Clinical Edge Journal Scan Commentary: HCC September 2021

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.

Patients with hepatocellular carcinoma (HCC) that has not spread outside the liver have several treatment options available. This month we will review articles that analyze outcomes after liver transplantation, liver resection, as well as radiofrequency ablation.

In HCC patients within the Milan criteria, the 5-year overall survival rate after transplant is about 70%, and the 5-year HCC recurrence rate is about 10%. Patients with tumors beyond the Milan criteria are frequently down staged with locoregional therapies to fall within the Milan criteria. The incidence of HCC recurrence in these patients is around 15.5% at 5 years. In this study, Lee et al demonstrated that statin use substantially reduced the risk of HCC recurrence. In this retrospective analysis of a longitudinal cohort of 430 patients transplanted between September 1995 and December 2019, 323 patients (75.1%) were statin non-users and 107 (24.9%) were statin  users. Statin use was defined as at least 90 days of statin therapy, prescribed according to the treatment guidelines for dyslipidemia for primary or secondary prevention of CVD.   At a median follow-up of 64.9 months, HCC recurred in 79 patients (18.4%), including 72 (22.3%) in the statin non-user group and 7 (6.5%) in the statin user group. Of those, 61 (77.2%) patients had HCC recurrence that initially presented at extrahepatic site regardless of the presence of intrahepatic tumors.  Sixty-three patients (79.7%) had recurrence within 2 years of liver transplantation. The cumulative incidence of HCC recurrence at 2 and 5 years was 18.9% and 22.3% in the statin non-user group, and 3.8% and 5.7% in the statin user group, respectively (P < 0.001).

Liang et al evaluated the importance of tumor size in predicting the likelihood of HCC recurrence following surgical resection. In this retrospective study, a total of 813 cirrhotic patients who underwent curative-intent hepatectomy for solitary HCC without macrovascular invasion between 2001 and 2014 were evaluated. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival.

Finally, Sulaiman et al reported the survival rate of the early and intermediate stage HCC patients who underwent radiofrequency ablation (RFA). In this retrospective analysis, patients with BCLC A and B HCC who underwent RFA treatments between January 2015 to December 2017 were evaluated. Out of 62 patients 46 (74.2%) were reported to have RFA as their only first line of treatment, while 12 (25.8%) were reported to have a combination of RFA and other therapeutic modalities. At a mean follow up of 27 months, the survival rate at 12 and 36 months in patients who received RFA was 82.3% and 57.8%, respectively. A relatively high 36-month survival rate was seen in patients who had a response to RFA compared to the non-response group (100% vs 44.8%, P = 0.021). In terms of prognosis, BCLC staging of liver cancer and response after RFA were significantly associated with survival.