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141
11 Early Colorectal Cancer Management
11.2 Early Colon Cancer
The risk factors for malignant transformation in polyps relate to their size, degree of
dysplasia, and villous nature. In patients undergoing colonoscopic screening, the
risk of malignancy in polyps 1–5 mm was 1 in 3,744; 6–9 mm was 0.2%; and 1 cm
or greater was 2.6% [ 3 ] . In a paper by Nusko et al. none of 5,137 adenomas of 5-mm
diameter were malignant [ 4 ] . The risk of malignancy increased progressively with
size to almost 80% chance in adenomas of more than 42 mm. They showed that the
risk of malignancy in a pure tubular adenoma is much less than if there is a villous
pattern. To make a defi nitive diagnosis of an adenoma and rule out malignancy, the
pathologist must look at the entire specimen; biopsy carries an 18.5% false-negative
result compared with examination of the entire specimen [ 5 ] .
Case Scenario 1
A 75-year-old man with congestive cardiac failure and chronic kidney disease
stage 3 opts into the Bowel Cancer Screening Programme. Colonoscopy
detects a 2.5-cm polypoid lesion on the lateral wall of the rectum at 9 cm.
There are no clinical features of malignancy. Biopsy of the lesion shows a
high-grade tubulovillous adenoma.
He is referred for consideration of transanal resection.
Which of the following is true about transrectal ultrasound for rectal tumors?
a. It can distinguish T1 from T2 lesions in 80% of cases.
b. It can distinguish T0 from T1 lesions in 80% of cases.
c. It can stage nodal status in 60% of cases.
d. It is less accurate in T staging than MRI scanning.
e. It is mandatory before performing endoscopic submucosal resection for
rectal neoplasms.
Case Scenario 2
Histology from the above case shows a moderately well-differentiated pT1 sm1
carcinoma, with no evidence of lymphovascular invasion. The report indicates
that resection is complete, and the deep resection margin is measured at 2 mm.
What advice would you give to the patient?
a. Recommend proceeding to anterior resection.
b. Need to wait for MRI scan before discussing management.
c. Mortality risk of anterior resection is around 10%.
d. Risk of cancer recurrence is 5% or less.
e. Careful follow-up is essential.
142
J. Hill
11.3 Clinical Assessment
The most important clinical assessment of a neoplastic lesion in the colon relevant
to the endoscopist is whether it can be safely removed. The pathological report is
the key to future management. Nearly all pedunculated polyps can be safely excised
endoscopically, even those with broad stalks. The value of pit pattern recognition
and the lifting sign are to prevent attempts at polypectomy in T2 lesions. Not only
would this treatment be noncurative but would increase the risk of perforation.
Recent technological developments in colonoscopy include high-defi nition, wide-
angle lenses, narrowband imaging, autofl uorescence, and i-Scan. There are no con-
sistent data to indicate that any of the new technologies increase adenoma detection
rate except perhaps chromoendoscopy [
6 ] .
11.4 Pathological Assessment
11.4.1 Depth of Invasion (Fig. 11.2 )
Haggitt levels
0 – In situ or intramucosal severe dysplasia
1 – Carcinoma invading the area above the junction of the adenoma and the stalk
(head)
2 – Carcinoma invading the junction between the adenoma and the stalk (neck)
3 – Carcinoma invading any other part of the polyp
4 – Invasion into the submucosa of the bowel wall below the stalk in the peduncu-
lated polyp and in the submucosa of the sessile polyp
Level 0
Level 1
Level 2
Level 3
Level 4
Muscularis
mucosa
Muscularis
propia
Submucosa
sm1 - invasion
into the upper 1/3
of the submucosa
sm2 -invasion
into the mid third
of the submucosa
sm3 - invasion into
the lower 1/3 of the
submucosa but not
reaching the
muscularis mucosa
Pedunculated
polyp
Sessile polyp
Fig. 11.2 Levels of invasion in different types of polyps. Note difference between a polypoid
confi guration and a sessile polyp
143
11 Early Colorectal Cancer Management
As seen in the diagram, levels 1, 2, and 3 pertain only to invasion in pedunculated
polyps. In polypoid lesions, Haggitt identifi ed the level of invasion into the stalk of
the polyp as being important in predicting outcome and found that “level 4” inva-
sion, in which tumor extended beyond the stalk of the polyp into the submucosa but
did not invade the muscularis propria, resulted in an increased risk of adverse cancer
outcomes [
7 ] .
