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33
Management of Locally Advanced and
Recurrent Rectal Cancer
Robert R. Cima and Heidi Nelson
Of patients with newly diagnosed colorectal cancer who will
undergo surgery with curative intent as part of their treatment,
approximately 5%–12% will have tumors that have spread
beyond the anatomic landmarks of a standard resection and
have invaded adjacent organs or structures.
surgery in such cases is a wide, en bloc resection of the tumor
and any involved adjacent organ or structure. Of patients who
undergo resection with curative intent and receive adjuvant
therapy, between 7% to 33% develop isolated local or
regional recurrences.
resection can be curative.
Although tumor biology must influence the rate and location of recurrence, no tumor-specific characteristics have been
clearly associated with local recurrence. The most important
factor that influences tumor recurrence is the stage of disease
at presentation.
presentation, adjacent organ involvement, tumor aneuploidy,
increased tumor grade, mucin production, or evidence of
venous or perineural invasion. Over the last decade, the adequacy of surgical resection and the use of preoperative
chemoradiation have been shown to influence the rate of
pelvic recurrence.
rectal cancer treatment is addressed elsewhere in the textbook. The focus of this chapter is to discuss the evaluation,
operative management, and multimodality treatment of
patients with locally advanced rectal cancer. Because the preoperative evaluation, operative approach, and often the perioperative oncologic therapy are similar for primary locally
advanced and recurrent rectal cancer, they will be discussed
together. The outcomes for the different approaches are evaluated later in the chapter.
Locally advanced primary rectal cancers include tumors
that are T4 N1-2 MX at the time of initial presentation. They
are often associated with a higher rate of metastatic disease at
the time of diagnosis and have a poorer overall prognosis than
earlier-stage disease.
physical examination or to be invading adjacent organs or
structures by diagnostic imaging studies. For T4 tumors,
4,5
In up to 20% of these recurrences,
4,6,7
8
Others include obstruction or perforation at
9–12
Detailed discussion of these aspects of
8
T4 tumors are found to be fixed by
1–3
The goal of
standard surgery alone offers a limited chance of significant
local tumor control and/or long-term survival. In cases in
which an extended en bloc resection cannot be performed to
achieve complete resection, patient survival is dismal: after no
treatment or after palliative surgery, mean survival time is less
than 1 year.
Multimodality therapy incorporating radiation, chemotherapy, and surgery should be used to achieve local tumor control and to prevent or control systemic tumor dissemination,
thereby improving patient survival for patients with locally
advanced primary or recurrent colorectal cancers. To achieve
these goals, appropriate surgery is combined with externalbeam radiation therapy (EBRT), and, under ideal circumstances, intraoperative radiation therapy (IORT) and adjuvant
or neoadjuvant chemotherapy.
Patients with isolated hepatic or pulmonary metastasis
from a rectal cancer are known to have reasonable survival
after surgical treatment; however, survival with an isolated,
untreated, locoregional, rectal cancer recurrence is quite
poor.
tions, including severe pain from bony or nervous tissue
involvement, urinary obstruction, fecal obstruction or incontinence, or persistent bleeding. Nearly 90% of rectal cancer
recurrences after surgery alone occur in the central or posterior pelvis, and 19% occur at the anastomosis.
mary tumors are significantly associated with relapse in the
anterior pelvic region.
temic chemotherapy may result in temporary improvement of
symptoms, but the 5-year survival rate is less than 5%.
Surgical palliation without the addition of systemic
chemotherapy and radiation therapy adds little to the overall
survival. For these patients, length of survival is perhaps less
important than quality of life.
A patient who presents with a locally advanced primary or
recurrent rectal cancer must be thoroughly evaluated for the
presence of extrapelvic disease. If extensive extrapelvic disease is found, the degree and scope of surgical resection
should be changed from one of curative intent to palliation.
13
14,15
Most of these patients develop disabling complica-
16
Stage T4 pri-
16
EBRT alone or combined with sys-
14,15
450
33. Management of Locally Advanced and Recurrent Rectal Cancer 451
An exception may be considered in younger patients with no
significant comorbidities in whom a single, isolated, hepatic
metastasis is found that could be surgically resected.
However, if a patient has multiple sites of spread or significant comorbidities, extensive surgery involving multiple
structures is not warranted, as the chance for cure is quite
small. Whether a patient is a candidate for surgery is influenced by a number of factors, including the patient’s overall
physical condition and comorbid diseases and the extent of
spread and fixation of the tumor outside of the rectum.
