Volume 210, Number 2
In General Surgery
Resection of Hepatic Metastases
from Colorectal Cancer
GLENN STEELE, JR., M.D., and T.S. RAVIKUMAR, M.D.
During the past decade the results of slightly fewer than 1000
resections of liver metastases from colorectal carcinoma have
been analyzed, retrospectively reanalyzed, and reviewed. The
following are confirmed conclusions: major liver resection can
be performed safely (less than a 5% operative mortality rate);
20% to 25% ofthese patients are cured; no other regional therapy
options have any curative potential. The following caveats are
also obvious: most patients who are operated on are not cured;
although predictors have been proposed to select patients most
likely to benefit from surgery, none is discriminating in and of
itself; most therapy questions in this group of patients have not
been addressed in any formal way, surgery for isolated regionally
recurrent colon and rectum carcinoma remains an important
stopgap only until effective systemic therapy is discovered. This
review of our own and other single and multi-institutional pro-
spective and retrospective data will be framed by the following
questions. (1) Does resection of liver metastases cure patients
or simply select those who would have survived in the long-term
without any therapy? (2) In the absence ofany formalized, prop-
erly designed trial, how can one judge the benefit of resection?
(3) Why do metastases recur only in the liver? (4) What new
therapies should focus on the predominant secondary failure sites
in the majority of patients who do not benefit from hepatic me-
From the Department of Surgery, New England Deaconess
Hospital, Harvard Medical School, Boston, Massachusetts
Selection of Patients
Before examining the outcome of resection of hepatic
metastasis from colorectal carcinoma, one must determine
the degree of selection for patients with isolated, poten-
tially resectable liver metastases. Pestana et al.' in an au-
topsy series, reported that the liver was involved in 70%
ofall patients who died from disseminated colon and rec-
tum carcinoma. Because 147,000 new cases ofcolon and
rectum carcinoma will be diagnosed this year and roughly
50% ofpatients will experience recurrence within 5 years,
liver metastasis remains a prevalent mode offailure. Fur-
thermore, numerous studies220 of the natural history of
colorectal carcinoma, including our own, have shown that
liver metastasis is the primary determinant ofpatient sur-
vival. However, this large number of patients with the
liver as one site of disseminated disease is irrelevant to
the surgeon. For effective regional therapy, there must be
no extraregional disease. As shown in recent prospective
adjuvant treatment trials,21'22 the liver is the first or only
site offailure in fewer than 20% ofpatientswho experience
recurrence after primary colon and rectum cancer resec-
Correspondence and reprint requests to: Glenn Steele, Jr., M.D., De-
partment ofSurgery, New England Deaconess Hospital, Harvard Medical
School, 110 Francis Street, Boston, MA 02215.
Accepted for publication: February 8, 1989.
STEELE AND RAVIKUMAR
tion. Some of these patients who present initially with
regional disease (for instance, those with poorly differ-
entiated adenocarcinoma) will show rapid proliferation
of disease outside the liver. In addition, one third of the
patients who have liver only or liver-predominant colo-
rectal cancer metastases staged by any of the presently
available noninvasive diagnostic tests will be found at
surgery to have extrahepatic disease or metastases in the
liver not amenable to surgical resection.23 New staging
techniques, such as intraoperative ultrasound (IOUS),24
will exclude even more patients found to have additional
deep liver metastases as small as 2 mm to 4 mm in di-
ameter. As the surgeon becomes stricter in excluding pa-
tients with multiple liver lesions or with disease outside
the liver, resection results will seem better. Furthermore,
as the surgeon selects patients with more indolent disease
(i.e., metastases isolated to the liver or lung that grow
slowly and do not spread to other organs), results from
resection will also seem better. The varying selection bias
may explain differences in outcome among the many sin-
gle institution hepatic metastasis resection series. Com-
posite series will offer a more realistic survival estimate
but are impossible to analyze because individual surgeon's
criteria for patient exclusion is not possible to extract.
Adson et al.'6 and Fortner25 have attempted to estimate
the maximum potential therapeutic benefit ifhepatic me-
tastasis resection were applied to all appropriately selected
patients with colon and rectum carcinoma recurrence.
We have modified their estimates as follows. If one as-
sumes that 50% ofthe 147,000 patients who will be newly
diagnosed with colon and rectum carcinoma this year will
fail within 5 years, approximately 70,000 patients will be
at risk for liver metastases as part of their recurrence.
