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Colorectal Cancer
More recent experience has demonstrated that patients outside the The largest study reported so far
20
was a consecutive series of 1,439
above traditionally accepted factors can experience long-term survival patients with CRLM managed over an 11-year period. Of these patients,
following liver resection.
15-16
Thus, a shift has occurred in the criteria 1,104 (77%) were initially considered unresectable and were treated with
used for assessing resectability, from morphological criteria to new chemotherapy, mainly in the form of 5-FU and folinic acid combined with
criteria based on whether a macroscopically and microscopically oxaliplatin (70%), irinotecan (7%) or both (4%). Of these 1,104 patients
complete (R0) resection of the liver can be achieved. Instead of with unresectable CRLM, 138 (12.5%) had a good response to
resectability being defined by what is removed, resectability should chemotherapy, enabling potentially curative liver surgery to be performed
now be determined by what will remain. in 93% of these cases. Survival was 33 and 23% at five and 10 years,
respectively, with a median survival of 39 months, although this was
Specifically, CRLM should be determined as resectable if: significantly lower than that of patients resected primarily within the
same period at the same institution (48 and 30% at five and 10 years,
• the disease can be completely resected; respectively). These data suggest that the ability to achieve secondary
liver resection of initially inoperable CRLM is directly proportional to the
• two adjacent liver segments can be spared with adequate vascular degree of response to the chemotherapy regimen.
24
inflow and outflow and biliary drainage; and
Phase II and III studies evaluating novel biological agents, such as the
• the volume of the liver remaining after resection, i.e. the future monoclonal antibodies directed against vascular endothelial growth
liver remnant (FLR), will be adequate.
11
Clearly, the FLR limit for safe factor (bevacizumab) and epidermal growth factor receptor (cetuximab
resection varies from patient to patient, but in those with an and panetumumab), suggest even greater response rates (and possibly
otherwise normal liver the safe FLR volume is 20%.
17
higher secondary CRLM resection rates) compared with conventional
chemotherapy alone. Therefore, even more patients with initially
These new standards clearly challenge the ‘1cm rule’, which required unresectable CRLM may respond to treatment with combinations of
that liver resection be attempted only if a margin of at least 1cm systemic treatments in the future.
25
could be achieved. In fact, various studies show that the width of the
surgical margin has no effect on survival, as long as the margin is What Role for Ablative Therapies?
microscopically clear.
18,19
Much of the current interest in radiofrequency ablation (RFA) derives from
its low morbidity and mortality.
26
A recent meta-analysis of 95 published
series reported a complication rate of 8.9%,
27
with the most common
Ablative therapies are often used
complications being intra-abdominal bleeding, sepsis and biliary tree injury.
for the treatment of metastases
Mortality rates range from 0 to 0.5%. An apparent disadvantage of RFA is
a high rate of local recurrence, ranging from 1.8 to 12%, with a surgical
that are often too close to major
approach to as high as 40% with percutaneous placement. Undoubtedly,
vascular structures to be considered this relates to the types of lesions being treated by RFA. Ablative therapies
resectable with a clear margin.
are often used for the treatment of metastases that are often too close to
major vascular structures to be considered resectable with a clear margin.
Just as a surgical margin would be likely to be compromised, blood flow
New Surgical Strategies to Improve Resectability will conduct away heat, leading to incomplete ablation and recurrence.
2
In conjunction with neoadjuvant therapy, new surgical strategies have
been increasingly employed in patients with unresectable CRLM to The efficacy of RFA in unresectable CRLM has been established by several
improve resectability. Portal vein embolisation induces atrophy of the large cohort studies, with median survivals of 28.9–36 months being
liver to be resected and hypertrophy of the liver that will remain (i.e. achieved.
26
There are currently no prospective randomised, controlled
increases the FLR). Similarly, two-stage hepatectomies involve delayed trials to show an advantage for RFA over chemotherapy alone in
re-hepatectomy after hypertrophy of the residual liver and may be unresectable CRLM, but this deficiency is being addressed by a trial of
used for large bilateral lesions in which a one-stage resection of all of chemotherapy plus local ablation versus chemotherapy alone (CLOCC
the involved segments would lead to liver failure.
20,21
trial). A significant improvement in the chemotherapy plus RFA group
would provide strong evidence of its value, but it is difficult to foresee a
Extrahepatic colorectal metastases may be resected with curative successful trial comparing RFA with surgical resection, as the results of the
intent, such as direct diaphragmatic invasion, adrenal metastases and latter are good and operative mortality is low. However, RFA may have a
lung metastases that are few in number and readily resectable.
1
Recent future role in combination with surgery as part of the effort to expand the
data suggest that if pulmonary colorectal metastases are resectable, definition of resectability.
20
35% of patients are alive at five years.
22
Management Strategies for Patients Presenting with
Neoadjuvant Chemotherapy and ‘Rescue Surgery’ Synchronously Detectable Colorectal Liver Metastases
Modern chemotherapeutic regimens combining fluorouracil (5-FU), In a number of cases, this can be relatively straightforward.
28–30
Patients
folinic acid and oxaliplatin and/or irinotecan are associated with high who present with a technically ‘easily’ resectable primary tumour (right,
response rates of up to 50% and can allow 10–30% of patients with transverse, left and sigmoid colon) and peripherally placed low-volume
disease that is initially considered unresectable to be successfully liver disease (segments 2, 3, 4B, 5, 6 and subcapsular lesions in segments
brought to liver surgery.
20,23
4A, 7 and 8) are amenable to synchronous resection of both primary and
84 EUROPEAN ONCOLOGY
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