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Part III
Malignant Disease
Anal Cancer
DanaR.Sands andNajjiaN.Mahmoud
20
Key Concepts
• Tumors of the anal region are divided into anal and perianal cancers with different paths of lymphatic drainage.
• Squamous cell carcinoma (SCC) is the most common
type of anal cancer.
• Chemoradiotherapy is the mainstay for anal (SCCa). The
standard chemotherapy consists of 5-FU and mitomycin.
The minimum dose of radiation is 45Gy to the primary
tumor.
• Inguinal node metastasis can be diagnosed with PET-CT
and managed with radiation.
• Surgery for anal canal cancer is limited to very small
lesions and salvage situations following failed
chemoradiotherapy.
• Anal adenocarcinoma can arise from an anal gland or
chronic stula tract. They can be difcult to distinguish
from distal rectal cancers. These tumors are staged and
treated similar to rectal cancers with a lower overall
survival.
• Verrucous carcinomas are characterized by large size and
lack of invasion. Treatment is mainly wide surgical
excision.
• Anal melanoma is a rare and aggressive tumor. Survival is
very poor. Abdominoperineal resection may help to control
local disease but does not prolong life expectancy; therefore, local excision is often a rst choice when possible.
• Perianal Paget’s disease – or intraepithelial adenocarcinoma– is frequently associated with other malignancies.
Treatment is focused on surgical excision and may require
mapping biopsies to plan resection.
D. R. Sands (*)
Cleveland Clinic Florida, Department of Colorectal Surgery,
Weston, FL, USA
e-mail: Sandsd@ccf.org
N. N. Mahmoud
Division of Colon and Rectal Surgery, University of Pennsylvania,
Department of Surgery, Philadelphia, PA, USA
e-mail: najjia.mahmoud@pennmedicine.upenn.edu
• Basal cell carcinoma of the perianal region is treated with
wide local excision.
• Gastrointestinal stromal tumors can be managed with
wide local excision or radical excision depending on margin status. Preoperative treatment with tyrosine kinase
inhibitors may enhance resectability.
Introduction andEpidemiology
Although anal cancers encompass a variety of histologic
types, the overwhelming majority of these tumors are of
squamous cell origin. Adenocarcinoma, gastrointestinal stromal tumors (GISTs), melanomas, and neuroendocrine
tumors can be found in the anal canal as well, and this chapter will touch on those rare tumors, but emphasis will be on
the diagnosis, staging, and treatment of anal canal and perianal squamous cell carcinoma.
In contrast to many cancers that have seen a decrease in
incidence related to better detection, treatment, and in some
cases prevention, the incidence of SCCa continues to rise
worldwide [1]. The increased prevalence of human papillomavirus (HPV) infection is thought to be the major driver of
this trend. From 2001 to 2015, the incidence of SCCa rose
2.7% per year [2]. The number of those found to have dis-
tant disease at the time of diagnosis has tripled in this time
period [2]. The rise has not affected all races equally– the
rate in young black men has risen vefold while doubling in
whites of both genders [2]. Overall, anal cancer mortality
rates have increased 3.1% per year particularly in those
greater than 50 years of age [2]. It is estimated that there
will be 8590 new cases of anal cancer in 2020in the United
States with a preponderance of women diagnosed (5900
female/2690 male). Deaths from anal cancer will total 1350
(810 female) [3].
Effective treatment of cancer of the anus requires a thor-
ough understanding of the anatomy of the anus and anal
canal and of the various histologic types of tumors that can
© Springer Nature Switzerland AG 2022
S. R. Steele et al. (eds.), The ASCRS Textbook of Colon and Rectal Surgery, https://doi.org/10.1007/978-3-030-66049-9_20
357
358
D. R. Sands and N. N. Mahmoud
Table 20.1 World Health Organization (WHO) histological classication of malignant tumors of the anal canal
Carcinoma
Squamous cell carcinoma
Adenocarcinoma
Rectal type
Of anal glands
Within anorectal stula
Mucinous adenocarcinoma
Small cell carcinoma
Undifferentiated carcinoma
Others
Carcinoid tumor
Malignant melanoma
Nonepithelial tumors
Secondary tumors
Adapted from World Health Organization (WHO)
Table 20.2 Risk factors commonly associated with anal malignancy
HIV infection
Immunosuppression after transplantation
Immunosuppression with chronic glucocorticoid therapy
HPV infection
Cigarette smoking
Multiple sexual partners
Anoreceptive intercourse
History of previous or current intraepithelial neoplasia of the cervix
and vulva or anus
HPV human papillomavirus, HIV human immunodeciency viruses
afict this area. The most common type of cancer arising
from the anus is squamous cell carcinoma, accounting for
approximately 85% of cases [4, 5]. Evolution of the treatment of squamous cancer of the anal canal has shifted away
from radical surgery toward a nonsurgical multidisciplinary
team approach. The cooperation of the members of the
team – surgeon, radiologist, medical oncologist, radiation
oncologist, and pathologist– has resulted in improved quality of life and survival for patients with squamous cell
carcinoma.
