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Recurrent Rectal Cancer
Todd D. Francone and Martin R. Weiser
Key Points
• Preoperative considerations in the setting of locally
recurrent rectal cancer are extensive. Meticulous
evaluation before surgery is necessary to determine
if the patient is medically fi t and the tumor is resectable. In some cases, determination of resectability
can only be made intraoperatively.
• Proper radiographic imaging can demonstrate the
local extent of tumor recurrence, facilitating
a detailed operative plan for en bloc resection.
• The single most important factor in optimizing outcomes is complete excision of the tumor with negative macroscopic and microscopic margins.
• Management of recurrent rectal cancer is often
complex, requiring the involvement of a multidisciplinary team. Designing a care plan should be based
not only on clinical, diagnostic, and physical fi ndings but also on the individual patient’s goals and
expectations.
Introduction
Key Concept: Pelvic recurrence of rectal cancer is one of the
most challenging clinical situations you may encounter.
While multiple factors contribute to recurrence, technical
factors, including the ability to achieve negative margins,
are imperative to limit recurrent disease and improve
T. D. Francone , MD, MPH
Division of Surgery, Department of Colon and Rectal Surgery ,
Lahey Clinic , 41 Mall Road , Burlington , MA 01805 , USA
e-mail: todd.d.francone@lahey.org
M. R. Weiser , MD (
Department of Surgery , Memorial Sloan-Kettering Cancer Center ,
1275 York Avenue , New York , NY 10021 , USA
e-mail: weiser1@mskcc.org
*)
1 5
long- term outcomes following operative therapy for recurrent rectal cancer.
Rectal cancer reportedly recurs within the pelvis at a rate
of 4–33 % following curative-intent resection of the primary
lesion. Recurrence typically presents within 5 years of the
index operation; however, later recurrences are possible.
Pelvic recurrence is associated with a poor prognosis and
distressing symptoms that are diffi cult to palliate.
Multiple factors, including surgeon experience, have been
shown to infl uence oncologic outcomes [ 1 ]; surgeons who
perform more than 12 cases per year appear to have lower
local recurrence rates than those who operate less [ 2 ].
Pathologic factors such as lymphovascular invasion and poor
differentiation also increase the risk of local recurrence [ 3 , 4 ].
Although the reasons for recurrence are numerous, extent of
resection is the most critical factor; positive distal and/or positive circumferential margins are associated with local recurrence rates as high as 55 % [ 2 , 3 , 5 ]. Conversely, negative
microscopic resection margins (R0) are associated with the
lowest recurrence rates and the most favorable prognosis [ 6 ].
For patients with recurrence limited to the pelvis, multivisceral/extended rectal resection is the defi nitive surgical therapy.
However, in recurrent disease, the surgical planes are disrupted
by initial resection of the primary tumor, making re-resection
signifi cantly more challenging. These procedures are associated with considerable morbidity and require extensive surgical
planning. A multidisciplinary team including surgeons, medical and radiation oncologists, radiologists, intensivists, specialized nurses, and occupational and physical therapists should be
assembled to address the multifaceted issues that are likely to
arise. The surgical team alone may include specialists in
colorectal, urologic, gynecologic, orthopedic, neurologic, and
plastic/reconstructive surgery. Multimodal therapy has played
an essential role in the trend towards improved oncologic
outcomes, including re-irradiation with external beam and
intraoperative radiotherapy (IORT).
In this chapter, we will discuss the diagnosis, evaluation, and
multimodal management of locally recurrent rectal cancer, as
well as the associated perioperative and oncologic outcomes.
S.R. Steele et al. (eds.), Complexities in Colorectal Surgery,
DOI 10.1007/978-1-4614-9022-7_15, © Springer Science+Business Media New York 2014
231
232
T.D. Francone and M.R. Weiser
Presentation
Key Concept: Identifying local recurrence is challenging, as
patients can present with or without symptoms.
Locally recurrent rectal cancer usually manifests months
to years after the initial operation, with a mean time to
recurrence of 25–36 months [ 6 – 11 ]. In a population-based
study by Palmer et al. of 141 patients with locally recurrent
rectal cancer, 70 % presented within the fi rst 2 years and
85 % within 3 years after initial surgery [ 9 ]. The majority
presents with symptoms, precipitating work-up and diagnosis. The most common symptoms are pain, rectal bleeding,
or changes in bowel habits. Thirty-fi ve percent or fewer are
asymptomatic, and the recurrence is discovered on routine
surveillance follow-up [ 8 , 9 ]. Pelvic pain indicates possible
involvement of other organs, bones, or nerves. Therefore,
pain as a presenting symptom is of concern and portends a
poor prognosis. If the initial operation was abdominoperineal resection (APR), a palpable mass in the perineum or
nonhealing wound may indicate perineal recurrence. Small
bowel obstruction suggests involvement of the small
intestine.
Preoperative Evaluation and Staging
Preoperative Planning
Key Concept: Prior to embarking on surgery for recurrence,
you must determine the feasibility of resecting all disease
with negative margins. Patients must be evaluated for comorbid conditions, and their ability to tolerate and recover from
reoperative surgery.
Proper preoperative evaluation is imperative when contemplating radical surgery for recurrent rectal cancer. A
thorough examination of the patient’s medical records,
including operative reports and history of previous chemoradiation treatments, provides valuable information regarding
anatomy and prognosis and helps determine a plan of care.
Patients of advanced age, with signifi cant comorbidities or
poor performance status (ASA IV–V), are rarely candidates
for the extensive surgery that is necessary. Appropriate risk
assessment requires consideration of patient cognitive function as well. Distant metastatic disease must also be ruled
out. In the presence of distant metastasis, such potentially
morbid surgery offers little possibility of cure.
