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336
I. White and S. Avital
E.Evaluation andPlanning
Following histological conrmation, anatomical
assessment and the condition of the patient, a
multidisciplinary evaluation, including all specialties involved in diagnosis, surgery, and oncological treatment, should evaluate curative intent
and the best possible treatment plan. This step
cannot be overemphasized as it is vital to the success of surgery and all other treatments. It is this
multi-team approach of planning and working as
a unit that increases the ability to reach R0 resection and thus the most optimal disease-free survival rates. This has been demonstrated in one
specialized center in the UK that found that a
minimum of 14 cases was required to acquire the
necessary experience to optimize overall perioperative complication rate associated with exenterative pelvic surgery. Group decisions are
made at the MDT regarding resectability, cure,
pre-operative neoadjuvant radio-chemotherapy,
and palliative care.
Patients must be extensively pre-operatively
counselled due to the high morbidity and risk of
complications, including signicant blood loss,
long intensive care and overall hospital stay,
sepsis, abscess, stulas, wound and perineal
infection and dehiscence, urinary infection,
prolonged bowel ileus, and obstruction, reoperation, and re-admission. The mortality risk
is quoted as <5%.
F.Surgical Treatment
Although multimodal treatment is usually
required, surgery is usually the only solution that
achieves cure. Approximately 50% of local recurrences are amenable to R0 resection; palliative
surgery may help signicantly decrease pain,
bleeding, obstruction, and tenesmus. These issues
must all be discussed and planned in advance.
For curative surgery, as stated earlier, preplanning must involve all the necessary teams
including the anaesthetist. Surgery should commence only after scans have been completed and
assessed, biopsy achieved, and resectability conrmed. Moreover, reconstruction must be possible
if resection is to be considered, which often
involves a highly skilled plastic surgery team with
previous experience in multiple free and rotation
aps to enable rebuilding of the perineum.
Additional team members include gynecology,
urology, neurosurgery, spine surgery, or vascular
surgery. Ureteric catheters are a very useful adjunct.
Absolute contraindications to resectability
include:
• Poor performance status/medically unt
patients
• Bilateral sciatic nerve involvement
• Circumferential bone involvement
• Frozen pelvis
Relative contraindications include:
• Extension of tumor through the sciatic notch
• Encasement of external iliac vessels—requiring en bloc resection and/or reconstruction of
external iliac vessels
• High sacral involvement—resection above the
S2/3 junction can be performed with suitable
surgical expertise and equipment in superspecialist centres
• Unresectable distant metastases
Superspecialist surgical techniques (such as
high sacrectomy—S2 and above) should only be
offered in surgical units with appropriate multidisciplinary expertise. Most commonly, gynaecologists will be needed for complete en bloc
excision of the uterus, ovaries, and closure of the
vagina after removal, and urologists for creation
of an ileal conduit although there is a wide range
of bladder reconstruction options.
Every surgical procedure must begin with
explorative laparoscopy or laparotomy. Peritoneal
seeding, unexpected liver metastases, and invasion of para-aortic lymph nodes are generally
contraindications to continue. It is suggested that
injury to critical structures should be avoided
until resectability has been proven.
The majority of patients will have a perma-
nent end colostomy, although very highly motivated patients with favourable pathology may be
able to undergo reconstruction with a coloanal
43 Recurrent Rectal Cancer
337
anastomosis. If there is the possibility of postoperative radiotherapy, then clips should be placed
at the area in question.
G.Radio-Chemotherapy
• Radiotherapy—The majority of patients have
either had neoadjuvant radiotherapy before
their original surgery or prior to surgery for
local recurrence. However, an additional
30–40Gy can be administered after an R1 or
R2 resection, although all attempts to avoid
the small bowel should be undertaken.
• Chemotherapy—Local relapse is a precursor
of distant metastases in about 50% of patients;
therefore chemotherapy is recommended as
an important treatment component.
Carbon-Ion Radiation (CIRT)
Carbon-Ion Radiation (CIRT) offers unique physical and biological advantages over conventional
radiation, with the proffered advantage of improved
dose localization and delivery to the tumor while
minimizing surrounding tissue damage. Its advantage is high linear energy transfer, inducing
increased double-strand breaks in DNA structures,
causing irreversible cell damage independently of
cell cycle or oxygenation. The literature has shown
CIRT to be effective with complete and partial
response in approximately 40% with symptomatic
response, most often improvement in pain, maintained in over 80% at 1 year. Yamada et al. published 5-year local control and survival rates at 88%
and 59%, respectively. The long-term safety aspects
are still under surveillance but as an alternative to
surgery or when surgery is not a possibility, CIRT
offers much lower morbidity and mortality rates.
