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15 Recurrent Rectal Cancer
241
minimal mortality of 0.6 %. Although it was not statistically
signifi cant, complications were more common in patients
undergoing extended resections (requiring removal of at least
one of the adjacent organs); the majority of these were perineal wound complications or pelvic abscess. A study from the
Mayo Clinic reported 0.3 % in- hospital mortality and a 32 %
rate of major complications in 304 patients undergoing resection for recurrent rectal cancer [
8 ].
Complications and perioperative mortality increase with
more radical procedures, such as sacropelvic resection. In
1994, Wanebo et al. reported 8.5 % perioperative mortality
in 47 patients undergoing exenteration for recurrent rectal
cancer [
perineal and abdominal wound sepsis. It should be noted that
a signifi cant proportion of these procedures involved relatively high sacrectomies (S1 and S2). A 2006 study from the
Memorial Sloan-Kettering Cancer Center reported on complications following sacropelvic resection in 29 patients with
recurrent rectal cancer. Sacral resection was performed at the
S2/S3 level in 55 % and at the S4/S5 level in 45 % of the
study cohort. Previous surgery predicted the type of salvage
operation required: total exenteration with sacrectomy was
performed in 69 % of patients who had previously undergone
APR; a less radical procedure was done for those who had
75 ]. The majority of complications were related to
undergone sphincter-saving surgery. In 59 % of patients,
Table 15.2 Postoperative complications (%)
Wound infection [ 56 , 58 , 59 ] 3.1–13
Obstruction [
Pelvic abscess [
Urinary complications [
Enterocutaneous fi stula [
Perineal wound complications [
Neuropathy [
Table 15.3 Summary of long-term outcomes for multimodality therapy of recurrent rectal cancer
Study Pts Resected
Haddock
et al. (2009)
56 ]
[
Pacelli et al.
(2009) [
Hansen et al.
(2009) [
Dresen et al.
(2008) [
Heriot et al.
(2007) [
Asoglu et al.
(2007) [
Boyle et al.
(2005) [
Valentini
et al. (2004)
52 ]
[
Hahnloser
et al. (2002)
8 ]
[
Wiig et al.
(2002) [
Shoup et al.
(2002) [
Abbreviations: dash(-) not reported, y year, OS overall survival, LR local recurrence, DR distant recurrence, IORT intraoperative radiotherapy,
EBRT irradiation in those patients who had already received radiation therapy with their primary tumor, morb morbidity, mort mortality
a
Contains both colon and rectum; 427 (70 %) rectum
b
3 years
c
Study only includes those who underwent intraoperative radiation (111 of 634)
d
Disease-free survival
7 , 8 , 56 ] 5.3–13
7 , 8 , 57 – 59 ] 4–26
7 , 56 – 59 ] 4.4–23
8 , 58 ] 1.2–4.3
8 , 58 ] 4.6–9.4
56 ] 15
Cases
a
427
607
(rectum)
58 44 62.5 + (20) + − 20.9 7 25.7 11.5 − 54.2 72.4
15 ]
577 185 52.4 − + 48 (R0) − 1.6 − 17.5 25.1 14.9 62
74 ]
184 147 57.2 + (136) + (39) 28 58.5 4.8 % 45.9 31 20.4
57 ]
160 153 61.2 + (12) − 43 27 0.6 − − − 36.6 50
58 ]
72 50 48 − − 19 24 0.0 12.5 33 33.3 33 36
7 ]
64 57 36.8 − − 33.6 43.9 1.6 − 49 − 40
45 ]
59 30 35.6 − + (59) 42 15.4 2.6 31 17.8 30.5 39.3 66.8
429 304 45 + (131) + (244) 31 32 0.3 − − − 25 37
107 107 36 + (59) + 40 44 1.6 50 30 − 30 60
59 ]
48 ]
c
634
111 64 + (111) − 31.2 − 0 33 − 45 22 d 31.2 d
(%R0)
37 + (586) + (228) 36 50 1 28 28 53 30 46
IORT
+/− ( n )
EBRT
+/− ( n )
pedicle fl aps were used to reconstruct the pelvis. The total
complication rate was 59 %; 45 % were major complications, and most involved perineal wound breakdown and pelvic sepsis. There was one perioperative death [ 76 ].
Stoma
Key Concept: Permanent or temporary diversion is
routine in these cases and is associated with its own set of
Median
survival
(mos)
Morb.
