Hepatocellular carcinoma (HCC) is a complication of liver disease that accounts for most cases of primary liver cancer. Hepatocellular carcinoma affects an estimated 30,000 adults in the United States each year, with a greater prevalence in men than women.1 Although most cases of HCC in the United States are associated with hepatitis C virus (HCV), other patients with HCC have hepatitis B virus (10% to 15%), both viruses (<5%), or neither virus (30% to 35%).2,3

Hepatocellular carcinoma primarily affects older adults, typically people with cirrhosis.1 In patients with HCV, the risk for HCC increases more than 15-fold after the age of 65 years.1 The incidence of HCC is increasing along with the growing population of HCV-infected baby boomers who are living into advanced age. According to data from the Surveillance, Epidemiology, and End Results (SEER) registries, there was a 3-fold increase in HCC incidence from 1975 to 2007 in both men and women.3

The 5-year survival rate in patients with HCC is less than 12% in the United States, where approximately 21,000 deaths occur annually as a result of this disease.1,3 Despite the recent availability of curative treatment for HCV, many people do not receive timely or adequate treatment — or any treatment — and the risk for HCC persists for more than 10 years after viral cure.2 These findings underscore the need for a range of treatment approaches to care for patients with HCC throughout the various stages of illness.

Current options include “surgical resection, liver transplant, interventional radiology procedures (embolization), chemotherapy, and immunotherapy, in addition to the management of the underlying chronic liver disease,” according to a 2018 review by Christopher D. Woodrell, MD, Brookdale department of geriatrics and palliative medicine, Icahn School of Medicine at Mount Sinai, New York, New York,  and colleagues published in Clinical Therapeutics.1

“Older adults often face multimorbidity, requiring many medical visits; thus the uniquely complex treatment scheme of HCC for this population is potentially quite burdensome, when added on top of the numerous other visits needed to treat their other medical illnesses,” according to Woodrell, et al.

A great deal of uncertainty exists for patients and loved ones regarding prognosis and treatment of HCC because of the complex and unpredictable course of the disease, including with regard to transplant eligibility.

The Role of Palliative Care in HCC

In addition to the central involvement of hepatologists and other specialists in the management of patients with HCC, the review authors explained that early and consistent palliative support could enhance their care throughout the disease course.1 They described the potential benefits of such services in HCC, especially in older adult patients. Although there is a dearth of research regarding palliative care in HCC specifically, various studies have demonstrated the benefits of palliative care interventions in reducing patient and family distress, as well as healthcare utilization and cost, including a 2010 study showing improved quality of life, better symptom control, longer survival, and less aggressive end-of-life care in patients with advanced lung cancer.1

“Palliative care clinicians are uniquely suited to help patients navigate the process of treatment decisions while considering how to best define and maintain quality of life while living with a serious illness like HCC,” wrote Woodrell and colleagues.1 “The focus of palliative care is on quality of life, through the management of symptoms, discussion of treatment preferences, provision of psychosocial support, including religion and spirituality, and coordination of care.”

They provided an algorithm to help guide the integration of palliative care at each stage of HCC treatment, according to the Barcelona Clinic Liver Cancer (BCLC) staging system.1 For example, patients with BCLC stage 0 or stage A HCC may be eligible for curative treatments including liver transplant, and thus could benefit from support in advance care planning and decision making regarding treatment options.

A significant number of patients listed for liver transplant become ineligible while waiting, as reflected by studies showing 1-year waitlist dropout rates of approximately 18% in patients with HCC.1

“These data suggest that the event of waitlist removal may mean patients have a greater need for palliative care, both for their disease severity and resulting symptom burden, and for support during a time of uncertainty and distress over their inability to receive curative therapies,” stated the review authors. “Removal from the transplant waiting list may therefore be an important point in the HCC trajectory for treating physicians to refer their patients to palliative care as an added layer of support.”

In later stages of HCC, the emphasis of palliative care may shift to care coordination among the growing number of specialists who become involved in HCC treatment as the illness progresses and to management of the worsening symptom burden and complications of the disease. A focus on supportive care and help with hospice referral may become the main aspects of palliative care in the latest stages of HCC (BCLC stages C and D).

Among other aspects of care throughout the disease course, pain “management is an area where palliative care can complement the management of HCC specialists because of the complexity of dosing analgesics for patients with hepatic impairment (most [patients with HCC]), prevalent history of substance use among patients with chronic liver disease, and the opioid addiction epidemic in the US,” Woodrell and colleagues noted.1

Challenges and Next Steps

They described 2 major challenges to the integration of palliative and medical care in HCC: the relative shortage of palliative care providers and resources in the United States and misperceptions among physicians that “may impact when and how often [patients with HCC] are referred to palliative care as a complement to disease-directed therapy.”1

For example, according to a 2014 survey of 74 medical oncologists at US academic cancer centers with well-established palliative care clinics, a substantial number of respondents believe that palliative care was incompatible with cancer-directed treatment and many were generally unclear about the role of this approach.4

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“We propose that integrating palliative care into the multidisciplinary approach to care may be [the] most feasible and effective model…. [which] may be accomplished through both provision of specialty level palliative care, particularly at specific points in the disease course, and by incorporating specific elements of palliative care into routine HCC care,” the review authors concluded.1

There is a need for research focused on palliative care interventions for patients with HCC at all stages of illness, with “outcomes that include quality of life measures and design that incorporates patient and family voice,” they summarized.

References

1. Woodrell CD, Hansen L, Schiano TD, Goldstein NE. Palliative care for people with hepatocellular carcinoma, and specific benefits for older adults. Clin Ther. 2018;40(4):512–525.

2. Baumert TF, Jühling F, Ono A, Hoshida Y. Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals. BMC Med. 2017;15(1):52.

3. Mittal S, El-Serag HB. Epidemiology of hepatocellular carcinoma: consider the population. J Clin Gastroenterol. 2013; 47(suppl):S2-S6.

4. Schenker Y, Crowley-Matoka M, Dohan D, et al. Oncologist factors that influence referrals to subspecialty palliative care clinics. Oncol Pract. 2014;10(2):e37-e44.