2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

less informative than the GRETCH and CLIP classifications.
11 Clinicians should become familiar with some of
these staging systems, their limitations, and controversies
in the assessment of HCC. Although genomic analysis and
molecular markers have been used to identify possible
sub-classification of HCC, these findings would require additional
validation and have not been incorporated in clinical
staging.
Management of Early-Stage HCC
Despite some variation of practice patterns worldwide, it
is clear that early-stage HCC can be cured by several
treatment options including surgical resection, liver transplantation,
and ablative therapies (Table 1).
The aim of surgical resection is to remove the entire portal
territory of the neoplastic segment(s) with a clear margin,
while preserving maximum liver parenchyma to avoid hepatic
failure. Because of the presence of extrahepatic disease,
severe underlying cirrhosis, anatomic location of
tumor, and vascular invasion, less than 20% of patients with
HCC are suitable for surgical resection. Resection and
transplantation achieve the best outcomes in well-selected
candidates (5-year survival of 60% to 80%) and compete as
the first option in patients with early tumors on an
intention-to-treat perspective. Hepatic resection is the treatment
of choice for HCC in noncirrhotic patients, 12 where
major resections can be performed with low rates of lifethreatening
complications and acceptable outcome (5-year
survival: 30% to 50%).
Orthotopic liver transplantation is considered to be the
first-line treatment option for patients with single tumors
less than 5 cm or 3 nodules or less with each measuring 3 cm
or less (Milan criteria) and advanced liver dysfunction not
suitable for resection. In a landmark study by Mazzaferro
KEY POINTS
● Management of hepatocellular carcinoma (HCC) requires
a multidisciplinary approach with careful
evaluation of the extent of the tumor, the presence
and severity of underlying cirrhosis, and performance
status before a treatment decision can be made.
● Surgical resection, liver transplantation, and radiofrequency
represent curative treatment options for
HCC. There is no established role of adjuvant therapy.
● Transarterial chemoembolization and other localregional
therapies including drug-eluting beads, radioembolizaton,
and radiation are evolving treatment
options for unresectable HCC. The role of sorafenib,
when given in combination with these treatments, is
under investigation.
● Sorafenib remains the only agent approved for advanced
HCC. Careful selection of patients and timely
management of side effects are important to optimize
the efficacy of sorafenib.
● Molecularly targeted agents are under active development
and hold promise to improve the outcomes in
patients with HCC.
276
Table 1. Management of Hepatocellular Carcinoma
Early stage:
● Surgical resection
● Transplantation
● RFA, PEI
Intermediate stage:
● TACE
● drug-eluting beads
● radioembolization
● radiation
Advanced stage:
● Sorafenib
● Clinical trials
● Best supportive care
Abbreviations: RFA, radiofrequency ablation; PEI, percutaneous ethanol injection;
TACE, transarterial chemoembolization.
and colleges, patients with HCC who meet the Milan criteria
have an expected 4-year overall survival rate of 85% and a
recurrence-free survival rate of 92%. 13 Therefore, Milan
criteria have been adopted by the United Network for Organ
Sharing (UNOS) and widely around the world. Efforts have
been made to expand the transplant criteria, for example,
the University of San Francisco criteria (solitary HCC measuring
up to 6.5 cm in diameter or up to three lesions, each
measuring no more than 4.5 cm in diameter, with a total
combined measurement of less than 8 cm) has been proposed
and used in select centers. 14
For patients with small HCCs who are poor surgical
candidates because of impaired liver function or serious
comorbid medical conditions, local ablative therapy represents
another attractive treatment option. RFA has become
the most commonly used local ablation therapy, as recent
randomized trials have shown RFA to be more effective than
percutaneous ethanol injection (PEI) in treating patients
with small HCC (2–3 cm in diameter), with lower rates of
local recurrence and higher rates of overall and disease-free
survival. 15 In addition, a randomized controlled trial has
compared RFA with surgical resection and shown no significant
differences in overall or recurrence-free survival, with
lower rates of complications and hospitalization associated
with RFA. 16
An ongoing study is assessing the benefits of sorafenib
in the adjuvant setting following surgical resection and
RFA. Various bridging therapies including RFA and TACE
are continuing to be used while patients are waiting for
transplant, although the definitive benefits remain to be
defined (p � 0.05).
Management of Intermediate-Stage HCC
ANDREW X. ZHU
For patients with intermediate-stage disease with multifocal
lesions and without vascular invasion, TACE has
been the default treatment option (Table 1). TACE takes
advantage of the fact that HCCs derive their blood supply
almost entirely from the hepatic artery. The experience
with TACE has been mixed, leaving many unanswered
questions and controversies. Although several studies
have shown negative survival benefits, two studies have
demonstrated improved OS compared with best supportive
care (BSC) alone in highly selective patient populations.
In a randomized controlled trial, Llovet and colleagues
demonstrated that patients (more than 80% with underlying
HCV-related cirrhosis) who received doxorubicin-based