Association of Coloproctology of Great Britain & Ireland (ACPGBI): Guidelines for the Management of Cancer of the Colon, Rectum and Anus (2017) – Anal Cancer

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Abstract

In these guidelines, anal cancer refers specifically to squamous cell carcinoma (SCC) of the anus. The key recommendations from the ACPGBI position statement for the management of anal cancer (Lindsey, 2011) are referenced here. Although anal cancer remains an uncommon tumour, its incidence has increased significantly in the past 20 years (Wilkinson et al., 2014) and is now ~1.2 per 100 000 population, with 1233 new cases diagnosed in the UK in 2013 (Cancer Research UK). There is a female preponderance, with a female to male ratio of 1.8:1. Human papillomavirus (HPV) infection is the main predisposing factor in 90% (Frisch et al., 1997), with subtype 16 and 18 found in 81% and 4% of tumours (Alemany et al., 2015). The presence of HIV or other causes of immunosuppression may accelerate anal cancer development. Anal cancers are sub-divided into anal canal and anal margin tumours (within 5 cm radius of anal orifice). Anal canal SCCs have different patterns of locoregional spread to low rectal adenocarcinomas and are staged and treated differently. Anal margin SCCs arise from the hair-bearing skin, distal to the anal verge. However, the distinction between anal canal and anal margin may not be possible when a patient presents with a locally advanced tumour involving both sites. Anal cancer requires a specialist MDT approach to deliver appropriate treatment and optimize outcomes (Renehan & O'Dwyer, 2011a). In 2004 regional Anal Cancer MDTs were established within each cancer network (NICE, ). The underlying principles have been maintained for NHS Commissioning from 2013 onwards (NHS England, 2013). The agreed Anal Cancer MDT service includes a core team of colorectal surgeons, oncologists, radiologists and pathologists, supported by a dedicated MDT coordinator, clinical nurse specialist (CNS) and data manager. The extended team includes a plastic surgeon and a gynaecological oncologist, with a surgical practice in the treatment of vulval and vaginal cancers. All patients with suspected or newly (histologically) diagnosed anal cancer should be referred to the Anal Cancer MDT, for primary management. As the primary treatment modality for most anal cancers is by synchronous chemoradiotherapy (CRT), the MDT should comprise of one or at most two oncologists. The MDT should have two designated surgeons specializing in the surgery of anal cancer. All surgery (including local excision and salvage surgery) should be undertaken by these surgeons. Histopathology specimens should be reviewed by the Anal Cancer MDT pathologist. The MDT may need to seek advice and assistance from other surgical specialties, including urologists, vascular surgeons. Colorectal MDTs should have defined pathways to refer all patients with a new anal cancer diagnosis or recurrence to a specialist Anal Cancer MDT. Recommendation grade D Anal cancer may present with pain, bleeding, discharge, mass and occasionally tenesmus or sepsis. These symptoms may be mistaken for other benign conditions, resulting in delayed referral. Pelvic or perineal sepsis with, or without, fistula formation is sometimes seen with advanced tumours. Among men who have sex with men (MSM), and who are HIV positive, the incidence is approximately 80 per 100 000 population in the modern highly active antiretroviral therapy (HAART) era. Amongst MSM who are HIV negative, risk remains increased compared with the general population (approximately 5 per 100 000 population) (Machalek et al., 2012). Despite these increased risks, HIV positive patients account for 2 to 5.0 cm, T3 >5 cm) and in T4 tumours, invasion of adjacent organs such as vagina, urethra and bladder. Sphincter involvement does not constitute T4 disease. The N stage reflects the pattern of lymphatic spread (N1: mesorectal nodes, N2: unilateral internal iliac or/and inguinal nodes, N3: mesorectal and inguinal, or bilateral internal iliac or bilateral inguinal nodes). Less than 15% of patients have distant metastases at diagnosis. The TNM 8th edition was published in December 2016 (Brierley et al., 2017), but will only be implemented on 1st January 2018. The main change is that tumours of the anal margin and perianal skin, defined as within 5 cm of the anal margin will be classified with carcinomas of the anal canal. Anal cancers should be routinely staged by detailed clinical assessment, magnetic resonance imaging (MRI) of the pelvis, computed tomography (CT) of the chest, abdomen and pelvis. The additional use of 18-fluorodeoxyglucose positron emission tomography (18F-FDG PET/CT) can improve locoregional lymph node and metastatic staging, as well as aid radiotherapy planning (Jones et al., 2015). Endoscopic ultrasound (EUS) may provide better delineation of small T1 tumours (Otto et al., 2009) compared with A detailed clinical is to the size and in to the anal and the of anal canal involvement and its on and should be in of patients will have inguinal lymph at but up to may be to an or who are to tolerate rectal should have for local assessment and assessment with or should be when management is on the of an lymph node However, may not be if the lymph node is on or is clinical of based on The staging and management of inguinal lymph was reviewed in the ACPGBI for Anal Cancer node is not an established staging in patients with anal cancer. staging should of a detailed clinical assessment, and chest, abdomen and pelvis. The use of in should be if