While squamous cell cancer is certainly the most common, there are a number of less common tumors that are
often associated with abysmal survival rates, as mentioned
previously. Table20.1 summarizes the current World Health
Organization histologic classication for tumors of the anus
[6]. The widely recognized risk factors for anal carcinoma
are summarized in Table20.2.
Evaluation andStaging
The initial evaluation and staging of patients with anal cancer
begins with a history and physical examination. Patients with
anal cancer are often diagnosed at an advanced stage because
of confusion of symptoms with those of common benign con-
Table 20.3 Relevant historical information in the evaluation of
patients with anal cancer
Bleeding
Pain
Presence of mass
Skin irritation
Obstructive symptoms
Weight loss
Continence
Duration of symptoms
History of STD/HPV
Anoreceptive intercourse
History of dermatologic conditions
History of other malignancies
Prior colonoscopy
STD sexually transmitted disease, HPV human papillomavirus
ditions. Pain, bleeding, small masses, and irritation are often
misattributed by both patients and physicians alike to hemorrhoids or ssures. Duration of symptoms may be different
from benign disease, with those suffering from neoplasia noting a relatively recent onset in pain and bleeding that worsens
with time, often with an associated palpable mass and duration
of symptom onset of months rather than years.
Social history, including sexual practices and HIV status,
is relevant for patients with suspected squamous cell carcinoma. Of particular importance is a history of gynecologic
malignancies, abnormal pap smears, or head and neck squamous cell carcinoma, given the common etiology (HPV).
Diagnosis of anal dysplasia, the precursor lesion to anal
squamous cell carcinoma, or anal squamous cell carcinoma
should prompt evaluation for cervical dysplasia in women
who lack current testing (within 1 year). Please see Table20.3
for a list of pertinent historical information [7]. There is no
association between squamous cell cancer of the anus and
colonic malignancies; thus colonoscopy is not indicated,
unless otherwise warranted for colorectal cancer/polyp
screening or investigation of other symptoms. However,
patients with Paget’s disease of the anus should undergo
colonoscopy to rule out associated adenocarcinoma.
Physical Examination
A complete physical examination is mandatory, with attention paid to the inguinal region as well as the anus and
perineum. The anal examination should carefully characterize the mass. The size and location in the anal canal or
perineum, with attention to both laterality and distance from
the anal verge, sphincter muscles, and adjacent structures
(vagina, prostate), are critical. The mobility of the mass and
presence of ulceration should be noted. Abdominal palpation and the assessment for inguinal adenopathy are important. Evaluation of the rest of the anogenital region for any
synchronous HPV-related lesions completes the physical
20 Anal Cancer
359
evaluation. HIV testing for newly diagnosed SCCa may
help with management of the chemotherapy or radiation
regimens and helps evaluate for other health-related issues
that may be present. Histologic conrmation of the diagnosis is necessary prior to initiation of treatment, but large
excisional biopsies should usually be avoided so as not to
delay treatment due to the resultant large wounds. Tissue
sampling in the ofce or operating room should sufce in
most cases.