Preoperative Evaluation and Patient
Selection
Complete resection of a locally advanced primary or recurrent
rectal cancer is a significant undertaking. Complete resection
may be technically possible in some patients, but if their overall physical condition does not make them an appropriate candidate, surgical palliation combined with chemoradiation is
the more prudent course of action. To be considered for a
complete resection, the patient should be in generally good
health. Any significant cardiac or respiratory conditions
should be thoroughly evaluated and treated. Patients who are
in poor health, or who will not be able to tolerate multimodality therapy combined with complete surgical resection,
or have an ASA classification of IV–V are not considered
acceptable surgical candidates. Nearly as important as their
physical condition is consideration of the patient’s motivation
and emotional preparedness for undergoing this extensive
treatment. They should be thoroughly informed about and
accepting of the short-term and long-term risks associated
with the surgery, as well as possible subsequent surgeries or
interventions required for postoperative complications.
If the patient is deemed an acceptable candidate for surgery, the next step is evaluation for the extent of local spread
and the possibility of extrapelvic spread. A detailed history
should be obtained. Symptoms that may suggest metastatic
disease, such as back or bone pain outside of the pelvis, new
respiratory symptoms, or headaches need to be carefully
examined. A thorough physical examination, with particular
attention placed on the rectal and vaginal examination, needs
to be performed and any fixation of the tumor to rigid pelvic
structures needs to assessed. Complete endoscopic evaluation
of the colon needs to be performed, if technically possible, to
rule out the presence of a synchronous lesion. Endoluminal
ultrasound of the rectum may be combined with this evaluation in cases of recurrent disease to determine if there is a discrete mass adjacent to the intestine that might be amenable to
endoscopic biopsy. Imaging should be repeated before surgery is considered and compared with similar previous studies to give some reassurance that there has been no
progression or spread of the disease that might change or preclude any surgical intervention. The abdomen and pelvis need
to be evaluated with a double contrast (intravenous and oral)
computed tomography (CT) scan to exclude extrapelvic
spread and to assess the extent of possible resection. CT scans
are generally reliable for identifying the extent of disease and
adjacent organ involvement but are less discriminating for
17
predicting local tumor resectability.
Any suspicious hepatic
lesion should be examined with ultrasound. If the lesion is
worrisome for metastatic disease, it should be biopsied.
Questionable findings on the chest X-ray film should be further investigated. Any worrisome lesion that is technically
accessible should be biopsied percutaneously.
Although the above tests are the standard evaluation for
diagnosing recurrence and excluding extrapelvic spread of the
tumor, other, more tumor-specific tests have been proposed as
adjuncts. Magnetic resonance imaging (MRI) might be more
accurate than conventional CT scanning for detecting recurrences in the pelvis or elsewhere in the abdomen because of
better image resolution. However, similar to CT scans, MRIs
provide only anatomic details and may not be any better at
distinguishing tumor recurrence from scar in a postoperative
field, particularly after pelvic irradiation. To overcome this
limitation, a metabolic-based imaging modality such as
positron emission tomography (PET) has been studied.
18–22
Colorectal cancer is known to rapidly metabolize fluorine-18
fluorodeoxyglucose (FDG), which therefore can be used as a
metabolic label to detect tumor deposits, not only in the
pelvis, but throughout the entire body. Numerous nonrandomized studies have shown that FDG-PET imaging for
recurrent colorectal cancer has a significantly higher sensitivity and specificity than CT scanning. When CT scanning was
compared with FDG-PET imaging in postoperative patients
with colorectal locoregional recurrences, the sensitivity of
FDG-PET was significantly higher than CT plus colonoscopy
(90% versus 71%, respectively), although the specificities
were similar (92% versus 85%, respectively).
23
FDG-PET
imaging has been shown to maintain this high sensitivity and
specificity, 84% and 88%, respectively, even in the setting of
the previously irradiated and postoperative pelvis.
18
Thus,
FDG-PET might be a useful tool in the postoperative patient
in whom there is a suspicion of recurrence but equivocal CT
findings, and in whom extensive reoperative surgery might be
extremely high risk.
Even the combination of physical examination and radiographic studies may not be able to prove that there is a pelvic
recurrence of a rectal cancer, especially if the patient has
undergone a previous pelvic operation or pelvic irradiation.
We generally accept three ways of differentiating postoperative changes from tumor. The first is to document a change in
the lesion, such as increase in size over time; the second is
invasion of the adjacent organs; the third is histologic evidence obtained from endoscopic, CT- or ultrasound-guided
biopsies of the suspicious tissue. However, occasionally
pelvic disease is suspected from an increasing carcinoembryonic antigen or development of symptoms without any definable anatomic change on examination. In such situations,
histologic proof should be vigorously sought. Exploratory
452 R.R. Cima and H. Nelson
pelvic surgery should be strongly discouraged because it
poses an extreme risk to the patient and makes future evaluation of the pelvis even more difficult.