(%)
Mort. 30
d (%) LR (%)
LR
(R0) DR (%) OS (%)
b
28 48.4
b
−
5-y OS
R0
242
T.D. Francone and M.R. Weiser
complications, which you should be prepared to manage.
Proper marking, preoperative involvement of an enterostomal therapist, and adequate technical construction can minimize stoma-related morbidity.
The reported incidence of ostomy complications has varied over the past three decades, ranging from 14 to 70 %
[
77 – 81 ]. Retrospective studies have identifi ed several risk
factors associated with increased overall stomal complications: poor perioperative siting, lack of stoma education by an
enterostomal therapist [ 82 , 83 ], height of the stoma (<10 mm)
[ 84 ], creation of a stoma after emergency surgery [ 78 ], and
patient comorbidities such as obesity [ 83 , 85 ], Crohn’s dis-
ease [ 83 ], and advanced age. Diabetes and smoking are asso-
ciated with poor wound healing and, on several univariate
analyses, have been found to play a potential role in ostomy
separation, retraction, and parastomal hernia [ 78 , 86 ].
Stoma-related complications can be categorized as early
or late. The most common complications occur in the immediate postoperative period (less than 30 days) and include
peristomal skin breakdown, stomal retraction, stomal necrosis, mucocutaneous separation, poor location, surgical
wound infection, and sepsis. Late complications (typically
6–12 weeks after surgery) include parastomal hernia, prolapse, retraction, stenosis, obstruction, and stomal bleeding.
Preoperative counseling has been shown to help patients
adapt psychologically to the signifi cant lifestyle changes
associated with having a stoma. Patients experience physical, psychosocial, and emotional stress, often because of
changes in sexual function, self-esteem, social acceptance,
and economic burden [ 87 ]. An enterostomal therapist should
educate patients about their upcoming surgery and prepare
them for what to expect afterwards. Counseling is not limited
to preoperative education but also includes stoma site selection, pre- and postoperative technical advice, emotional support for the patient and family, discharge planning, outpatient
follow-up, and ongoing rehabilitation [ 88 ]. Appropriate pre-
operative counseling has been associated with decreased
stoma-related complications [
stoma profi ciency, earlier discharge from hospital [
overall improvement in quality of life.
78 , 82 ], better postoperative
89 ], and
Oncologic Outcomes of Multimodal Therapy
Key Concept: With proper patient selection and (most importantly) the ability to achieve negative surgical margins, substantial improvements in survival and local control can be
achieved.
Results from multimodality treatment of locally recurrent
rectal cancer are encouraging, demonstrating improved survival and local control in select patients (Table 15.2 ). The
recent literature reports a broad range of 5-year overall survival ranging from 15 to 50 %, with local recurrence rates
between 12 and 50 % (Table 15.2 ). This wide variation may
be related to different regimens of multimodal therapy used
at different institutions. That being said, it is vital to reiterate
that the most important factor infl uencing prognosis in recurrent rectal cancer is complete surgical resection [
Multiple studies have linked R0 resection with 5-year local
recurrence rates as low as 12 % and 5-year overall survival as
high as 70 % [ 15 ].
Salo et al. [ 90 ] completed a 10-year retrospective analysis
of 131 patients with locally recurrent rectal cancer undergoing curative-intent surgery at the Memorial Sloan-Kettering
Cancer Center from 1986 to 1995. The goals of this study
were to determine predictors of resectability and assess postsalvage survival. Resection was accomplished in 79 % of
patients. Median hospital stay was 14 days. Overall 5-year
survival was 31 %. Concomitant salvage procedures included
sacrectomy (16 patients), partial vaginectomy [
tomy [
9 ], and pelvic sidewall dissection [ 21 ]. APR was per-
formed in 46 patients, low anterior resection in 20, total pelvic
exenteration in 18, Hartmann’s resection in 11, perineal
sacrectomy in 3, perineal excision in 3, and abdominal resection in 2. Fifty-two patients received IORT. Of the 71 patients
who had R0 resection, median survival was 42 months; 3-year
survival was 57 %; 5-year survival was 35 %. In patients with
R1 resection, median survival was 32 months; 3-year survival
was 38 %; 5-year survival was 23 %. In patients with an
incomplete R2 resection (with gross residual disease), median
survival was 27 months; 3-year survival was 36 %; 5-year
survival was 9 %. In the 28 patients who were not resected,
median survival was 16 months; 3-year survival was 4 %;
5-year survival was 0 % [ 90 ]. In a study of 29 patients under-
going sacropelvic resection, Melton et al. reported a median
disease-specifi c survival of 49 months for patients with R0
resection and 23 months for those with R1/R2 resection [ 76 ].
