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Management of patients with primary colorectal cancer and
Management of Patients with Primary
Colorectal Cancer and Synchronous
Approximately 40% of patients treated with colorectal cancer will develop liver
metastasis following treatment of primary cancer, these are termed as
Almost 15% percent of patients diagnosed with Colorectal malignancies will have
radiological evidence of Liver metastasis, these patients are said to have
Synchronous lesions are found to have poorer prognosis as compared to
Metachronous lesions, as they are known to have aggressive biological traits such
Increased incidence of multiple, bilobar, large dimensional disease and hence end up
Colorectal liver metastasis presenting within 1 yr of primary disease are likely to
behave biologically as synchronous lesions.
Despite the differences, both synchronous and metachronous lesions are treated
surgically in a similar fashion.
The classical strategy is sequential resection, i.e., primary tumor is resected first
adjuvant chemotherapy liver resection.
In some cases reverse sequential approach is applied where liver lesion is resected
first followed by treatment of the primary
In advanced Rectal cancers where the liver lesion is the primary cause of poor prognosis,
thereby avoiding unnecessary rectal surgery.
This approach has shown to have survival benefits.
These patients should be approached in a multidisciplinary manner with a team
including a surgical oncologist, medical oncologist and radiologist.
Selection for surgery
Full characterization of extent and distribution of the disease is essential.
All patients who are planned for radical treatment should undergo
CT scan of the chest, abdomen and pelvis
MRI dedicated for liver with contrast
PET CT to identify extrahepatic metastasis
In case of a rectal primary an MRI is performed.
Untreated patients with SCLM have a five year survival of 3%
Only surgical intervention gives possibility of long-term cure and survival ranging
Previously held criteria for inoperability such as more than 3 liver lesions, bilobar
disease and extrahepatic mets are no longer considered contra indications.
Patients with controllable serosal disease, retroperitoneal nodal disease and even
for maximally debulking operations may even be eligible for treatment with
curative intent in 13-15% patients.
In an era of Chemotherapy, all patients who’s primary disease can be controlled
adequately are amenable for liver resection provided there is sufficient residual
liver volume (25% of good quality liver and 40% if liver appears damaged), with
adequate inflow and outflow to support the patient in the post operative phase.
The availability of Portal venous embolization, downsizing chemoRx,
Radiofrequency ablation and two stage hepatectomies have increased the
proportion of eligible patients.
As majority of the patients will have significant medical comorbidities, which will
impact on the decision, timing and strategy of the operation, multidisciplinary
approach is essential.
MRI, PET CT
Lower GI and Hepatobiliary
RAS testing followed by
suitable chemotherapy +/-
monoclonal agent (4-6
Resectable hepatic lesion
Operation at 6 weeks
after use of
At diagnosis, patient may have a resectable disease or a borderline/irresectable
For patients with de novo resectable disease, EORTC 40983 trial which
randomized, 364 patients with 12 cycles of perioperative FOLFOX (oxaliplatin +
fluorouracil) or surgery alone.
This demonstrated a three year progression free survival of 8.1%, in favor of
Overall survival though was not statistically significant.
7% patients progressed during chemotherapy, these patients were shown to have
aggressive tumor behavior.
For patients with borderline/irresectable disease receiving chemotherapy, the
speed and quality of response which is measured by dimensional, morphological
and functional changes which is correlated with probability of eventual resection
and both to PFS and OS.
This implies that most appropriate chemotherapy should be selected which could
be either a doublet or triplet chemotherapy using a Flouropyridine backbone with
either or both of irinotecan and oxaliplatin.
Triplet therapy is not only associated with better response but also increased
Anti angiogenic antibody – Bevacizumab
Anti EGFR antibodies – Cituximab or panitumumab
These have significantly improved survival of stage IV irresectable cancers.
Bevacizumab does not consistently improve response when used along with
Despite this controversy cytotoxic chemotherapy + Bevacizumab for patients with
RAS mutant stage IV disease is a reasonable option as it improves OS.
With respect to anti EGFR therapy, extension of exon 2,3 & 4 of KRAS and NRAS
has aided further refining of the patient population who may benefit from these
Retrospective analysis of Chemotherapy + cetuximab/panitumumab with
previously unexamined RAS mutations demonstrates that the addition of anti
EGFR therapy has significantly increased response rates for these patients.
Hence for all patients RAS testing should be done prior to initiation of anti EGFR
Preoperative assessment of pre-existing liver disease should be done.
In addition, patient would have also received at least doublet therapy and likely ,
in addition, monoclonal Ab such as bevacizumab.
Irinotecan can induce steatohepatitis, fibrosis or even cirrhosis.
Oxaloplatin may lead to sinusoidal injury and intra-hepatic veno-occlusive disease.
Hence preoperative, percutaneous biopsy of the future remnant liver should be
An interval of 4-6 weeks should be considered before surgery following Chemo
and VEGF inhibitors.
Liver resection is performed with a curative intent.
Should be simultaneous whenever possible.
If simultaneous resection is done then the primary tumor is resected first.
If any complexity noted during surgery of the primary then the liver resection could be
deferred for a later date.
During liver resection, things to be considered are, the use of intraoperative USG
to identify the lesion, extent and anatomical relations.
If surgical field cannot encompass the lesion then use of RFA
Steps to be considered are
To avoid ischemia of chemo-exposed liver, inflow clamping is not done.
Liver resection is carried out with bipolar coagulator initially followed by CUSA.
To avoid imaging artefacts, metal clips are avoided over the resected surface.
Standard treatment for SCLM is sequential resection.
However there is a growing trend towards simultaneous resection.
Applicable only in a selected group of patients
Who are expected to have straight forwards colonic and hepatic resections.
Where the patients performance status is of concern the simultaneous resection is inappropriate.
Long term benefits of simultaneous resections is yet to be studied.
The advantages though are,
Avoiding repeat surgery
Early onset of adjuvant therapy
Decrease in hospital stay
Irresectable synchronous liver mets:
Majority of patients presenting with colorectal mets will initially irresectable.
Patients should undergo neoadjuvant chemo and should be restaged after
downstaging the tumor.
12%-40% of the cases may become resectable.
The use of monoclonal Abs increases this percentage.
With this approach OS of 33% have been noticed, which is almost comparable with
patients with initial resectable lesions.
There is no consensus regarding optimal management of primary tumor in patients
with irresectable disease.
For the management of which nature & severity of primary disease should be taken
into consideration .
Treatment is aimed at improvement of the QOL, control of symptoms and prolong the
Patients with Rectal Cancers with better performance score should undergo
Chemoradiation when there is a high risk of obstruction or likelihood of
developing debilitating pelvic symptoms.
Otherwise, following options are considered: defunctioning colostomy, primary
tumor resection, stenting, chemo, chemoradiation or laser recanalization to
achieve effective palliation.
Hepatic arterial infusion of chemo + Systemic chemo (OR) Intra-arterial infusion of
Yttrium 90 microspheres + systemic chemo are found to be effective in
Stereotactic Body RT (SBRT) has been shown to have low toxicity and can prevent
progression in patients with limited hepatic disease and presently thought to have
implications in irresectable liver mets too.
Until recently extrahepatic metastasis was considered to be absolute
contraindication to surgery.
28-40% five year survival is reported in patients where extra-hepatic disease is
controlled by systemic or surgical treatment.
Though patient undergoes a liver resection with curative intent, most of them
develop recurrence in the liver within 2 years.
Close surveillance of these patients as with earlier detection will be amenable to