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171
12 Colon Cancer: Advantages of the Laparoscopic Approach
62. van Dam RM, Hendry P, Coolsen MME, Bemelmans MHA, Lassen K, Revhaug A, Fearon
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173
S.R. Brown et al. (eds.), Contemporary Coloproctology,
DOI 10.1007/978-0-85729-889-8_13, © Springer-Verlag London Limited 2012
13.1 Introduction
The evidence base for the management of rectal cancer is now considerable.
Randomized trials and other good quality studies have provided the clinician with a
rationale for the management of most tumors. Malignancies whose distal margin is
measured at 15 cm or less from the anal verge using a rigid sigmoidoscope are clas-
sifi ed as rectal. This chapter will consider staging, adjuvant therapy, and surgery of
rectal malignancy with special emphasis on supporting evidence in the surgical lit-
erature that should to inform management decisions.
13.2 Multidisciplinary Teams
Recommendations in the latest Association of Coloproctology of Great Britain and
Ireland guidelines for the management of colorectal cancer (CRC) [ 1 ] are that all
patients be discussed at a Multidisciplinary Team Meeting (MDT) and have access
to colorectal clinical nurse specialists (CNSs) for advice and support from the time
they receive the diagnosis. In a recent survey of colorectal surgeons, over 95% con-
sidered that MDTs improved the overall quality of care of CRC patients, and 80%
felt it that they improved training [ 2 ] .
P. Rooney, FRCS (*) • N. Pranesh, FRCS
Department of Surgery , Royal Liverpool University Hospital ,
Prescot St , Liverpool , L7 8XP , UK
e-mail: paul.rooney@rlbuht.nhs.uk
Chapter 13
Evidence-Based Management of Rectal Cancer
Paul Rooney and Nagarajan Pranesh
174
P. Rooney and N. Pranesh
13.3 Staging (see Chap. 10 )
Once the diagnosis of rectal cancer is made (biopsy proven), staging investigations
are performed. If a confi dent clinical diagnosis is made, it is reasonable to initiate
these before biopsy confi rmation.
13.3.1 Local Staging
13.3.1.1 Ultrasound
Endorectal ultrasound (ERUS) is accurate in assessing the depth of invasion of
tumors, especially in early rectal cancer [ 3 ] . In a meta-analysis that compared
ERUS, CT, and MRI imaging in rectal cancer staging, ERUS had a sensitivity esti-
mate of 94% in assessing muscularis propria invasion (similar to MRI). The speci-
fi city value for ERUS (86%) was signifi cantly higher than that for MR imaging
(69%) [ 4 ] . As with other radiological staging techniques, ERUS is relatively poor at
assessing nodal status (sensitivity of 73% and specifi city of 76%) [ 5 ] . The differen-
tiation of T1 and T2 tumors is the most important factor determining whether or not
a lesion should be removed by local or standard excision (see Chap. 11 ).
13.3.1.2 Magnetic Resonance Imaging
An R0 resection in rectal cancer indicates that the tumor is greater than 1 mm from
the circumferential resection margin (CRM). Assessment of the CRM is a critical
step in the preoperative phase of treatment. In a prospective study, clinical examina-
tion, which assessed mobility/fi xity of the tumor on rectal examination, understaged
the disease in 47% of cases. The same study found that MRI performed better than
rectal examination and EUS in assessing the depth of extramural invasion, nodal
involvement, and prediction of CRM status [ 6 ] . The MERCURY Study Group, a
multicenter multidisciplinary collaboration, prospectively evaluated the accuracy of
MRI in predicting the extramural depth of tumor invasion in patients with rectal
cancer, with the histopathology results as the reference standard. The study found
that in 273 (92.5%) of the 295 patients, the depth of tumor spread depicted on the
thin-section MR images was within 5 mm of the histopathologic measurement [ 7 ] .
Many other studies have demonstrated the high accuracy of MRI staging, and there
is suffi cient good quality evidence to justify the conclusion that preoperative MRI
scanning should be routine in rectal cancer.