H.Distant Recurrence
(See Fig.43.2 and Chap. 40)
Surgical resection has the best prognosis for
metastases discovered during follow-up after primary treatment for rectal cancer. The approach is
similar to all metastases with the principle of
achieving R0 from the target organ. The most
commonly affected organs are the liver and lungs,
followed by the abdominal cavity (peritoneum)
and other organs. Pelvic and sacral bone involvement is considered a local recurrence.
Liver or lung metastases have the best results.
If the lesions are deemed resectable, the patient
should be referred to a thoracic and/or hepatobiliary surgeon.
The criteria for resection of pulmonary metastases were rst described by Thomford in 1965
and although there has been advancement in
recent years, there are still no standardized indications. One set of criteria is unilateral or bilateral resectable lung lesions, no local recurrence
of primary lesions, no evidence of extrapulmonary metastases except for resectable hepatic
metastases, and adequate cardiorespiratory function for complete resection of all pulmonary
lesions. Using these criteria, the 5-year survival
after pulmonary resection is reportedly 45.5%.
The liver is the most frequent site for metastases
from colorectal cancer and, if present before or
synchronously with pulmonary metastases, there
is no effect on patient survival if an R0 resection
can be achieved. Many authors have shown favorable survival for patients with solitary pulmonary
metastasis and poor prognosis for patients with
two or more pulmonary metastases. Moreover,
treatment that includes both hepatic and pulmonary resections has been shown to result in survival and safety outcomes comparable to isolated
hepatic or pulmonary resections.
In current studies, multivariate analyses for
time after initial metastasectomy revealed that
the primary site, the number of hepatic tumors,
and simultaneous or sequential metastases were
independent prognostic factors. These prognostic
factors may be good indicators for the selection
of candidates for intensive postoperative adjuvant
therapy.
Overall, the rates of hepatic and/or pulmonary
resection for colorectal metastases have increased
during the last decade, which could be attributable in part to advances in surgical techniques,
including the adoption of staged or repeated
resection of hepatic or pulmonary metastases.
338
I. White and S. Avital
Another contributing factor may be preoperative
Conclusion
systemic therapy consisting of neoadjuvant therapy for initially resectable disease and conversion therapy for initially unresectable disease.
Considering these advances, hepatic and/or pulmonary resection should be standard, at least in
high-volume centers, as long as R0 resection can
be achieved while maintaining functional residual liver and/or lung activity.
In summary, recurrent rectal cancer is a highly
difcult disease to treat with a high morbidity
and mortality rate. R0 resection is currently the
only cure, with palliative relief a second option.
Anastomotic local recurrence has higher cure
rates than does pelvic recurrence and MDTs optimize the results of salvage surgery.
For hepatic metastases, radiofrequency ablation (RFA) has been championed as a less invasive and less aggressive treatment option
compared to resection. In a Korean study from
2016 of patients with solitary hepatic metastases
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Locally Advanced Rectal Cancer
DanielW.Nelson andAntonJ.Bilchik
44
Refer toAlgorithm inFig. 44.1
A. Colorectal cancer represents the fourth most
frequently diagnosed cancer in the United
States, but the second or third leading cause of
cancer-related death. According to the National
Cancer Institute’s Surveillance, Epidemiology
and End Results Program, of the 145,600 new
cases of colorectal cancer estimated to occur in
2019, nearly 30% will be primary rectal cancer. Over the last 40 years, the overall incidence rate of colorectal cancer has been
declining. Furthermore, 5-year survival rates
which were once 48% for rectal cancer in 1975
had risen by 20% by 2019. This progress can
be attributed to earlier diagnosis through endoscopic screening programs, standardized surgical techniques, and more effective
neoadjuvant/adjuvant therapies.
