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MR TOM ANDREW MACCABE (Orcid ID : 0000-0002-5168-4970)

Article type : Original Article

TITLE PAGE

Outcomes following Local Excision of Early Anal Squamous Cell Carcinomas of the Anal Canal and
Perianal Margin

T.A. Maccabe1, I. Parwaiz1, R.J. Longman1, M.G. Thomas1, D.E. Messenger1

Affiliations:

1Department of Colorectal Surgery, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol,
UK

Corresponding Author:

Mr David Messenger

Department of Colorectal Surgery

University Hospitals Bristol & Weston NHS Foundation Trust

Bristol Royal Infirmary

Upper Maudlin Street

Bristol

BS2 8HW

Email: David.Messenger@UHBW.nhs.uk.

Tel: 0117 342 2808

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process, which may lead to
differences between this version and the Version of Record. Please cite this article as doi:
10.1111/codi.15424
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Accepted Article
Disclaimer: The authors declare that they have no conflict of interest

Funding: None

Word Count: 3,482

ABSTRACT

Aim: There is a paucity of data on outcomes from local excision (LE) of early anal squamous cell
carcinomas (ASCCs). This study aimed to assess survival outcomes according to tumour location; perianal
(PAT) or anal canal (ACT), determine factors associated with R1 excision and outcomes according to T-
category.

Methods: This was a retrospective cohort study of consecutive patients with early ASCC treated by LE
from 2007 to 2019. Data were collected on baseline demographics, tumour location, staging, excision
histology, adjuvant treatment, site and timing of recurrence. The main outcome measures were R1
resection, locoregional recurrence (LRR), disease free survival (DFS) and overall survival (OS).

Results: Of 367 patients treated for ASCC, 39 patients (10.6%) with complete follow up data underwent
LE: 15 ACTs and 24 PATs. R1 resections were obtained in 27 patients (69.2%) and occurred more
frequently in ACTs than PATs (93.3% vs 54.2%, p=0.006). Eighteen of 27 patients (66.7%) received
adjuvant therapy [chemoradiotherapy (n=11), radiotherapy alone (n=7)] for R1 excision or re-excision,
following which LRR developed in 1 of 10 patients (10.0%) in the ACT cohort and 1 of 8 patients (12.5%) in
the PAT cohort. There was no difference in five-year LRR-free survival (82.0% vs 70.1%, p=0.252), DFS
(58.2% vs 78.4%, p=0.200) or OS (86.2% vs 95.7%, p=0.607) between the ACT and PAT cohorts.

Conclusions: LE is a feasible treatment option for early ASCCs of the perianal margin, but not the anal
canal. Acceptable long-term outcomes can still be achieved with adjuvant therapy in the presence of a
positive margin. Larger prospective studies to assess LE as a treatment strategy, such as the ACT3 trial, are
warranted.

What does this add to the literature?

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 This is one of the largest cohort studies of outcomes following local excision of early anal squamous cell
Accepted Article
carcinomas and demonstrates that this is only feasible for tumours located at the perianal margin. In the
presence of a positive margin, acceptable oncological outcomes can still be achieved with adjuvant
oncological therapies.

MANUSCRIPT

Introduction

The incidence of anal squamous cell carcinoma (ASCC) is rising (1). The use of combination
chemoradiotherapy (CRT) as the primary treatment modality is well established and treatment regimens
have changed little since the seminal work of Nigro et al in the early 1970s (2). Survival outcomes are
favourable with contemporaneous five-year overall survival (OS) of 65-70% reported in North America
and Europe (3, 4). Approximately 10-15% of patients with ASCC present with T1 tumours for whom local
excision (LE) alone is increasingly being adopted as a treatment option (5), particularly for smaller lesions
located in the perianal region. However, there is limited data to inform clinicians as to which lesions can
be successfully managed by LE and whether adjuvant treatment therapy following LE confers any
additional benefit (6). The ACT3 trial, within the personalising radiotherapy dose for anal cancer (PLATO)
trial platform, is currently assessing the difference between these treatment strategies (7).