Physical Examination
Key Concept: Physical examination is an important part of
the work-up of recurrent disease.
A proper physical evaluation (including digital rectal and
vaginal examination) is crucial. Whenever possible, rectal
examination with proctoscopy should be done. This may reveal
the level, position and extent of tumor, as well as its fi xation to
adjacent organs and/or the bony pelvis. In addition, you will be
able to get a sense for the response to any prior chemotherapy
or additional radiation therapy. Vaginal exam in female patients
is essential in order to clarify posterior vaginal wall involvement that may require en bloc resection. Additionally, it will
highlight the need to involve your plastic surgery colleagues for
a potential fl ap to close the resultant defect. In patients whose
initial operation was an APR, careful examination of the
perineum and surgical scar may reveal the presence of a palpable mass. A thorough pelvic exam is often the simplest, most
direct method of determining whether sphincter-sparing surgery is feasible, or multivisceral resection or exenteration necessary. A complete colonoscopy should also be done whenever
possible, to rule out synchronous primary tumors. Tissue diagnosis is typically necessary to differentiate scar from recurrent
disease, especially if the tumor extends intraluminally.
Carcinoembryonic Antigen
Key Concept: Although CEA monitoring is controversial,
persistently elevated levels of CEA warrant work-up for
recurrent and metastatic disease.
The American Society of Clinical Oncology currently
recommends that postoperative serum carcinoembryonic
antigen (CEA) testing be performed every 2–3 months, for
≥3 years after diagnosis, in patients with stage II or III disease [ 12 ]. An elevated CEA level warrants further evaluation
for metastatic as well as locally recurrent disease. The relevance of CEA in evaluating recurrence remains controversial. A few studies demonstrate signifi cant association
between high levels of CEA and poor prognosis, including
decreased overall survival [ 7 , 13 – 15 ].
Radiologic Imaging
Key Concept: Radiologic imaging is the most commonly
used tool in staging locally recurrent rectal cancer. Accurate
imaging can clarify the size, location, level, and extent of
recurrence (both local and extrapelvic); delineate potential
invasion into adjacent structures; and help determine
appropriate patient selection for resection.
Local Disease
Verifi cation of recurrent disease, often done by computed
tomography (CT)-guided biopsy, is recommended before
undertaking surgery. However, the challenge of imaging
recurrent disease is complicated by the fact that previous surgery for the primary tumor makes it diffi cult to differentiate
recurrent tumor from fi brosis. Magnetic resonance imaging
(MRI), if available, is often the tool of choice.
15 Recurrent Rectal Cancer
233
Computed Tomography (CT)
Key Concept: While not as accurate as MRI, CT is a great
initial examination to assess the gross extent of local disease
and rule out distant recurrence.
Contrast-enhanced CT scanning and MRI are the imaging
tools most often used to diagnose recurrent rectal cancer. The
accuracy of CT in showing tumor invasion (in both primary
and recurrent rectal cancer) has consistently proven inferior
to the accuracy of MRI. For example, in a study by BeetsTan et al., the sensitivity of CT in predicting tumor invasion
was 70 %, with an associated specifi city of 85 % [
16 ]. This
is because CT does not accurately differentiate between
fi brosis, normal tissue, and recurrent tumor. Nevertheless, in
our experience, CT has been very useful in the initial work up of a locally recurrent tumor mass, or when distant disease
in the abdomen is suspected.
Magnetic Resonance Imaging (MRI)
Key Concept: MRI has better accuracy than CT in detecting
recurrent disease and delineating pelvic anatomy.
At the present time, MRI provides the best imaging of
pelvic and extra-rectal involvement available. The inherently
high soft tissue contrast resolution of MRI enables it to differentiate between normal tissue, scar tissue, and tumor. This
is because tumor has a relatively high water content, and
therefore a high T2w image; scar tissue has a comparatively
low water content, and low signal intensity, on both T 1 weighted and T 2 -weighted images.
Although MRI is consistently more accurate than CT in
identifying local recurrence, it has limitations. In the setting
of primary rectal cancer, MRI has demonstrated a sensitivity
of 95 % and a specifi city of 85–100 % in identifying local
invasion [ 16 , 17 ]. However, recent literature suggests that
MRI may not be as reliable in evaluating locally recurrent
rectal cancers, showing a sensitivity of 77–100 % and a specifi city of 29–92 % [ 18 – 22 ]. A few studies have concluded that
the accuracy of MRI varies according to anatomical location,
with lower accuracy as regards the pelvic sidewall and pelvic
fl oor. Messiou et al. reported their experience using MRI
phased-array coil to identify recurrent tumor invasion at specifi c sites in the pelvis, prior to salvage surgery, in 49 patients
over a 6-year period. In 30 of these patients, pelvic sidewall
invasion was identifi ed with MRI before surgery, but only 21
were confi rmed on histologic examination. The authors concluded that tumor detection with MRI showed a sensitivity of
70 % and a specifi city of 94 % [ 20 ].
As is the case with other imaging modalities, inaccuracy
in MRI may be due to disruption of the anatomic planes from
previous surgery (which increases the likelihood of fi brosis,
granulation, and hematoma formation) or to radiationinduced infl ammatory changes [ 22 , 23 ]. Tumor tissue and
fi brosis commonly coexist, resulting in relatively low signal
intensity on T
-weighted imaging. This is true not only in
2
recurrent disease but in tumor radiated before the index
surgery; in either case, it may result in a false negative. These
limitations support the practice of biopsying any fi brotic tissues suspicious for malignancy. Dynamic MR has been utilized to distinguish fi brosis from tumor, based on the
principle that recurrent tumor tissue shows earlier and greater
degrees of enhancement than fi brosed tissue. The results for
dynamic MR vary in the literature, with reported sensitivity
ranging from 83 to 97 % and specifi city from 81 to 100 %
[
19 , 21 , 24 ].
