Multimodal treatment modalities are associated with improved long-term outcome in patients with recurrent hepatocellular carcinoma

Question:

Orthotopic liver transplantation (OLT) is considered as the best treatment for HCC as it treats both the tumor and the underlying liver disease. Unfortunately, the low availability of liver allografts has been a major problem while waiting list mortality remains high. As such, liver resections also in patients with underlying chronic liver disease are becoming increasingly popular. Tumor recurrence after liver-resection, however, continues to impose a major problem in hepatocellular carcinoma (HCC). Here we aimed to evaluate prognostic markers for recurrence-free (RFS) and overall survival (OS) in HCC-patients who underwent liver-resection in curative intent. In addition, we investigated the effects of multimodal treatment modalities in a subgroup of patients with HCC-recurrence.

Methods:

Between 2009 – 2016 111 patients (BCLC-0: n = 3, BCLC-A: n = 67, BCLC-B: n = 27, BCLC-C: n = 17) underwent surgical resection for HCC at our institution. Surgical complications were assessed using the Clavien-Dindo complication score. Patients with tumor recurrence (n = 50) were treated with repeated liver-resection alone (n = 5), liver transplantation (n = 1), local-ablative procedures (n = 5), transarterial chemoembolization (TACE) (n = 3), sorafinib therapy (n = 10), best supportive care (n = 16) or a combination or multiple treatment modalities (n = 15). The associations of RFS and OS with histo-pathologic characteristics were assessed using univariate and multivariable cox regression analyses.

Results:

Median RFS was 31 months and median OS was 27 months. 62 of 111 patients developed surgical complications, whereas only 13.5% of the patients (15/111) developed Clavien-Dindo > 3b. Macrovascular invasion (p < 0.001), number of tumor nodules (p = 0.003) and red blood cells transfused (p = 0.045) were independently associated with RFS. Tumor recurrence per se did not show an association with OS (p = 0.228). However, patients with HCC-recurrence who underwent repeat-surgical or interventional treatment showed significant improved OS compared to patients treated with palliative or sorafinib treatment alone (OS: 18 months vs. 2 months; p < 0.001).

Conclusion:

Tumor recurrence alone is not associated with poor oncological outcome and repeat liver resections as well as local-ablative procedures are crucial to improve OS in HCC. Large prospective trials are needed to validate our findings.