Following the study by Haggitt, there have been a large number of studies exam-
ining risk factors for local recurrence and metastatic disease in malignant polyps.
Hassan et al. performed a pooled-data analysis on 31 such studies which included
1,900 patients [ 8 ] . The pooled data were from retrospective studies which limit the
data quality, but as there are no large prospective studies, this represents the best
data available.
Hassan’s study looked at three histological risk factors – the positivity of the
resection margin, poor differentiation, and lymphovascular invasion – and fi ve clini-
cal outcomes: residual disease, recurrent disease, lymph node metastasis (in patients
who had a resection), distant metastasis, and mortality.
1. Positive resection margin – the study showed that residual and recurrent disease
was much more common, odds ratio was 22 (95% CI 10.3–46.6), and a positive
margin was seen more frequently in sessile polyps.
2. Differentiation – poor differentiation was described in 7% of polyps. The major-
ity of patients underwent surgical resection. The risk of lymph node metastases
was 23%, and the risk of metastatic spread was 10%.
3. Lymphovascular invasion – this was present in 18% of polyps. Lymph node
metastasis occurred in 35% when it was present and 7% when it was absent.
The authors classifi ed polyps into low risk (375 polyps) with no adverse histo-
logical features present and high risk (268 polyps) with at least one adverse factor
present. Of the 375 low risk polyps, 295 had no surgery and local disease occurred
in one patient. Eighty were treated surgically. Nodal disease was found in four. All
these were from one study by Colacchio et al. containing only 39 patients [ 9 ] . The
risk of nodal metastases was therefore 0% in the other series. Metastatic disease
occurred in 1 of the 375 patients (0.3%) and mortality in 2 (0.7%).
In the high risk group, residual disease was found in 21%, recurrent disease in 9%,
lymph node metastases in 11%, and metastatic disease in 7%. Eighty-three of the 268
polyps had lymphovascular invasion as the only adverse risk factor. When low risk
polyps were compared with the group who had lymphovascular invasion as the only
adverse risk factor, there was a very low risk of metastatic disease (0.5%) and mortal-
ity (0.9%), but lymph node metastases were present in 8/116 patients (7%).
The Royal College of Pathologists Dataset for Colorectal Cancer (2nd Edition
2007) recommends that poor differentiation (including signet ring cell adenocar-
cinoma) should be based on the worst area in the carcinoma (rather than the
assessment being based on the predominant area). This document also comments
that sometimes fi xation artifact around tumor aggregates can make assessment of
lymphovascular invasion uncertain [
10 ] . Pathology reports frequently state this
uncertainty, and there is also evidence of interobserver variation in such an
144
J. Hill
assessment [ 11 ] . There is no universal agreement about the margin of clearance,
but most authorities would regard a clearance of <1 mm as a positive margin and
an indication for further therapy. If the deep margin is clear, but the lateral mar-
gin shows residual adenoma, further local excision is reasonable (if there are no
other adverse histological risk factors).
11.5 Patient Counseling for Early Colonic Cancer
This takes time and needs to provide the patient with an estimate of their risk of
residual nodal disease, metastatic disease, and an estimate of their expected morbidity
and mortality from resectional surgery. If there are no adverse histological features, the
risk of residual disease appears to be very low, and it would be appropriate to advise
patients that no further treatment is required. If there is concern about local clearance
(excision margin of less than 1 mm) or there is poor differentiation, most patients
would be encouraged to undergo resection unless predicted mortality was signifi cant.
The discussion is more complex if there is lymphovascular invasion, but no other
adverse features, particularly if there is a small focus of lymphovascular invasion or
uncertainty about lymphovascular invasion. The best estimate of the risk of nodal
metastases in the presence of lymphovascular invasion is probably from Hassan’s
study and is of the order of 7%. It is important to explain to the patient that this par-
ticular pathological assessment can be diffi cult and not always accurate. If patients
do proceed to resectional surgery, they should be told that there a strong likelihood
of there being no detectable residual disease. Even in cases where there are adverse
risk factors, there will be no residual disease in more than 70% of cases.
11.6 Early Rectal Cancer
11.6.1 Clinical Assessment
This is more involved than for colonic polyps. The assessor needs to determine
(a) Whether the lesion is benign or malignant
(b) How should it best be removed
11.7 Benign Versus Malignant
Risk factors for malignancy are size, ulceration, type of pit pattern, and fl at polyps
(more likely to be villous tumors). If the tumor is low enough for palpation, then this
provides additional useful information, although digital examination is not very
accurate at assessing stage.