Determining Resectability
Locally advanced primary or locoregional recurrences of rectal cancers can extend to involve any of the pelvic organs or
rigid bony structures of the pelvis. Resectability is based on
the anatomic location and what other structures are fixed to
the lesion. Although there are other schemes for assessing
resectability, we use the following one to classify our patients
who are being considered for possible resection. The tumor is
classified as F0 when it is not fixed to any pelvic organ or
structure, FR when the tumor is fixed but resectable, and FNR
when the tumor is fixed and not resectable. FR is further subdivided by noting the anatomic extent of the fixation (anterior,
posterior, and lateral).
vides a better appreciation of the scope of the required resection. For example, anterior fixed lesions may require a
hysterectomy, vaginectomy, a partial or complete cystectomy,
or prostatectomy, whereas lesions that are fixed posteriorly
may require a sacrectomy (Figures 33-1 to 33-3).
24
Identifying the anatomic extent pro-
Although we have found this classification scheme to be
extremely useful, it does not reliably predict resectability
before surgery because new findings may be discovered at
operation. However, in our experience, some factors are
clearly associated with an unresectable tumor (Table 33-1).
Any circumferential tumor that extends to the pelvic sidewall
is considered unresectable. Evidence of bilateral ureteral
obstruction is a very worrisome finding. Unless there is focal
infiltration of the bladder trigone causing bilateral ureteral
obstruction, this finding usually indicates that a bulky tumor
has invaded both lateral pelvic sidewalls. This means that the
disease is present at the level of the pelvic inlet, making complete resection impossible. Finally, S1 and S2 nerve root
involvement or evidence of invasion of the sacral bone at the
level of S1 and S2 indicates an unresectable tumor. A sacrectomy proximal to S2 results in sacroiliac joint instability and
although internal fixation is possible, it is not warranted for
cases of locally recurrent rectal cancer. Pain from nerve root
involvement with tumor occasionally needs to be differentiated from sciatic nerve compression. Nerve compression
symptoms may completely resolve after pelvic irradiation and
chemotherapy. However, persistent buttock and perineal pain
usually resulting from tumor expansion and ingrowth is a
more ominous symptom.
FIGURE 33-1. A A primary T3N0M0 rectal cancer treated with a low anterior resection without adjuvant therapy. The anterior recurrent tumor
fixed at the base of the bladder was treated with preoperative chemoradiation and then resection with IORT. B After a primary low anterior
resection for T2N0M0 rectal cancer without adjuvant therapy, this patient developed a lateral pelvic recurrence. After preoperative chemoradiation, the patient underwent an abdominal perineal resection with negative margins.
33. Management of Locally Advanced and Recurrent Rectal Cancer 453
FIGURE 33-1. (Continued) C A recurrence after a T3N0M0 lesion treated with postoperative chemoradiation therapy was found to invade the
sacrum. After additional EBRT and chemotherapy, IORT combined with an en bloc resection of the tumor and distal sacrum was performed
with negative margins. D A massive recurrent cancer found in the pelvis after an abdominal perineal resection and postoperative chemoradiation. The tumor was fixed to vital pelvic structures and was deemed unresectable. (Reprinted from Nicholls RJ, Dozois RR, eds. Surgery
of the Colon and Rectum. New York: Churchill Livingston © 1997 Elsevier Ltd., with permission from Elsevier.)
FIGURE 33-2. The IORT suite, showing the equipment, the position of the patient on the operating room table, and the linear accelerator.
454 R.R. Cima and H. Nelson
FIGURE 33-3. A The assortment of the lucite tubes used to direct the electron beam to a fixed site in the operative field in order to deliver the
IORT. B Place of a large lucite tube to deliver the IORT into the pelvis. The tube is fixed in place by securing it to an external support
apparatus attached to the operating table.
T
ABLE 33-1. Symptoms or findings suggestive of unresectability for
cure
Sciatic pain
Bilateral ureteral obstruction
Multiple points of tumor fixation to the pelvic sidewall
Circumferential involvement of the pelvic sidewall
S1 or S2 bony or neural involvement
Extrapelvic disease
improve outcomes, surgery is combined with multimodality
therapy, radiation, and chemotherapy. Radiotherapy is used to
improve local control and systemic chemotherapy is used to
treat possible disseminated disease.
Although EBRT may relieve symptoms and pain resulting
from a large primary or recurrent rectal tumor, it alone does
not offer a significant chance of cure.
25
However, when it is
combined with sensitizing chemotherapy, the probability
of achieving a resection with negative margins and the rate of
Multimodality Therapy for Advanced
or Locally Recurrent Rectal Cancer
local tumor control increases.
advanced or recurrent rectal cancer, centers have combined
26–29
In the setting of a locally
multimodality therapy with intraoperative radiotherapy—as
Surgery with curative intent is the mainstay of treatment for
advanced or locally recurrent rectal cancer. However, surgery
alone results in a high rate of local and distant failure.