nent of the staging and management of patients with anal
cancer and should be utilized for evaluation of any suspicious lesions on conventional CT scans. Initial staging PET
scan has been shown to alter the eld of radiation when
compared to standard CT scan [8]. Although it is not recommended routinely, it can result in both up- and downstaging
in a small percentage of patients (between 5% and 38%) [9,
10]. Some studies suggest that although it can change
locoregional nodal staging in up to 40% of patients, it does
not typically change treatment planning and it does not
replace the need for a contrast-enhanced CT of the chest,
Radiologic Evaluation
abdomen, and pelvis. Negative post-treatment PET/CT is
associated with a very good 2-year disease-free survival
Systemic staging is completed with computed tomography
(CT) scan of the chest, abdomen, and pelvis. Positron emission tomography (PET) scan can be an important compo-
Table 20.4 Anal cancer TNM staging (AJCC manual 8th edition)
Primary tumor (T)
T category T criteria
TX Primary tumor not assessed
T0 No evidence of primary tumor
Tis High-grade squamous intraepithelial lesion (previously deemed carcinoma in situ, Bowen disease, and intraepithelial neoplasia
T1
T2
T3 Tumor >5cm
T4 Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder
Regional lymph nodes (N)
N category N criteria
NX Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes
N1a Metastasis in inguinal, mesorectal, or internal iliac lymph nodes
N1b Metastasis in external iliac lymph nodes
N1c Metastasis in external iliac with any N1a nodes
Distant metastasis (M)
M
category
M0 No distant metastasis
M1 Distant metastasis
Prognostic stage groups
When T is When N is When M isThen the stage group
Tis N0 M0 0
T1 N0 M0 1
T1 N1 M0 IIIA
T2 N0 M0 IIA
T2 N1 M0 IIIA
T3 N0 M0 IIB
T3 N1 M0 IIIC
T4 N0 M0 IIIB
T4 N1 M0 IIIC
Any T Any N M1 IV
Copyright © American College of Surgeons 2017
TNM tumor, node, metastasis, AJCC American Joint Committee on Cancer, UICC Union for International Cancer Control
II–III, high-grade anal intraepithelial neoplasia)
Tumor <2cm
Tumor >2cm but <5cm
M criteria
(DFS) [11]. Pelvic magnetic resonance imaging (MRI) may
be helpful for staging and treatment planning of locally
advanced disease.
is
360
D. R. Sands and N. N. Mahmoud
Unlike colorectal or anal adenocarcinoma, for which
staging is staged based on the depth of invasion, SCCa is
staged based on the size of the primary lesion and locoregional lymphadenopathy. The staging of anal squamous and
adenocarcinoma is summarized in Table20.4 according to
the eighth edition AJCC Cancer Staging Manual [12].
Anal Anatomy
A thorough understanding of the anatomy of the anal canal
is necessary to properly categorize anal cancers (Fig.20.1a,
b). The length of the anal canal is somewhat variable but in
many adults is between 3 and 4cm in length. Clinically, the
proximal extent of the anal canal is at the apex of the
puborectalis sling, which is palpable as the anorectal ring.
The distal extent is the mucocutaneous junction with the
perianal skin. This includes 1–2cm of glandular mucosa
and the transitional mucosa near the dentate line. The dentate line appears as mucosal undulations formed by the anal
glands and the vertical columns of Morgagni. The transition to non- keratinized squamous mucosa occurs at this
level. The varied cellularity of this region, also called the
“anal transition zone,” accounts for the histologically
diverse nature of anal cancers. The pathology of anal cancer is of squamous cell origin and has been called “basaloid” in the past to describe the microscopic appearance of
the cells. Transformed, carcinogenic squamous cells are
thought to originate in the anal transition zone (ATZ) in the
anal canal. The more distal the anal canal tumor is, the
more likely it is to lack glandular elements and have keratinizing features and appear more like perianal tumors [13].
Fig. 20.1 Anatomy of the anal canal with possible locations of anal
squamous cell cancers
The dentate line provides a reference point to predict lymphatic drainage. Tumors situated proximal to the dentate
line typically drain via the superior rectal channels to the
inferior mesenteric nodes and laterally along the middle
and inferior rectal vessels to the internal iliac nodes.
Lesions distal to the dentate line will have a drainage pattern via the inguinal and femoral lymphatics. Tumors situated at the dentate line can follow any or both of the above
patterns. The perianal skin, previously referred to as the
anal margin, is characterized by the keratinized stratied
squamous epithelium-lined hair-bearing skin beginning at
the anal verge and extending 5cm radially outward. Anal
tumors can therefore be categorized as either anal canal or
perianal in origin.
Anal canal cancers are tumors that develop from mucosa
(either keratinized or non-keratinized) that cannot be visualized entirely while gentle traction is placed on the buttocks.
Perianal cancers are tumors that arise within the skin at or
distal to the squamous mucocutaneous junction and can typically be seen entirely with gentle traction on the buttocks and
are within 5cm of the anus.
