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Sullivan et al. Hepatoma Res 2018;4:68 I http://dx.doi.org/10.20517/2394-5079.2018.95 Page 7 of 10

Table 1. Compilation and comparison of reported data from prospective clinical studies
†
Treatment modality Local control Overall survival at 1 year Rate of adverse events (grade ≥ 3 )
Open surgical resection [57-61,78] 96%-99% 93%-98% 16%-55%
Percutaneous or laparoscopic ablation *[26,30,57-60,78] 87%-96% 87%-98% 4%-9%
TACE or TARE **[36-38,61,72] 45%-68% 40%-77% 7%-54%
External radiation ***[47,48,72] 78%-96% 58%-94% 0-39%
† * **
Based on the Clavien-Dindo classification system; predominately radiofrequency ablation rather than MWA; these studies use largely non-
***
selective techniques (e.g., lobar treatment); both photon and proton radiotherapy included. TACE: transarterial chemoembolization; TARE:
transarterial radioembolization; MWA: microwave ablation
personalized medicine, the spectrum of minimally invasive liver-directed therapies outlined above allows
for a greater number of patients to potentially benefit from these survival-prolonging treatments. Advances
in precise tumor targeting have led to better preservation of hepatic function in patients with underlying
liver disease; this is particularly relevant to those who are not transplant candidates. Based on current
evidence, the rates of local tumor control following hepatic resection, thermal ablation, and external beam
radiation therapy are approaching parity for small HCCs, but there has not been any direct comparison
across all modalities to account for confounders, and long-term results are lacking for the newer techniques
[Table 1]. Excluding transplantation, which benefits a small fraction of patients, surgical resection offers the
best chance of cure while the results of thermal ablation for HCC ≤ 3 cm is on par with that of hepatectomy.
At present, both modalities are considered curative with the major difference between the two being the
severity of treatment-related morbidity, but through the use of laparoscopic or robotic liver resection, the gap
has been minimized. The choice between resection and ablation for small HCCs comes down to provider’s
preference based on tumor location, liver reserve and co-morbidities. For those who are at higher risk for
general anesthesia, radiation, either internal (Y90) or external (SBRT), offers excellent local control. While
these options are considered palliative in the past, current evidence using selective Y90 segmentectomy and
SBRT/proton radiation yield approximately 90% local control at 2 years. Currently, there are only a handful
of studies using radiation segmentectomy reporting such high rates of success, but if confirmed in larger
long-term studies, radiation may carry similar efficacy as ablation or resection. Results from on-going trials
will better define the role of these modalities, but if they live up to their expectations, clinicians will have
the luxury to offer a variety of minimally invasive treatment options that best suit the patient and his/her
clinical scenario including factors related to the tumor, liver reserve, performance status, as well as cost
and social circumstances. The large socioeconomic impact of new therapies has led to financial toxicity for
many patients diagnosed with cancer, which can limit access and treatment adherence leading to adverse
[73]
outcome . Greater emphasis on fiscally responsible care is particularly relevant to HCC management
given the wide disparity in the cost of surgery, ablation, radiation and systemic therapies. Based on Markov
modelling, it has been suggested that RFA is more cost-effective than SBRT as the initial management of
[74]
unresectable HCC, however, for recurrent disease, SBRT was favored over repeat RFA . Another study
demonstrated that the addition of TACE to sorafenib or non-sorafenib chemotherapy is more cost effective
[75]
than systemic therapy alone . As the financial burden rises, some resources may become limiting, and
physicians and their patients will need to have open discussions regarding the wise utilization of available
options that meet their personal goals.

In summary, loco-regional treatments of HCC are improving across all disciplines. Current and future
directions include the investigation of combination strategies. For example, a number of trials have
examined the addition of radiation therapy to TACE, which was shown to have improved OS and
progression free survival in patients with macroscopic vascular invasion compared to sorafenib .
[76]
Combination TACE plus radiation therapy also showed improved rate of complete response and DFS
[77]
compared to TACE alone . Further, the combined use of minimally invasive loco-regional therapies and
systemic drugs such as kinase inhibitors and immunotherapies is also being examined with the hope of
improving the chance of cancer-free survival while preserving quality of living.