13
electron beam radiation therapy, high-dose-rate brachytherapy, or traditional perioperative brachytherapy to further
improve patient outcomes.
To
30–37
These forms of locally
33. Management of Locally Advanced and Recurrent Rectal Cancer 455
directed radiation reduce toxicity by limiting normal tissue
exposure and deliver a high biologically equivalent dose to
the localized area of the tumor.
In general, for patients who never received prior pelvic
radiation therapy, a full course of EBRT (5040 cGy) is administered with concurrent 5-fluorouracil chemotherapy. Often,
patients with recurrent rectal cancer have previously received
a full course of pelvic EBRT. We treat such patients with an
additional course of 2000 cGy of EBRT combined with additional 5-fluorouracil chemotherapy before repeating pelvic
surgery. Therapeutic synergy between external beam and
intraoperative radiation reaches its peak within 8 weeks of
completion of external beam therapy. The disease is restaged
clinically and radiographically 4 weeks after completion of
the external beam and chemotherapy course. If there is no evidence of disease progression in the pelvis or extrapelvic
metastasis, the patient is scheduled for surgery within the next
4 weeks.
Surgery
Before surgery, the magnitude of the operation and the possible complications are discussed in depth with the patient and
family members. Very rarely in cases of locally advanced primary rectal cancers can the sphincter mechanism be preserved. In recurrent cancers, there is little role for an attempt
at sphincter preservation. Therefore, the patient must be
accepting of a permanent colostomy. In addition, the resection
of adjacent structures or organs and the functional implications and reconstruction alternatives, such as an ileal conduit,
need to be discussed.
Patients are admitted the night before surgery for mechanical and antibiotic bowel preparation, intravenous hydration,
and instruction in preoperative incentive spirometry. At our
institution, all cases of locally advanced or recurrent rectal
cancers are scheduled in a dedicated IORT suite. This suite
within the operating room complex houses the standard operating room equipment, a linear accelerator, and special anesthetic equipment that permits the anesthetized patient to be
moved from operating to irradiating positions (Figure 33-2).
In addition, remote controls are used to monitor the patient
outside the suite while radiation is given. The patient is placed
in the lithotomy position with both arms tucked and the legs
supported in Allen stirrups. Special care is taken to ensure
that the arms are well padded and in a neutral position to
avoid any nerve injury. The calves are positioned and padded
to avoid any pressure from directly resting on the stirrups
because the lengthy operation may result in compartment syndrome and/or venous thrombosis.
are inserted cystoscopically preoperatively.
A midline incision is usually made. Transverse abdominal
incisions should be avoided because they compromise the
placement of any stomas and may injure the inferior epigastric
vessels, the primary blood supply of the rectus muscle.
38
Bilateral ureteral stents
Preservation of the rectus muscle is important in case a
transpelvic rectus abdominis flap is required to reconstruct the
pelvic floor. If the patient has had prior abdominal surgery, all
adhesions need to be lysed. If any of the small bowel is
adhered into the pelvis or in a region that might be indicative
of tumor, a sample should be sent for intraoperative biopsy. If
the bowel is involved with tumor, then that portion of the small
bowel will need to be resected with the rectal tumor en bloc.
Once all adhesions have been lysed, the entire abdomen needs
to be thoroughly explored for evidence of extrapelvic tumor
deposits. The liver, omentum, retroperitoneum, peritoneal lining, and the area of any prior surgical incision need to be carefully examined because they are frequently involved with
recurrent disease. Any suspicious finding should be analyzed
by frozen section. The presence of extrapelvic disease would
be a contraindication to radical resection. Very rarely, exceptions may be made in a young patient who has limited pelvic
and liver disease; in such cases, the pelvic recurrence and secondary liver tumor are resected simultaneously.
A self-retaining retractor is placed and the small bowel is
packed into the upper abdomen to facilitate pelvic exposure.
Because pelvic irradiation or prior pelvic surgery will have
induced significant fibrosis in the tissues of the pelvis, we
begin the dissection at the level of the aortic bifurcation.
Starting at this level allows us to enter a virgin fascial plane,
which aids in the posterior dissection to the level of the pelvic
floor. Similarly, the ureters are identified before they enter the
pelvis and are then mobilized along their length along the
pelvic sidewall and into the bladder. Identifying the ureters all
the way to their insertion into the bladder is important to
ensure adequate length if an ileal conduit is required for urinary tract reconstruction.
For rectal cancer recurrences that are not fixed to any pelvic
structure (F0), a completion abdominoperineal resection
(APR) is required. The scope of the resection is similar to a
standard APR but the pelvic fibrosis induced by any prior surgery will have distorted or eliminated the ideal, relatively
bloodless plane between the mesorectum and sacral fascia.