A study based on data from the Nordic Cancer Registry suggested that the addition of post-operative CRT
improved survival outcomes in patients undergoing LE for T1-T2N0M0 tumours, but this cohort also
included patients undergoing primary abdominoperineal excision (APE) (8). Other studies have reported
favourable outcomes with the use of radiotherapy, but evidence relating to the sequence of LE, either
before or after radiotherapy, and radiotherapy dosage remains inconclusive (9). Guidelines published by
specialty associations in the UK, US and Europe all recommend that T1N0 tumours can be adequately
managed with LE providing adequate surgical margins are obtained (3),(4, 10) although there is little
guidance on risk stratification to guide the use of adjuvant therapy.

A key challenge in the management of early ASCC is that these tumours often present as an incidental
finding at the time of surgery for other pathology, and therefore, completeness of excision is not the main
concern. Consequently, multidisciplinary discussions of early ASCCs are often centred around the

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 adequacy of excision and what constitutes an acceptable margin. Prior to the 8th edition of the American
Accepted Article
Joint Committee of Cancer (AJCC) Classification of Cancer, perianal ASCCs were treated as skin cancers
requiring resection margins of 4-6mm (11) (12). Perianal tumours were subsequently redefined as ASCCs
within 5cm of the anal margin (13), with UK guidelines stating that a distance of >1mm from the invasive
tumour component could be considered a clear margin (10).

Another factor to consider is the prognostic impact of tumour location, either perianal or anal canal, as
this may impact on the adequacy of excision with regards to anal sphincter muscle preservation, but this
has never previously been reported. At the current time, evidence for the management of patients in
whom R1 resection is obtained after LE is lacking, although in practice it is likely that these patients would
be offered adjuvant therapy or a repeat excision.

Local excision is an attractive treatment option in early ASCC, but its justification requires further analysis
from large multicentre studies. While LE may avoid the morbidity associated with chemoradiotherapy,
this needs to be tempered against its effectiveness in obtaining locoregional control. Therefore, the aims
of this study were (1) to review outcomes from LE of early perianal and anal canal squamous cell
carcinomas in a large series from a single cancer network in the UK, (2) to determine which factors were
associated with obtaining R1 excision and their impact on disease recurrence and (3) to assess outcomes
according to T-category status with reference to current ACPGBI guidelines (10).

Patients and Methods

The study was conducted in accordance with PROCESS guidelines for case series (Appendix A)(14).
Institutional approval was obtained from the University Hospitals Bristol and Weston (UHBW) NHS
Foundation Trust audit department (CAID: 5170). Data were collected on consecutive patients with ASCC
referred to the Anal Neoplasia Multidisciplinary Team (MDT) at UHBW between January 2007 and January
2019. Patients were referred from within the regional cancer network in the Upper South West of
England, covering a population of approximately 2.5 million (15).

Data were collected on age, gender, ASA grade, primary treatment modality, radiotherapy dosage,
chemotherapy regimen, tumour location (anal canal or perianal), tumour size, microscopic features TNM
stage, distance to closest margin, need for re-excision, date of recurrence and date of death. Data was
input into a Microsoft Excel database.

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 The database was then searched to identify all patients with ASCC who had undergone LE. If the diagnosis
Accepted Article
of ASCC had been confirmed prior to LE, then patients with T1 or T2 tumours (considered amenable to
local excision at MDT) without evidence of nodal involvement on pre-operative cross-sectional imaging
were included. Cases were excluded that had been locally excised, but then found to have nodal
involvement on computerized tomography (CT) or magnetic resonance imaging (MRI).

Staging and pathology

Independent histological review of all patients referred with a new diagnosis of ASCC from referring
hospitals in the regional cancer network was undertaken by sub-specialist gastrointestinal pathologists. A
structured reporting template for locally excised ASCC was not in use, but margin status, distance to
margin and lymphovascular invasion were routinely reported. In cases where invasive carcinoma could
not be conclusively demonstrated, specimens were reviewed by a second gastrointestinal pathologist. The
staging of tumours was undertaken in accordance with the TNM classification of malignant tumours 7th
edition (16).