13 , 15 ].
15 ], hysterec-
Palliative Management
Key Concept: You and your patients should have realistic
expectations when dealing with recurrent rectal cancer.
Patients who are not viable candidates for surgery, or for whom
the desired surgical results cannot be achieved, should undergo
individualized palliative therapy based on their symptoms.
Despite progress in multimodality therapy, R0 resection is
achieved in 60–65 % of patients at best, and many patients
with recurrent disease are not eligible for surgery. Palliative
treatment strategies should be considered for those who are
not candidates for a potentially curative resection. The goal of
palliative therapy is to relieve symptoms—including bleeding, urinary or fecal obstruction, and pain secondary to nerve
root or bony involvement by tumor—and improve quality of
life. A palliative care plan should be tailored to the individual
patient, taking symptoms, age, comorbidities, and extent of
15 Recurrent Rectal Cancer
243
disease into account. For patients who are unresectable due to
diffuse metastatic disease or failure to meet resection criteria,
chemotherapy remains the fi rst-line treatment. Management
of symptomatic patients is challenging and may require multimodal interventions, including radiation, endoscopic stenting, fecal diversion, and laser or argon photocoagulation.
Radiation
Key Concept: In the setting of unresectable disease, reirradiation (delivered with palliative intent) may provide
symptomatic relief.
As part of palliative management, radiation has been shown
to improve pain and bleeding in patients with or without a prior
history of radiotherapy. Re-irradiation is generally well tolerated. A retrospective study by Mohiuddin et al. of 103 patients
receiving re-irradiation for recurrent rectal cancer demonstrated that bleeding was palliated in 100 % of patients, and that
this was durable in 80 %, until death. Pain was also well con-
a
trolled, although only 39 % were completely relieved of their
discomfort [ 51 , 53 , 91 ]. In a study by Valentini et al., 83 % of
patients who had previously been irradiated obtained pain
relief from combined chemotherapy and re-irradiation [
52 ].
Self-expanding Metallic Stents (SEMS)
Key Concept: Stents may be used for palliation of obstructing rectal cancer in select patients.
In patients under close surveillance after their index operation, rectal obstruction is rare. This is because, before
developing obstruction, the majority present with symptoms
such as changes in bowel habits or rectal pressure. In the
event of an obstructing recurrent tumor, there are several
treatment options, including self-expanding metallic stents
(SEMS), operative fecal diversion, or palliative resection
(Fig. 15.5a, b ). Stents may provide a less invasive alternative
to palliative surgery, resulting in shorter hospital stays and
less morbidity and mortality. Data on stents in the setting of
Fig. 15.5 ( a ) Endoscopic view
of a stent or near-obstructing
rectal cancer (Courtesy of W.
Brian Sweeney, MD). ( b ) Plain
radiograph demonstrating the
stent in place (Courtesy of W.
Brian Sweeney, MD)
244
T.D. Francone and M.R. Weiser
b
Fig. 15.5 (continued)
recurrent rectal cancer is limited, but in primary stage IV
rectal cancer, the success rate of stent placement is reportedly as high as 95 %, and SEMS have been found to provide
long-term relief in a majority of patients [ 92 , 93 ]. Stent fail-
ure may occur, however. Early complications include malposition or perforation, and long-term complications include
stent migration or occlusion. Stent placement in obstructing
low rectal cancers (less than 5 cm from the anal verge) has
traditionally been contraindicated because of increased pain,
tenesmus, incontinence, and greater risk of migration. One
small 2008 study suggested otherwise, concluding that stents
placed within 5 cm of the anal verge can be tolerated and
provide acceptable relief [ 94 ]. In either case, a stent failure
rate of approximately 20 % can be expected, and this requires
surgical intervention [
92 , 93 ].
Surgery: Fecal Diversion vs. Palliative Resection
A diverting stoma is preferred to palliative resection, and is
a helpful alternative to endoscopic stenting if obstruction
has occurred.