The distinction between fibrosis and tumor infiltration into
adjacent tissue can be very difficult to discern at the time of the
operation. If there is any question about the nature of the tissue, particularly when it occurs outside the realm of planned
resection, for example, at the level of the sacral promontory or
the lateral pelvic walls, a frozen section should be analyzed. If
tumor cells are seen, a complete resection with negative
margins is not feasible. As will be discussed later, it is in this
setting that the use of IORT improves clinical outcomes.
When the tumor is fixed, either anteriorly or posteriorly, the
scope of the operation is much larger than for the non-fixed
lesion (F0). If the fixed tumor is considered resectable, we
classify it as a FR (fixed, resectable) lesion. For anteriorly
fixed tumors there are different operations that need to be
considered, whereas for a primary or recurrent posteriorly
fixed tumor that is fixed posteriorly, our operation of choice is
an en bloc distal sacrectomy.
456 R.R. Cima and H. Nelson
For the anteriorly fixed lesion, the choice of operation is
influenced somewhat by the sex of the patient. In a woman,
depending on the level and extent of the tumor, the resection
may require only an en bloc excision of the posterior wall of the
vagina, with immediate reconstruction. When the upper vagina
or lower uterus is involved more extensively, en bloc hysterectomy and posterior vaginectomy would be necessary. A woman
who has her uterus usually does not need a cystectomy.
However, a man with an anteriorly fixed tumor usually needs a
cystectomy or cystoprostatectomy. A partial cystectomy with a
wide margin may be an option for an upper rectal lesion, but the
functional results may be poor because of a decrease in bladder
size and radiation-induced injury to the bladder. In such
patients, an ileal conduit at the time of resection may be preferable to subjecting the patient to a second surgery.
Posteriorly fixed lesions require an en bloc distal sacrectomy. The proximal extent of the resection is to S2-3. A more
proximal resection would require internal fixation of the
sacroiliac joints to stabilize the pelvis. We consider a resection of this magnitude too extensive for primary or recurrent
rectal cancer. Furthermore, when the resection is limited to
the S2-3 level, it is generally possible to preserve one S3 root,
which is usually sufficient to preserve bladder function. The
sacrectomy proceeds through four distinct steps: 1) the anterior resection, 2) the posterior resection, 3) the use of IORT if
required, and 4) the reconstruction of the pelvic tissue defect.
The abdominal dissection is begun as described previously.
The dissection in the posterior plane is performed to the level
of proximal tumor extent along the sacrum. This permits
reevaluation to ensure that the tumor does not extend above
the S2-3 level. If it does, then the rectum is dissected free in
the anterior and lateral planes, leaving the point of sacral fixation as the only point of attachment. A sacrectomy that needs
to include a resection proximal to S3-4 requires bilateral ligation of the internal iliac arteries and veins. This is done to
decrease blood loss during the sacrectomy. Once the rectum is
completely freed anteriorly and laterally, all required abdominal wall stomas are created and an omental or rectus abdominis flap is mobilized and placed into the pelvis to be used
for later reconstruction. The abdominal incision is closed and
the patient is repositioned in the prone-jackknife position.
A posterior midline incision from the region of the last lumbar vertebra to the coccyx is made. The gluteal muscles are
dissected free of the sacrum and the proposed site of transection is identified. The important nervous structures to the
lower pelvis and extremities, the pudendal and sciatic nerves,
respectively, are identified and preserved. With the assistance
of our orthopedic or neurosurgical colleagues, the sacrum is
transected and the dural sac is closed. The defect is closed
either over an omental flap or the mobilized rectus abdominis
flap. Because the resulting tissue defect can be quite sizable,
local muscle flaps may need to be mobilized in order to close
the defect. Multiple closed suction drains should be used,
because any pelvic fluid collection can easily become
infected and lead to wound breakdown. The wound compli-
cations and breakdown in this heavily irradiated field are not
uncommon and occur in as many as 65% of patients who
39
undergo radical resection with concurrent IORT.
These
postoperative wounds often require transfer of nonirradiated,
well-vascularized tissue like muscle flaps to heal if that transfer was not done at the initial operation.
Use of IORT
In cases of close margins, known microscopically positive margins, or minimal gross unresectable disease in the pelvis or after
the sacrectomy, our policy is to use intraoperative electron-beam
radiation therapy (IORT). To give IORT, a lucite cylinder is
positioned in the pelvis to target the at-risk area (Figure
33-3A,B). The patient is then positioned under the linear accelerator. Between 1000 to 2000 cGy is delivered, depending on
the extent of margin involvement. A dose of 1000 cGy is recommended for minimal residual disease; 1500 cGy is given for
gross residual disease less than 2 cm; and 2000 cGy is reserved
for unresected or gross residual disease more than 2 cm. The
IORT dose that can be given should take into account the total
of any prior EBRT that has been administered.