Tumour depth was measured from the epidermal granular layer or ulcer base to deepest contiguous
tumour cell. The deep margin was defined as the distance in millimetres beyond the deepest level of the
invasive tumour component and the peripheral margin defined as the distance in millimetres beyond the
lateral most extent of the tumour. In this study, R1 resection was defined as tumour ≤1mm from any
resection margin in accordance with ACPGBI guidelines (10) and reflecting the definition used within the
ACT3 trial (7).

Tumours were subdivided according to tumour location into anal canal tumours (ACT) and perianal
tumours (PAT). PATs were defined as tumours arising from within a 5cm radius distal to the anal margin in
accordance with the 8th edition of the American Journal of Cancer Classification (AJCC) (13). Any tumour
arising proximal to the anal margin and located within the anal canal was defined as an ACT. This
distinction was made due to its potential implication for prognosis and management. Superficially
invasive squamous cell carcinomas of the anus (SISCCA) were recorded as a sub-category of T1 tumours
and defined as invasive lesions of ≤ 3mm stromal invasion and ≤ 7mm superficial spread (17). SISCCAs
were reported in this study because previous research has suggested that these lesions may be followed
up with watchful follow-up alone if completely excised (17).

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 Treatment and Follow up
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Patients managed by LE alone were followed up in a dedicated anal neoplasia clinic by specialist anal
cancer surgeons and patients who received adjuvant chemoradiotherapy were followed up by a specialist
gastrointestinal clinical oncology team. Patients were reviewed every 3 months in the first-year post-
treatment and 6-monthly, thereafter. Clinical follow-up consisted of digital rectal examination, inspection
of the perianal skin and proctoscopic evaluation where feasible. Surveillance with routine cross-sectional
imaging was not undertaken due to a lack of evidence or recommendations for an appropriate follow up
regimen. If recurrent disease was suspected, then examination of the anorectum under general
anaesthesia and cross-sectional imaging with computerized tomography and magnetic resonance imaging
were performed. When chemoradiotherapy was given following LE, radiotherapy was given in doses
between 45-55Gy, given over 5 ½ weeks with concomitant Mitomycin and either Fluoruracil (5-FU) or
Capecitabine.

Outcomes

Locoregional recurrence (LRR) was defined as the time from LE to the detection of recurrent disease at
either the primary site of tumour or mesorectal, pelvic or inguinal lymph nodes by radiological imaging or
biopsy. Disease Free Survival (DFS) was defined as the time from LE to the detection of recurrent disease,
either LRR or distant metastases, or to when death occurred from any other cause. Overall survival (OS)
was defined as the time from LE to when death from any cause occurred.

Statistical analysis

Data were presented as frequencies, means with standard deviations, medians with ranges or
percentages. Comparative analyses were performed using Pearson chi squared/Fisher’s exact test,
student’s t-test and the Mann-Whitney U test as appropriate. Univariate analyses of LRR and OS were
conducted using the log-rank test. Cox regression analyses were not performed owing to the low number
of events in each group and the potential for unstable effect estimates. A p-value of <0.05 was considered
statistically significant. Data were analysed using Stata version 13.0.

Results

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 Patient characteristics
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A total of 367 patients were identified with ASCC during the study period, of which 307 patients (83.4%)
of all stages underwent primary treatment with curative intent. LE was undertaken in 45 of these 307
patients (14.7%), although three patients were excluded from the LE cohort after nodal disease was
identified (figure 1). The median age at presentation was 62 years (range, 38-87 years) and 29 of 42
patients (69.0%) were female (Table 1). 26 of 42 patients (61.9%) had PATs and 27 of 42 patients (64.2%)
had tumours <2cm (pT1) excised. LE was performed in the referring hospital in 19 of 42 cases (45.2%) and
11 patients (26.2%) had a known history of anal or vulval intraepithelial neoplasia (AIN/VIN) and were
already under surveillance.