145
11 Early Colorectal Cancer Management
The most diffi cult lesions to assess are the large adenomas that may have a focus
of malignancy within them. Ultrasound is not sensitive enough to identify a small
focus of malignancy (especially in a large polyp), but is able to distinguish T1 and
T2 lesions in about 80% of cases. This is an important distinction because a T2
lesion is a relative contraindication to local excision. MRI is not accurate at dif-
ferentiating early cancer from benign disease and tends to overstage early
malignancy.
11.8 How Should the Lesion be Removed?
The issues to be determined are endoscopic versus transanal resection and full
thickness versus mucosectomy or partial thickness excision. This is at least partly
determined by the requirement to provide the best possible specimen for histologi-
cal analysis. The proponents of EMR believe that polyps of almost any size can be
removed using this technique, but the larger the lesion, the more likely the excision
specimen is to be disrupted and fragmented and hence more diffi cult to assess
histologically. If the upper limit of the lesion can be palpated digitally, it may be
suitable for standard transanal excision. Transanal endoscopic microsurgery is
able to reach lesions at any height and position in the rectum, and there is some
reasonably good evidence that it produces better results than standard transanal
techniques [ 12, 13 ] .
If the lesion is assessed to be at low risk of malignancy, if it is too large for full
thickness excision, or if the lesion is in the intraperitoneal portion of the rectum,
submucosal resection is performed leaving the muscularis propria intact. Full-
thickness excision should be performed where there is a suspicion of malignancy
and it is technically possible to excise the lesion. If the lesion is a biopsy-proven
malignancy and appears to meet the criteria for curative local excision, then a full
thickness excision with a 1-cm margin is required.
Decisions about further management are then made following histopathologi-
cal analysis. Data for the UK TEMS cancer database have demonstrated that
when patients with unfavorable histology following TEMS excision proceed to
rectal excision, there are no adverse oncological consequences [ 14 ] . Thus, TEMS
can be considered to be a “big biopsy” that provides further histological informa-
tion used to inform decisions about further treatment (Box 11.2 ). As for early
colon cancer, the pathological assessment is used to predict the risk of nodal
metastases.
Box 11.2: Criteria for Local Excision of Rectal Cancer as “Big Biopsy”
3 cm or less
pT1 (as assessed clinically and radiologically)
Not poorly differentiated on biopsy
146
J. Hill
11.9 TEMS (TEO)
Transanal endoscopic microsurgery (TEM) is a technique of local excision for rec-
tal tumors. This method greatly improves accessibility, visualization, and precision
of resection of early rectal tumors compared to the standard transanal method. Using
a 40-mm proctoscope with magnifi ed binocular vision, the rectum is insuffl ated
with carbon dioxide, and laparoscopic style tools are introduced through airtight
ports (Fig. 11.3 ). The rectal tumor is removed by sharp dissection under direct
vision with a 1-cm margin of normal tissue. For malignant lesions, the muscular
wall of the rectum is removed with the specimen.
Series of patients that utilized TEM for resection of pT1 tumors have demon-
strated very variable local recurrence rates between 2% and 24% [ 15– 21 ] . The
high-reported recurrence rates in some series are of genuine concern. Some of the
case series have not used histological selection criteria to guide resectional sur-
gery. T1 and T2 cancers with adverse histological features will have high locore-
gional failure rates. When total mesorectal excision (TME) is performed for pT1
cancers, nodal tumor deposits are found in 2–23% of cases [ 22– 24 ] . Radical
resection of pT1 tumors does not, however, guarantee cure as 1.7–6% of patients
later develop local recurrence, and 3% manifest systemic recurrence within
5 years [ 22, 23, 25 ] .
Fig. 11.3 The transanal endoscopic microscope
147
11 Early Colorectal Cancer Management
Currently, it is acceptable practice to perform local excision alone for early rectal
cancer where there are no high risk features as long as the advantages and disadvan-
tages of TME surgery are explained to the patient. Local excision alone for higher
risk lesions is also acceptable in patients at higher risk of major surgery with the
same proviso. There is currently no evidence from randomized trials comparing
local excision and standard resection in early rectal cancer.