Locally advanced rectal cancer includes
stage II and III disease (Table 44.1 and
Fig.44.2). These tumors invade through the
muscularis propria into pericolorectal tissues
(T3), penetrate to the surface of visceral peri-
D. W. Nelson (*)
Department of Surgery, William Beaumont Army
Medical Center, El Paso, TX, USA
e-mail: daniel.w.nelson.mil@mail.mil
A. J. Bilchik
Department ofSurgical Oncology, John Wayne
Cancer Institute, Santa Monica, CA, USA
toneum (T4a), directly invade or adhere to
other organs or structures (T4b), or are
accompanied by evidence of locoregional
nodal disease (N1-2). Whereas patients with
T1-2N0M0 rectal cancer can achieve 90%
5-year survival rates with surgery alone, those
with T3-4N1-2 disease have local recurrence
rates ranging from 30–65% with surgery
alone. This chapter focuses on the workup,
staging and management of locally advanced
rectal adenocarcinoma (stage II/III).
From an anatomic perspective, the rectum
is dened as the distal 12–15 cm of bowel
leading to the anal verge. From the surgeon’s
viewpoint, the lower limit of the rectum is
typically regarded as the top of the anorectal
ring whereas the upper limit of the rectum is
represented by where the taeniae splay and
can no longer be distinctly identied, at the
level of the sacral promontory. The rectum is
subdivided into three separate 5cm sections:
upper, middle and lower rectum. These subdivisions are often based on anatomical folds of
the rectum known as the valves of Houston.
This anatomy has important prognostic and
therapeutic implications. For one, the lymphatics of the upper rectum drain via the portal venous system similar to the colon,
whereas lymphatics of the middle and lower
rectum drain into both the portal and systemic
venous circulation. This circulating pattern
explains why the incidence of lung metastasis
© Springer Nature Switzerland AG 2020
S. R. Steele etal. (eds.), Clinical Decision Making in Colorectal Surgery,
https://doi.org/10.1007/978-3-319-65942-8_44
341
342
D. W. Nelson and A. J. Bilchik
Fig. 44.1 Algorithm for the workup, staging and treatment of locally advanced rectal cancer. DRE digital rectal
examination
Table 44.1 AJCC (Eighth edition) staging systems for rectal cancer
AJCC
Tumor
T1 Tumor invades submucosa
T2 Tumor invades muscularis propria
T3 Tumor invades through the muscularis propria into pericolorectal tissues
T4a Tumor invades through the visceral peritoneum
T4b Tumor directly invades or adheres to adjacent organs or structures
Nodes
N0 No regional lymph node metastasis
N1 Metastasis in 1-3 regional lymph nodes
N1a Metastasis in 1 regional lymph node
N1b Metastasis in 2-3 regional lymph nodes
N1c Tumor deposit(s) in the subserosa, mesentery, or nonperitonealized pericolic or perirectal tissues
without regional nodal metastasis
N2 Metastasis in 4 or more regional lymph nodes
N2a Metastasis in 4-6 regional lymph nodes
N2b Metastasis in 7 or more regional lymph nodes
Metastasis
M0 No distant metastasis
M1 Distant metastasis
M1a Metastasis conned to 1 organ or site (e.g., liver, lung, ovary, nonregional node)
M1b Metastases in 2 or more organs or sites
M1c Metastasis to the peritoneal surface alone or with other organ or site
Stage
I T1, N0, M0
T2, N0, M0
IIA T3, N0, M0
IIB T4a, N0, M0
IIC T4b, N0, M0
IIIA T1-T2, N1/N1c, M0
T1, N2a, M0
IIIB T3-T4a, N1/N1c, M0
T2-T3, N2a, M0
T1-T2, N2b, M0
44 Locally Advanced Rectal Cancer
Table 44.1 (continued)
AJCC
IIIC T4a, N2a, M0
T3-T4a, N2b, M0
T4b, N1-N2, M0
I VA Any T, any N, M1a
IVB Any T, any N, M1b
IVC Any T, any N, M1c
AJCC American Join Committee on Cancer
Stage 0
Stage I
Stage II
Spread to other
organs
Serosa
Muscle
layers
Submucosa
Lymph
node
343
Normal
Blood
vessel
Stage III
Stage IV
Fig. 44.2 Stages of cancer
is higher in rectal cancer compared to cancer
of the colon. Because the upper third of the
rectum is above the anterior peritoneal reection and outside the bony pelvis, treatment of
lesions in this region typically is similar to
treatment of colon cancer: surgery, adjuvant
chemotherapy when indicated, but not radiation therapy.