Fecal diversion can be accomplished effectively with an
ileostomy or colostomy, though a sigmoid colostomy is preferable and more commonly used. The stoma can be created
via a laparoscopic or open approach. The laparoscopic
approach is more diffi cult in the setting of severely dilated
intestine; however, given the numerous benefi ts such as
reduction of pain and shorter hospital stay, a minimally invasive approach is preferred whenever feasible.
Palliative resection to relieve symptoms should generally
be avoided in patients with incurable disease. Such procedures are associated with increased morbidity, but provide
little improvement in quality of life.
Multidisciplinary Approach
Key Concept: Optimal decision-making requires interdisciplinary communication and coordination among multidisciplinary teams (MDTs).
Ideally, all treatment should be individually tailored,
based on clinical, diagnostic, and physical fi ndings, as well
as on the patient’s values and overall quality of life. A multidisciplinary approach is the most effective way to meet these
goals. The importance of formal multidisciplinary meetings
has been acknowledged in many European countries since
the late 1990s and is gaining favor in the United States. The
National Institute for Clinical Excellence in London has
published updated guidelines for organizing MDTs
(Improving Outcomes in Colorectal Cancers) [
Recommendations include a designated team coordinator
and weekly meetings, attended by core members, providing
peer review of tumor pathology and radiology.
Although there is limited data on MDTs in colorectal surgery, the evidence from esophageal, gastric, hepatobiliary,
breast, and ovarian cancer surgery suggests that this approach
improves patient selection and overall survival [ 96 – 99 ].
Multidisciplinary teams also provide a framework for assessing quality assurance. Outcomes such as TME grading, positive circumferential margins, and sphincter-sparing
techniques have been used as surrogates to determine if
MDTs are benefi cial. In 2007, an audit by the National
Health Service Team in Yorkshire, UK, demonstrated that
the presence of MDTs is associated with increased use of
preoperative radiation and higher rates of anterior resection
in patients with primary rectal cancer, and a [nonsignifi cant]
trend towards increased survival rates [ 100 ]. A recent retro-
spective case–control study by MacDermid and colleagues
[ 101 ] examined the impact of MDTs on outcomes in 310
patients undergoing colectomy for colorectal cancer. Patients
in the MDT cohort were more likely to receive adjuvant chemotherapy, and this may have contributed to a signifi cant
survival advantage: a 3-year survival of 58 % for Dukes C
patients in the control group, and a 3-year survival of 66 % in
95 ].
15 Recurrent Rectal Cancer
245
the MDT group ( p = 0.023). On hazard regression analysis,
MDT status was also shown to be an independent predictor
of survival ( p = 0.044).
Centers of Excellence
Key Concept: While somewhat controversial, improved outcomes have been associated with high-volume, subspecialtytrained surgeons and designated centers.
The implementation of multidisciplinary teams may pose
challenges with respect to hospital resource allocation, organization and coordination of specialists’ schedules, attendance and participation in MDT meetings, and broad
acceptance of the team approach. The MDT is more likely to
exist in large academic institutions where there are more
subspecialist physicians. Consequently, the data suggests
that high-volume colorectal cancer centers with experienced
subspecialty teams have better mortality and higher sphincter-sparing rates. Archampong et al. [ 102 ] performed a recent
meta- analysis of 11 studies including over 18,000 patients,
examining the relationship between surgeon caseload and
patient outcomes. They demonstrated that high surgeon volume was associated with lower rates of permanent stomas
and APRs, as well as improved 5-year survival. At Memorial
Sloan- Kettering Cancer Center and other cancer specialty
centers, multidisciplinary evaluation and discussion are considered part of the standard of care for all patients with rectal
cancer.
Summary Pearls
The surgical management of recurrent rectal cancer is complex, requiring detailed preoperative work-up and careful
selection of patients for resection. Proper radiologic imaging
may provide critical information on the extent of local recurrence and tumor invasion, so that a detailed operative plan
can be formulated. Resection of recurrent rectal cancer is
characteristically extensive and associated with high morbidity. You should undertake it only when cure is considered
possible. Even with combined modality treatments, including neoadjuvant therapy and complementary use of IORT,
the ability to achieve adequate, microscopically negative
margins is the single most important factor in achieving better outcomes, including cure.