FDG-PET
Key Concept: FDG-PET can help distinguish benign fi brosis
from recurrent disease.
Fluorine-18 fl uorodeoxyglucose positron emission
tomography (FDG-PET) may also be of value in the preoperative staging of locally advanced and recurrent rectal cancer. FDG-PET identifi es changes in tumor glucose
metabolism [ 25 ] and can be useful in the setting of recurrent
disease [ 26 – 30 ]. Furthermore, FDG-PET may supplement
other imaging modalities in distinguishing viable tumor
from scar. In a meta-analysis by Huebner et al. including 366
patients with local pelvic recurrence, FDG-PET showed an
overall sensitivity of 94.5 % (95 % CI, 90.8–98.2 %) and a
specifi city of 97.7 % (95 % CI, 95.7–99.7 %). The authors
found that—when added to standard imaging techniques in
diagnostic work-up—FDG-PET fi ndings led to a change in
clinical management in about 30 % of patients with recurrent
disease [ 31 ].
Integrated FDG-PET/CT combines the benefi ts of functional and anatomical/morphological imaging, and appears
to hold additional promise in distinguishing benign from
viable malignant tumor. In a study by Votruba et al. of 84
patients with suspected colorectal cancer recurrence, FDGPET demonstrated overall sensitivity and specifi city of 80
and 69 %, respectively. When integrated FDG-PET/CT was
used, sensitivity and specifi city increased to 89 and 92 %,
respectively [ 32 ]. Similarly, in a study of 62 patients with
local recurrence after APR or low anterior resection,
Evan-Sapir et al. reported that integrated FDG-PET/CT
demonstrated better accuracy than FDG-PET in differentiating between malignant and benign lesions, with an overall
accuracy of 74 and 92 %, respectively [ 27 ].
Distant Disease
The usefulness of CT scans of the chest and abdomen in
identifying hepatic metastases is well accepted. However,
CT reportedly misses or underestimates extent of disease in
a signifi cant proportion of patients [ 33 ]. Several recent stud-
ies have suggested that FDG-PET/CT is superior to CT,
EUS, and MRI in this regard [
34 – 36 ]. A meta-analysis by
Kinkel et al. concluded that FDG-PET/CT is more sensitive
than ultrasound, CT, or MRI in detecting gastroesophageal
and colorectal hepatic metastases [ 34 ], and studies by Bipat
et al. [
36 ] and Mainenti et al. [ 35 ] concluded that PET/CT
234
T.D. Francone and M.R. Weiser
showed superior sensitivity in detecting colorectal hepatic
metastases. In a study comparing FDG-PET and CT fi ndings
in 103 patients with suspected colorectal cancer recurrence,
Flamen et al. concluded that FDG-PET had higher sensitivity than CT in identifying metastatic lymph nodes, as well as
lung and peritoneal disease [ 37 ]. Because of its ability to
detect early metastatic disease, FDG-PET/CT has infl uenced
clinical management in up to 40 % of patients with recurrent
colorectal cancer [
38 – 40 ].
Imaging Summary Recommendations
In our experience, most patients will present after undergoing imaging with an abdominopelvic CT. We use this as a
general guide to look for gross disease, pelvic sidewall
involvement, or other indications of potentially nonresectable disease (i.e., bilateral hydroureter, extensive iliac
involvement). We routinely use MRI to give us a preoperative roadmap for helping with fascial planes or in cases
where there is still a question regarding differentiation
between recurrent disease and post-therapeutic changes. In
our hands, FDG-PET is most useful both in differentiating
benign from malignant disease locally in the pelvis and
determining the activity of small distant lesions (i.e., liver,
lung) that may represent metastatic disease.
Histology
Key Concept: Tissue confi rmation should be attempted
whenever possible, before subjecting a patient to radical surgery for a suspected local recurrence.
In the event of an intraluminal recurrence, endoscopic
retrieval of a tissue specimen is the obvious choice. When a
suspected pelvic recurrence is not amenable to endoscopic
biopsy, radiographic-guided biopsy is recommended. CT
and MRI have both been used in tissue sampling. In some
circumstances, however, tissue diagnosis is not feasible, or
biopsy results are inconclusive. Nevertheless, if there is convincing radiologic evidence for recurrence, it is reasonable
to proceed with surgical exploration. The patient should be
properly educated and counseled preoperatively. He or she
must be willing to accept the risks of the procedure despite
the possibility that tumor will not be found within the surgical specimen.
Classifi cation and Patterns of Recurrence
Key Concept: The pattern of recurrence is a factor when
determining resectability.
Patterns of recurrence signifi cantly infl uence the possibility of achieving an R0 resection. A useful and simple classifi cation system by Moore et al. [
6 ] utilized anatomical
location to categorize tumors: (1) axial, not involving anterior, posterior, or lateral pelvic walls (this includes anastomotic recurrence after low anterior resection, local recurrence
after transanal or transsphincteric excision, and perineal
recurrence after APR); (2) anterior, involving the urinary
bladder, vagina, uterus, seminal vesicles, or prostate; (3)
posterior, involving the sacrum and coccyx; and (4) lateral,
involving the bony pelvic sidewall or sidewall structures,
including the iliac vessels, pelvic ureters, lateral lymph
nodes, pelvic autonomic nerves, and sidewall musculature.
This system contributes to a standardized approach in the
pre- and postoperative management of local recurrence.
D e fi ning Resectability
Key Concept: Resectability pertains not only to the pattern of
recurrent disease but also to the individual patient’s ability
to tolerate the morbidity of the operation and the potential
functional challenges that may occur postoperatively.