Perianal Squamous Cell Carcinoma
The perianal region is dened as the keratinized squamous
epithelium extending from the anal verge radially for a distance of 5cm. This area was formerly classied as the anal
margin. Tumors of the perianal region are ve times less
common than anal canal tumors and occur with a frequency
of 1–1.5 per 100,000 persons [14]. They represent 15% of
all tumors of the anal region [15]. It has been suggested that
perianal tumors have a different histogenetic origin than
their counterparts in the anal canal. As opposed to anal
canal carcinomas, perianal carcinomas show expression of
CK 5/6 and CK 13, whereas CK7, CK18, and CK19 were
rarely expressed [16]. This may account for the different
biologic behavior of the two lesions. Few series look exclusively at perianal tumors; thus, characterizing behavior is
somewhat challenging. Overall, the prognosis of perianal
SCCa is considered better than SCCa of the anal canal [17].
Tumors are typically slow growing and well differentiated,
with a female predominance and a peak incidence in the
seventh and eighth decade [18]. Metastasis is uncommon.
Recurrences are typically locoregional. Small lesions, less
than 2cm, rarely have lymph node metastasis. Nearly one
quarter of lesions 2–5 cm in size will have lymph node
metastasis, and large tumors have been shown to have nodal
spread in 67% of cases [19]. Symptoms of perianal tumors
are often attributed to hemorrhoids, often leading to a delay
in diagnosis. Jensen etal. noted that SCCa of the perianal
20 Anal Cancer
361
skin is misdiagnosed in nearly 1/3 of cases resulting in a
delay in diagnosis of a median of 6 months [20]. Perianal
SCCa resembles SCCa of the skin in other areas of the
body with a distinct border, raised edge, and central ulceration (Fig.20.2).
Primary treatment of stage I perianal squamous cell
cancer consists of wide local excision with a 1cm margin
when technically feasible. Re-excision is recommended
for margin positivity [21]. More advanced lesions are often
not amenable to local excision without harm to the anal
sphincter and require radiation- and/or chemotherapybased treatment regimens. Radiotherapy or chemoradiotherapy can be considered as a primary treatment when a
perianal tumor is large and/or threatens the anal sphincter
muscle or as an adjunct to surgical treatment when there is
a close or positive margin and re-excision would require
partial anal sphincter resection [22]. Newlin etal. reported
use of radiation with or without chemotherapy for a cohort
of 19 patients with perianal carcinoma [23]. Local control
was achieved in all patients. One patient developed distant
disease. No patient required a colostomy. The authors recommended that patients with well or moderately well-differentiated small tumors undergo excision with clear
margins and those with poorly differentiated lesions or
larger tumors undergo radiotherapy with inguinal node
treatment. Chemotherapy was added for T3 and T4 tumors
or those patients with involved inguinal nodes. Treatment
regimens for both radiotherapy and chemoradiotherapy for
perianal tumors, when utilized, are similar to that given for
anal canal SCCa.
Anal Canal Squamous Cell Carcinoma
While perianal tumors are typically treated like skin cancer
and locally excised as described above, the treatment of anal
canal SCCa is fundamentally different. These tumors are not
completely visualized with traction of the buttocks and
extend into the anal canal. Figure 20.3a, b illustrates the
gross and histopathologic appearance of SCCa. Historically
treated with wide local excision or abdominoperineal resection (APR), current treatment of SCCa takes advantage
of the exquisite sensitivity of anal canal SCCa to the
combination of radiation and chemotherapy. Local excision
or radical resection of anal canal cancers is reserved for spe-
Fig. 20.2 Perianal squamous cell carcinoma. (With permission from
Beck [125] © Copyright 2019)
cial circumstances, with chemoradiotherapy as the initial
treatment in nearly all cases.
ab
Fig. 20.3 (a) Anal canal squamous cell carcinoma. (b) Histology of anal squamous cell carcinoma 10× and 40×
362
D. R. Sands and N. N. Mahmoud
Prior to 1974, most anal canal cancers were treated with
either wide local excision or APR. Overall survival rates
were poor, even after radical resection, ranging from 30% to
70% in most small series with local recurrence rates of
25–70% depending upon stage [24]. In the early 1970s,
Norman Nigro, a colorectal surgeon at Wayne State
University in Detroit and president of the American Board of
Colon and Rectal Surgery, began using neoadjuvant chemoradiotherapy prior to APR and observed a complete histologic response (pCR) in a sizeable fraction of patients after
neoadjuvant treatment with a modest dose (3000 Gy) of
radiation and 5-uorouracil (5-FU) and mitomycin C [25].
