thermoablation as the best potential treatment and 0% for chemoembolization as the best potential treatment. Those profiles were used to constitute a patient-tailored algorithm for the best potential treatment allocation.Conclusions and RelevanceThe herein presented algorithm should help in allocating patients with recurrent HCC to the best potential treatment according to their specific characteristics in a treatment hierarchy fashion.

Resection remains the treatment of choice achieving 5-year survival rates of 22% to 40%. The aim of this analysis was to examine the outcomes of patients with solitary ≤5 cm intrahepatic cholangiocarcinoma.A retrospective chart review was performed on 123 patients undergoing resection for primary intrahepatic cholangiocarcinoma from 1995 to 2013. Group 1 included patients with asymptomatic solitary intrahepatic cholangiocarcinoma measuring ≤5 cm.Group 1 (n = 33, 27%) had a greater rate of underlying liver disease, cirrhosis, minor resection, favorable pathologic features including decreased rate of perineural invasion, vascular invasion, lymph node involvement, and satellite nodules (P .05). Factors associated with overall poor outcome were patients in Group 2 (P=.025), positive margin (P=.04), presence of satellite nodules (P = .008), and multinodularity (P=.058). Factors associated with recurrence in Group 1 were presence of satellite nodules (P=.004), and tumor size ≥4 cm (P=.031). Factors associated with decreased survival in Group 1 was transfusion requirement (P = 0.018). The 5-year recurrence and survival rates were (39% vs 67%) and (71% vs 53%) in Group 1 versus Group 2, respectively (P=.111).Resection of solitary intrahepatic cholangiocarcinoma ≤5 cm can achieve 5-year survival rates up to 71%. Results were comparable to those of patients undergoing transplantation for hepatocellular cancer within the Milan criteria.