Resectable recurrent rectal cancer is defi ned as tumor that
may be completely removed with curative intent (i.e., with
histologically negative margins (R0)). The literature is consistent in this regard [
however, resectability should also be defi ned in terms of
acceptable morbidity for the individual patient. Careful
patient selection and proper risk assessment are critical.
Patients with signifi cant comorbidities or poor performance
status (ASA IV–V) are rarely candidates for the extensive
surgery that is required. Several other patient-related factors
associated with decreased probability of an R0 resection
include male gender [ 41 ], advanced age at initial diagnosis
[ 42 ], advanced stage of the primary tumor [ 42 ], and previous
APR [ 41 , 42 ].
In a series of 116 patients treated at Memorial SloanKettering Cancer Center, Moore et al. [ 6 ] found that tumors
confi ned to the axial location, or to the axial and anterior
locations, were more likely to be completely resectable than
tumors involving the pelvic sidewall or lateral structures.
The authors reported that negative margins were achieved in
90 % of patients with axial recurrences only (anastomotic
recurrence), and in 71 % of patients with axial and anterior
recurrences only. Negative margins were also achieved in
64 % of patients with lateral involvement by tumor, and in
55 % of patients without iliac vessel involvement. However,
negative margins were obtained in only 43 % of patients with
tumor located anywhere but axially and anteriorly. Where
there was lateral involvement by tumor, negative margins
were achieved in only 35 % (and reportedly in as few as 0 %,
in other studies) [
nephrosis or iliac vessel involvement was associated with an
R0 resection in only 17 and 29 % of patients, respectively.
Other studies have supported these fi ndings, suggesting that
6 ]. Because of the rigors involved,
43 ]. Involvement of the ureter with hydro-
15 Recurrent Rectal Cancer
235
bilateral hydronephrosis and tumor encasement of the iliac
vessels are contraindications to re-resection.
Posterior recurrence is associated with an even lower
probability of R0 resection [ 43 – 45 ]. Complete removal of
these tumors requires technically challenging procedures
involving en bloc resection of the tumor and part of the
sacrum. The major sequelae associated with such operations
include neurologic defects involving the bladder, anorectal
and sexual function, and potential musculoskeletal defects
related to wound dehiscence. High sacrectomy (S1/S2) is
associated with greater morbidity than mid-level or low
sacrectomy. Nerve root involvement is a contraindication to
resection because of the potential for resulting neurologic
defects. Although bony and neurologic constraints may preclude resection, when curative-intent surgery is feasible and
an R0 resection accomplished, there are lower recurrence
rates and improved survival [ 44 ]. As the sacrectomy level
decreases, the possibility of a complete resection increases.
In a recent study by Sagar and colleagues [
46 ], R0 resection
was achieved in 13 of 40 patients undergoing abdominosacrectomy for recurrent rectal cancer. Complete resection was
associated with a signifi cantly improved median survival (56
months for R0 vs. 32 months for R1; p = 0.048). Moriya et al.
described abdominosacral resection in 69 patients with
recurrent rectal cancer, reporting an R0 rate of 83 % and
3-year disease-specifi c survival of 62 % in patients with
negative margins [ 47 ].
The degree of tumor fi xation within the pelvis signifi cantly
infl uences the feasibility of curative surgery and overall survival. In 2003, Hahnloser and associates demonstrated that
patients with two or more sites of fi xation had a signifi cantly
worse outcome compared to patients with mobile tumors or
only one site of fi xation. Degree of fi xation was determined
on preoperative imaging or at the time of surgery. Local
recurrences were classifi ed as not fi xed (F0), fi xed at one site
(F1), fi xed at 2 sites (F2), or fi xed at three or more sites (F3).
A greater number of fi xation sites indicated more extensive,
locally advanced tumors requiring technically more challenging radical surgery, and outcomes were worse with respect to
local failure and long-term survival [ 8 ].
Other factors associated with poor long-term outcomes
include APR as the original procedure, elevated preoperative
CEA, preoperative pain, vascular invasion, and aggressive
tumor biology [ 6 , 10 , 48 ].
For patients deemed to be resectable, counseling regarding the impact of surgery on quality of life is critical. While
a low anterior resection restores intestinal continuity, it may
also result in signifi cant urgency or incontinence. Patients
undergoing an APR with end colostomy should receive
proper preoperative teaching and counseling regarding the
potential physical, social, and psychological diffi culties
associated with having a stoma. However, surgery should
generally be avoided in patients with disease characterized
by circumferential pelvic sidewall involvement, bilateral
ureteral obstruction, S1 or S2 bony or neural involvement,
sciatic pain and pelvic imaging evidence of sciatic nerve
involvement, or unresectable extrapelvic metastases. Patients
who are not resectable should be counseled regarding the
eventual worsening of their symptoms, including pain,
bleeding, and obstruction. Palliative care professionals can
help provide some relief of symptoms, as well as psychosocial and supportive care for patients and their families.
Management of patient expectations in these circumstances
requires understanding and compassion on the part of the
surgeon and multidisciplinary team.
Multimodal Therapy
Role of Neoadjuvant Therapy
Key Concept: Neoadjuvant chemoradiation therapy plays a
signifi cant role in the setting of recurrent disease, as it does
in primary rectal cancer. Prior treatment and total dosage
will help determine appropriate selection of agents and
treatment strategies.
In both primary and recurrent rectal cancer, multimodality therapy including chemotherapy and radiation is the standard of care. In primary disease, preoperative chemoradiation
has been shown to reduce local recurrence more effectively
than postoperative chemoradiation [ 49 ]. Preoperative
chemoradiotherapy may effect tumor downsizing [ 49 , 50 ],
potentially facilitating complete resection of locally
advanced disease. Therefore, neoadjuvant chemoradiation
has become a standard practice in the treatment of locally
advanced rectal cancers.