Although we only have experience with EBRT, other institutions have used other ways of delivering intraoperative or
prolonged local radiation therapy. At Memorial SloanKettering, a combined-modality treatment protocol uses highdose intraoperative brachytherapy (HDR-IORT).
radiation is delivered via an array of catheters that are imbedded in a flexible rubber pad. This pad is then sutured to the
area of concern and other normal tissue is packed away and
protected. The catheters are connected to a high-dose-rate
source. After the total dose is delivered, the pad is removed
and the operation proceeds. Another approach is to use perioperative brachytherapy as a way to combine local delivery of
radiation with extended surgery.
31–34
With this method,
brachytherapy catheters are loosely secured to a mesh material
that is then secured to the region of interest. The operation is
completed and the ends of the catheters are brought out
through a separate skin incision and secured to the skin. Then,
usually between postoperative day 3 and 5, removable radioactive elements are placed into the brachytherapy catheters.
Once the desired total dose is delivered, the catheters are
removed at the bedside without the need for sedation or anesthesia. These techniques do not require a dedicated operating
room with a linear accelerator to administer radiation regionally and may therefore expand where this type of surgery can
be performed. One possible disadvantage with the use of the
postoperative brachytherapy catheters is that it is difficult to
protect normal tissue, particularly the small intestine, once the
operation is complete. However, these alternative methods for
delivering local radiation therapy, when combined with
extended surgery and chemotherapy, seem to result in morbidity and survival outcomes that are comparable to our experience with intraoperative EBRT.
30
The
192
Ir
33. Management of Locally Advanced and Recurrent Rectal Cancer 457
Results of Multimodality Treatment
for Advanced Primary or Locally
Recurrent Rectal Cancer
Disease recurrence and survival in patients with rectal cancer is
highly dependent on the stage of disease and the mode of treatment. In recent reports, the combination of preoperative EBRT
and total mesorectal excision surgery for resectable rectal cancer resulted in a recurrence-free rate of 94% for Stage II and
85% for Stage III tumors.
rectal cancers often have a higher recurrence rate.
the cause of death in these patients is usually attributable to systemic disease, a mortality rate of 16%–44% has been attributed
to isolated local failure.
recurrences in the pelvis are associated with significant pain,
bleeding, and urinary or neurologic complications that often
dominate the clinical picture and affect the patient’s quality of
14
life.
Traditionally, palliative pelvic radiation has been used,
but it often only provides short-term palliation of symptoms or
of local disease progression.
cant symptoms associated with advanced primary or recurrent
rectal cancer and to perhaps improve survival, a number of
institutions have used multimodality therapy, including preoperative chemoradiation, extensive surgery, and intraoperativedirected local radiation therapy.
For patients with advanced primary rectal cancer, studies
have shown the benefit of combined preoperative chemoradiation followed by radical surgery. In a retrospective review of
60 patients with primary locally advanced rectal cancers,
81% were able to undergo curative resection. Their overall
2-year survival was 91%, and their local regional recurrence
rate was 7.5%. In another study, preoperative chemoradiation
with extensive surgery improved overall survival and control
of pelvic disease compared with preoperative radiation therapy alone.
35
In that study, the use of IORT improved local
control in patients with microscopic residual disease or clinically fixed tumors. None of the patients treated with IORT
developed local failure in the pelvis. Similar findings of
improved local control and survival were reported in a series
of patients with primary advanced rectal cancers who were
given HDR-IORT.
sectable rectal cancer underwent multimodality therapy
including preoperative chemotherapy, external beam irradiation, and extensive surgery with intraoperative brachytherapy,
which led to actuarial 2-year local control of 81%. Local
tumor control was 92% for patients who underwent resection
with negative margins versus 38% for those with microscopic
positive margins. The overall 2-year actuarial disease-free
survival rates were 77% for patients with negative margins
and 38% for patients with positive margins. In sum, series of
patients with locally advanced primary rectal cancer who
were treated with intraoperative radiation and surgery have
shown an overall improvement in local control compared with
historical controls.
40
However, more locally advanced
42,43
Also, advanced primary disease and
14,44
To better address the signifi-
36
These 22 patients with primary unre-
41
Although
45
Surgery alone has been used to treat recurrent rectal can-
46
cers. In the series by Garcia-Aguilar et al.
of 87 patients
with recurrent rectal cancer, 64 patients underwent surgical
exploration, and only 42 were able to undergo resection with
curative intent. The estimated 5-year survival rate for patients
who had curative-intent surgery was significantly better than
that for patients who had only palliative or no surgery (35%
versus 7%). In most series, recurrence and survival rates for
patients with recurrent rectal cancer treated with surgery
alone are less than those for patients with primary advanced
rectal cancer, but are still better than historical data for
patients treated with palliative therapies. In general, patients
treated with multimodality therapy including IORT experience 3-year local control rates ranging from 25% to 78%, and
long-term survival has been reported to be between 25%
and 40%.
