The recurrence rate after primary resection for hepatocellular carcinoma (HCC) has been reported to be up to 80%. There is no consensus or guideline about the best treatment option for such recurrent HCC (rHCC). It is therefore of paramount importance to select patients for suitable treatment due to the high risk of associated morbidity and mortality. In this paper, we review the literature on treatment for rHCC and propose a strategy based on the best evidence available. Even in rHCC, it is still possible to achieve cure and good survival rates through careful patient selection. Repeat hepatectomy is recognized as a feasible and safe procedure even in cirrhotic patients and should be considered as the best option with curative intent when the patient is fit enough. Greater adoption of minimally-invasive liver surgery could have the potential to increase the number of candidate patients with rHCC for repeat resection in the next few years. Liver transplantation offers longer disease-free survival compared to repeat resection, curing the underlying cirrhosis, but is not widely available due to organ shortage. When surgery is not feasible, locoregional treatments such as radiofrequency ablation and transarterial chemoembolization have an important role for patients who cannot tolerate repeat hepatectomy and are not suitable for transplantation. For advanced cases, systemic therapy could be considered.
Hepatocellular carcinoma (HCC) is the third most common cause of cancer related death worldwide[
To date, many papers have been published on the treatment algorithm for rHCC but evidence and consensus are still lacking. These studies are mainly from Eastern centers and almost all are retrospective data.
In this paper, we reviewed the literature on treatment for rHCC and propose our personal strategy based on the available evidence.
Liver resection is recognized as the mainstay of treatment in patients with HCC. In both Eastern and Western countries[
According to the BCLC algorithm, patients with a single, very early- or early-stage HCC and preserved liver function should be offered liver resection[
Currently, there are no guidelines or clinical algorithms for the best treatment option in rHCC[
Most case series of rHCC treated with RH are from Eastern Asia. Since none were randomized trials and patients were selected for resection according to different clinical criteria and hospital policies, comparison is difficult. Nagasue
Larger series have since been published in the last 20 years, again mainly from Eastern institutions, with 5-year overall survival (OS) ranging from 30% to 60%[
Several studies have been published in recent years and have established RH as safe in referral centers
Review of the literature on the surgical treatment of recurrent hepatocellular carcinoma
Ref. | Year | No of pts | Mortality (%) | 5-year OS (%) |
---|---|---|---|---|
Zou |
2016 | 635 | 7 | 47 |
Huang |
2012 | 85 | 1 | 22 |
Faber |
2011 | 27 | 0 | 42 |
Roayaie |
2011 | 35 | 0 | 67 |
Kubo |
2008 | 51 | 0 | 48 |
Itamoto |
2007 | 84 | 0 | 50 |
Tralhão |
2007 | 16 | 1 | 31 |
Kobayashi |
2006 | 80 | 0 | 53 |
Sun |
2005 | 57 | 0 | 31 |
Minagawa |
2003 | 67 | 0 | 56 |
Sugimachi |
2001 | 78 | 0 | 48 |
Shimada |
1998 | 41 | NR | 45 (3-y) |
Hu |
1996 | 59 | 0 | 44 (3-y) |
OS: overall survival
The adoption of laparoscopic liver resection (LLR) has increased over the past decade. Laparoscopy for HCC has been shown in studies to produce superior short-term and equivalent long-term outcomes compared to the open approach. However, due to the formation of intra-abdominal adhesions, LLR for rHCC after previous hepatic resection may represent a challenge. For this reason, there are only a few studies reporting a laparoscopic approach to treat liver recurrence. However, this number is believed to rise in the next few years since liver resection will increasingly be approached laparoscopically. A recent meta-analysis showed that LLR for rHCC offered a benefit in terms of lower in-hospital complication rates, blood loss and a shorter hospital stay compared to open resection, although similar 90-day mortality was observed between the two groups[
Many transplant centres recommend LT as salvage for rHCC. Salvage LT (SLT) was proposed as an ideal treatment for patients fulfilling the Milan criteria, treating both the cancer and the underlying cirrhosis at the same time[
The decision to proceed with either strategy is clearly biased by institutional practices and for this reason, any comparison between SLT and RH may not be completely reliable. However, it is our opinion that patients should be listed for LT in case of worsening liver function, or any other case such that a second liver resection will not be tolerated. When feasible, any attempt to rescue these patients without affecting the donor pool should be made[
Radiofrequency ablation (RFA), applicable both via the percutaneous or open approach, is considered a safe procedure and as effective in achieving long-term survival as surgical resection, in selected patients[
A further treatment option for rHCC is trans-arterial chemoembolization (TACE), although it is not applied with curative intent[
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[
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.
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.
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.
Patients with deteriorated liver function can be treated with TACE. Patients planned for LT should also be considered for TACE as bridging.
Patients with decompensated liver function, severe portal hypertension and single or even multiple liver recurrences, but still fulfilling LT criteria, may be referred for SLT.
In the setting of rHCC not amenable to other treatments due to disease that is far too advanced, systemic therapies can be employed in selected cases.
Recurrent HCC may occur after liver resection in up to 80% of cases. A standardized treatment algorithm for rHCC does not exist but surgical resection should be attempted whenever possible, since it may provide favourable long-term outcomes with acceptable perioperative risk comparable to primary resection. In experienced hands, laparoscopic liver resection for both primary and recurrent HCC should be considered. LT should be considered in all cases where surgical resection cannot be performed, especially in the context of underlying cirrhosis, if conventional transplantation criteria are met. The use of RFA or TACE as a bridge to LT, or for palliation represent alternatives for these patients.
Made substantial contributions to conception of the paper, reviewed the literature and drafted the manuscript; equally contributed to the work: Pasini F, Serenari M
Supervised the work, reviewed the manuscript, provided technical support and expert guidance: Cucchetti A, Ercolani G
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All authors declared that there are no conflicts of interest.
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© The Author(s) 2020.