Most patients presenting with locally recurrent cancer
have already been irradiated. Patients with pelvic recurrence
who have not previously received radiation for their primary
tumor should be considered for preoperative chemoradiotherapy. Treatment usually consists of external beam radiation up to a dose of 50.4 Gy, with concurrent 5-fl ourouracil
(5-FU)-based chemotherapy [ 49 , 50 ]. Because of the risk of
late toxicity, fi stula formation, and bowel obstruction, radiation is generally contraindicated in patients who have already
received radiotherapy to a total dose up to or greater than
50.4 Gy. However, recent studies demonstrate that
re- irradiation is reasonably well tolerated if the previous
dose was less than 50.4 Gy, and a signifi cant percentage of
re- irradiated patients go on to radical surgical salvage. The
American College of Radiology recommends that additional
doses of radiation be based on the initial dose given, amount
of small bowel in the treatment fi eld, length of time to
recurrence, size of the previously treated cancer, and size of
the recurrent tumor. The dose typically ranges from 20 to
40 Gy, with acceptable late toxicity rates of 12 and 21 %,
236
T.D. Francone and M.R. Weiser
respectively [ 51 ]. A study by Valentini et al. evaluated the
response rate, resectability rate, local control, and treatmentrelated toxicity of preoperative hyperfractionated chemoradiotherapy in patients with locally recurrent rectal cancer
who had previously received radiation. They found that
86.4 % of patients completed treatment without interruption,
with a 5.1 % rate of acute lower GI toxicity and no grade 4
toxicity. More than 44 % had either a complete or partial
response after re-irradiation [
52 ].
In a study by Pacelli and colleagues involving 58 patients
with recurrent rectal cancer, the authors found that patients
who had undergone previous radiotherapy tolerated either
23.4 Gy in 1.8 Gy fractions, or 1.2 Gy BID to 40.8 Gy preoperatively. Radiation treatment was completed in all patients,
with no major complications reported. In 2002, Mohiuddin
and colleagues [ 53 ] reported on the long-term results of re-
irradiation in patients with recurrent rectal carcinoma. A total
of 103 patients with recurrent rectal carcinoma received reirradiation with concurrent 5-FU-based chemotherapy. After
a median dose of 3,480 cGy, 34 patients underwent surgical
resection for residual disease. The median and 5-year survival
of patients undergoing surgical resection after re-irradiation
was 44 months and 22 %, compared with 14 months and
15 % for patients treated with re- irradiation only ( p = 0.001).
Patients who cannot undergo any additional radiation
may be candidates for aggressive chemotherapy. First-line
multi-agent chemotherapy typically includes a combination
of oxaliplatin or irinotecan along with the 5-FU/leucovorin
regimen. Second-line regimens may include a combination
of other targeted agents, including bevacizumab and
cetuximab.
Imaging should be done at 4–6 weeks from the completion of treatment to rule out interval progression of local disease or development of distant metastasis. If the patient
remains a candidate for potential curative resection, surgery
is typically performed 6–8 weeks after therapy. Intraoperative
radiation therapy (IORT), if used, may provide additive
tumoricidal effect.
Intraoperative Radiation Therapy (IORT)
Key Concept: Although controversial, IORT is an evolving
intraoperative treatment modality for patients with recurrent
rectal cancers, including those who have received prior
external beam pelvic radiation.
A major goal of radiation oncologists is to increase the
dose delivered to tumor, relative to the dose delivered to normal adjacent tissues. As Willett and colleagues noted, this
has led to the use of fi eld-shaping techniques with multi-leaf
collimation, multiple fi eld techniques, and intensitymodulated radiotherapy, as well as intracavitary and interstitial brachytherapy [ 54 ]. IORT delivers radiation to the tumor
bed while normal tissue is shielded. Two alternative but
complementary IORT techniques have evolved: intraoperative electron radiation (IOERT), which uses a linear accelerator to deliver electron particles, and high-dose-rate
brachytherapy (HDR-IORT), which delivers an iridium seed
(192-Ir) along after-loading catheters. In either technique,
normal tissues are simultaneously moved aside or physically
shielded. Because the tumor can be visualized intraoperatively, it is possible to more accurately defi ne areas at risk for
tumor involvement [ 54 ].
The decision to perform IORT is based on anticipated risk
of residual microscopic disease. Intraoperative frozen section analysis can help identify at-risk margins (<5 mm) that
may benefi t from IORT [ 55 ]. The dose of IORT (10–20 Gy)
depends on the amount of residual disease and, in some
cases, the dose of external beam radiation delivered preoperatively (Table 15.1 ) [ 54 , 59 – 61 ].
Table 15.1 Outcomes following intraoperative radiation therapy (IORT) for rectal cancer
Study
Haddock et al.
56 ]
(2009) [
Pacelli et al.
15 ]
(2009) [
Dreseen et al.
57 ] a
(2008) [
Heriot et al.
58 ] a
(2007) [
Hahnloser et al.
(2002) [
8 ]
Wiig et al.
59 ]
(2002) [
Shoup et al.
