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Page 6 of 10 Sullivan et al. Hepatoma Res 2018;4:68 I http://dx.doi.org/10.20517/2394-5079.2018.95

offer a minimally invasive approach for either ablation or resection that will provide optimal local control
while preserving liver reserve.

Resection vs. TACE
As trans-catheter based techniques developed in managing HCC, the effectiveness of TACE was evaluated
against resection as the standard. To date, one RCT in China has been performed directly comparing the
two treatment modalities in patients with multiple resectable HCC lesions that fell outside of the Milan
criteria. The 3-year OS was significantly higher in the hepatectomy group at 52%, compared to 18% in the
[61]
TACE group . Similar results are reported in several propensity score matched non-randomized clinical
trials, all showing an overall statistically significant improved OS with resection (18%-54% at 5 years)
compared to TACE (12%-34% at 5 years) [62-66] . A recent meta-analysis which included an additional 12 non-
randomized controlled trials also found improved OS, 1-, 3-, and 5-year OS with resection compared to
[66]
TACE with equivalent procedure related mortality . Across all studies, the findings of improved survival
after resection compared to TACE were consistent across BCLC stages studied. Therefore, in patients
with resectable HCC, hepatectomy is superior to TACE, however, there exists a role of catheter-based
approaches in patients with potentially resectable HCC but with limited hepatic reserve.

Ablation vs. TACE
In patients with HCC who are not resection candidates, other treatment options of the loco-regional
disease include ablation or catheter-based approaches. While no RCT has been performed comparing
the two, they have been compared using propensity-score matching analysis in retrospective studies.
A retrospective study from Taiwan found that in patients within the Milan criteria (single tumor less
than 5 cm, or 3 or fewer nodules less than 3 cm) with performance status of 0, OS was significantly
better in the RFA group compared to the TACE with drug eluting beads group (77% vs. 62% at 3 years,
[67]
respectively) . In patients with worse performance status (≥ 1), survival difference was no longer evident.
In other retrospective studies from China and Japan, RFA improved survival of BCLC 0/A patients
compared with patients who were also BCLC 0/A but instead received TACE, but this difference was
attributable to differences in co-morbidities between the two groups [68,69] . One of these studies did find
that the cumulative recurrence rate was higher following TACE. Currently when HCC is unresectable but
ablatable, thermal ablation remains the treatment of choice in BCLC 0/A patients. Otherwise, TACE is a
viable alternative in providing a survival benefit over supportive care.

Radiation therapy vs. other loco-regional treatments
Radiation therapy has grown in popularity for its potential uses in loco-regional management of HCC.
Few retrospective studies have evaluated radiation vs. ablation; a propensity matched analysis based
on SEER database (2004-2012) found that ablation was associated with improved survival compared to
EBRT in patients with tumors greater than 3 cm, while EBRT and ablation were equivalent in patients
[70]
with tumors less than 3 cm . A separate retrospective study of SBRT vs. RFA also showed no significant
[71]
difference in survival between SBRT and RFA, nor time to progression for tumors less than 2 cm .
However, for larger tumors, it reported the opposite findings with improved time to local progression in
the SBRT group vs. the RFA group. One RCT has been performed comparing proton therapy to TACE
therapy for HCC meeting transplant criteria. Results of an interim analysis demonstrated no difference
in OS at 2 years, but there is a trend towards improved progression-free survival and local tumor control
[72]
favoring the proton radiation therapy group . Further prospective evidence is needed in order to draw
conclusions about the effectiveness of radiation therapy, but the data thus far indicates it will play a major
role in the management of HCC.

SELECTION OF TREATMENT MODALITY
With the expansion of options that are currently employed in loco-regional management of HCC, clinicians
are faced with the challenge of selecting the most appropriate treatment for individual patients. In the era of