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34 Colorectal Cancer: Surveillance After Curative-Intent Therapy
451
(continued)
British Society of
Gastroenterology,
Association of
Coloproctology
Society of
Medical
Oncology
Cancer Care Ontario European
American Society of
Clinical Oncology
Not addressed
for Great Britain
and Ireland
Every
Every 6months for
3–6months
for 3years,
then every
6months to
5years
5years
“Role of CEA is
uncertain”
Every
3–6months
5years.
for 3years,
Every 6months for
5years
5years
then every
6months to
5years
Not recommended
“Reasonable to
offer” CT of the
liver within
2years of
recommended
CT scan or
contrast-
enhanced
ultrasound
CT scan annually for
3years. US every
6–12months may be
substituted
3years. Consider
6–12months for high
risk
resection
every
6–12months
for 3years for
patients at
higher risk of
recurrence
Not specically
recommended
Not
specically
recommended
CT scan annually for
3years for rectal
cancers only
6–12months for
2–3years, then
annually up to 5years
American Cancer
Society, US
Multisociety Task
Force on
Colorectal
National
Comprehensive
Cancer Network
of Colon and
Rectal Surgeons
Modality American Society
Table 34.1 Summary of surveillance guidelines
Not addressed Every 3–6months for
Cancer
Every 3–6months
for 2years, then
every 6months to
5years
Every 3–6months
for 2years, then
every 6months to
5years
History and
physical exam
Not addressed Every 3–6months for
Every 3–6months
for 2years, then
every 6months to
5years
for 2years, then
every 6months to
5years
CEA Every 3–6months
Not addressed CT scan annually for
CT scan annually
for 5years
CT scan annually
for 5years.
Not recommended Not recommended Not addressed Not recommended Not recommended Not
Other laboratory
testing
Consider more
Abdominal
Imaging
a
frequent for
highest risk
Not addressed CT scans every
CT scan annually
for 5years
b
for 5years.
Consider more
frequent for
highest risk
Pelvic imaging CT scan annually
452
Not specically
recommended
CT scan every
6–12months
for 3years for
CT scan annually for
3years. CXR every
6–12months may be
patients at
higher risk of
recurrence
substituted
Every 5years
after resection,
Not recommended
Not
recommended
for routine
surveillance
Not recommended for
routine surveillance
until benets
1year after
resection, then
every
1year after resection
(or within 6months if
previously
outweighed by
comorbidity
3–5years
thereafter
incomplete). If
normal, repeat in
5years
S. E. Regenbogen and K. M. Hardiman
3years. Consider
6–12months for high
risk
Not addressed CT scan annually for
CT scan annually
for 5years
for 5years.
Consider more
frequent for
Chest Imaging CT scan annually
Table 34.1 (continued)
routine surveillance
Not addressed Not recommended for
Not recommended
for routine
surveillance
b
highest risk
for routine
surveillance
PET Scan Not recommended
1year after resection
or upon completion of
adjuvant therapy if
previously incomplete.
If normal, repeat in
5years. Otherwise,
according to
1year after
resection (or
1year after
colonoscopy that
cleared
synchronous
disease before
1year after
resection (or
within 6months if
previously
incomplete). If
normal, repeat in
3years, then
resection (or
within 6months if
previously
incomplete). If
normal, repeat in
3years. If
Colonoscopy 1year after
endoscopic ndings
primary
treatment). If
normal, repeat in
3years, then
5years. More
frequent if
5years. If
advanced
adenoma, repeat in
1year. Annual
colonoscopy for
patients with
adenomas, repeat
in 1year. Annual
colonoscopy for
patients with
suspected familial
syndromes who
high-risk
adenoma(s) or
suspicion for
Lynch syndrome
suspected familial
syndromes who
have not
undergone
have not
undergone
proctocolectomy
proctocolectomy
34 Colorectal Cancer: Surveillance After Curative-Intent Therapy
Not addressed
453
Not addressed Not addressed
Recommendations
apply to Stage II and
III disease only
apply to Stage II and
III disease only.
