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radiotherapy reduces the dose of radiation to surrounding structures, though sup-
porting evidence is limited regarding a benefit over conventional radiotherapy [48].
To maximize tumor response, surgery is planned for 6–8 weeks following comple-
tion of radiation [49].
As part of a multimodal treatment approach, intraoperative radiotherapy (IORT)
has been shown to increase survival by 15 % or more and improve local control in
selected patients [50, 51]. Intraoperative radiotherapy overcomes the dose restriction
of EBRT by limiting exposure to surrounding unaffected structures. The total dose
administered is dependent on preceding amounts of preoperative radiotherapy deliv-
ered. The Mayo Clinic has a dedicated operating room with a linear accelerator to
provide electron beam radiotherapy, and a dose of 1000 cGy is given for minimal
residual disease (margin microscopically involved or clear by <5 mm), 1500 cGy for
unresectable gross disease less than 2 cm, and 2000 cGy for more than 2 cm [52].
Other means of administering locally directed radiation include high dose intraop-
erative brachytherapy (HDR-IORT), perioperative brachytherapy, and photon radio-
surgery [53, 54]. Multiple institutions have shown improved disease free and overall
survival, as well as local control, following R0 and microscopically positive (R1)
resections when IORT is incorporated into a multimodal treatment regimen, regard-
less of the IORT approach chosen [50, 51, 55–62]. Others have not been able to
document a benefit [42, 63–65]. The largest series evaluating 304 patients with
locally recurrent rectal cancer was reported by the Mayo Clinic in 2003. Of those,
138 underwent a R0 resection, 27 a R1, and 139 had gross (R2) residual disease. The
5 year survival rates were greatest for R0 versus the R1 and R2 resections (37 versus
16 %, p < 0.001). Survival after extended procedures (sacrectomy, pelvic exentera-
tion, cystectomy with ileal conduit) was comparable to more limited resections (28
versus 21 %, p = 0.11) [31]. Overall, results from specialized centers support an onco-
logic advantage for IORT in select patients. However, there is a significant amount of
heterogeneity between centers, making broad consensus statements challenging.
A R0 resection provides the highest rate of local control as well as cancer spe-
cific and overall survival. The presence of microscopically or grossly positive (R2)
margins decreases survival [66]. Resection is based on defining invasion into adja-
cent structures, as well as the presence of metastatic disease. Factors typically asso-
ciated with the inability to pursue a curative (R0) resection include poor performance
status, encasement of external iliac vessels, presence of venous or lymphatic
obstruction, distant metastasis, fixation to two or more sites (F2 or F3 involvement),
predicted R1/R2 resection, sacral invasion above S2, extension though the greater
sciatic notch, circumferential or multiple sites of pelvic sidewall involvement, bilat-
eral ureteral obstruction outside the bladder trigone, and S1/S2 nerve root involve-
ment [35, 67–70].
Upwards of 50 % of patients with local recurrence will have a metastatic lesion
noted during initial evaluation. If resectable, surgical intervention can be pursued in
a synchronous or staged approach, and in highly selected patients outcomes are
favorable [71, 72]. En bloc resection of involved ureteral or iliac vessels is possible
and is associated with an increased R0 resection rate [6, 35, 69, 73–75]. Extended
resections to achieve negative margins, including a high sacrectomy, improve local
S.R. Kelley and D.W. Larson
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245
control and survival [6, 8, 68, 73, 76–84], though can result in significant life alter-
ing morbidity. Complications are higher for fixed tumors, and reduced tumor free
resection margins and survival has been demonstrated in those with symptomatic
pain and fixation to more than one area [30, 31]. Other factors noted to decrease R0
resections are male sex, increased age, previous abdominoperineal resection, higher
stage of primary tumor, and elevated CEA level [35]. If the morbidity of an extended
resection to obtain a R0 margin outweighs the potential benefit, an R1 resection
with IORT should be pursued.
Following radiation, surgery, and IORT, complications occur in upwards of 65 %
of patients owing to the heavily irradiated field [31, 46]. The most common compli-
cations include pelvic abscesses (6.6 %), bowel obstruction (5.3 %), enteric fistulas
(4.3 %), and wound complications (4.6 %). Those with extended resections and
more than two sites of fixed recurrence, experience the highest rates of postoperative
complications [31]. Nelson and colleagues from the Mayo Clinic reported reduced
wound complications and length of hospital stay when flap repairs were utilized in
comparison to primary closure. Other studies have corroborated the benefit of peri-
neal defect closure/reconstruction with techniques including omentoplasty com-
bined with biologic implants, vertical rectus or myocutaneous oblique abdominis
muscle flaps, gluteal rotation flaps, gracilis flaps, and free flaps [85–91].
If cure is not possible (R2 resection would be required), then palliation of symp-
toms may be sought with a combination of modalities (chemoradiotherapy, urinary
and colonic stents, nephrostomy tubes, endoscopic laser ablation, targeted surgery),
all of which have been shown to improve quality of life, though rarely halt disease
progression [92–96]. External beam radiation, therapy (EBRT) including reirradia-
tion when necessary, has been noted to control pain in 50–90 % of patients [97, 98].
The addition of chemotherapy to EBRT also improves symptoms, but not 5 year
survival [41, 99, 100]. Improvement in symptoms and quality of life has been
shown to be superior following surgery compared to non-surgical approaches, even
for selective cases with distant metastasis, although less so for extended resections
[25, 101, 102].
Recommendations Based on the Data
The available evidence regarding the management of locally recurrent rectal cancer
consists primarily of single institution case control and retrospective studies. Few
multicenter studies exist and there are no randomized trials.
