LAVA: Liver resection surgery versus thermal Ablation for colorectal liVer metAstases.

Bowel cancer is the UK*s second biggest cancer killer. About 30% of people with
colorectal cancer develop liver metastases. Liver resection is effective in
improving the life expectancy in people with colorectal liver metastases (CLM).
However, only about 7% to 20% of people with colorectal liver metastases
undergo liver resections because of age or comorbidities of the patient or
because of the extent of cancer spread. Increasing the number of patients who
can undergo potentially curative therapy for liver alone metastases is a main
NHS goal for improving the outcome for bowel cancer patients in the UK. In
light of this, specialist liver resection centres are carrying out more
extensive and complex resections including elderly patients with major
co-morbidity. This more extensive surgery in patients with co-morbidity is
associated with an increased morbidity and mortality (high risk patients).
Thermal ablation is a lower risk alternative modality for treatment of CLM and
involves destruction of cancer by heat. Thermal ablation includes established
modalities such as radiofrequency ablation (RFA) or microwave ablation (MWA).
Thermal ablation may be associated with a lower chance of cure. A systematic
review of ablative methods in patients with CLM concluded that there is a
group of patients in whom the risk and benefits of surgical resection are less
evident and that good quality evidence is required for the clinical outcome and
cost effectiveness of thermal ablation in comparison to surgery in these high
risk patients.
Thermal ablation is currently used for patients with colorectal liver
metastases not suitable for surgical resection and not for patients with a
possibility of curative liver resection surgery because of high local
recurrence rates with thermal ablation. Multiple studies have highlighted the
superiority of surgery to ablation for preventing recurrence within the liver.
A recent series from Nishiwada et al showed a 13% recurrence after surgery as
opposed to 46% after thermal ablation. Other newer modalities of thermal
ablation include laser ablation and high intensity focused ultrasound (HIFU).
To determine the evidence for thermal ablation, a NIHR (National Institute for
Health Research) HTA (Health Technology Assessment) funded systematic review of
literature was commissioned and subsequently published in February 2014
(Loveman et al). We have reviewed this information along with subsequently
published literature. There are no adequately powered trials comparing surgery
with ablation therapy in patients with colorectal liver metastases. The
systematic review identified one non-randomised study in which the survival in
patients with radiofrequency ablation (RFA) was similar to liver resection
surgery despite the RFA group having more comorbidities or more extensive liver
metastases. An exploratory cost-effectiveness analysis performed by the group
on the basis of this non-randomised study showed that radiofrequency ablation
has the potential to be cheaper and might result in better health-related
quality of life. Another non-randomised study published since this systematic
review has also shown that patients undergoing RFA have survival comparable to
surgery despite having more extensive liver metastases. Similarly, an
underpowered randomised controlled trial showed no difference in survival
between MWA and liver surgery in resectable CLM. However, in another
non-randomised study published after the systematic review by Loveman et al,
people who were eligible for surgery but preferred RFA had poorer survival than
those undergoing surgery.

The aim of this research is to compare the effectiveness and cost-effectiveness
of thermal ablation versus liver resection surgery in high surgical risk
patients eligible for liver resection.

A prospective, UK and Netherlands multi-site, parallel-group, randomised trial
with an internal pilot investigating the effectiveness and cost-effectiveness
of liver resection surgery versus thermal ablation in high surgical risk
patients eligible for liver resection. High surgical risk patients are defined
as those with a high risk of post operative morbidity, mortality and reduced
long term survival due to the age of the patient, their history of concurrent
medical problems (co-morbidity), or the need for extensive liver resection
surgery of a poor prognosis cancer.

Liver resection will be carried out within regional centres according to
individual centre protocol. The majority of patients will have undergone
resection of the primary cancer. Patients may be offered open or laparoscopic
liver resection depending on site and stage of disease. In selected cases, the
liver first approach may be considered.
For thermal ablation, RFA or MWA will be used according to local availability
and expertise. Ablation maybe performed at laparoscopic or open surgery if the
percutaneous approach is contra-indicated.

Current evidence suggests that thermal ablation has lower complication rates
and better health-related quality of life than surgery. Thermal ablation is
also less expensive than liver resection, which will result in cost savings to
NHS. Ablation therapy has the potential to decrease the pain after treatment
and time taken for recovery from cancer therapy which will decrease the number
of work days lost by the patient and their carer resulting in a financial
impact on patients, their carers, and their employers.
The major concern about thermal ablation is the high incidence of local
recurrence. As a result it would be anticipated that it will not offer similar
cancer related outcomes as liver resection surgery. However in patients who are
high risk but would currently be considered for liver resection the short and
long term outcomes after surgery are likely to be poorer than the normal
surgical cohort and hence thermal ablation for this group may produce
comparable results.