Treatment Options for Hepatocellular Carcinoma #348

Introduction

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. ¹ This Fast Fact provides an overview of staging and treatment options for generalist and palliative care clinicians who are often asked to navigate complicated decision making in HCC patients.

HCC Staging

Prognosis and Quality of Life

Only 10%–15% of HCC patients have curative options at the time of diagnosis. ² This clinical factor plus the high prevalence of cirrhosis as a comorbidity contributes to a five-year survival rate of only 10%. ³ Barcelona clinic liver cancer (BCLC) staging is an important prognostic factor. Whereas the one-year survival rate is 77%–83% with treatment (33% without treatment) when HCC is localized to the liver, the one-year survival of metastatic disease is only 15%. ³ HCC patients often suffer from pain, jaundice, anorexia, and depression as well as ascites, fatigue, and edema from coexisting cirrhosis. ⁴ This debilitating symptom burden leads to a diminished health-related quality of life (QoL). ⁴

Localized, Arterially Directed Therapy

While normal liver tissue is perfused by the hepatic artery and portal vein, HCC is almost exclusively supplied by the hepatic artery. ⁵ This has led to the development of arterially directed techniques to block hepatic tumor perfusion through the localized delivery of chemotherapy or radiotherapy. These procedures are performed and clinically monitored by specialized interventional radiologists. They are reserved for patients with unresectable HCC who have preserved liver function, an ECOG PS of 0–2, and no evidence of extrahepatic disease. ⁶ Relative contraindications include infection, leukopenia, renal insufficiency, decompensated heart failure, hepatic encephalopathy, and biliary obstruction. The goal of this therapy is to improve QoL, prolong survival, and, in some cases, downstage the tumor in hopes of making the mass surgically resectable.

Commonly Used Localized, Arterially Directed Therapies

Treatment Effect on Symptoms and QoL

Studies have demonstrated survival benefits as well as improvements in patient-reported outcomes, including QoL, pain, function, and emotional well-being with cTACE, DEB-TACE, and Y-90 in patients with BCLC B or C disease.^10–12 Compared with cTACE, Y-90 was associated with less nervousness, less side effects, less hospitalizations, and an improved QoL. ¹² However, Y-90 is more expensive with an approximate cost of $31,000 to $48,000 compared with $17,000 for cTACE. ¹³ In many centers, cTACE is more commonly utilized, but controversy remains regarding the optimal localized, arterially directed therapy.

Treatment Complications

Postembolization syndrome characterized by a resolving, three-day course of pain, nausea, and vomiting can occur with cTACE and DEB-TACE. A short course of IV opioids, corticosteroids, 5HT3 receptor antagonists, and/or ketorolac in a hospital setting has been described as an effective way to manage this syndrome. ¹⁴ In more rare circumstances, chemoembolization can lead to vascular injury, hepatic failure, abscess formation, tumor rupture, ulcer formation, and biliary duct injury. ¹⁵ Y-90 is not associated with postembolization syndrome and severe complications appear to be rarer. As a result, hospitalization is often unnecessary.^6,16

Progression after Localized Therapy

Many with advanced HCC are faced with the complicated decision of whether to pursue systemic targeted therapy, most usually oral sorafenib. Although sorafenib is associated with a significant improvement in median survival (10.7 months vs. 7.9 months with placebo) for patients with BCLC Stage C,^17,18 several trade-offs need to be considered. These trade-offs include a substantial risk for diarrhea, nausea, liver dysfunction, and cytopenia. It is also associated with increased healthcare costs and clinic visits that can be barriers for hospice initiation. Hence, QoL, not just prognostic, concerns need to be elicited before deciding about sorafenib. For HCC patients with life-prolonging goals who progress through sorafenib therapy, the Food and Drug Administration approved the use of nivolumab based on phases 1 and 2 data showing a 18.2% response rate. ¹⁹