Initial Local Excision

Three patients had incomplete follow up data, leaving 39 patients for analysis of outcomes: 24 PATs and
15 ACTs. R1 resection was obtained in 27 of 39 patients (69.2%) and was more likely to occur in ACTs than
PATs (93.3% vs. 54.2%, p=0.006). No other tumour characteristic was associated with incomplete excision
(R1) (Table 2). Among T1 PATs excised in the regional centre, R1 excisions were obtained in 3 of 9 patients
(33.3%). In LE specimens where R1 resection was obtained, concomitant peripheral and deep margin
involvement was present in 8 of 14 ACTs (57.1%) and in 8 of 13 PATs (61.5%). The median distance to the
peripheral margin was 0mm (range, 0-8.0 mm) in PATs and 0mm (range, 0-0.5mm) in ACTs (p=0.113),
with a median distance to the deep margin of 1.4mm (0-4.5mm) in PATs and 0.2mm (range 0-1.0mm) in
ACTs (p=0.026).

Re-excision

Nine patients (six PATs and three ACTs) underwent repeat excision if the initial LE was either R1
(incomplete) or Rx (indeterminate margins). Among these 6 PATs, the margins at re-excision were
involved in 3 of 4 patients (75%) if the initial LE was R1 and 1 of 2 patients (50%) that were previously
deemed histologically Rx (figure 2). No residual tumour was identified in the three ACTs that underwent
re-excision.

Adjuvant Therapy

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 Of the 13 LEs that were initially R1 in the PAT group, 7 patients received adjuvant therapy: 3 patients
Accepted Article
following R1 re-excision and 4 patients without re-excision (figure 2). Of the 2 LEs in the PAT cohort that
had an initial Rx excision, one patient received adjuvant therapy after subsequent R1 re-excision.

Ten of the 14 ACTs with initial R1 excision received adjuvant therapy. None of the three patients that had
R0 re-excision of an ACT received adjuvant therapy. Six patients did not receive further treatment after R1
excision (5 PAT and 1 ACT) due to frailty (n=2), declined adjuvant treatment (n=3) or risk of wound
breakdown (n=1).

Locoregional Recurrence

The median follow-up for the entire study population was 44 months (range, 2-121 months). Five-year
LRR-free survival was 70.1% (95%CI 38.5-87.7%) in the PAT cohort, compared to 82.1% (95% CI 52.3-
94.2%) in the ACT cohort (p=0.252). Among the 11 patients in the PAT cohort, who were either R0 at
initial excision (n=9) or after re-excision (n=2), one patient (9.1%) developed LRR. One of five patients
(20%) in the PAT cohort developed LRR after initial R1 excision without receiving adjuvant radiotherapy.
Eight patients in the PAT cohort received adjuvant therapy after an initial R1 excision (n=4) or R1 re-
excision (n=4), of which one patient (12.5%) developed LRR. Among the ACT cohort, 1 of 10 patients
(10.0%) with an initial R1 excision who received adjuvant therapy developed LRR. All three patients in the
ACT group who had R0 re-excision after an initial R1 excision developed LRR. No other clinicopathological
factors were predictive of a difference in LRR-free survival (table 3).

Survival Outcomes

There were 5 deaths in the follow up period among the entire study population: 2 deaths in the ACT
cohort and 3 deaths in the PAT cohort. None of these deaths were attributable to disease, although one
patient in the ACT cohort died from chemotherapy toxicity. There was no difference between the ACT and
PAT cohorts in either 5-year DFS [58.2% (95% CI 29.4-78.7%) vs. 78.4% (95% CI 50.4-91.7%, p=0.200] or 5-
year OS [86.2% (95% CI 55.0-96.4%) vs. 95.7% (95% CI 72.9-99.4%), p=0.607]. LVI was the only
clinicopathological variable predictive of survival with its presence associated with poorer DFS [Hazard
Ratio = 8.47 (95%CI 1.53-46.8), p=0.014] (table 3).

