Pierre M. Gholam, MD
The elderly constitute an important population of patients with unresectable hepatocellular carcinoma (HCC). In a recent retrospective single-center study, patients with advanced HCC received systemic therapy with sorafenib combined with transarterial chemoembolization (TACE), and outcomes were compared between elderly (≥70 years) and nonelderly (<70 years) patients.1
These investigators found a similar benefit of the intervention, with similar tolerability, in the both subgroups among a population treated at The First Affiliated Hospital of Nanjing Medical University in China (Table)
spoke with Pierre M. Gholam, MD, about managing elderly patients with advanced HCC, including current practices and emerging strategies. Gholam is the medical director at the Liver Center of Excellence and Digestive Health Institute at University Hospitals Case Medical Center, and associate professor of medicine at the Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine.Q: Why is the management of unresectable HCC, particularly in elderly patients, becoming an increasingly important issue?
The three options that we know can cure HCC are resection for cure, or R0 resection, liver transplantation, in patients who have limited disease—usually patients who meet the Milan criteria—and radiofrequency ablation, for solitary lesions less than 2 cm. For everyone else who does not undergo one of those three [options], the goals are to improve survival and quality of life.
About 80% of patients in most Western populations have what we would describe as unresectable HCC, so the bulk of patients who come into care are not amenable to definitive therapies, including resection or liver transplantation. However, these patients still need treatment options that can help them have better quality and quantity of life.
The mean age of diagnosis for HCC, across the board, in studies that are typically conducted in the West, is somewhere between 60 and 65 years—so to begin with, the average age of a person with HCC is usually in the 60s by the time they are diagnosed. Based on our own database, easily about 30% of patients are over the age of 70 years, so a large number of those patients would be considered elderly by any definition.
In addition, patients usually take a while to develop HCC. If you take a patient with cirrhosis, their average risk of developing HCC if they have hepatitis C, which is the most common cause of cirrhosis in the United States, would be 3% to 5% per year. Therefore, it would take them more than a decade to have a substantial cumulative risk of developing HCC. This is a process that takes time, beyond the initial time it takes patients to develop cirrhosis, which typically is anywhere between three to four decades.
It’s therefore not surprising that patients develop HCC later in life. Another reason is the fact that we now have better tools and medications to make patients with cirrhosis live longer, and as they live longer, they have a greater statistical chance of developing HCC over time, because of this ongoing risk factor.Q: What are the principal palliative options for elderly patients with unresectable HCC?
For patients who have small lesions (<3 cm, and in most cases <2 cm), and a limited number of lesions, radiofrequency ablation is not an unreasonable option. I should also say that radiofrequency ablation was the dominant modality up until the past 5 to 10 years, and is now being challenged by other tumor destruction modalities that achieve the same goal, but are not actually “heat” applications. These include cryotherapy, which is performed in some centers, but mainly microwave coagulation therapy, which has become fairly common among our own interventional radiologists. I would call these direct tumor destruction therapies by application of heat, cold, or microwave energy. So this would be one option, for small lesions that are limited in number.
For lesions that are bigger, typically >3 cm, or if you have more than one of these, and the patient is not otherwise a candidate for liver transplantation, the dominant treatment modality is in the form of catheter-mediated interventions. These come in two [main types]: transarterial chemoembolization, where chemotherapy is injected into the tumor followed by an embolic process; or the administration of radiotherapy to tumors in a similar manner, through the application of Yttrium-90– loaded glass beads that can also be injected into tumors to achieve a very potent, but localized irradiation effect in the tumor.