Based on these encouraging results, Nigro and colleagues
then suggested that chemoradiotherapy may be considered
as denitive treatment for SCCa. This observation was transformative and provided the foundation for the direction of
treatment of SCCa for the next 35 years [26].
Chemotherapy
It has become clear that the addition of chemotherapy to
radiotherapy treatment is necessary to maximize clinical and
pathologic response. Studies from Europe (EORTC Phase III
and the UKCCCR ACT I) comparing the use of 5-FU and
mitomycin with radiation alone denitively showed that both
locoregional control and overall survival were positively
affected by the addition of a chemosensitizing regimen to the
use of radiation [27, 28]. An 18% higher rate of local control
at 5 years coupled with data showing an increase in median
survival from 5.4in the radiation alone to 7.6 years in those
treated with chemoradiation is convincing [27, 28].
Studies aimed at rening the exact chemotherapeutic regimen that is most effective support the use of 5-FU or
capecitabine combined with mitomycin C. Efforts to omit
mitomycin resulted in a lower 4-year disease-free survival
rate of 51% vs 73% for those with combination therapy [29].
Also, the need for salvage surgery increased from 9% to 22%
[29]. Capecitabine has been used effectively in rectal adenocarcinoma treatment as an alternative to infusional 5-FU, and
retrospective studies evaluating it as a substitute for infusional 5-FU in SCCa treatment support its use in combination with mitomycin C [30]. In multiple small retrospective
reviews, efcacy is identical, and in one study, high-grade
toxicity was signicantly reduced [31–33]. Overall survival,
colostomy-free survival, locoregional recurrence rates, and
clinical complete response rates are the same, with 6-month
locoregional control for stage I–IIII cancers at 86% [34]. In
sum, capecitabine is an acceptable alternative to infusional
5-FU in treatment algorithms for stage I–III SCCa.
The role of cisplatin in the treatment of SCCa has been
the subject of numerous investigations in an effort to rene
and identify the most effective and least toxic regimen. The
Phase III ACT I UK trial directly compared the use of cisplatin with mitomycin C [35]. Both trial arms used infusional 5-FU, and both used 50.4Gy radiation. Additionally,
this trial tested the hypothesis that giving more chemotherapy after chemoradiotherapy (5-FU with cisplatin for two
cycles) would be benecial. The trial concluded that there
was no difference in any of the primary or secondary trial
endpoints (disease-free survival, overall survival, locoregional recurrence, or colostomy-free survival) between the
two groups. Furthermore, the addition of more chemotherapy as an adjunct treatment failed to improve long-term
disease- specic metrics [35]. Similarly, the RTOG 98-11
trial compared mitomycin with cisplatin but added the two
cycles of 5-FU and cisplatin prior to chemoradiation. In
contrast to the ACT I study, the RTOG 98-11 trial found that
the mitomycin arm had a superior 5-year DFS and OS with
a 5-year colostomy-free survival that trended toward an
advantage [36].
Retrospective studies and a recent meta-analysis have
examined the use of chemotherapy without radiation in the
neoadjuvant setting in the treatment of anal cancer, and there
seems to be no clear advantage [37, 38]. However, patients
with T4 lesions, in special circumstances, may benet from
induction chemotherapy [37]. Patients who have been treated
with prior pelvic radiation and those who are minimally
symptomatic or have widespread systemic disease may be
candidates for this approach.
Other approaches to chemotherapy for SCCa have
included the use of concurrent cisplatin and mitomycin as
well as a regimen that includes the use of the epidermal
growth factor receptor (EGFR) inhibitor cetuximab. Both
strategies resulted in unacceptable toxicity that abbreviated
the clinical trials that featured them [39–42].