Insufcient data to
make
recommendations for
Not addressed Recommendations
Stage I
No additional
testing
specically
recommended
Proctosigmoidoscopy
every 6months for
2–5years for patients
who did not receive
radiotherapy. Pelvic
Proctosigmoidoscopy
every 6months for
2–5years for patients
who did not receive
radiotherapy, those
Proctoscopy,
exible
sigmoidoscopy,
or endorectal
ultrasound every
imaging for rectal
tumors only
with T4 or N2 tumors.
Pelvic imaging for
rectal tumors only
3–6months for
patients with
anastomosis
Stage 1:
colonoscopic
surveillance only
Stage 2: all
Stage 3: all
Stage 4: when
c
Stage 2: all
Stage 3: all
Stage 4: when
Stage 1: high risk
only
Stage-specic
recommendations
metastases are
metastases are
resected for cure,
CT scan every
3–6months for
2years, then every
resected for cure
6–12months to
5years
No additional
testing specically
recommended
Proctoscopy every
6–12months for
patients with
Rectal
surveillance
anastomosis, every
6months after
local excision, for
3–5years.
d
Endorectal
ultrasound for high
risk
High risk of recurrence in Stage I disease is to be dened by provider(s) according to features such as margin positivity, unknown lymph node status (e.g. local excision), inad-
CEA carcinoembryonic antigen, CT computed tomography, PET positron emission tomography
a
Highest risk for systemic recurrence includes patients with N2 disease or after curative-intent metastasectomy
equate lymph node sampling, lymphovascular invasion, poorly differentiated histology, and/or T2 disease
b
High risk for local recurrence includes local excisions with poor histology (T2+, poorly differentiated), positive margins, T4 or N2 disease
High risk of recurrence in Stage I disease is to be dened by provider(s) according to features such as margin positivity, unknown lymph node status (e.g., local excision), inad-
equate lymph node sampling, lymphovascular invasion, poorly differentiated histology, and/or T2 disease
c
d
454
S. E. Regenbogen and K. M. Hardiman
Physical Examination
• Most of the major societies’ guidelines include
periodic clinical examination, including
assessment of symptoms and physical
examination.
– Findings suggestive of disease recurrence
may include weight loss, fatigue, anemia,
cough, abdominal pain, rectal bleeding, or
changes in bowel habits.
• Symptomatic recurrences, however, are
far less likely to be amenable to curativeintent therapy.
– Physical examination should focus on the
abdomen, including evaluation for wound
implants, lymph nodes, and rectal exam (or
perineal wound exam after abdominoperineal resection).
• In addition to their role in colorectal cancer
surveillance, these visits also serve an important survivorship role in overall health maintenance and management of physical and
psychosocial function after colorectal
resections.
• The American Society of Colon and Rectal
Surgeons (ASCRS) recommends visits every
3–6months for 2 years, followed by every 6
months until 5years.
surveillance have included regular CEA
evaluations.
– CEA elevations identify disease in the
absence of abnormal imaging in up to 23%
of patients with recurrent colorectal cancer
but may be more commonly elevated with
metachronous liver metastases than with
pulmonary metastases and luminal or
locoregional recurrences.
– About a third of colorectal cancers do not
produce CEA, but the signicance of CEA
elevation during surveillance seems to be
independent of the preoperative CEA
level.
• Recommendations for management of asymptomatic CEA elevation are outlined in guidelines from both NCCN and ASCRS.
– After conrmation of serial elevation in
CEA level, a complete physical examination, endoscopy, and CT imaging of the
chest, abdomen, and pelvis are performed.
– If these are all negative, consideration is
given to PET-CT and/or repeat imaging
every 3 months until levels decline or
recurrence is detected.
Abdominal Imaging
Laboratory Testing
• None of the major guidelines currently
endorse the routine evaluation of complete
blood count, liver function tests, fecal occult
blood testing, or blood chemistries.
• It is recommended to check levels of carcinoembryonic antigen (CEA), an oncofetal antigen that may be elevated in patients with
recurrent colorectal cancer.
– CEA detects about 30–60% of recurrences,
the positive predictive value of CEA is
about 65%, and more than 15% of patients
in surveillance have falsely elevated CEA
in the absence of recurrence.
– Yet, elevations in CEA may precede symp-
tomatic presentation of metastasis, and the
trials showing greatest benet to intensive
• The most common site of metachronous metastatic colorectal cancer is the liver.