47–54
The institution with the most experience using multimodality therapy including IORT for recurrent rectal cancer is the
Mayo Clinic. Between 1981 and 1996, 394 patients were
treated, 90 of whom had unresectable local or extrapelvic disease at the time of surgical exploration.
47
Although 304
patients underwent resection of the recurrent tumor, only 138
(45%) underwent a histologically confirmed curative resection. The 166 remaining patients had a palliative operation
because of either gross (n = 139) or microscopic (n = 27)
residual cancer in the pelvis. Nine percent of the patients who
had surgery with curative intent underwent extended resections (i.e., sacrectomy, pelvic exenteration, cystectomy with
ileal conduit) because of the advanced nature of the tumor.
These patients were prospectively monitored to determine
long-term survival and the factors influencing survival.
The 1-, 3-, and 5-year survival rates for the 304 patients
were 84%, 43%, and 25%, respectively. The median survival
time was 31 months. The 5-year survival rate was greater after
curative (i.e., negative histologic margins) than after palliative
surgery (37% versus 16%, P < .001). The presence of gross
residual disease in patients who underwent nonpalliative
resections resulted in decreased survival compared with those
patients with microscopic residual disease. However, survival
for patients who had extended resections was not significantly
different than that for patients who had a limited resection
(28% versus 21%, P = 0.11, respectively). Logistic regression
analysis found several independent factors that contributed to
the ability to perform a curative resection. On univariate
analysis, initial surgery with end colostomy or painful recurrence were associated with having palliative surgery. On multivariate analysis, increasing number of tumor fixation sites
was associated with a palliative resection. These factors also
affected overall survival; patients with pain and more than one
site of fixation had significantly lower survival rates. The best
5-year survival rates were in patients who had nonfixed
tumors (41%) or asymptomatic recurrences (41%). Other
institutions that have used a multimodality approach that
included some form of intraoperative radiation have reported
similar improvements in local recurrence and survival.
51–54
458 R.R. Cima and H. Nelson
Patients whose tumors can be resected with negative margins often have better outcomes. Because of this, some
investigators have questioned the routine use of the intraoperative, locally directed radiation therapy.
and colleagues
56
reported a nonrandomized, prospective
55
Recently, Wiig
study evaluating the value of IORT in reoperative surgery
for recurrent rectal cancer. The estimated overall 5-year survival was 30%. However, patients who had an R0 resection
had a 60% survival compared with 25% and 0% for R1 and
R2, respectively. The use of IORT did not improve survival
or local recurrence when controlling for R-stage resection.
However, other reports indicate that IORT improves local
control and survival even in patients with R1 resections
when compared with most control series of patients.
48
In
addition, many series report that pelvic recurrences after
multimodality therapy that included IORT occurred outside
the intraoperative radiation field. In the most recent study to
look specifically at the rate of local recurrence after the use
of high-dose-rate brachytherapy, significantly more recurrences occurred outside of the IORT field than within the
radiation field.
54
In that series, the time to pelvic recurrence
was 16 months in patients who had a pelvic recurrence outside the radiation field, and 31 months in patients who had a
pelvic recurrence within the radiation field; however, the
difference was not statistically significantly (P = .07). To
specifically address the benefit of adding IORT to the combined multimodality treatment of patients with advanced
primary or recurrent rectal cancer would require a prospective, randomized trial. However, this would be a difficult
undertaking given the relatively few institutions capable of
delivering this complex therapy, the variations in different
intraoperative radiation techniques, and the relatively limited number of patients for whom this therapy is appropriate.
For now, most studies, although retrospective and often
based on single institutions, suggest that combined multimodality therapy that includes IORT provides the best
chance for cure for patients with locally advanced or recurrent rectal cancer.
Perioperatively related mortality was very low in patients
who underwent this multimodality treatment (0.3%).
However, treatment-related morbidity was relatively high. In
one series of 304 patients who underwent surgery with curative intent, 96 (32%) required prolonged hospitalizations, 78
(26%) of whom required readmissions and/or additional surgical procedures. The most frequent complications included
pelvic abscesses (6.6%), bowel obstructions (5.3%), enteric
fistulas (4.3%), and perineal wound complications (4.6%).
The complication rate was significantly higher in patients
who underwent extended surgical resections and in patients
who had recurrences fixed in more than two sites in the pelvis.
These findings underscore the need for thorough preoperative
patient selection to ensure that the patient is fit enough to
tolerate the surgery and the potential complications, and
that there is no evidence of disease outside of the region of
resection.