Radiation Therapy
The most efcacious dose of radiation associated with least
toxicity is desired when treating anal cancer. In general,
increasing dosages of radiation correlate with increased local
control and disease-free survival; however, increased dosage
can be accompanied by symptoms that necessitate treatment
breaks such as local tissue destruction, fatigue, nausea, and
pain [43, 44]. Treatment breaks during radiation are associated with reduced locoregional control, so striking a balance
between dosage, symptoms, and efcacy is of paramount
importance [45]. The RTOG 98-11 trial set forth protocols
that are considered optimal for both tumor control and symptom mitigation, and recommendations regarding doses follow the multield technique used in this trial. All patients
should receive a minimum radiation dose of 45Gy to the
primary tumor. The recommended initial dose is 30.6Gy to
the pelvis, anus, perineum, and inguinal nodes with patients
20 Anal Cancer
363
clinically staged as node-positive or T2–T4 receiving an
additional boost of 9–14 Gy. Carefully planned intensitymodulated radiation therapy (IMRT) is preferred over 3D
conformal radiation therapy in the treatment of anal carcinoma as outlined by NCCN guidelines [46].
Complications of radiation therapy are particularly difcult in those with anal canal cancer. The radiation elds
affect the perineum, sphincter complex, and pelvic bones.
Both acute and chronic problems may result from radiation
and can be dose related. Acute radiation injury to the perineal
skin, vagina, and urinary bladder can produce pain, bleeding,
and urinary frequency. Chronic injury can result in vaginal
stenosis, fecal incontinence, impotence, and pelvic or hip
fractures. It is important to counsel patients in advance that
these symptoms may develop. Efforts to mitigate damage in
the acute and chronic phase include barrier ointments,
creams, and mechanical aids such as vaginal dilators to alleviate stenosis. Patients who experience acute effects of radiation can be expected to improve gradually over time;
however, the interval it takes to see improvement may take
months, and some symptoms, like fecal incontinence and
impotence, may improve but never fully resolve.
Inguinal Lymph Node Metastases
Recent data suggests that inguinal lymph node metastases
detected via palpation or through imaging are present in
about 13% of patients who have SCCa [47]. Evidence from
case series indicates that the presence of inguinal lymph
node metastases increases with tumor size or stage and with
age. Older patients with larger tumors harbor these metastases in 20–25% of cases [47]. These data support administration of routine inguinal radiation as part of initial therapy. As
expected, inguinal node tumor recurrence is stage dependent– for patients with N0 or N1 disease at presentation, the
rate of development of post-radiation malignant inguinal
adenopathy is less than 2%. For those who present with N3
or N4 disease, that rate increases to 11–15% [48]. Radiation
is effective at treating both occult, latent inguinal disease and
more obvious cases detected at initial diagnosis by physical
exam or imaging.
Some advocate ne needle aspiration (FNA) of palpable
inguinal enlarged lymph nodes prior to treatment of SCCa. If
positive for tumor, FNA establishes a baseline should the
groin basin be resistant to treatment or develop a recurrence
post-therapy. It can also help establish accurate staging in
cases where the primary is inaccessible (completely excised
for example), an additional or different malignancy is suspected, or if concomitant infection clouds the diagnostic picture. FNA is not helpful in routine cases given the possibility
of sampling error, the relative accuracy of CT-PET, and the
fact that treatment rarely changes based on the results of
FNA. It is not necessary to surgically excise suspicious LNs
or do a supercial inguinal groin dissection pre-chemoradiation– the morbidity and high rate of wound complications
for this operation could compromise timely administration
of therapy that is very effective for treatment of both the primary and the inguinal nodal metastasis. Those with inguinal
nodal metastases that are not palpable, but are suspicious on
CT scan, do not require FNA.NCCN guidelines suggest that
radiation planning or simulation be accomplished via
PET-CT; therefore, a metabolic signal would be seen prior to
treatment if it were indeed neoplastic, as anal squamous
tumors are typically FDG avid and signal strongly with PET
imaging. Comparison of pre- and post-PET images can, in
most of these cases, establish the diagnosis and be used for
surveillance [49].
Surgery
Local excision is utilized rarely in the treatment of anal canal
SCCa, although it is the predominant therapy used for perianal squamous tumors. However, there are several situations
where local excision followed by close local surveillance
may be appropriate. APR for anal cancer is typically reserved
as a salvage therapy in those patients with a persistent primary tumor despite chemoradiotherapy, although there are
rare situations where surgery as a primary approach may be
indicated.
Supercially invasive anal cancer, dened as anal cancer
that is excised with negative margins, with less than 3mm
basement membrane invasion and a maximal spread of less
than 7mm (T1NX) may be treated with excision alone [50].
