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Pasini et al. Hepatoma Res 2020;6:26 I http://dx.doi.org/10.20517/2394-5079.2019.47 Page 5 of 9

In particular, RFA is proposed for small primary HCC up to 3 cm in diameter [54,55] . However, some authors
have also proposed RFA for rHCC because of its low morbidity compared to surgical treatments, negligible
[56]
blood loss and sparing of adjacent normal liver parenchyma . Furthermore, in patients not amenable to
surgical resection due to liver dysfunction, multifocal nodules, tumour location or postsurgical adhesions,
[57]
RFA represents a potentially curative alternative. In a recent metanalysis, Gavriilidis et al. demonstrated
similar 5-year OS and DFS between RFA and RH in treating rHCC although a significant difference in
morbidity was reported (2% for RFA vs. 17% for RH). However, a systematic review of 18 previous studies
[58]
published by Thomasset et al. concluded that RFA for rHCC had a very low rate of complications but
was still less efficacious than RH and thus, should be offered only to patients who cannot tolerate surgical
resection.

A further treatment option for rHCC is trans-arterial chemoembolization (TACE), although it is not
applied with curative intent [26,59] . A median survival of 30 months and a 3-year survival of 29% has been
reported in the treatment of primary HCC with TACE [60,61] ; outcomes reported for rHCC are arguably
[26]
poorer . This interventional radiology procedure should be offered to patients who are not candidates for
surgical resection, SLT or RFA. Although a recent study reported TACE to be superior to RH and RFA in
[63]
[62]
cases of microvascular involvement , the majority of the literature consider TACE to be palliative so it
is widely used as a treatment for tumours with greater sizes or number of nodules which cannot be treated
[64]
with RH or RFA. A review from Erridge et al. reported a 5 year survival of 15.5% in patients with rHCC
treated with TACE.
Systemic therapies
When recurrence presents beyond the limits of transplantation criteria and is not amenable to locoregional
treatment, survival rates are dismal but systemic therapies can still be considered in selected cases. Effective
systemic treatment for HCC have been available only in recent years - since sorafenib was introduced, it
has become the standard of treatment for advanced HCC [4,65] . Several compounds have since been tested
in this setting but few have proven to be effective: regorafenib was approved as a second-line treatment for
[66]
patients with HCC disease progression on sorafenib and levatinib recently showed non-inferiority as
[67]
first-line therapy . Since good cardiovascular status and preserved liver function are both necessary for
chemotherapy to be tolerated, most reports are on the use of sorafenib in patients with rHCC after LT ,
[67]
[68]
given the poor results obtained in the adjuvant setting after resection . On the contrary, when no clinical
benefit is expected from chemotherapy, the management of end-stage rHCC is symptomatic and only
[68]
supportive care should be offered .

SUMMARY
Herein, we propose our recommendations for selecting the best candidate, and limiting the risk of re-
recurrence in cases of rHCC, based on the above literature review, available guidelines on primary HCC
and our personal experiences.

RH
Patients presenting with a single rHCC should undergo repeat resection whenever possible. Candidates
for RH are required to have preserved liver function and no or limited signs of portal hypertension. The
laparoscopic approach should be considered for RH in rHCC when the requisite expertise is available.

RFA
Patients with preserved liver function and a single rHCC ≤ 3 cm can be considered for RFA. RFA should be
preferred over RH, especially in cases of patients with high surgical risk.