Patients should be advised about the well-documented adverse effects of TME
surgery both in terms of perioperative morbidity and mortality and long-term func-
tional outcome. Anastomotic leakage complicates 8–20% of sphincter-preserving
operations and can result in chronic pelvic sepsis [
26 ] . Pelvic autonomic nerve sup-
ply to the bladder and sexual organs is frequently injured leading to diffi culty mic-
turating or sexual dysfunction [ 27, 28 ] . As many as 60% of patients will suffer a
degree of fecal incontinence [ 29 ] , and a third experience urgency, incomplete emp-
tying, and stool frequency on a daily basis [ 30 ] . Current rates of permanent stoma
formation following rectal cancer excision are as high as 40%, although permanent
stoma rates should be less for early rectal cancer. A predicted mortality can be cal-
culated using the Association of Coloproctology of Great Britain and Ireland linked
site www.riskprediction.org.uk .
11.10 Pathological Assessment
The depth of submucosal invasion (so-called Kikuchi levels sm1, sm2, and sm3) is
the most important determinant of nodal invasion [ 31 ] with reported rates of nodal
involvement of 2%, 8%, and 23% in sm1, sm2, and sm3, respectively [ 24 ]
(Fig. 11.2 ).
Bach et al. used clinical, pathological, and follow-up data to construct a predictive
model of local recurrence after TEM surgery using semiparametric survival analyses.
This model used tumor size, pT stage, depth of invasion (Kikuchi), and lymphovas-
cular invasion [ 12 ] . Best outcomes were obtained following resection of pT1 sm1
well-/moderately differentiated LyV0 R0 tumors <3 cm diameter, with local recur-
rence rates of 3–5%. For pT1 sm2/3 or pT2 well-/moderately differentiated tumors
LyV0 R0 <3 cm diameter local recurrence rates were 10–15% (Table 11.1 ).
Other factors are likely to infl uence the risk of nodal disease. Recently, Ueno
et al. proposed that of the absolute thickness of the invasive tumor (beyond the mus-
cularis mucosae) provides a further objective measure of the risk of adverse onco-
logical outcomes [ 32 ] .
While most units use the Kikuchi staging system, The Royal College of Pathologist
have concluded that in view of the uncertainty and lack of consensus, a fi rm recom-
mendation for one method of assessing local invasion cannot be made [ 9 ] .
Preoperative short course radiotherapy (SCRT) improves local recurrence, above
that achievable by optimal TME surgery [ 25 ] . Radiotherapy and TEM may lead to
cancer-related outcomes comparable with TME surgery, but without the morbidity
and mortality associated with radical surgery. Nonrandomized studies suggest that
148
J. Hill
Table 11.1 Local recurrence rates (%) at 36 months predicted using Cox regression model for well or moderately differentiated tumors locally excised using
TEM in patients less than 80 years of age [
14 ]
pT stage Kikuchi LyV
Maximum tumor diameter in cm
£ 1 1.1–2 2.1–3 3.1–4 4.1–5 5.1+
pT1 Overall − 6.3 7.9 9.8 12.2 15.1
18.6
+ 12.0 14.8 18.3 22.4 27.3 33.1
sm1 − 3 . 0 3 . 6 4 . 4 5 . 4 6 . 6 8 . 1
+ 5 . 2 6 . 4 7 . 7 9 . 4 11 . 4 13 . 7
sm2/3 − 10 . 5 12 . 7 15 . 3 18 . 5 22 . 1 26 . 4
+ 17 . 8 21 . 4 25 . 5 30
. 3 35 . 7 41 . 8
pT2 − 9.8 11.9 14.3 17.3 20.7 24.7
+ 16.7 20.0 23.9 28.5 33.7 39.5
pT3 − 19.7 23.6 28.0 33.2 39.0 45.4
+ 32.2 37.9 44.1 51.0 58.3 65.7
Data derived according to pT stage, Kikuchi (sm) stage, presence of lymphovascular invasion and maximum tumor diameter
149
11 Early Colorectal Cancer Management
this approach is valid, yielding local recurrence rates of 5% at 5 years for endorectal
ultrasound of stage I and II disease [ 33 ] .
The TREC trial (transanal endoscopic microsurgery (TEM) and radiotherapy in
early rectal cancer) aims to randomize patients between local excision and radio-
therapy and standard resection for rectal cancer. It will compare data on morbidity,
bowel function, and quality of life to test and to determine how patients make clini-
cal decisions in this situation.
A recent systematic review by Winter examining the role of rectum-conserving
surgery in the era of chemoradiotherapy reports that the data support transanal exci-
sion of rectal tumors showing a good response to chemoradiotherapy. A complete
response in the T stage (ypT0) indicates a less than 5% risk of nodal metastases. He
concludes that this approach may result in equivalent outcomes to radical surgery
and that this should be tested in prospective trials in specialist centers [
34 ] .