for all patients with tumours and are for chemoradiotherapy Recommendation grade C The TNM staging system should be The current is the 7th but will be by the 8th edition on January 2018. Recommendation grade D The of anal cancer can from tumours to tumours, involving of lymph The of treatment is to in of locoregional and at in of and and treatment for most patients with anal cancer is chemoradiotherapy The main of CRT in patients with tumours, not to local is to with and to anal the of the CRT to patients with tumours, in most excision may small tumours at the anal margin and can local et al., & The tumour should be with a margin of perianal and the a small of the distal internal anal may be to an is patients should be of a risk of may be may of or to should be by an anal cancer MDT within the MDT to a In locally anal margin tumours, the margin of excision is as have been published on to in the PLATO is is a trial to if patients with local excision of anal margin tumours, who additional have low of locoregional the other anal canal SCCs are to due to it is to margin et al., at local excision of an anal canal cancer should be as to a than a the is as with a margin CRT should be considered. anal canal can be locally for assessment, may sometimes a of the excision margin may be There is an known as squamous cell carcinoma of the defined by an with invasion and spread et al., 2015). In with a may be a role for and in these patients. excision is the primary treatment of for most anal not to local excision There are a small of for as primary when radiotherapy is or cervical when the patient is unfit for CRT but for a or the patient with advanced tumours may need a prior to commencing treatment. and sepsis. such as vaginal tenesmus or are to improve the of the patient CRT with treatment are in patients with tumours cm et al., but 5 cm, the with size et al., 2012). Despite tumour of CRT the of is low et al., 2012; et al., These patients have of the as well as and of the anal canal. the of that is should be with the that it is to be and an is the most is patients need to be the and outcomes in of and The presence of a perianal fistula should be by a prior to commencement of of CRT due to sepsis is associated with a and is inguinal lymph are treated with the primary tumour radiotherapy to the is of lymph or of lymph may be as of the T1 anal margin cancers cm) may be locally as as can be should be by an anal cancer MDT within the MDT to a Recommendation grade C T1 anal canal cancers are to be locally should be by an anal cancer MDT within the MDT to at local excision should be as to a it can be that are Recommendation grade D a is patients should be that such are in the presence of local Recommendation grade C synchronous and with low radiotherapy was in the by et al., in clinical and most patients to surgery outcomes with CRT et al., et al., The and local and with CRT compared with radiotherapy et al., et al., Anal Cancer UK on Cancer The trial and in patients CRT with compared to et al., The trial compared of by CRT of standard CRT with of treatment in significantly in of tumour and et al., et al., 2012). The UK trial was a CRT with or of There was in between and and from et al., 2013). The trial was also a of and a standard a was not by or a of radiotherapy et al., 2012). radiotherapy a to of the associated is now that of the treatment by of a or use of is to local et al., et al., et al., The trial was to deliver in with commencing of Despite a in both compared to other 90% of patients clinical advanced tumours have outcomes et al., et al., et al., 2011) than advanced tumours. trial data not or use of and are to treatment particularly for advanced tumours & the other patients with anal cancer will not tolerate standard CRT due to or performance low CRT can be a and for tumours but data are et al., et al., et al., is an has been to be as as for and treatment in colorectal cancer et al., as well as with radiotherapy in rectal cancer et al., but with a Although has not been in a anal cancer its use of is supported by et al., 2014) and within and et al., Cancer low radiotherapy to inguinal lymph is in recurrence and should be routinely to all tumours of the anal canal and recurrence have been et al., 2012). The UK and the to lymph to and significantly the of tumours have a risk of inguinal lymph node recurrence inguinal may be in most T1 tumours et al., 2012). However, as the and associated with inguinal radiotherapy when modern radiotherapy is with of recurrence in patients et al., the position is to the inguinal lymph in the low of radiotherapy the UK has all to routinely deliver highly radiotherapy a of such as therapy and The use of the of et al., to of and In for of to planning to clinical including the of radiotherapy known as Although have been of for anal the only trial was et al., 2013). The outcomes to treated patients but data on are to be The for planning and are highly and to between and Therefore of treatment is particularly to of cancer outcomes et al., et al., 2012). A UK for and and is at has into account the in the with a of radiotherapy planning and to patients in the trial and has in an of the et al., These have been into the UK PLATO trial will also a for of radiotherapy for A of the UK recommendations is as to the within the UK on to and the is with by for the The and for in anal cancer additional et al., 2012). should be prior to commencing CRT may enable female patients to have but will a in and will commencement of treatment. to the team for of options may be can and to a for advice and of vaginal should be in all of treatment. patients should