48 ]
(2002) [
Abbreviations : dash(−) not reported, y year
a
3-year OS, LR
b
Disease-free survival
Patients ( n )
R0 R1 R2 R0 R1 R2 R0 R1 R2 R0 R1
227 (37) 224 (37) 156 (26) 12.5 15 20 28 32 32 46 27 16
– – – 10–15 10–15 10–15 – – – – – –
84 (57.2) 34 (23/1) 29 (19.7) 10 12.5 15–17.5 25 29.2 28.5 58.7 26.5 24.1
98 (61.3) 40 (25) 14 (8.8) 10 10 10 – – – – – –
138 (45) 27 (3.3) 139 (45.7) – – – – – – 27 – –
18 29 12 15 15 17.5–20 30 50 – 60 20 0
64 (64) 30 (30) 6 (6) 12.5–15 15–17.5 15–17.5 – – – 31.2
IORT dose (Gy) 5-y local recurrence (%)
5-y overall survival (%)
R2
b
9 b 14 b
15 Recurrent Rectal Cancer
237
Haddock et al. [ 56 ] recently reported on a retrospective
analysis of 607 patients with recurrent colorectal cancer
who received IORT. IORT was preceded or followed by
external radiation in 583 patients (96 %), 70 % of whom had
tumors located within the pelvis. The median IORT dose
was 15 Gy (range, 7.5–30 Gy). Survival estimates at 5 years
were 46, 27, and 16 % for R0, R1, and R2 resections, respectively. On multivariate analysis, R0 resection was the only
independent factor associated with improved survival.
Although no randomized trials evaluating IORT have been
performed to date, data from large single institution studies
suggest that IORT may infl uence local control and survival.
As one would expect, multiple studies suggest that the
extent of surgical resection, and therefore the volume of
residual disease, is an important factor in improving local
control with IORT. The experience with intraoperative
brachytherapy at the Memorial Sloan-Kettering Cancer
Center was reported by Alektiar et al. [
62 ] in a study of 74
patients treated from 1992 to 1998. Median follow-up was
22 months. Fifty of these patients had negative margin (R0)
resection. Five-year local control was 39 %; 5-year diseasefree and overall survival was 23 %. Negative margins predicted local control: a 5-year rate of 43 % in patients with
R0 resection vs. 26 % in those with R1 resection. Patients
with negative margins had 5-year survival of 36 %, compared to only 11 % in patients with positive margins. More
recently, Dresen et al. [ 57 ] reported on 57 patients receiving
re-irradiation of 30.6 Gy with IORT, in addition to preoperative re-irradiation with external beam radiotherapy. The
IORT dose was dependent upon completeness of resection.
Five-year overall survival was 48 % in patients with an R0
resection. On univariate analysis, R0 resection was more
likely in patients receiving re-irradiation, compared to
patients who had previously received radiotherapy and were
treated with surgery alone. In addition, patients who were
re-irradiated with IORT had improved overall survival and
decreased local and distant recurrence. Radical resection
and stage of the primary tumor were the only factors predicting overall survival on multivariate analysis [ 56 ].
The morbidities associated with IORT are generally
acceptable, but may be diffi cult to distinguish from diseaserelated toxicity. Common side effects include wound infection, ureteral obstruction, gastrointestinal complications
such as obstruction or fi stula, and peripheral neuropathy. In
the series reported by Alektiar et al., morbidities included
wound complications (24 %), bladder complications (20 %),
ureteral stricturing (23 %), and peripheral neuropathy (16 %)
[ 62 ]. In the study of over 600 patients by Haddock et al. [ 56 ],
32 % of patients developed neuropathy, the most common
radiation-induced toxicity. Seven patients developed ureteral
narrowing or obstruction.
We currently use IORT in cases in which there are
anticipated close margins. Care must be taken to shield
radiation- sensitive structures; input from the surgeon is
critical.
Surgical Technique
Key Concept: Distinguishing tumor invasion from adherence
is diffi cult, and wide resection provides the best chance for a
margin negative resection. While it is important to preserve
as much healthy anatomy as possible, these procedures typically require extensive resection and subsequent surgical
reconstruction.
In order to achieve complete resection of tumor with negative margins, all organs involved by tumor must also be
resected. Therefore, these extensive procedures often require
the coordinated involvement of surgical specialists in urology, gynecology, orthopedics, neurology, radiation oncology,
vascular surgery, and plastic surgery. In the absence of the
rectum after APR, recurrent cancers are more likely to invade
adjacent organs such as the sacrum and sacral nerves posteriorly, the vagina and uterus, or seminal vesicles and prostate,
and the bladder anteriorly, and the ureters, autonomic nerve
plexus, internal ileac lymph nodes, and vessels laterally.
Tumor that adheres to regional anatomic structures is generally assumed to invade them; all or part of these organs
must be removed en bloc with the tumor. Focal invasion of
adjacent organs, or metastatic lymph nodes in the pelvic
sidewall, requires extended resection. The type of procedure—total pelvic exenteration, posterior exenteration, anterior exenteration, APR with sacrectomy, and sacropelvic
exenteration—depends on the extent of tumor spread as well
as distance of tumor from the anal sphincter musculature.
Preoperative Regimen
Key Concept: Developing a routine is important to achieving
intraoperative success and minimizing morbidity.
Preoperative evaluation, including physical examination
and imaging, will determine the need for additional studies
such as pelvic ultrasound, cystoscopy, or dedicated sacral
bone evaluation. Cystoscopy may be performed before
resection or intraoperatively. Placement of ureteral stents can
be done preoperatively to help identify and protect the ureters. Patients undergo bowel prep the day before surgery.
Antibiotics are delivered in the operating room along with
anesthesia. The patient is placed in the lithotomy position,
giving the surgeon anterior access to the pelvis and perineum.
Surgery will be performed in one or two stages, depending
on the type of resection.
Rectal Washout
Key Concept: Rectal washout has theoretical advantages to
reduce tumor shedding, with minimal downside.
The practice of rectal washout remains controversial.