• A Cochrane collaborative meta-analysis concluded that there was a survival benet associated with liver imaging, with an odds ratio for
mortality of 0.64 (95% condence interval
0.49–0.85).
– This conclusion was derived from the
results of ve randomized trials, which
used varying combinations of liver ultrasonography, abdominal CT, or both.
• The current ASCRS practice parameter and
recommendations from other US-based agencies recommend CT imaging, due to increased
sensitivity for identifying early liver lesions,
and the opportunity to evaluate the remainder
of the abdomen and pelvis for other sites of
metastasis (such as retroperitoneal lymph
34 Colorectal Cancer: Surveillance After Curative-Intent Therapy
455
nodes and ovaries) and to identify local recurrence in the resection bed.
• There is currently no organization that
endorses routine use of PET-CT scans or liver
MRI.
Chest Imaging
• Whereas plain radiography was the mainstay
of surveillance for pulmonary metastasis in
the past, most of the major guidelines now
recommend the use of cross-sectional imaging
at least annually.
• This change has come with the recognition
that pulmonary metastasis may present as
a solitary site of disease recurrence and
may even represent the most common site
of distant metastasis for distal rectal
cancers.
• However, it should be noted that crosssectional chest imaging is recommended in
spite of a lack of high-level evidence to support its effectiveness in practice.
Colonoscopy
• Surveillance endoscopy after colorectal cancer resection can serve three purposes:
– Clearance of remaining colon when preop-
erative colonoscopy was incomplete
– Anastomotic surveillance for detection of
local luminal recurrence, which should be
a rare event
– Most importantly, detection of metachro-
nous neoplasia.
• The BSG/ACPGBI guidelines suggest
waiting until 5 years after resection,
whereas all of the other guidelines
include a complete colonoscopy at 1
year, though the rate of clinically signicant ndings may be low.
• The ASCRS guideline recommends that
the subsequent colonoscopy schedule be
tailored to the ndings at the 1-year
examination and to other patientspecic risk factors and circumstances.
• Patients with high-risk adenomas
(high-grade dysplasia, size greater
than 1cm or more than three adenomas) and those with a diagnosed or
suspected hereditary colorectal cancer syndrome may require annual
colonoscopy for more intensive
surveillance.
• On the other hand, the very elderly
and patients with limited life expectancy are unlikely to benet from the
detection of an asymptomatic cancer
and may be selected for less frequent,
or no, endoscopic surveillance.
Stage 1 Disease
• Most of the major guidelines for and studies
of colorectal cancer surveillance pertain primarily to Stage II–III disease and to Stage IV
tumors that have been resected with curative
intent.
• Stage I patients have been largely excluded
from many of the randomized trials of
surveillance.
• As a result, there remains controversy regarding approaches to the surveillance of resected
Stage I colon cancers (see Table34.1).
• Against routine imaging surveillance for
Stage I disease
– Several of the guidelines specically rec-
ommend against routine imaging.
• For example, NCCN and ASCO recommend only endoscopic surveillance for
anastomotic recurrence or metachronous cancers.
– There is presumed to be a low incidence of
systemic recurrence, as 5-year colon cancer survival rates exceed 90%, and very
few operations for metachronous metastatic recurrence occur in patients who initially presented with a Stage I tumor.
– There is concern that surveillance will
identify more incidental ndings than treatable recurrences. It is estimated that it
would take nearly 200 patients with Stage I
disease in surveillance to detect each cur-
456
S. E. Regenbogen and K. M. Hardiman
able metastasis, and many authors caution
against over-testing in this setting.
• For routine imaging surveillance for Stage I
disease
– Some authors have found equivalent rates
of salvage and better survival for recurrences after resection of early-stage disease
and have thus recommended active survival
for patients with early-stage disease,
though they do not distinguish between
Stage I (T1–2, N0) and Stage 2a (T3N0) in
their studies.
– The most recent ASCRS Practice Guideline
recommends consideration of active surveillance for Stage I patients but limits the
recommendation to those designated at
higher risk– for example, close or positive
margins, unknown lymph node status (e.g.,
local or endoscopic excision), inadequate
lymph node sampling, lymphovascular
invasion, poorly differentiated histology,
and/or T2 disease.