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 Outcomes according to T-category
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In T1 tumours, R1 excisions were obtained in 15 of 24 (62.5%) patients compared to 12 of 14 patients
(85.7%) with T2 tumours (p=0.236) (table 2). All T1 R0 cases were PATs, from which only one patient
developed LRR (14.3%) (figure 3). After initial R1 or Rx excision of T1 tumours, nine received adjuvant
therapy of whom none developed LRR, compared to 3 LRR from the 8 (37.5%) who did not receive further
treatment (all 3 had R0 re-excision of an ACT). Two patients fulfilled criteria for SISCCA, neither of whom
developed LRR.

Among the T2 cohort, LRR developed in 1 of 10 patients (10.0%) who received adjuvant therapy
compared to 1 of 5 patients (20.0%) who did not. All 5 patients with T2 tumours who did not receive
adjuvant therapy had PATs, of which 2 patients had R0 excisions.

Discussion

This study shows that after LE of ASCCs, complete excision is more common if performed for PATs
compared to ACTs when using a histological margin clearance of >1mm (10). Successful management of
early ASCC by LE alone is only a feasible treatment option for PATs, due to the high risk of involved
margins in ACT, which is likely a consequence of attempting to preserve anal sphincter integrity. If R1
resection is obtained following resection of a PAT or ACT, then an acceptably low rate of LRR can still be
achieved with the use of adjuvant chemoradiotherapy. All patients with ACTs, in this study, that had no
residual disease after re-excision for an involved margin went on to develop LRR, suggesting that re-
excision is not a viable strategy for early ACTs.

This is one of the largest studies to report on the adequacy of tumour excision and outcomes of LE
stratified by tumour location. Current guidelines only advocate LE for small (<2cm) PATs in the absence of
nodal disease due to historically poorer survival outcomes for ACTs (3,10) , although there is limited
published evidence to justify this strategy. While R1 excisions were obtained in 54% of PATs in this study,
long-term survival outcomes were favourable and this probably reflects the mitigating effect of adjuvant
therapy. Despite the R1 excision rate for PATs appearing to be high, the rate reduced to 33% for T1 PATs
excised in the regional centre and was more in keeping with R1 rates reported elsewhere in the literature
(8, 17, 23-25). This would advocate treatment in specialist regional centres. The high overall R1 excision
rate in this series likely reflects the inclusion of a significant proportion of patients with ACTs and T2
tumours. The majority of patients included in this study were treated prior to the publication of the

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 ACPGBI guidelines when the decision to undertake LE was made by the regional anal neoplasia MDT on a
Accepted Article
case-by-case basis. The fact that R1 excisions were obtained in 93% of ACTs and 86% of T2 tumours
confirms that LE is not a viable primary treatment strategy in these patients.

Currently, there is no consensus concerning the required distance from tumour to tissue margin.
Published guidelines vary considerably, with recommended distances of: 1cm in the United States of
America (4), 5mm in mainland Europe (3) and 1mm in Great Britain and Ireland (10). A cause for concern
with adopting wider margins for ACT, is the increased risk of sphincter involvement and potential
functional consequences (18). This compromise between sphincter function and oncological adequacy of
resection explains the difficulty in obtaining clear margins in ACTs, particularly at the deep margin.
Despite this evidence, all patients with ACTs in this study who had either R1 or Rx excision, the reported
rate of LRR was 9%, which suggests that the effectiveness of adjuvant therapy was not compromised by
an incomplete LE and justifies the management strategy outlined in the ACPGBI guidelines for early ACTs
(10). Despite the number of patients undergoing re-excision in this study was small, the results suggest
that this strategy may only be feasible for PATs, as all patients who underwent R0 re-excision of an ACT
developed LRR.