The accuracy of MRI scanning [ 8 ] in predicting an involved CRM is such that if
the CRM is involved radiologically, the patient should have neoadjuvant downstag-
ing treatment [
9 ] .
175
13 Evidence-Based Management of Rectal Cancer
13.3.2 Staging for Metastatic Disease
A CT scan of the chest, abdomen, and pelvis is recommended in the preoperative
workup of rectal cancer. This supplements the MRI in determination of local extent
of the disease and in assessing metastatic disease in the liver and lungs (see chapter 10
on “Imaging of Colorectal Cancer ”).
13.3.3 Assessment of Synchronous Disease
The incidence of synchronous colon cancer is 2–3%. Preoperative examination of the
whole colon is recommended. If the rectum is stenosed such that endoscopic examina-
tion of the proximal colon is not possible, completion colonoscopy is recommended
within 6 months of treatment of the rectal cancer. In the presence of stenosis, barium
enema examination may miss a proximal lesion; this is less likely with CT colonogra-
phy (this can be carried out simultaneously with the staging scan) [ 10, 11 ] .
13.4 The Preoperative MDT and the Need
for Adjuvant Therapy
The important task of the preoperative MDT is an assessment of the TNM stage, assess-
ment of the patients’ fi tness for surgery, and to consider any relevant psychosocial
issues. For patients with a T2N0M0 stage, surgery alone may be considered. For T3
lesions, the depth of invasion into the mesorectum is important as a guide of the need
for adjuvant treatment. For T4 lesions which include cases where the circumferential
resection margin (CRM) is involved and where the patient has no distant metastatic
disease, preoperative adjuvant therapy is almost always used. The CRM refers to the
nonperitonealized surface of the resection specimen and corresponds to the radial
embryological nonperitonealized limit of the rectum and its mesenteric envelope. The
CRM status is the single most critical factor in predicting local recurrence and is also
important in predicting distant metastasis and survival. In a study of 568 assessable
patients who underwent surgery for rectal cancer, 165 showed CRM involvement by
tumor. Of these, 66 had margin positivity, and 97 had tumor within a millimeter of the
CRM: the local recurrence rates were 36/66 (54.5%) and 27/97 (27.8%), respectively.
If the tumor was >1 mm from the CRM, the local recurrence rate was 42/421 (10%).
The CRM positivity also refl ected the stage of the disease with more advanced disease
showing higher CRM involvement. For potentially curative operations, the Kaplan–
Meier 5-year survival estimates for patients with an uninvolved and with involved mar-
gins were 79% and 40%, respectively [ 8 ] . In CRM + patients, local and distant
recurrence rates as well as survival rates are worse than in CRM- patients [ 9 ] .
176
P. Rooney and N. Pranesh
The MDT discussion has to balance the risks and benefi ts of radical surgery and
preoperative radiotherapy with or without chemotherapy in an effort to achieve a
curative resection (Boxes 13.1 and 13.2 ).
13.4.1 Total Mesorectal Excision
The principles of total mesorectal excision (TME) are now well established. This
procedure is applied to mid and low rectal tumors. It should be noted that while there
is no randomized trial evidence to support this operation, there are many studies which
demonstrate reduced rates of local recurrence using TME when surgeons are trained
in TME techniques [ 10 ] . The procedure is increasingly being performed laparoscopi-
cally; a concern is being expressed that the short-term benefi ts of a minimally invasive
technique may be gained at the expense of oncological outcomes [ 11 ] .
13.5 Surgery Alone (For Local Excision, see Chap. 10 )
In patients without a threatened or involved CRM, it is appropriate in some patients
to proceed straight to surgery. This particularly applies to patients with a low risk of
local recurrence as it avoids the risks associated with the use of radiotherapy. The
earlier the tumor stage and the earlier the T stage, the lower the risk of local
recurrence.
Reported rates of local recurrence following resection of rectal cancer have his-
torically been very variable.
