Post liver transplant recurrence in patients with hepatocellular carcinoma: not necessarily the end of the road!

Aim: We analysed outcomes using multimodality therapy in patients with hepatocellular carcinoma (HCC) recurrence post living donor liver transplantation (LDLT).Methods: Of 2363 LDLT’s performed between 2005 to mid 2018, 435 (18.4%) were for HCC within our expanded selection criteria (absence of extrahepatic disease and vascular invasion, irrespective of tumor size and number). Survival after recurrence, and prognostic factors for these patients were studied.Results: Of 435 LDLT patients, 51% had HCC beyond Milan and 43% beyond UCSF criteria at the time of LDLT. pre-LT AFP > 100 ng/mL and tumour FDG-18 PET avidity predicted overall survival (OS), whereas pre-LT AFP > 100 ng/mL, UCSF criteria, and FDG-18 PET avidity predicted recurrence-free survival. Hundred patients (23%) developed HCC recurrence at a median time of 16 months (range 2-108 months) post LDLT. Lungs (53%), liver (37%), and bone (21%) were the most common sites of recurrence. Ninety-five patients received tyrosine kinase inhibitors (TKI) after recurrence and 62 received mTOR inhibitors (protocol-based after LDLT, or post recurrence). Surgical resection of metastases was performed in 14 patients, 15 received stereotactic body radiotherapy, and 18 underwent ablation (radiofrequency, microwave ablation, transarterial chemoembolisation, or percutaneous ethanol injection). One- and 3-yr OS after recurrence were 57%, and 24% respectively, with a maximum post recurrence survival of 7.5 years. HCC recurrence within one year after LDLT (P = 0.004, HR = 2.38, 95%CI: 1.325-4.276), AFP > 200 ng/mL at the time of recurrence (P =0.02, HR = 2.075, 95%CI: 1.121-3.841), and recurrence at multiple sites (P = 0.047, HR = 1.831, 95%CI: 1.009-3.321) were poor prognostics factors for post recurrence survival. Multimodality management of recurrence using combined medical, surgical, ablative treatments and radiotherapy significantly improved survival compared to the use of TKI’s or mTORi’s alone, or in combination.Conclusion: In patients accepted for LDLT beyond the conventional size-number criteria, even after HCC recurrence, an aggressive approach using multimodality therapy, when possible, aids in further prolongation of survival