High resolution MRI is the preferred imaging modality to evaluate for pelvic
recurrence. Computed tomography of the chest, abdomen, and pelvis should be
obtained to assess for extrapelvic metastasis. Questionable findings can be further
investigated with PET – CT (evidence moderate, strong recommendation).
A classification system to assess for tumor resectablilty and prognostic informa-
tion should be incorporated into the preoperative workup and evaluation (evidence
moderate, strong recommendation).
22 Selection Factors for Reoperative Surgery for Local Recurrent Rectal Cancer
246
Neoadjuvant chemoradiotherapy should be administered to radiotherapy naïve
patients (evidence moderate; strong recommendation) and re-irradiation prior to
surgery can be administered in those previously irradiated (evidence low, weak
recommendation).
Re-staging should be performed 4–6 weeks prior to surgery (evidence low, strong
recommendation) and surgery should be planned 6–8 weeks after completing neo-
adjuvant therapy (evidence moderate, strong recommendation). IORT, when indi-
cated, should be part of the multimodal treatment regimen (evidence moderate,
strong recommendation). To decrease issues with postoperative pelvic wound com-
plications, flap reconstruction should be pursued for large defects (evidence moder-
ate, strong recommendation).
The best chance for survival is a R0 resection, which may require an extended
radical resection (evidence moderate, strong recommendation). If morbidity out-
weighs the benefit of an extended resection to achieve a R0 margin, an R1 resection
with IORT should be pursued, which has better outcomes than R1 without IORT
(evidence moderate, strong recommendation). Surgery does not offer adequate sur-
vival or local tumor control following a R2 resection and should be avoided (evi-
dence moderate, strong recommendation).
If curative resection is not possible, palliation of symptoms should be sought
with a combination of modalities to improve quality of life (evidence moderate,
strong recommendation).
A Personal View of the Data
Based on our experience at the Mayo Clinic, as well as the literature, we perform a
high resolution CT of the chest, abdomen, and pelvis to evaluate for metastases. A
high resolution musculoskeletal pelvic MRI that includes axial, sagittal, and coro-
nal/oblique views is the imaging modality of choice when evaluating for local
recurrence. Questionable findings are further investigated with PET – CT. A classi-
fication system to assess for tumor resectablilty and provide prognostic information
should be incorporated into the preoperative workup and evaluation. Tumor loca-
tion and local extent of involvement are two of the most important factors in deter-
mining resectability. For those cases with a high probability of an R0 resection, the
collaboration of an experienced multidisciplinary team (colorectal surgery, urology,
gynecology, plastic reconstructive, vascular, neurosurgery, orthopedics, radiation
oncology) should be pursued.
Although the literature is controversial regarding the benefit of reirradiating pre-
viously irradiated patients, we have found it to be beneficial in our patient population.
A short course boost is often followed by surgery within a week. Unless contraindi-
cated, all radiotherapy naïve patients should receive neoadjuvant chemoradiation.
Multimodal therapy with IORT improves local control and survival and offers the
best possibility of cure, though is does not compensate for inadequate or incomplete
resections (R2). IORT reaches its peak effect if delivered within 8 weeks following
S.R. Kelley and D.W. Larson
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EBRT. Imaging should be repeated 4 weeks after completion of CRT and if no pro-
gression or metastasis is found, surgery should be pursued within the next 4 weeks.
It has become widely accepted that the surgical management of locally recurrent
rectal cancer offers the potential for cure and improved quality of life in patients
who are candidates for re-resection. A planned R2 resection should be avoided since
outcomes are no different than non-operative measures. These high-risk surgeries
should be performed in dedicated referral centers capable of managing such com-
plex patients.
Abstracted Recommendations
High resolution MRI is the preferred imaging modality to evaluate for pelvic
recurrence. Computed tomography of the chest, abdomen, and pelvis should
be obtained to assess for extrapelvic metastasis. Questionable findings can
be further investigated with FGD\PET – CT (evidence moderate, strong
recommendation).
Histologic confirmation of recurrence should be ascertained whenever possible
(evidence moderate; strong recommendation).
Neoadjuvant chemoradiotherapy should be administered in radiotherapy naïve
patients (evidence moderate; strong recommendation).
Re-irradiation prior to surgery can be administered in those previously irradiated
(evidence low, weak recommendation).
Re-staging should be performed 4–6 weeks prior to surgery (evidence low, strong
recommendation).
Surgery should be planned for 6–8 weeks after completing neoadjuvant therapy
(evidence moderate, strong recommendation).
IORT, when indicated, should be part of the multimodal treatment regimen (evi-
dence moderate, strong recommendation).
To decrease postoperative pelvic wound complications closure/reconstruction should
be pursued for large defects (evidence moderate, strong recommendation).
The best chance for cure is a R0 resection, which may require an extended radical
(involvement of surrounding organs/structures) resection (evidence moderate,
strong recommendation).
If morbidity outweighs the benefit of an extended resection to achieve a R0 margin
a R1 resection with IORT should be pursued, which has better outcomes than R1
without IORT (evidence moderate, strong recommendation).
Surgery does not offer adequate survival or local tumor control following a R2
resection and should be avoided (evidence moderate, strong recommendation).
If the potential for cure is not possible palliation of symptoms should be sought with
a combination of modalities to improve quality of life (evidence moderate, strong
recommendation).
Patients with local recurrence of rectal cancer, or suspicion of, should be referred to
dedicated centers for care (evidence low, strong recommendation).
22 Selection Factors for Reoperative Surgery for Local Recurrent Rectal Cancer
248
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S.R. Kelley and D.W. Larson
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Part IV
Anal Dysplasia/Cancer