Palliative Care for Advanced or
Recurrent Rectal Cancer
Patients who present with locally advanced or recurrent rectal
cancer must first be evaluated with the intent to cure. An
equally important consideration is palliation of symptoms if a
cure does not seem to be achievable. The local effect within
the pelvis of an advanced or recurrent rectal cancer drives the
need to address control of symptoms. These symptoms often
include rectal bleeding, rectal obstruction, urinary obstruction
caused by local invasion, and severe pain related to invasion
of the pelvic sidewall or direct invasion of pelvic nerves. Over
the past decade, the choice of palliative options has expanded
and choice of option requires careful consideration of the presenting symptoms, possible future symptoms, extent of local
and distant spread of the disease, and the overall physical condition of the patient.
Palliative interventions may be broadly classified as noninvasive, minimally invasive, and surgical. The primary noninvasive palliative option is radiotherapy. In patients who have
never received pelvic radiation, a full course of external beam
irradiation may be a very effective treatment for bleeding,
pelvic pain, and near obstruction. The use of external beam
radiotherapy may result in palliation of severe pelvic pain in
50%–90% of patients.
experience progression of the tumor and recurrent symptoms
before they die. Lingareddy and colleagues
there is a significant use for palliative reirradiation in treating
recurrent rectal cancers. In their study of 52 patients with
recurrent rectal cancer, pelvic reirradiation resulted in complete palliation of bleeding, pain, and mass effect in 100%,
65%, and 24% of cases, respectively. The median initial radiation dose to the pelvis was 50 cGy; the median reirradiation
dose was 30 cGy. Most patients had palliation of their symptoms until their deaths. Grade 3 and 4 toxicity were seen in
23% and 10% of patients, respectively. The 2-year overall
actuarial survival was 25%.
Minimally invasive approaches to palliation usually involve
47
mechanical means to reduce symptoms related to pelvic
tumors. These include ureteral stents to alleviate urinary
obstruction and expandable metal colonic wall stents or the
use of lasers to relieve rectal obstruction. Self-expanding
metal stents (SEMS) are useful for the nonsurgical management of rectal obstructions, bleeding, and malignant fistulas.
In a review of the literature, palliation with SEMS was
47
achieved in 90% of patients.
SEMS for malignant rectal obstructions, stents could be
deployed successfully in 36 of 37 patients with rectal obstruc-
61
tions,
and 28 had good long-term results with no need for
subsequent intervention.
Endoscopic lasers are an alternative to SEMS. The
neodymium yttrium argon garnet (Nd:YAG) laser is the most
frequently used. Endoscopic laser treatments remove the
tissue intraluminally by coagulative necrosis or immediate
57,58
However, virtually all patients will
44
have shown
60
In the largest series to report on
61
59
33. Management of Locally Advanced and Recurrent Rectal Cancer 459
tissue vaporization, depending on the amount of energy
applied. Palliation of symptoms and marked improvement in
quality of life is achieved after repeated laser sessions (usually 2–5) in 80%–90% of patients.
62,63
Unfortunately, laser
therapy does not seem to be a durable treatment. Effective
palliation decreases as a patient survives longer; successful
palliation at 1 year was only 42%.
64
There are no data on the use of palliative resections in
patients with locally advanced or recurrent rectal cancer.
However, a report from Memorial Sloan-Kettering has evaluated the role of palliative resection in 80 patients with Stage
IV rectal cancer.
65
Twenty-four percent had clinical evidence
of obstruction and 94% had either T3 or T4 lesions. None had
received prior surgical or radiation therapy. They underwent
radical resection of the primary lesion and surgical treatment
of solitary hepatic metastasis, if present. There was one death,
a 15% postoperative morbidity, and a 20% colostomy rate.
The overall local recurrence rate was 6%, actuarial local control at 2 years was 94%, and median survival was 25 months.
This study shows that in appropriately selected patients with
Stage IV disease and complicated or advanced rectal cancer,
surgical resection of the primary tumors can achieve very reasonable oncologic results and provide good palliation of
symptoms related to the tumor.
Summary
For patients with advanced primary or recurrent rectal cancers, the only hope of cure requires a coordinated multidisciplinary approach to treatment. In general, EBRT,
chemotherapy, extensive surgery, and the use of directed
IORT seem to improve local control and survival. Surgery in
these patients carries a higher morbidity rate than surgery for
primary rectal cancer, but one that is acceptable in appropriately selected patients. Before proceeding with multimodality
therapy, patients should be thoroughly evaluated for the presence of disseminated extrapelvic or metastatic disease, which
would, in most instances, preclude a curative operation.
Experience indicates that isolated anterior or posterior fixation of the tumor does not preclude a curative resection. In
these cases, en bloc resection of involved organs or bony
structures can result in resection with negative margins.
However, tumors fixed to the lateral pelvic sidewall, fixed at
multiple points, or fixed circumferentially are often unresectable or incurable. Available data from many institutions
indicates that multimodality therapy for advanced primary or
recurrent rectal cancer results in better local control and
higher survival rates than palliative therapy.
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