By: James Pitt  Nov. 21, 2018
Hepatocellular carcinoma (HCC) is the most common liver cancer.
The prognosis is notoriously poor.
Chronic liver injuries that cause cirrhosis are associated with HCC.
Why is HCC incidence and mortality increasing in the US? Metabolic syndrome may be part of the picture. Diabetes, obesity, and both alcoholic and non-alcoholic fatty liver disease are associated with HCC.
The opioid epidemic may also be increasing HCC rates. The Department of Health and Human Services also attributes rising liver cancer rates to rising hepatitis virus rates, which it attributes in turn to injection drug use in the opioid epidemic. The US as a whole has low hepatitis rates by international standards, but this does not hold for every community. Appalachia in particular has seen growth in hepatitis virus in recent years. Acute hepatitis C infections increased 364% from 2006 to 2012 in Kentucky, Tennessee, Virginia, and West Virginia; acute hepatitis B infections increased 114% in Kentucky, Tennessee, and West Virginia.
The AASLD 2018 practice guidance uses the Barcelona (BCLC) staging system and GRADE levels of evidence.
Stage 0
Single nodule smaller than 2 cm
Child-Pugh class A
ECOG PS 0 or 1
Stage 0 Treatment options:
Preferred treatment: resection
Alternate: radiofrequency ablation, microwave ablation
Stage A
One to three nodules smaller than 3 cm
Child-Pugh class A or B
ECOG PS 0 or 1
Stage A Treatment options:
Resection
Liver transplant (if patient meets Milan criteria of single tumor ≤5 cm in diameter or no more than three tumors ≤3 cm in diameter)Ablation
Transarterial chemoembolization
Transarterial radioembolization (also known as microbrachytherapy or selective internal radiation therapy)
Stereotactic body radiation therapy
Stage B
Multinodular
Child-Pugh class A or B
ECOG PS 0 or 1
Stage B treatment options
Preferred: transarterial chemoembolization
Alternate:
Transarterial radioembolization
Apply locoregional therapy until patient meets Milan criteria, then liver transplant (“downstaging” or “downsizing”; see Bryce and Tsochatzis 2017)
Stage C
Portal vein invasion, nodal metastasis, or extrahepatic metastasis
Child-Pugh class A or B
ECOG PS 0-2
Stage C treatment options
Sorafenib or lenvatinib as 1st-line drug.
Nivolumab, regorafenib, or cabozantinib as 2nd-line drug.
Alternate: Transarterial radioembolization
Stage D
Child-Pugh class C
ECOG PS 3-4
Stage D treatment options
Liver transplant
Supportive case
Sorafenib is the first-line chemotherapy for patients with nonresectable HCC. It has remained so since its approval in 2007. However, lenvatinib showed noninferiority in a phase 3 trial, and is approved for first-line use as of August 2018.
The AASLD recommends regorafenib and nivolumab as second-line options. A phase 3 clinical trial of nivolumab as first-line treatment was delayed due to too few patient deaths, and is now expected to conclude in July 2020. Clinical trials of combination therapies as first line treatment are in Phase 1 for regorafenib (NCT03347292) and Phase 2 for nivolumab (NCT03439891, NCT03695250, NCT03071094).
As hepatocellular carcinoma primarily strikes patients in their 60s, Medicare data is a particularly good source for insights into it. Dexur's databases include information on incidence, quality outcomes, and procedure volume for this population.