Box 13.2: Potential Causes of Local Recurrence
1. Disruption of the mesorectal envelope with failure to respect the mesorec-
tal plane.
2. Presence of viable tumour cells in the staple line (from local implantation
of viable exfoliated cancer cells or from an involved distal resection
margin)
3. Lateral pelvic wall lymph node involvement
4. Inadequate excision of contiguous organ involvement
Box 13.1: Aims of Surgery in Rectal Cancer
Minimizing of the risk of local recurrence
Minimizing the risk of complications
Maintaining an acceptable quality of life postsurgery
177
13 Evidence-Based Management of Rectal Cancer
The variability in local recurrence rates fuelled a prolonged debate about the
benefi ts of adjuvant radiotherapy in rectal cancer patients. The advocates of TME
alone pointed to their impressively low rates of local recurrence and the fact that
local recurrence rates could be improved by formal training of TME surgery in
established consultants. The advocates of short-course preoperative radiotherapy
(SCPRT) were able to show reduced recurrence rates and low complication rates in
patients receiving SCPRT. The TME alone surgeons suggested that SCPRT might
be compensating for poor operative technique. The debate was largely silenced as a
result of the Dutch TME study and the CR07 trials.
13.5.1 Evidence for Short-Course Preoperative Radiotherapy
With both SCPRT and TME training independently improving local recurrence
rates, the Dutch TME trial was designed to determine if the addition of SCPRT (5 G
on each of 5 days) to TME (best surgery) would lead to further improvements in
local control. Measures were taken to ensure quality control of the surgery and his-
tology, and local recurrences were confi rmed radiologically or histologically and
checked by a radiation oncologist. In the Dutch TME trial, patients undergoing
surgery alone had a higher local recurrence rate at 2 years (8.2% vs. 2.4%) but less
blood loss (900 vs. 1000 ml) and fewer perineal complications after AP resection
(26% vs. 18%) compared to patients assigned to SCPRT + Surgery [ 12 ]
(Table 13.1 ).
In univariate and multivariate analyses, treatment-group assignment, the location
of the tumor (distance of the tumor from the anal verge), and TNM stage were sig-
nifi cant predictors of the risk of local recurrence. The risk of recurrence of tumors
of the lower one third was 2.8 times higher than in the upper third. The risk of local
recurrence of stage II, III, and IV tumors was 3.5, 9.7, and 16.2 times stage I tumors.
The type of resection (low anterior resection/AP resection/Hartmann’s) had no
independent prognostic value with respect to the risk of local recurrence in multi-
variate analysis. There was no difference between the two treatment groups with
respect to distant or overall recurrence and no difference in overall survival [ 12 ] .
The CR07 trial was designed to compare SCPRT (25 Gy in 5 fractions) with
selective postoperative CRT (45 Gy in 25 fractions with concurrent fl uorouracil)
when the CRM was positive ( £ 1 mm) [ 13 ] . 1350 patients with operable rectal can-
cer (determined by clinical evaluation and supplemented by CT, MRI, or endorectal
Table 13.1 Recurrence (at 2 years) and distance from anal verge from the Dutch TME trial [ 12 ]
Distance of tumor from anal
verge (cm)
Local recurrence
Surgery (%)
SCPRT + Surgery (%)
10–15 3.8
1.3
5–10 10.1 1
0–5 10 5.8
178
P. Rooney and N. Pranesh
ultrasound) without metastatic disease were randomized to either of the above two
approaches. Patients who underwent preoperative radiotherapy and surgery had a
statistically signifi cant 61% reduction (hazard ratio 0.39, 95% CI 0.27–0.58) in the
relative risk of developing local recurrence compared with the selective postopera-
tive radiotherapy group with an absolute difference of 6.2% at 3 years (4.4% vs.
10.6%). Preoperative radiotherapy was associated with a higher clinical anastomotic
leak rate (9% vs. 7%, not signifi cant) and signifi cantly higher rates of nonhealing
perineum after AP resection (22% vs. 35%) [ 13 ] (Table 13.2 ).