be and the for may be with and treatment et al., may be due to low or by may be treated for locally advanced tumours from or to and management by the can be In a may be the only small can present with symptoms and et al., but are due to the low standard used for anal cancer. Pelvic in up to of patients, in or et al., The may be for CRT with synchronous and or is the standard treatment for all anal cancers that are not to local radiotherapy is Recommendation grade A is an important of the CRT but can be used if is The routine use of or is not Recommendation grade A radiotherapy should be for all patients in CRT is in to and of radiotherapy planning and should be based on published Recommendation grade The for should be in or in the inguinal lymph should be routinely treated in all tumours, but may be in small T1 tumours. Recommendation grade or are to local should be with treatment of a prior to commencing CRT should be in patients with symptoms to enable better treatment Recommendation grade Anal is but may be associated with bleeding, and is by HPV infection and its clinical has strong with cervical and All can in the The clinical of is that it is for anal A of on the management of have to key in are a of are with is as and aid management the of and and squamous cell was a to to and the and and were et et al., that have to of the et 2016 that the is HIV status and MSM status are important in of does not in clinical treatment and In a of patients with the to was to be in patients et al., that to anal in the general population were is now and advanced to to anal cancer of one in patients in in the per in HIV-positive and one in patients per in (Machalek et al., 2012). These should the for in management. a clinical based on the of and other such as risk HIV and should be considered. The of management of to is that if one can or can be However, is to to of anal is for to cervical and to the anal canal to can of is in but its role in clinical practice is not The diagnosis of can be suspected or with the aid of but can only be and the risk of of and for the diagnosis of should be by the specialist within the Anal Cancer MDT. There are and as including and therapy have also been used et al., 2013). from a trial in HIV positive MSM that is better than and in the treatment of the was but that recurrence were et al., 2013). The of patients with and is at the of carcinoma that can be treated by local excision or CRT with patients should be up at for at 5 with of the perianal There should be a low to of or should be by has been is of risk of perianal and pain, with on management. new are carcinoma of the is defined by an squamous carcinoma that has an of from the of the of and has a spread of in and has been et al., 2012). are small but it may be that of these can be by et al., 2015). be a specialist Anal Cancer MDT. such as perianal have been All anal should be or of anal for is in to disease. Recommendation grade D All cases of and should be reviewed and by the specialist Anal Cancer MDT. Recommendation grade D Female patients with should be for synchronous and Recommendation grade D HIV testing in patients with or Recommendation grade C In HIV-positive the use of may have better compared with and Recommendation grade The HIV has published for et al., The key on the management of HIV patients with anal cancer are in Although anal cancer is not an its incidence is in with HIV and at a age et al., et al., et al., et al., is in HIV positive MSM (Machalek et al., 2012). anal cancers are to HPV infection and the is in et al., Despite the of therapy the risk of developing anal cancer has et al., due to significantly in for the from HPV infection the of anal to anal cancer. stage at diagnosis between HIV-positive and et al., et al., et al., et al., 2012). As may if anal symptoms are to and are in population, should be a low for all suspected cases for and of the anal canal and Although is that screening for anal cancer by identifying and the risk of developing anal cancer et al., the of in is with of up to in MSM et al., for these patients should have to There is that HIV patients can be treated with CRT and that the outcomes are to in the general population et al., 2012; et al., et al., et al., et al., 2012; et al., 2008). Although grade in patients with low CD4 cell is not a The use of to have the of CRT et al., 2012; et al., et al., et al., et al., et al., et al., but a and in CD4 cell can continued use of et al., 2012; et al., 2008). Therefore patients with anal cancer should be for infection prior to commencing in with HIV The HIV has published for the treatment and of et al., should be in patients newly diagnosed with HIV and continued CRT in known to be HIV surgery may be appropriate for with locoregional in population is et al., with metastatic or salvage surgery may be for or In of has significantly the of including with anal cancer. The principles of HIV patients with anal from to the regional Anal Cancer MDT, to staging, treatment and up should be the as in patients, as in these of anal cancer in with HIV should be a low for all suspected cases for and of the anal canal and Recommendation grade D The principles of HIV patients with anal from to the regional Anal Cancer MDT, to staging, treatment and up should be the as in patients, as in these Recommendation grade C who are to be treated with CRT should be on therapy and infection should be prior to commencing Recommendation grade C The of up of CRT for anal cancer are to (Renehan & O'Dwyer, of patients should be within a by the Anal Cancer MDT, for of local Recommendation grade D of anal cancers may be