Local Surveillance forRectal Cancer
• Additional surveillance recommendations for
rectal cancer are predicated on the greater risk
of locoregional recurrence, compared with
colon cancers, due to both anatomic and biologic differences between the tumors.
• Locoregional recurrence of rectal cancer can
occur either intraluminally, typically at the
site of anastomosis, or extraluminally, likely
associated with residual lymphatic disease,
close radial margins, or tumor shed during
resection.
• Although the use of total mesorectal excision
(TME) and chemoradiotherapy for locally
advanced rectal cancers have substantially
reduced local failure after primary resection,
between 4% and 22% of patients still experience local recurrence.
• The resulting downstaging that may occur
with the use of preoperative therapy for rectal
cancer also may create confusion about how
to classify future risk of recurrence.
– In the ASCRS practice guidelines, it is rec-
ommended that pre-treatment clinical staging be used to guide surveillance intensity.
• Early identication of local recurrence may
offer the opportunity for curative-intent salvage resection. Therefore, surveillance of
colorectal anastomosis and pelvic imaging are
recommended beyond what is performed for
colon cancer surveillance.
• Physical assessment
– Pelvic and groin examinations should be
performed every 6 months. For patients
with a low anastomosis or distal tumor with
local excision or non-operative management, digital exam of the anastomosis or
tumor site should be included.
– For patients who have undergone abdomi-
noperineal resection (APR), careful palpation of the perineum and, in women, the
posterior wall of the vagina is
recommended.
– Special attention should be paid to areas of
nodularity or changes over time.
– Any suspicious lesions should undergo
biopsy as local recurrences after APR are
frequently perineal or presacral.
• Proctosigmoidoscopy
– Endoluminal evaluation of the rectum is
recommended in the most recent ASCRS
practice parameters every 6–12months for
3–5years for those who have undergone a
low anterior resection with anastomosis
and more frequently for those considered
to be at higher risk of local recurrence.
• Imaging
– Endorectal ultrasonography (ERUS).
• The most recent ASCRS and ACS/
MSTF guidelines also suggest consideration of ERUS for patients considered
high-risk for local recurrence. Although
controversial, there are a handful of
studies that suggest that ERUS can identify asymptomatic rectal cancer recurrence that was otherwise undetected by
digital exam, endoscopy, CT, or CEA.
– Cross-sectional imaging
• ASCO and CCO both recommend pelvic CT imaging for rectal cancers only,
34 Colorectal Cancer: Surveillance After Curative-Intent Therapy
457
as a means of detection of local recurrence. MRI of the pelvis can also be
used and is highly accurate for the diagnosis of pelvic recurrence, but its use in
routine surveillance did not improve the
detection of resectable recurrence in a
single trial, and its cost-effectiveness
has not been evaluated.
• Rectal cancer initially treated by local
excision
– Particular attention must be paid to both
endoluminal and mesorectal surveillance
due to the relatively high risk of local pelvic failure
• At least semiannual digital rectal examination and rectal endoscopic surveillance after local excision are highly
recommended, and consideration may
be given to the use of ERUS for these
patients.
• Rectal cancer initially treated by denitive
chemoradiotherapy
– Because non-operative treatment is primar-
ily limited to clinical trials, none of the
guidelines include formal recommendations for such patients.
– However, the non-operative trials reported
to date have employed remarkably intensive surveillance, including very frequent
physical examination, endoscopy, and
imaging, often with pelvic MRI.
Compliance withGuidelines
• Despite published recommendations for surveillance after resection for colorectal cancer,
compliance with surveillance remains challenging both for patients and their physicians.
• There is evidence that patients who adhere to
recommended surveillance have a greater
likelihood of curative-intent reoperation for
recurrence and improved overall and diseasespecic 5-year survival.
• Yet anywhere from 25% to 42% of patients
have poor completion of recommended surveillance, and 11–21% have no surveillance at all.
• There is also little consensus regarding who
should manage cancer surveillance– the operating surgeon, medical oncologist, gastroenterologist, or primary care doctor.
– This ambiguity may contribute to nonad-
herence in many patients, as responsibility
for ordering and managing testing can be
undened.
Quality ofLife
• Apart from the cancer-specic outcomes of
surveillance, an essential question is the effect
of intensive surveillance on psychological
health and quality of life. While reassuring
surveillance examinations may allay fears of
cancer recurrence for some patients, there
could be others for whom the conduct of surveillance examinations subjects them to additional unwarranted worry and investigations
for false positive or incidental ndings.