Eventually, 60% to 70% of these patients will have the
liver as one involved organ. However, the liver will be the
first or predominant site of failure in only 20% of these
patients. Thus at most, 9000 patients could be considered
for liver resection. However, if one assumes some prob-
ability ofcomorbid disease that would exclude any major
operation, and if one assumes that some patients would
rapidly show progressive extrahepatic disease, then per-
haps another 1000 to 1500 patients would be excluded
from surgery. At the time of surgery, one third of these
7500 patients would be ineligible for resection.226 Thus,
approximately 5000 patients would be potential candi-
dates for resection each year. Ifone accepts the cumulative
operative mortality rate of 5%, 250 patients would not
survive the perioperative period. With the theoretical 4750
patients operated on and alive after their operations, and
a 20% to 25% 5- and 10-year disease-free survival, it is
apparent that using the most optimistic estimates no more
than 1000 patients per year could be cured by surgical
resection. This puts the clinical discussion into proper
The Natural History of Hepatic Metastases
At the time of surgery, no surgeon who finds that his
or her patient has a resectable liver metastasis will ran-
domize that patient to resection versus sham laparotomy.
Analysis ofpatient benefit from hepatic metastasis resec-
tion, therefore, must include comparison to outcome in
natural history series that include comparably selected
With the single exception of Adson et al.,27'28 all sur-
geons who report their hepatic metastasis resection series
have stated that their only goal was to cure the patient.
Although Adson's palliative approach for some ofhis pa-
tients and his attempt to define a postoperative quality-
of-life index is interesting, most patientswho present with
pain and deterioration of liver function chemistries or
synthetic function have, in general, far-advanced liver tu-
mors that should not be considered for major surgical
resection. In our own series,23'29 and in all single institu-
tional series with the exception of Dr. Adson's, patients
are operated on with curative intent. By and large these
patients are asymptomatic or only mildly symptomatic
at the time their liver metastases are diagnosed and when
they come to surgery. In addition, most patients have no
comorbid disease. Such selected surgical patients, then,
cannot be compared to the general population ofpatients
with synchronous or metachronous liver metastases from
colon and rectum cancer who have been predicted to have
a mean survival rate ofonly 6 to 9 months after diagnosis.'
Among the natural history studies listed in Table 1,
several have characterized survival among selected pa-
tients similar to those included in hepatic resection series.
These include 1970 and 1983 reports by Cady et al.,6"14
the Goslin et al.2 study published in 1982, and the recent
Finley and McArdle study20 ofoccult hepatic metastases.
The patients with limited liver involvement described in
these natural history series are undoubtedly more anal-
ogous to those on whom we operate. The benefits of our
surgical therapy should be evaluated by a comparison with
these historical nontreated controls.
Our investigation of 125 patients who were referred to
a tertiary cancer center during an era when hepatic me-
tastasis resection was not in vogue is representative ofthe
other natural history series in which most patients were
asymptomatic at the time of diagnosis. The following
conclusions were evident. First, the simplest way to es-
tablish prognosis was to ask the patient how he or she felt.
In the majority of our patients there was no deficit in
work or life style, so called Eastern Cooperative Oncology
Group (ECOG) functional status 0. As can be seen in
Figure 1A, the patients with no dysfunction had a median
survival of 18 months, regardless of the extent of their
liver disease. Second, patients who were found to have
more disease died more quickly than those with less dis-
Ann.Surg* August 1989
Vol. 210.No. 2 RESECTION OF HEPATIC METASTASES 137
more, metastases must be accessible to probe placement
(i.e., not high over the dome ofthe right lobe). Thus, the
hope for an increase in patients appropriate for regional
therapy has not occurred. What has evolved is the gradual
substitution ofcryosurgical ablation in place ofresection,
particularly in high-risk patients. Early indications show
that the survival curves ofcryosurgically treated patients
may be the same as our patients who have had successfully
resected liver metastases. Confirmation by other investi-
gators, greater numbers, and median follow-up in our se-
ries will be necessary before this becomes a conventionally
applied alternative to surgical resection.
Application ofconventional and new serologic markers
to patients undergoing therapy for isolated regional liver
recurrence has allowed us to define a semi-quantitative
relationship between CEA and tumor volume,83 and has
helped to define the kinetics of CEA fall after complete
or incomplete liver metastasis resection.23 Serial CEA
monitoring after successful freezing of liver tumors gives
a completely different slope of decline, presumably be-
cause the frozen tumor is left in situ (Figs. 5A and B).
Molecular biologic probes, which will eventually predict
what primary colon and rectum cancers will metastasize
and where, are presently being investigated.84 The char-
acterization of various cell-surface and transmembrane
receptors, such as EGFr and laminin binding molecules,
on primary tumor, regional lymph node metastases, and
hepatic metastases from the same patient will help us elu-
cidate the mechanisms of invasion and site-specific me-
Key future goals will be to predict the biologic behavior
of colorectal carcinomas with precision and to predict
which regional metastases do not represent early markers
ofwidespread systemic recurrence. Until we can prevent
metastases altogether or have available effective systemic
therapy options, we must continue to use excellent clinical
judgment to select the most appropriate patients with liver
metastases for surgical resection. We must continue to
improve our surgical techniques and refine our approaches
based on analysis of immediate and long-term failure.
And we must remember that currently surgery offers the
only hope ofcure to these patients.
We thank Suzanne Altman Offit and Janet Morse Fox for expert
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