There was an absolute difference of 6% in disease-free survival favoring SCPRT
( P = 0.01) but no difference in the overall survival. Multivariate subgroup analyses
showed no difference in benefi t from SCPRT with respect to height of tumor from
anal verge or tumor stage, although the absolute difference in local recurrence was
greatest in stage III patients. The 3-year local recurrence rate in TNM stage I/II/III
tumors was 1.9%/1.9%/7.4% in the SCPRT group and 2.8%/6.4%/15.4% in the
postoperative CRT group, respectively. This trial did not mandate the use of MRI in
local staging which was only used in 41% of patients. Despite this, the overall nega-
tivity rate for CRM was an impressive 89% which compares well with the fi ndings
in the MERCURY study (87%).
In a prospective study of the effect of the plane of surgery on local recurrence
using data from the CR07 trial, excision respecting the mesorectal plane was associ-
ated with the lowest rate of local recurrence when compared with the intramesorectal
and muscularis propria plane with a local recurrence at 3 years of 4% vs. 7% vs. 13%,
respectively. SCPRT equally reduced local recurrence rates for all planes of surgery.
An involved circumferential resection margin was signifi cantly associated with surgi-
cal procedure (abdominoperineal excision: 16%; anterior resection: 7%), tumor posi-
tion (distal extent 5 cm from the anal verge: 15%; 5.1–10 cm: 9%; 10.1–15 cm: 9%),
higher tumor (T) stage and nodal (N) stage, and those tumors involving the anterior
quadrant (involved: 13%; not involved: 7%). 3-year local recurrence rates were 6%
and 17% for patients who were CRM negative and positive, respectively [ 14 ] .
Thus, the preoperative SCPRT trials have clearly demonstrated on overall reduc-
tion in local recurrence for those receiving radiotherapy.
One of the suggested mechanisms of action of SCPRT is treatment of involved
lateral wall nodes which are not resected in TME surgery. This is supported by the
Dutch TME and the CR 07 trials and by the fi ndings of a study of 1,316 patients
with rectal cancer who received SCPRT in two Swedish radiotherapy trials. The
impact of radiotherapy was studied by comparing resected specimens irradiated
before surgery with the nonirradiated specimens and found that the former group
Table 13.2 Local recurrence (at 3 years) and distance from anal verge from the MRC CR07 trial [ 13 ]
Distance of tumor from
anal verge (cm)
Local recurrence
SCPRT + Surgery (%)
Selective post-op RT (%)
10–15 1.2
6.2
5–10 5 9.8
0–5 4.8 10.4
179
13 Evidence-Based Management of Rectal Cancer
contained smaller tumors ( P < 0.00001) with less nodal metastases ( P < 0.001). In a
logistic regression model, radiotherapy decreased the risk for nodal involvement
especially when the time interval between start of radiotherapy and surgery equaled
10 days or more. These results demonstrate a downstaging effect of SCPRT [
15 ] .
13.5.2 Long-Course Preoperative Chemoradiotherapy
This has become standard treatment for a patient with involved or threatened CRM.
Twenty years ago, postoperative adjuvant chemoradiotherapy was in common
practice and recommended by the National Institute of Health consensus conference
in North America as standard treatment for stage II and III rectal cancer in 1990
[ 16 ] . Two studies, conducted by the Gastrointestinal Tumor Study Group (GITSG)
and the North Central Cancer Treatment Group (NCCTG), served as the basis for
this recommendation. Both studies showed a signifi cant survival benefi t with com-
bined-modality therapy. The latter trial also showed a signifi cant reduction in both
local recurrences (14% vs. 25%) and distant metastases (29% vs. 46%) with com-
bined-modality treatment compared to postoperative radiation alone.