The role of multidisciplinary teams in optimizing patient
outcomes is evolving. Implementation of MDTs can provide
the framework and the means for developing patient-tailored treatment strategies and a more seamless coordination of care. These teams include colorectal surgeons as
well as urologists, gynecologists, orthopedic, neurologic,
plastic and reconstructive surgeons, radiation and medical
oncologists, and others. Input from stoma therapy nurses,
dieticians, and preoperative counselors is also essential
in preparing patients for the rigors of treatment. Patients
must be psychologically prepared for extensive resection,
prolonged hospital stay, a high incidence of morbidity, and
the possibility that their disease will be found unresectable
intraoperatively.
Multimodality treatment, including radical R0 surgery,
offers the greatest potential for cure in patients with locally
recurrent rectal cancer. Following combined modality treatment in carefully selected patients, a 5-year survival of up to
60 %, with acceptable morbidity, can be achieved.
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The Approach to the Rectal Cancer Patient with a Suspected Complete Clinical Response: Selection of Patients to the Watch and Wait Strategy
Rodrigo O. Perez and Angelita Habr-Gama
Key Points
• Tumor response following neoadjuvant chemoradiation will help determine the subsequent management for locally advanced rectal cancer.
• Classical indications for neoadjuvant chemoradiation need to evolve to include earlier stage tumors
to achieve maximal effectiveness and avoid radical
surgery.
• Stringent criteria and appropriate evaluation are
critical to determining who can effectively and successfully partake in the watch and wait strategy.
• Your history and physical examination should be
the major determinant of clinical response, followed by adjuvant laboratory and radiological testing to confi rm or refute your clinical fi ndings.
Introduction
Rectal cancer management has become increasingly complex over the last few decades [
neoadjuvant therapies has introduced a new variable, tumor
response, which may dramatically change ultimate surgical
R. O. Perez , MD, PhD (*)
Division of Colorectal Surgery, Department of Gastroenterology ,
University of São Paulo School of Medicine ,
São Paulo , Brazil
Angelita and Joaquim Gama Institute , São Paulo , Brazil
e-mail: rodrigo.operez@gmail.com
A. Habr-Gama , MD
Department of Colorectal Surgery ,
Angelita and Joaquim Gama Institute ,
Rua Manoel da Nóbrega 1564 , São Paulo , Brazil
Department of Gastroenterology ,
University of São Paulo School of Medicine , São Paulo , Brazil
1 ]. The widespread use of
1 6
decision from radical surgery to local excision, transanal
endoscopic microsurgery, or even no surgery at all for the
management of these patients. In this setting, surgeons have
to consider many aspects of the disease prior to deciding on
a defi nitive treatment approach.
Indications for Neoadjuvant Therapy
Key Concept: Earlier stage tumors (cT2N0) may be more
likely to develop complete clinical response and benefi t the
most from neoadjuvant CRT.
Classical indications for neoadjuvant therapy in rectal
cancer are mostly derived from randomized controlled studies that showed a local control benefi t among patients with
cT3-4 or cN+ treated with radiation or chemoradiation followed by radical surgery [ 2 , 3 ]. However, recent updates
with longer follow-up of these same cohorts suggest that the
benefi ts in local disease control following neoadjuvant CRT
and radical surgery are marginal or even outweighed by
treatment-related toxicities [ 4 – 6 ]. Therefore, except for cir-
cumferential margin positivity, local control is not expected
to be signifi cantly increased with the use of neoadjuvant
CRT provided appropriate total mesorectal excision is performed, even for cT3 or cN+ disease.
On the other hand, neoadjuvant radiation alone, chemoradiation, or even chemotherapy alone may lead to signifi cant
tumor regression resulting in signifi cant changes in tumor
size, depth of penetration, nodal sterilization, and even complete tumor disappearance, also known as complete pathological response (pCR) [ 7 , 8 ]. Not only does this latter group
of patients with pCR have improved oncological outcomes
but also the opportunity of being spared from radical surgery
and its associated immediate morbidity, mortality, functional
disorders, and need for stomas [ 9 – 11 ].
The problem is that if you give neoadjuvant therapy only for
advanced stage disease patients, very few will develop complete tumor response (up to 30 %). However, neoadjuvant therapy may be extremely useful for the selection of those patients
S.R. Steele et al. (eds.), Complexities in Colorectal Surgery,
DOI 10.1007/978-1-4614-9022-7_16, © Springer Science+Business Media New York 2014
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