Some have theorized that viable exfoliated tumor cells
implant at distant sites of bowel mucosa, potentially resulting in some anastomotic and/or various locoregional recurrences. A few studies suggest that free malignant cells
collect on circular stapling devices during anterior resection
[ 63 , 64 ], implanting during construction of the anastomosis.
238
T.D. Francone and M.R. Weiser
A number of small studies suggest that rectal irrigation may
eliminate the free cells collected on circular staplers, reducing implantation and potential spillage into the pelvis
[ 65 , 66 ]. The type of rectal irrigation—saline vs. cytocidal—
also remains a point of contention. Although cytocidal rectal
washouts comprising solutions such as cetrimide or
povidone- iodine are used more commonly, there is no data
confi rming that these are more effective than simple saline
wash. A study by Church et al. concluded that rectal irrigation probably eliminates exfoliated malignant cells by
mechanical cleansing, rather than through any cytocidal
effect [
67 ]. Similarly, Jenner and colleagues showed that
saline wash effectively removes exfoliated malignant cells
from the distal rectum mechanically [ 68 ]. Even so, no study
to date has demonstrated the clinical relevance of rectal
washout in reducing the incidence of local recurrence. In
2005, the American Society of Colon and Rectal Surgeons
published practice parameters for the management of rectal
cancer, stating that there was insuffi cient evidence to recommend intraoperative rectal washout [ 69 ]. However, given the
minimal time involved and lack of detriment to the impending procedure, it is our practice to irrigate the rectum with
500 cc of 5 % povidone-iodine solution prior to incision.
Resection
Key Concept: You must maintain fl exibility during the operation. This includes making an early decision as to whether
you have the ability to perform an adequate resection that
will benefi t the patient.
Intraoperatively, you should fi rst examine the abdomen
for disseminated peritoneal disease, which would prevent a
curative resection. This can be done via diagnostic laparoscopy, when possible, thus avoiding the morbidity associated
with a major midline laparotomy. A laparotomy is often necessary, however, especially in the setting of adhesions.
The retroperitoneal lymph nodes should be examined for
metastasis, which—especially if the nodes cannot be completely removed—may indicate incurable disease. The ureters
are identifi ed and preserved, and will not be transected until
resectability is confi rmed. Following abdominal inspection,
the recurrent tumor is assessed. Dissection ideally begins in an
extraperitoneal plane free of adhesions and scar tissue
(Fig. 15.1 ). The inferior mesenteric artery is ligated and tran-
sected, followed by transection of the descending colon. The
surgeon dissects posteriorly down to the levator ani, taking
care to avoid the pelvic nerves whenever possible. The bladder
is now mobilized from the retropubic space (Fig. 15.2 ). The
bladder pillars attached to the lateral pubic rami are transected.
In a female patient, the cardinal supporting ligaments are
ligated and transected at the pelvic sidewall. In a male patient,
dissection continues anteriorly and includes the prostate.
A decision must now be made. Will you proceed with a
low anterior resection, or an APR? In recurrent rectal cancer,
Fig. 15.1 In TPE, lateral dissection begins on the common and external iliac vessels, which are lateral to the parietal layer of the endopelvic
fascia. The internal iliac artery and vein are clamped, cut, and tied distal
at their origin. The ureter is cut in the pelvis, with care taken to preserve
ureteral length for reconstruction
Fig. 15.2 The surgeon may perform dissection of the bladder before or
after posterior dissection of the pelvic organs. The bladder is dissected
from the symphysis and pubic rami, with dissection in the space of
Retzius. The bladder is freed by dividing the lateral peritoneal
attachments
15 Recurrent Rectal Cancer
239
Fig. 15.3 Perineal dissection is necessary in TPE that includes the
intra-levator organs (anal canal, labia majora, urethra). An elliptical
incision is made from the tip of the coccyx to the pubic symphysis. The
incision ends at the bulb of the penis (in a male patient), with the urethra
previously divided in the pelvis. The pelvic fl oor attachments are
divided widely, freeing the vagina (in a female patient), the urethra, and
the rectum
an APR is usually necessary. If it is determined that an APR
is required, dissection continues to the levator ani muscles,
and then perineal dissection begins. The anal canal and lower
rectum are dissected and removed through the ischiorectal
fossa and urogenital diaphragm (Fig. 15.3 ). Wide lateral dis-
section of the pelvic fl oor (cylindrical dissection) is necessary to clear tumor. If tumor is extensively invasive in a
female patient, the vagina, vulva, and urethra may have to be
removed. The entire specimen can then be extracted through
an abdominal or perineal incision.
Types of Procedures
Key Concept: The tumor location and extent of invasion will
determine the type of procedure you perform.
Total exenteration is usually done in the setting of large,
bulky lesions that invade the bladder or prostate. This procedure involves removal of the rectum, bladder, prostate, and
seminal vesicles in male patients, and removal of the rectum,
bladder, vagina, uterus, cervix, and parametrium in female
patients.
Anterior exenteration is done when cancer invades the
posterior bladder wall, anterior uterine wall, and organs in
the anterior plane of the pelvis.
Posterior exenteration is done in a female patient if tumor
invades the uterus. This procedure can be accomplished only
if the bladder is not involved by tumor. Uterus, cervix,
adnexa, and vagina (if required) are removed with the rectum. The operation is similar to total exenteration; however,
instead of dissecting anterior to the bladder in the retropubic
space, the peritoneum is incised over the bladder, and the
bladder is dissected sharply off the anterior surface of the
cervix and vagina and (depending on the level of tumor)
down to or beyond the levator ani muscles. The ureters are
dissected free from the anterior parametria distally, over the
ureteral tunnel running along the uterine artery.