Based on the reduction in local recurrence after SCPRT in the Swedish Rectal Cancer
(which also demonstrated improvement in overall survival) and other SCPRT trials, the
German Rectal Cancer Study Group compared preoperative chemoradiotherapy and
postoperative chemoradiotherapy in patients with locally advanced rectal cancer. Four
hundred and twenty-one patients with clinical stage T3 or T4 or node-positive disease
were randomly assigned to receive preoperative chemoradiotherapy and 402 patients to
receive postoperative chemoradiotherapy. The overall 5-year survival rates were 76%
and 74%, respectively ( P = 0.80). The 5-year cumulative incidence of local relapse was
6% for patients assigned to preoperative chemoradiotherapy and 13% in the postopera-
tive-treatment group ( P = 0.006). Grade 3 or 4 acute toxic effects occurred in 27% of the
patients in the preoperative-treatment group, as compared with 40% of the patients in
the postoperative-treatment group ( P = 0.001); the corresponding rates of long-term
toxic effects were 14% and 24%, respectively ( P = 0.01). The study concluded that pre-
operative chemoradiotherapy was the preferred treatment for patients with locally
advanced rectal cancer, with a superior overall compliance rate, an improved rate of
local control, reduced toxicity, and an increased rate of sphincter preservation in patients
with low-lying tumors [ 17 ] . A French trial (EORTC 22921) demonstrated that in
patients with rectal cancer who received preoperative radiotherapy and chemotherapy,
regardless of whether it was administered before or after surgery, conferred a signifi cant
benefi t with respect to improved local control ( P = 0.002) [ 18 ] .
A further French trial (FFCD 9203) also examined the benefi ts of adding chemo-
therapy to radiotherapy (45 Gy in 25 fractions) with randomization of 742 eligible
patients. The 5-year incidence of local recurrence was lower with chemoradiother-
apy (8.1% vs. 16.5%, P < 0.05). Overall 5-year survival in the two groups did not
differ. Grade 3 or 4 acute toxicity was more frequent with chemoradiotherapy
180
P. Rooney and N. Pranesh
(14.6% vs. 2.7%, P < 0.05). This trial did not show any difference in sphincter pres-
ervation. The authors concluded that preoperative chemoradiotherapy despite a
moderate increase in acute toxicity and no impact on overall survival signifi cantly
improves local control and is recommended for T3–4, N0–2, M0 adenocarcinoma
of the middle and distal rectum. The trial demonstrated complete sterilization of the
operative specimen in 11.4% of the chemoradiotherapy-treated patients [
19 ] .
Although an MRI scan is usually repeated postchemoradiotherapy to assess
response, the accuracy of MRI in determining the T stage in this setting is poor and
was reported to be 47% in a study that compared pre-op MRI and histopathology
post-op. This rises to around 70% in the prediction of nodal metastases [ 20 ] . Also,
in a study that assessed 297 patients after CRT and radical surgery, the survival of
patients with locally advanced tumors downstaged to stage 0 or 1 disease was equiv-
alent to patients who presented initially with stage 1 disease [ 21 ] . There is emerging
evidence that post-CRT stage is unrelated to pre-CRT stage with a complete patho-
logical response occurring in 10–30% of patients [ 22, 23 ] .