In comparison to primary chemoradiotherapy treatment alone, the overall LRR following LE was low and
portends well for long-term survival (19, 20). There was no significant difference in LRR or survival
between PATs and ACTs. Only the presence of LVI was associated with poorer survival and has previously
been described as an adverse prognostic feature in ASCC (21). Several other studies report on LE for ASCC,
reporting similarly favourable outcomes to the present study, (8, 17, 22-24). R1 excision ranged from 0 to
31% with an associated LRR of 9% to 15.4%. In the series by Alfa-Wali et al. that reported R1 excision of
0% (24), all patients were HIV positive and had T1N0 PATs with excision margins of >1cm and perhaps
unsurprisingly had 0% recurrence after a median of four years follow up. Leon et al. compared outcomes
from surgery alone with surgery and adjuvant radiotherapy/chemoradiotherapy (8), but there was
significant heterogeneity in this cohort as patients were included who had undergone either LE or
abdominoperineal excision as the primary surgical treatment. A recent US study based on Surveillance,
Epidemiology and End Results data reported no difference in long-term outcomes in patients with T1 N0
ACTs treated with surgery/ablation compared to radiotherapy or chemoradiotherapy (25). However, the
exact number of patients undergoing LE or ablation could not be determined, as this was a study based on
population level data, so the true effect of LE on outcomes could not be established.

While this is one of largest series in the literature, to date, to assess the outcome of LE stratified by
tumour location, these findings should be interpreted with caution due to the small sample size.

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 Additionally, three patients were excluded due to incomplete data, potentially introducing outcome
Accepted Article
reporting bias. Of the 39 patients included in the current study, 19 patients received adjuvant therapy
whose treatment pathway and outcomes might be considered equivalent to a diagnostic biopsy with
primary chemoradiotherapy, reflecting the findings of a recent propensity-matched study by Kim et al.
(26). There may also be other factors associated with R1 resection and survival outcomes that may not
have been demonstrated due to type II error and would merit further exploration. Our study population
had significant heterogeneity particularly regarding the indications for local excision; including patients
unfit for primary chemoradiotherapy, invasive cancer found during AIN surveillance, or an incidental
finding on histology from skin tags or haemorrhoids. Each of these factors may have had a bearing on
recurrence risk. Furthermore, patients who underwent LE at a referring hospital within the cancer
network were included where the intent of surgery was frequently unclear, i.e. diagnostic or curative,
which impacted subsequent decision-making behind further treatment once referred to the regional
centre. This highlights the importance of surgeon education in the management of anal lesions and how
excision technique, such as the avoidance of diathermy during lesion excision, may facilitate margin
assessment.

In summary, LE is an appropriate primary treatment option for T1 PATs, but should not be advocated for
ACTs or T2 tumours due to near certainty of obtaining an R1 excision, thus corroborating current ACPGBI
guidance (10). Acceptable long-term outcomes can still be achieved with the use of adjuvant therapy
among patients who have a positive margin. The authors strongly advocate that the surgical management
of early ASCC should be stratified by tumour location through detailed clinical examination with MRI or
endoanal ultrasound in selected cases, to assess tumour proximity to the anal sphincter. Where doubt
exists about the adequacy of any potential excision, then biopsies should be taken to confirm the
diagnosis and the patient referred to a regional centre for further management. Such an approach seeks
to minimise the confusion associated with operative intent and adequacy of excision that frequently
arises when LEs are performed outside of specialist centres. Given the relative rarity of early ASCC, there
still remains significant heterogeneity of reported data and limited high quality evidence available. Larger
prospective studies, such as the ongoing ACT3 trial, are warranted and may provide further evidence for
the effectiveness of LE as a primary treatment strategy.

Figure 1. Patient selection flow diagram

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Accepted Article
Figure 2. Treatment pathway and outcomes of Perianal Tumours (PATs) and Anal Canal Tumours (ACTs)

Figure 3. Outcomes from local excision according to T-category

Table 1. Clinicopathological features of the study population.