B. Due in large part to the success of endoscopic
screening programs, patients are frequently
referred to the surgeon after a diagnosis of
rectal cancer has been conrmed. However, a
thorough history and physical examination
remains critical for determining appropriate
staging investigations and planning treatment
options. Occasionally, patients may be
asymptomatic at presentation. More commonly, patients may note changes over time
Mucosa
in the character or caliber of their stool or
report rectal bleeding. Sensations of tenesmus, the continuous urge to evacuate, or pain
with defecation are more ominous symptoms
and may suggest more advanced disease,
such as a large tumor or a tumor invading the
anal sphincters or pelvic oor. A continence
history including use of a validated incontinence score will assist in eventual surgical
decisions. A complete family history is also
important as this information may implicate
hereditary cancer syndromes and guide further investigations for other associated
pathologies.
C. The digital rectal exam (DRE) remains the
cornerstone of a complete physical examination and is essential to surgical decisionmaking. The digital assessment provides
344
D. W. Nelson and A. J. Bilchik
information regarding tumor location and its
relationship to the anorectal ring. In addition,
tumor mobility or degree of xation can be
assessed through manual palpation. An
important adjunct to the DRE is rigid proctosigmoidoscopy. Proctoscopy allows direct
visualization of the tumor and accurate measurement of its distance from the anal verge.
DRE in conjunction with rigid proctosigmoidoscopy can indicate the feasibility of a
sphincter-preserving operation. Biopsy may
be performed at the time of proctoscopy if
histopathological diagnosis has not previously been obtained.
D. Routine laboratory tests during the initial
evaluation include complete blood cell counts
and liver function tests as well as any other
labs indicated based on patient co- morbidities.
A baseline carcinoembryonic antigen (CEA)
level is recommended. The primary role of
CEA monitoring is to detect recurrences after
treatment.
E. If not previously performed, a complete colo-
noscopy should be preoperatively obtained to
detect synchronous polyps (up to 30% of
cases) and synchronous cancers (1–3% of
cases). If complete preoperative colon clear-
ance is impossible due to an obstructing
tumor or other cause, it is acceptable to plan
for early postoperative evaluation within
3–6months.
F. The most common imaging studies used in
the staging assessment include computed
tomography (CT), endorectal ultrasound
(ERUS) and magnetic resonance imaging
(MRI). Although it is not the study of choice
for evaluating the extent of the primary
tumor, CT remains the most common initial
imaging study due in large part to its cost
effectiveness and utility in assessing the
patient for metastatic disease. The two most
frequent sites of distant metastasis from rectal cancer include the liver and lungs.
Therefore, a routine preoperative staging
workup should include a CT scan with intravenous and oral contrast of the chest, abdomen and pelvis (Fig.44.3).
Positron emission tomography (PET) and
combination PET/CT are alternative imaging
modalities that may be considered in the initial staging of rectal cancer, however, their
role currently remains investigational. While
combination PET/CT has similar diagnostic
accuracy to CT alone for evaluating T-stage,
Fig. 44.3 Computed tomography image demonstrating locally advanced rectal cancer. (With permission © Springer)
44 Locally Advanced Rectal Cancer
Fig. 44.4 Endorectal ultrasound image demonstrating
locally advanced rectal cancer
PET/CT appears to be superior in identifying
distant metastatic disease, particularly peritoneal and hepatic metastases. Conversely, PET
is limited by low overall sensitivity as this
modality cannot reliably differentiate malignancy from inammatory changes.
G. ERUS and MRI can accurately assess depth
of tumor invasion (T stage). Due to its ability
to differentiate the layers of the rectal wall,
ERUS is particularly useful for evaluating
supercial, early-stage lesions (T1-2)
(Fig.44.4). Although the overall accuracy of
ERUS in diagnosing T stage has been reported
to be as high as 87%, it becomes less accurate
when assessing more advanced lesions (T4).
In such situations, MRI with endorectal or
phased array coils has reported sensitivity
and specicity of 100% and 86%, respectively. MRI is particularly useful for assessing tumor encroachment of the circumferential
resection margin (CRM) between the rectal
tumor and the mesorectal fascia (Fig.44.5).