13.5.3 The Complete Response
There is considerable uncertainty about the management of patients who have an
excellent response to CRT. A recent study compared the long-term outcomes of
patients with T3 rectal cancer undergoing CRT followed by either local excision in
selected cases who demonstrated an excellent response ( n = 47) or TME ( n = 473),
retrospectively. In the local excision group, 23 patients (49%) had a complete response
to CRT, 17 (36%) had microscopic residual disease, and 7 (15%) had gross residual
disease, compared with 108 (23%), 89 (19%), and 276 (58%) TME patients, respec-
tively. There was no signifi cant difference in the 10-year actuarial local recurrence
rate between the two groups (10.6% and 7.6%, respectively, P = 0.52), and no signifi -
cant difference in disease-free survival, disease-specifi c survival, or overall survival
[ 24 ] . A landmark study in which patients with a complete endoluminal response
(with or without biopsy) 8 weeks post-CRT were managed conservatively instead of
surgically was published in 2004. Of 71 patients managed by observation alone (who
remained disease free after 1 year), only two developed an endoluminal recurrence at
around 5 years. Patients with an incomplete response post-CRT underwent radical
surgery. DFS and OS were equivalent in the two groups. Twenty-three patients in the
cohort managed conservatively developed recurrent disease within a year post-CRT
and underwent salvage surgery. There was no difference in DFS and OS between this
group and patients who underwent radical surgery [ 25, 26 ] . On the other hand, in a
study in which a complete clinical response was seen in 19% of 488 patients receiv-
ing CRT, the true pCR rate among this subgroup was only 25%. The remaining
patients were found to have persistent foci of tumor in the specimens [ 27 ] .
Postoperative CRT is now rarely used only in exceptional cases where there is an
unexpected CRM involvement (and the patient has not received preoperative radio-
therapy) [ 9 ] .
181
13 Evidence-Based Management of Rectal Cancer
13.5.4 MRI-Directed Treatment Strategy
The treatment of localized rectal cancer assessed by MRI as practiced in Sweden
was described in 2008 [
28 ] . Essentially, tumors were divided into the good, the bad,
and the ugly. Good prognostic indicators included T1 to early T3, N0 lesions with
clear CRM. These could be offered primary surgery. Bad lesions included the more
advanced T3 lesions, or nodal involvement, or lower position but with clear CRM.
These patients underwent radiotherapy with immediate surgery. The ugly lesions
had T4 stage with overgrowth into the prostate, seminal vesicles, base of urinary
bladder, pelvic sidewalls or fl oor, sacrum, or positive lateral nodes with CRM posi-
tivity. These patients required radiotherapy with delayed surgery.
13.5.5 Effects of Radiotherapy
As stated, the Dutch TME and the CR07 trials demonstrated a benefi t for SCPRT in
reduced local recurrence with SCPRT. In order to make decisions about individual
patients, it is necessary to know about the complications associated with radiother-
apy treatment.
A large study analyzed the acute side effects of SCPRT in 695 patients with rec-
tal cancer prospectively randomized to SCPRT followed by TME surgery (719
patients in the TME surgery alone group) [ 29 ] . Side effects were reported in 26% of
all patients receiving SCPRT; 19% were grade 1, and 7% grade 2/3 toxicities. Of the
17 patients suffering grade 3 toxicities, the majority ( n = 13) were neurological in
the form of severe gluteal or thigh pain. Of the remaining four patients, two suffered
thromboembolic complications, one required urinary catheterization, and another
blood transfusions as a result of severe proctitis.
Pollack et al. reported on the long-term functional outcomes in 64 patients ran-
domized within the Stockholm Radiotherapy Trials and operated on with low ante-
rior resection with or without SCPRT [ 30 ] . Twenty-one patients had received
preoperative radiotherapy, and 43 patients had been treated with surgery alone. They
found impaired anorectal function to be common after low anterior resection for
rectal cancer, and the risk was virtually doubled after radiotherapy.
In a large multicenter randomized trial comparing the impact of SCPRT on sex-
ual functioning and health-related quality of life (HRQL), although radiotherapy led
to more sexual dysfunction (in both males and females), there was little overall dif-
ference in HRQL [ 31 ] . Before treatment, 81% of SCPRT and 78% of the surgery
alone male patients and 53% of SCPRT and 50% of surgery alone female patients
were sexually active. Postoperatively, a decline in sexual activity was observed both
for male and female patients, which was larger in the SCPRT patients than surgery
alone patients. At 24 months, 76% of the surgery alone and 67% of the SCPRT male
patients who were previously active were still sexually active ( P = 0.06). For female
patients, these fi gures were 90% and 72%, respectively ( P = 0.01). For male patients,
sexual functioning (erection and ejaculation) deteriorated postoperatively more
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