These lesions are seen with growing frequency because anal
cancer screening in high-risk populations has become more
common. Small cancers are often completely excised at the
time of biopsy, and local surgical resection with negative
margins may be adequate treatment. Studies done in patients
with close surgical margins (less than 2mm) or with microscopically positive margins subsequently treated with radiation therapy showed no difference in 5-year outcomes when
compared with those who had supercial locally excised
anal canal cancers with negative margins and no chemoradiation [51].
A retrospective cohort study that included 2243 adults
from the National Cancer Database diagnosed with T1N0
anal canal cancer between 2004 and 2012 found that the use
of local excision in this population increased over time
(17.3% in 2004 to 30.8% in 2012; P<.001). No signicant
difference in 5-year OS was seen based on management
strategy (85.3% for local excision; 86.8% for chemoradiotherapy; P=.93) [52]. The limitations of this study should be
noted– it was a large database review, and local and regional
recurrence rates were not available. An older but more spe-
364
D. R. Sands and N. N. Mahmoud
cic study, with good follow-up, suggests that small (specically <1cm), well-differentiated anal canal SCCas that are
completely excised with negative margins are safe to excise
locally with no adjuvant or neoadjuvant treatment [53].
Overall, it is likely that only those with small, welldifferentiated supercially invasive anal cancers that can be
excised with negative margins qualify for consideration of a
local excision strategy. Although this is sometimes intentionally done, local excision is often done unintentionally while
excising anal lesions for therapeutic or diagnostic reasons.
The goal of surveillance in the post-treatment period is
centered around the concept of early detection and the potential for “salvage” surgery to provide a second chance for
cure. There is evidence that tumor regression can occur for
up to 6 months following the end of radiotherapy treatment.
Close monitoring in the time following the conclusion of
radiotherapy, typically starting 8–12 weeks following the
last dose of radiation (when post-irradiation inammation
has lessened), is done via direct examination with digital rectal examination and anoscopy. Routine biopsy of residual,
but shrinking, lesions in the anal canal is not generally indicated until the 6th month following radiotherapy, to allow
time for tumor regression and healing. After that time, persistent ulcers or masses should be evaluated via biopsy [54].
However, a tumor that appears to be regrowing after chemoradiotherapy prior to the 6-month window should be biopsied at the time regrowth is suspected and treatment initiated
if biopsies are positive.
Although chemoradiation is an effective initial treatment
for anal canal SCCa, about 10–30% of patients will suffer
from persistent/recurrent tumor, mostly in a locoregional
pattern. The risk of persistence/recurrence parallels stage.
Prior to initiating salvage therapy, patients should be
restaged, typically with physical examination and biopsy
conrming the presence of tumor, CT/PET, and pelvic MR in
select cases of locally advanced disease. Contraindications
to salvage surgery include very poor performance status
combined with advanced age, incurable distant metastatic
disease, and pelvic sidewall/levator or nerve root invasion.
For those without these concerning features, APR is appropriate prior to administration of systemic chemotherapy.
With APR, the 5-year survival rate is about 50–60%, better
than with salvage chemotherapy or chemoradiotherapy
where salvage rates in small series are only 30% [54, 55].
Positive margins, involved nodes, and distant metastatic disease are poor prognostic indicators postoperatively. En bloc
resection of locally invaded resectable structures (vagina,
prostate, distal sacrum) is possible and advisable with planning and involvement of a multidisciplinary team. Soft tissue
ap reconstruction of the perineum is often necessary with or
without additional organ involvement. Highly irradiated perineal tissue makes wound healing challenging, and these
patients have a higher rate of perineal wound infection and
dehiscence when compared to those undergoing APR for
adenocarcinoma. Comparison of perineal wound closure
with and without ap shows that those closed with aps are
also subject to infection or dehiscence, albeit at a lower rate,
and wound healing progresses faster with aps than with primary closure [56]. In other words, ap closure does not necessarily prevent wound infection from occurring but does
reduce the size of the wound, and its presence speeds wound
healing if infection or supercial dehiscence does occur.
VRAM or vertical rectus abdominis myocutaneous aps are
most effective for closing large perineal wounds (Fig.20.4a,
b) [57, 58]. Perineal wound complications are more likely in
patients with bulkier tumors and larger perineal defects.
ab
Fig. 20.4 (a) VRAM ap with bilateral gluteus advancements. (b) VRAM ap, early postoperative phase. (Reused with permission Horch etal.
[126]. Copyright Springer Nature)