• Most patients in surveillance report, however,
that these anxieties and inconveniences are
outweighed by the reassurance and optimism
imparted by negative results.
Cost
• As recommendations for surveillance imaging
have expanded in recent guidelines, another
important consideration will be the costs of
surveillance.
• Total costs of the surveillance regimens in
published studies vary 28-fold, without a clear
correlation between cost and efcacy.
• Between 1999 and 2006, the use of CT and MRI
scans in the follow-up of patients with colorectal
cancer increased at an annual rate of more than
5%, and the use of PET scans more than tripled.
• We can conclude from limited data that the
cost-effectiveness of colorectal cancer surveillance is likely to be within the range of other
interventions considered acceptably costly.
Caution must be taken, however, if an increase
in the cost, complexity, and frequency of recommended testing is contemplated.
Colorectal Cancer: Management
ofLocal Recurrence
EricJ.Dozois andDorinT.Colibaseanu
35
Key Concepts
• Patients with colorectal cancer at the highest
risk for local recurrence are those who
present with obstruction or perforation,
higher-stage disease, and adverse pathologic features or undergo an operation that
does not adhere to standard oncologic
principles.
• The most signicant predictor of survival
following surgery for local recurrence is the
ability to achieve a negative-margin (R0)
resection.
• The probability of achieving an R0 resection
is much greater in patients with recurrences
involving an anastomosis or urogynecologic
structures compared with those involving the
para-aortic tissue, sacrum, or lateral pelvic
sidewall.
• A dedicated multidisciplinary team at an
institution experienced in the management of
patients with local colorectal cancer recurrence can facilitate complex surgical decisionmaking and greatly enhance patient
outcomes.
• A multimodality approach that includes
chemotherapy and radiotherapy improves
E. J. Dozois (*) · D. T. Colibaseanu
Department of Surgery, Mayo Clinic,
Rochester, MN, USA
e-mail: Dozois.Eric@mayo.edu
local control and improves 5-year survival in
patients with local recurrence.
Introduction
• In the United States, despite improvements in
surgical technique and advances in adjuvant
treatment paradigms, local failure (recurrence)
remains a problem.
– Colon cancer: 8%–12%
– Rectal cancer: 5%–30%
• Patients with colorectal cancer at the highest
risk for local recurrence are those that have
higher-stage disease, high-grade tumors,
lymphovascular involvement, and positive
resection margins or present with obstruction,
perforation, or a locally advanced tumor at the
time of presentation.
• Operations done by noncolorectal-trained
surgeons, or by surgeons who perform less
than 20 rectal cancer resections per year, have
been reported to have higher local recurrence
rates.
• All efforts to reduce the risk of local recurrence
should be made when managing primary
colorectal cancer, and the best results are
achieved when patients are managed by
experienced teams.
• When patients with colorectal cancer develop
local recurrence, surgery offers the best
opportunity for cure.
© ASCRS (American Society of Colon and Rectal Surgeons) 2019
S. R. Steele et al. (eds.), The ASCRS Manual of Colon and Rectal Surgery,
https://doi.org/10.1007/978-3-030-01165-9_35
459
460
E. J. Dozois and D. T. Colibaseanu
• Due to the complexity of medical and surgical
decision-making, in addition to the surgical
expertise required to perform these
technically challenging operations, the treatment of patients with local recurrence should
preferentially occur at centers that have dedicated and experienced multidisciplinary
team.
Diagnosis ofLocal Recurrence
• The majority of colorectal cancer relapses
following surgery occur within 3 years of
resection.
• Most, but not all, patients with local failure
will have symptoms from recurrent disease,
and these will include pain, malaise, bleeding,
and symptoms of partial obstruction.
• In some patients, carcinoembryonic antigen
(CEA) levels will be elevated, and this nding
in the asymptomatic patient should trigger a
workup for recurrence.
• In patients with suspected local recurrence,
every attempt should be made to obtain tissue
for conrmation.
– Most patients with recurrent colon cancer
will have obvious ndings on imaging to
condently diagnose them with recurrence,
and a transabdominal biopsy should be
avoided.