and can for up to of CRT et al., A to for local should be such an tumours should be by clinical by the at clinical However, or tumours should be in for salvage assessment by or other imaging is and is not et al., 2010). However, data that assessment at and may be to at risk of who are to salvage et al., assessment at of clinical and Recommendation grade C between particularly in locally advanced or if is Recommendation grade C with local may be to salvage within the years et al., 2012). The up from the trial is in the of the the and from years is in with pattern of assessment should of of the and for inguinal In the of the patient should be by the in or be referred to the Anal Cancer MDT surgeon for and up is in all patients, the primary is to is to salvage surgical is to symptoms to the cancer and its treatment Recommendation grade C clinical and has been clinical assessment at 60 Recommendation grade C is to tumour and The of routine use of in to clinical assessment remains with general et al., & et al., 2012; et al., and are also on with as an within the but not the et al., Cancer There may be in risk with used for patients with at diagnosis and in with treatment These patients are the most to locoregional and may be the to In the PLATO and routine has been at and In patients with suspected or local with other imaging such as chest, and should be to appropriate patients for salvage surgery and plan the optimal surgical The routine use of to distant metastases symptoms arise may enable treatment but the in of of and The that may be in patients at risk or of developing lymph node recurrence or distant with the years Cancer chest, abdomen and can be as per the colorectal cancer at at Recommendation grade C use of is not is or local Recommendation grade C who formation of a prior to CRT to have advanced local disease. patients at risk of local CRT and have a poorer et al., 2012). is not a in a proportion of these patients due to or et al., 2012; et al., is imaging should be to the presence of lymph node and distant of the most of treatment is the primary Less of are inguinal or other lymph and distant including and lymph from the trial that of patients these in the in two and in In of the cases the was to the et al., 2012). treatment can be into local or local to of patients will have local defined as cancer at up to of recurrence is defined as local in a patient who clinical local will be within of of are on of new is when is of or disease. can and disease. for salvage surgery should be and surgery a of and should be for all local data that the proportion of patients with locally salvage surgery between and but is in from one MDT (Renehan & O'Dwyer, However, salvage surgery of patients will 5 The ACPGBI standard for the proportion of patients with local primary salvage surgery is (Renehan & O'Dwyer, clinical of local pelvis, chest, abdomen and pelvis, should be to Recommendation grade C All patients with treatment should be by the Anal Cancer MDT. The of patients with local and salvage surgery should be Recommendation grade D A detailed and should be by the Anal Cancer MDT particularly the and of the suspected disease. surgery for anal cancer is associated with and a In to patient is clinical and assessment of the patient should be on at salvage of distant metastases is associated with a and the patient from For the of patients, salvage surgery the of a The need to to adjacent and of the perianal and should be considered. A or is sometimes to of the with is when tumour has the or salvage surgery is and should be to perineal (Renehan et al., for anal cancer is a from for low rectal cancer. should be by an anal cancer supported by an Recommendation grade C lymph node recurrence is as regional inguinal lymph node recurrence should be by ultrasound and with chest, abdomen and and to distant surgery with lymph node should be considered. is associated with in patients who have CRT to In the patient who not inguinal salvage CRT may be but requires planning to radiotherapy of There is that to with due to of & with local recurrence of anal cancer who are not for salvage may from with or to the pelvis. to a small a and defined by the prior in the organs at risk and into account the of be radiotherapy may be possible in with the of a A from of CRT to recurrence for a to Although approach is to be it can of local and of The of distant metastases in the of local in anal cancer is at up to et al., 2010). metastases are and treatment with to and should be considered. There are published data on the optimal therapy but a of and a or is of eligible patients within clinical such as is There is reviewed to or of data may be a role for immune in of patients & should be in with the of et al., 2014) for colorectal cancer The of anal cancer et al., of has been to improve The size of the anal should be with and All local should be with the network anal cancer MDT. A of local excision for anal is the of the UK trial within the PLATO have been defined as and these patients will be with locoregional as the primary The new of of the has been detailed management of will be an excision for recurrence or up of the should on of invasion to involvement of adjacent organs and squamous but other can be such as and have been but these are in the TNM different compared to rectal the anal canal. T staging to and on clinical staging to invasion of adjacent organs and pattern of lymph node the patient has treatment the staging should have the The should be a and for and has from and and been a of the of is a HIV and of the other have of to

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