11.11 Follow-up After Local Excision
The purpose of follow-up is to identify locoregional recurrence at a stage that it can
be cured. The recurrence occurs most often locoregionally. There is no good evidence
base to recommend any particular follow-up technique or schedule. Regular endos-
copy should be able to identify mural recurrence, and sequential MRI scanning should
be able to identify enlarged and enlarging perirectal lymph nodes. Histological con-
fi rmation of nodal malignancy can be obtained by TEMS biopsy or fi ne needle aspira-
tion cytology at endoscopic ultrasound. A wide range of time to local recurrence has
been reported (a few months to 11 years). In a reported series of transanal excision for
T1 rectal cancer, salvage surgery for recurrence was performed in 41 of 45 patients.
Three- to fi ve-year cancer free survival rates are 50–60% in the larger series.
Given the results from the reported series, following local excision, patients
should be advised that if local recurrence occurs, it may not be amenable to salvage
surgery or be curable [ 35 ] .
Key Points
Early colorectal cancer is confi ned to the bowel wall and can be cured by •
local excision.
The detection of early cancer is increasing following the introduction of •
Bowel Cancer Screening Programmes.
Lymph node metastases can be predicted by depth of invasion, poor dif-•
ferentiation, and lymphovascular invasion.
Good quality pathology is essential when planning treatment strategies. •
Following polypectomy of polyp cancers, the risk of metastatic disease •
should be balanced with the mortality and morbidity of resection.
If case selection is good, local excision of early rectal cancer can achieve •
similar oncological outcomes to TME surgery.
150
J. Hill
References
1. UK Colorectal Cancer Screening Pilot Group. Results of the fi rst round of a demonstration
pilot of screening for colorectal cancer in the United Kingdom. BMJ. 2004;329:133.
2. Atkin WS, Cook CF, Cuzick J, Edwards R, Northover JM, Wardle J, UK Flexible Sigmoidoscopy
Screening Trial Investigators. Single fl exible sigmoidoscopy screening to prevent colorectal
cancer: baseline fi ndings of a UK multicentre randomised trial. Lancet. 2002;359:1291–300.
3. Liberman D, Moravec M, et al. Polyp size and advanced histology in patients undergoing
colonoscopy screening: implications for CT colonography. Gastroenterology. 2008;134:
1100–5.
4. Nusko G, Mansmann U, Altendorf-Hofmann A, et al. Risk of invasive carcinoma in colorectal
adenoma assessed by size and site. Int J Colorectal Dis. 1997;12:267–71.
5. Absar MS, Haboubi NY. Colonic neoplastic polyps: biopsy is not effi cient to exclude malig-
nancy. The Trafford experience. Tech Coloproctol. 2004;8:S257–60.
6. Brown SR, Baraza W. Chromoscopy versus conventional endoscopy for the detection of pol-
yps in the colon and rectum. Cochrane Database Syst Rev. 2010;(10):CD006439.
7. Haggitt RC, Glotzbach RE, Soffer EE, Wruble LD. Prognostic factors in colorectal carcinomas
arising in adenomas: implications for lesions removed by endoscopic polypectomy.
Gastroenterology. 1985;89:328–36.
Case Scenario Answers
1. Answer A
The test is not accurate in detecting a small focus of cancer in a rectal
polyp. A focus of cancer is found in around 20% of large rectal adenomas.
Nodal involvement in early cancer is more likely to be microscopic than in
more advanced carcinoma. No imaging modality will detect microscopic
disease. Ultrasound is at least as accurate as MRI in the T staging of early
cancer. MRI is more accurate than ultrasound in more advanced rectal can-
cer. EMR results in good quality histology and can be safely performed on
the basis of clinical assessment alone and should provide a good quality
specimen for histological analysis. In view of the risk of a general anes-
thetic, it is reasonable to perform EMR for this lesion rather than TEMS
excision.
2. Answers C and D
For high risk cases, it is worth calculating the mortality risk (
www.riskpre-
diction.org.uk ). This greatly assists the consultation, and the risk should be
documented. The risk of recurrent cancer is low and needs to be balanced
with the patient’s life expectancy from their comorbidity. Few patients
would want surgery if the risks of the operation were greater than the risks
of cancer recurrence. The chance of MRI detection of nodal metastases is
very small. Even if present, nodal metastases are likely to be microscopic.
There are no evidence based follow-up protocols. As recurrent disease is
usually nodal, MRI scanning is probably the most suitable modality. If
nodal enlargement is detected, PET scanning may confi rm recurrent dis-
ease. Transrectal biopsy is also possible.
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