– In contrast, every attempt should be made
to obtain tissue conrmation in patients
with suspected pelvic recurrence. One
should be hesitant to undertake a major
pelvic resection without tissue conrmation of recurrence.
• In our experience, computed
tomography (CT)-guided percutaneous
biopsy has been very useful to conrm
or refute the presence of recurrence.
• In the absence of a tissue diagnosis, a
rising CEA, with a notable change in
the size of the lesion on serial imaging, and lesions that are positron emission tomography (PET)-avid can be
considered consistent with recurrent
disease.
Preoperative Evaluation
andPatient Selection
• History and physical examination
– All records of previous treatments (surgical
and chemoradiotherapy) should be
reviewed.
– Pain and neurologic dysfunction may be a
sign of advanced pelvic disease.
– Bilateral lower extremity edema is an
indicator of venous or lymphatic
obstruction.
– If the rectum is intact, a digital rectal exam
can assess the relationship of the recurrent
cancer to the sphincter complex, prostate,
or posterior vaginal wall.
– Overall assessment of ability to withstand
long complex surgery.
• Colonoscopy
– A full colonoscopy should be done to rule
out any synchronous lesions.
• Carcinoembryonic antigen (CEA)
– A signicantly elevated CEA should raise
concern for occult metastatic disease.
• Imaging
– PET-CT to assess for distant metastatic
disease.
– Pelvic magnetic resonance imaging (MRI)
for recurrent rectal cancers to assess for
local invasion of surrounding structures.
• Enterostomal therapy marking and teaching
• Determining appropriateness for surgical
resection
– If palliation is the goal, surgery must have
a high probability of symptomatic relief
and not be signicantly morbid.
– If oncologic cure is the goal, the ability to
condently achieve a margin-negative (R0)
resection must be highly probable.
• Based on multiple studies in patients
with recurrent colorectal cancer, the
number one determinant of oncologic
benet is the ability to achieve an R0
resection.
• Multiple points of tumor xation may
limit the surgeon’s ability to achieve an
R0 resection, and this nding on evalua-
35 Colorectal Cancer: Management ofLocal Recurrence
461
tion has been associated with poor
outcomes.
• Patients operated for central recurrences
that extend anteriorly (urogenital, gynecologic organs) have the best opportunity for an R0 resection and, therefore,
good outcomes following surgery.
• When a recurrence in the pelvis extends
posteriorly to the sacrum, or lateral to
the pelvic sidewall, the ability to achieve
an R0 resection becomes much less
certain.
• In cases where there is signicant lateral
extension of the tumor, specically
through the sciatic notch, a positive
margin is almost certain unless an
extended resection such as a hemipelvectomy is done.
– Relative contraindications to surgery will
vary from institution to institution and from
surgeon to surgeon.
• Local recurrences that involve major
vascular structures, the high sacrum, or
extensive pelvic sidewall disease were
frequently listed in publications as contraindications to surgery in the past.
• In the modern era, several wellrecognized and respected centers have
expanded their indications in light of
increasing data demonstrating meaningful survival in patients undergoing
extended resections.
• In the author’s view, contraindications
to surgery should be based primarily on
the inability to completely clear the
tumor with the understanding that limited survival benet is achieved if gross
residual tumor remains.
Classication ofLocal Recurrence
• Locoregional recurrence in patients with
colon cancer:
– Peri-anastomotic (mural disease).
– Mesenteric (regional nodal disease).
– Retroperitoneal or pelvic (drop metastases,
distant nodal disease, or residual disease
transmural disease).
– Peritoneal metastases.
– Some cases of recurrence can be directly
attributed to inadequate mesenteric resec-
tions at the time of original surgery.
However, most nodal-based relapses are
found at nodal sites (iliac, para-aortic) not
typically removed during standard onco-
logic resection.
• Pelvic recurrence of rectal cancer (Fig.35.1):
a
Fig. 35.1 Classication of recurrence. (a) Anterior:
involves structures anterior to the neorectum. (b)
Posterior: involves structures posterior to the neorectum.
(c) Lateral: involves pelvic sidewall and associated struc-
tures. (d) Combined anterior-posterior: tumor includes
anterior and posterior structures. (©By permission of
Mayo Clinic Foundation for Medical Education and
Research. All rights reserved)