APR or LAR with partial cystectomy or vaginectomy may
be considered if tumor does not extend into the bladder
[involving the trigone] or the vagina far enough to require
total removal of these organs. A partial cystectomy and reimplantation of the ureters can be done with a psoas hitch
reconstruction. If only part of the vagina is involved by
tumor, local resection of the invaded portion may suffi ce. If
the resulting vaginal defect is too large for primary closure,
reconstruction can be achieved using a myocutaneous rectus
abdominis fl ap.
Sacral Resections
Key Concept: Sacral resections are generally done if tumor
broadly adheres to or invades the sacrum or coccyx.
APR with sacrectomy begins in the same manner as a total
pelvic exenteration: dissection in the ventral plane anteriorly,
preserving the bladder, female reproductive organs, or prostate, if possible. Dissection takes place in a dorsal and dorsolateral fashion, following the presacral plane down to the
level of the sacral transection. If transection of the sacrum at
the S2/S3 level (or lower) clears disease, the cancer is resectable. Resection above S2 involves signifi cant morbidity; the
need for tumor clearance at that level often indicates unresectable disease. The level of sacral transection is marked on
the anterior cortex of the sacrum using osteotome or K-wire.
Gauze may be packed into the presacral space to reduce
bleeding. The patient is turned and placed in the prone position. A dorsal longitudinal incision is made, starting at the
level of L5 down to and around the anal canal. The gluteus
maximus and gluteus minimus muscles are dissected off the
sacrum, and the fl aps are raised bilaterally. Transection of
240
T.D. Francone and M.R. Weiser
Fig. 15.4 After anterior dissection, the patient is placed in the prone
position for sacral resection. A posterior sacral incision is made with
excision of the anus. Flaps are raised to the lateral extent of the sacrum.
The gluteus maximus and gluteus medius muscles are dissected from
their sacral origins. The sciatic nerve is located by retracting the gluteus
maximus and underlying piriformis muscle superiorly, at the lateral
aspect of the mid-sacrum. The nerve is superfi cial to the obturator internus muscle, coursing inferolaterally between the ischial tuberosity and
greater trochanter. The sacrotuberous and sacrospinous ligaments are
incised at their attachments to the ischial tuberosity and ischial spine.
The surgeon inserts a fi nger anteriorly from the medial aspect of the
sciatic nerve, facilitating dissection beneath the piriformis muscle and
through the underlying endopelvic fascia. This exposure directs the
sacral ostectomy, ensuring suffi cient tumor clearance
sacrum, facilitating access to the pelvic fl oor muscles and
infra-piriformis opening. Medial to the infra-piriformis, you
should insert a fi nger into the presacral space to identify the
level of resection (Fig. 15.4 ). The sacrum is now resected,
with care taken to protect the nerve roots within the proximal
(preserved) sacrum. The distal sacrum, lateral pelvic walls,
and rectum are removed en bloc.
Sacropelvic exenteration is undertaken only in the setting
of very bulky tumors involving the lower sacrum and invading the reproductive organs in a female patient, the prostate
in a male patient, and the bladder. This is a two-stage procedure: posterior dissection for distal sacrectomy and anterior
dissection for pelvic exenteration. In the second stage, the
patient is turned and placed in the prone position [
70 ]. After
division of the sacrum in stage two, the rectum is removed in
continuity with the sacrum and resected visceral organs.
Pelvic Floor Reconstruction
Key Concept: Following resection of bowel, bladder, vagina,
and perineum, the resultant defect will typically require
reconstruction entailing multidisciplinary help and meticulous preoperative planning.
The major goals of reconstruction are to optimize healing,
prevent perineal sepsis, and, in some cases, restore function.
Type of reconstruction depends on the nature and extent of
the surgical resection. If the external sphincter muscles have
been left intact, the colon can be anastomosed to the distal
rectum or anal canal. Because anastomotic leak is probable
after such extensive treatment, a defunctioning ileostomy is
always recommended. In most circumstances, rectal anastomosis is not possible, and a permanent colostomy is created.
You will then normally confront a large, irradiated pelvic
“dead space” susceptible to abscess formation and woundhealing complications. This area should be fi lled with vascular tissue such as omentum or a rotated myocutaneous fl ap
[
71 – 73 ]. Prosthetic or biological meshes have also been
used, but are not favored by the authors due to risk of infection. Reconstruction of large vaginal defects, or defects in
the perineal skin, is best accomplished with myocutaneous
fl aps [ 71 ]. If a cystectomy is done, options for urinary diver-
sion include an ileal conduit or an orthotopic bladder substitution. Colon or ileum may be used for continent diversion
(i.e., Indiana pouch, Mainz pouch, Florida pouch, Miami
pouch). An ileal conduit, colonic conduit, or ureterocolostomy can also be constructed for urinary diversion [ 70 ].
Postoperative Complications
Key Concept: Due to the nature of the operation required for
optimal outcomes, morbidity rates are signifi cant, and you
should have a plan for early identifi cation and management
of morbidity.
Most of the recent literature reporting on radical resection
for locally recurrent rectal cancer describes acceptable perioperative mortality but signifi cant morbidity (Table 15.2 ).
Potential morbidities include surgical site infection, sepsis
(usually related to the non-collapsible empty pelvis), complications related to urinary diversion, and complications related
to IORT, including peripheral neuropathy and ureteral stenosis (Table 15.3 ). Dresen et al. [ 57 ] reported an overall compli-
cation rate of 59 % in their series of 144 patients undergoing
radical resection for local recurrence. Nineteen percent suffered urinary retention and required prolonged catheterization. Fifteen percent developed pelvic abscess, requiring
intervention. In another series of 160 patients undergoing
radical or extended radical resection for recurrence, Heriot
58 ] reported a relatively low morbidity of 27 % and
et al. [