Clinicopathological Feature Number of

patients (n,%)
Gender
Male 13 (31.0)

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Accepted Article Female 29 (69.0)
Median age at diagnosis (years) 63 (range: 38-87)
ASA grade
1 12 (28.6)
2 12 (28.6)
3 12 (28.6)
4 0 (0)
NS 6 (14.3)
Tumour Location
PAT 26 (61.9)
ACT 15 (24.2)
Unknown 1 (2.4)
T Stage
T1 27 (64.3)
SISCCA 2 (4.8)
Non-SISCCA 25 (59.5)
T2 15 (35.7)
Smoking Status
Current 5 (11.9)
Ex-Smoker 11 (26.2)
Non Smoker 9 (21.4)
Unknown 17 (40.5)
Grade
Well/moderate differentiated 23 (54.8)
Poorly differentiated 10 (23.8)
Unknown 9 (21.4)
Lymphovascular invasion
Yes 7 (16.6)
No 20 (4.8)
Not Stated 14 (33.3)
Hospital Performing LE
Regional centre 23 (54.8)

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Accepted Article Referring Hospital 19 (45.2)

Table 2. Risk factors for R1 resection

Factor R0 (n,%) R1 (n,%) p-value

Gender
Male 4 (44.4) 5 (55.6)
Female 5 (18.5) 22 (81.5) 0.120
Tumour Location
PAT 9 (40.9) 13 (59.1)
ACT 0 (0) 14 (100) 0.006
T-category
T1 7 (31.8) 15 (68.2)
T2 2 (14.3) 12 (85.7) 0.236
Tumour Grade
Well/Moderate 5 (25.0) 15 (75.0)
Poor 1 (11.1) 8 (88.9)
Unknown 3 (42.9) 4 (57.1) 0.347
Hospital Performing LE

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Accepted Article Regional centre 7 (31.8) 15 (68.2)
Referring hospital 2 (14.3) 12 (85.7) 0.236
Lymphovascular invasion
Yes 1 (14.3) 6 (85.7) 0.671
No 6 (31.6) 13 (68.4)
Unknown 3 (30.0) 7 (70.0)

Table 3. Univariate analysis of factors associated with five-year survival outcomes.

LRR – locoregional recurrence, DFS – disease-free survival, OS – overall survival, ACT – anal canal tumour,
PAT – perianal tumour

Survival Outcome
LRR-free survival DFS OS
Factor
HR (95% CI) P- HR (95% CI) P- HR (95% CI) P-
value value value
Gender
Female 1 1 1
Male 0.39 (0.05-3.21) 0.379 1.39 (0.40-4.77) 0.602 8.27 (0.85-80.0) 0.068
Tumour
Location
ACT 1 1 1

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 PAT
Accepted Article 0.43 (0.09-1.92) 0.252 0.47 (0.14-1.54) 0.200 0.60 (0.08-4.28) 0.607
T-category
T1 1 1 1
T2 3.91 (0.76-20.2) 0.104 3.07 (0.88-10.7) 0.078 1.41 (0.20-10.0) 0.733
R Status
R0 1 1 1
R1 1.74 (0.20-14.9) 0.613 1.43 (0.29-7.02) 0.661 1.02 (0.09-12.1) 0.985
Tumour Grade
Well/Moderate 1 1 1
Poor 0.76 (0.08-7.39) 0.814 0.81 (0.16-4.04) 0.793 0.89 (0.09-8.94) 0.922
Unknown 3.14 (0.61-16.1) 0.172 1.77 (0.42-7.43) 0.436 - -
Lymphovascular
invasion
No 1 1 1
Yes 8.79 (0.78-98.8) 0.078 8.47 (1.53-46.8) 0.014 7.13 (0.64-79.2) 0.110
Hospital
performing LE
Regional centre 1 1 1
Referring 2.04 (0.46-9.14) 0.349 1.89 (0.58-6.20) 0.294 1.40 (0.20-9.96) 0.736
hospital
Re-excision
No 1 1 1
Yes 3.74 (0.83-16.8) 0.085 2.33 (0.71-7.68) 0.163 0.73 (0.07-7.17) 0.783
Adjuvant
therapy
No 1 1 1
Yes 0.32 (0.06-1.67) 0.178 0.69 (0.21-2.29) 0.549 3.17 (0.33-30.6) 0.319

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