MRI can predict CRM involvement with an
accuracy of 91%. Although the exact number
of millimeters (mm) is controversial, the
CRM is considered positive when it is
≤1mm.
Both ERUS and MRI may also provide
information regarding locoregional nodal
345
Fig. 44.5 Magnetic resonance image of locally advanced
rectal cancer demonstrating the circumferential resection
margin. (With permission © Springer)
involvement. Nodal size is not a reliable
means of diagnosing nodal involvement.
Even in nodes measuring <5mm, as many as
18% may harbor metastases. Nevertheless,
with sensitivities and specicities of 67% and
78% for ERUS and 66% and 76% for MRI,
respectively, these modalities represent the
most accurate means for evaluating nodal
basins at this time. MRI is the preferred
modality.
H. Surgical resection of advanced rectal cancer
must clear all margins (proximal, distal and
radial) and remove at least 12 locoregional
lymph nodes. Total mesorectal excision
(TME) involves complete removal of the
node-bearing mesorectum along with its
346
Fig. 44.6 Total mesorectal excision specimen demonstrating intact mesorectum
intact enveloping fascia (Fig. 44.6). TME
requires sharp dissection in the extrafascial
plane between the presacral fascia and the
fascia propria of the rectum. This envelope
corresponds to the CRM. TME reduces the
incidence of positive radial margins by as
much as 18% compared to conventional blunt
dissection. This technique also preserves
parasympathetic and sympathetic nerve bundles, thereby reducing rates of impotence and
ejaculatory dysfunction.
Historically, proximal and distal resection
margins of 5 cm were recommended.
However, evidence now suggests that distal
intramural spread occurs in less than 10% of
cases and is rare beyond 1.5cm from the primary tumor. As a result, a 2cm distal margin
is now considered optimal; even a 1cm distal
margin may be adequate, particularly in
patients receiving preoperative neoadjuvant
chemoradiation. This has allowed more
patients to undergo oncologically sound,
sphincter- preserving operations (low anterior
resection with coloanal anastomosis).
However, in those patients with evidence of
direct sphincter involvement or in whom a
distal 1cm margin is unattainable, abdominal
perineal resection (APR) may be recommended. Because APR alone is associated
with high rates (12–30%) of positive CRM,
extralevator dissection can ensure negative
radial margins and thereby reduce the rate of
local recurrence. During extralevator dissection, the levator ani muscles are resected en
bloc with rectum and anus.
D. W. Nelson and A. J. Bilchik
Advanced T4 tumors can extend to invade
nearby pelvic organs or bony structures of the
pelvis. In such cases, all or part of these
organs or structures must be resected en bloc
with the primary tumor. In females, anteriorly
xed lesions may require concomitant hysterectomy, vaginectomy, and/or partial or complete cystectomy. Similarly, anterior xed
lesions in males may require simultaneous
prostatectomy. Posteriorly, tumors may
invade the sacrum and necessitate sacrectomy. Factors associated with unresectability
include circumferential tumor involvement
extending into the lateral pelvic sidewall.
This may be suggested preoperatively if there
is evidence of bilateral ureteral obstruction.
In addition, invasion of the S1 or S2 nerve
roots or into the sacral bone at the level of S1
and S2 is not amenable to resection. Following
total or partial pelvic exenterations, the resultant defect will require reconstruction with
well-vascularized muscle aps. Due to the
complex nature of these tumors, involving
surgical subspecialists from urology, gynecology, orthopedics and plastic surgery early
in the preoperative planning process is essential to optimize the surgical management of
these patients.
In addition to resection of tumor-negative
margins, the surgical procedure should
remove at least 12 lymph nodes by resecting
the segmental blood supply and lymphatics
up to the level of the superior rectal artery.
Lymph node yield may be increased by high
ligation of the inferior mesenteric artery pedicle, but ligation just inferior to the takeoff of
the left colic artery is also acceptable. High
ligation also has the advantage of improving
mobilization of the left colon to accommodate a tension-free coloanal anastomosis.
I. In 1985, a landmark study undertaken by the
Gastrointestinal Tumor Study Group (GITSG)
demonstrated the efcacy of postoperative
chemotherapy and radiation therapy for rectal
cancer. As compared with surgery alone, adjuvant chemoradiation reduced local recurrence
rates from 55% to 33%. The National Surgical
Adjuvant Breast and Bowel Project (NSABP)