Anal Cancer

Paul A.Hulse and Bernadette M.Carrington

BACKGROUND INFORMATION Epidemiology

Cancers of the anal canal are rare, accounting for approximately 1.5% of gastrointestinal tract malignancies. In the United States, there were an estimated 3400 new cases in 2000. In England, there were 245 new cases in men (1.0/100000) and 377 in women (1.5/100000) in 1997. It was originally thought that anal cancer was associated with chronic irritation from haemorrhoids, fissures, fistulae and inflammatory bowel disease. However, this is now known not to be so. The majority of anal cancers in both sexes are due to infection with human papilloma virus, particularly HPV1 6. There is an increased risk of anal cancer in men and women who practice anal receptive intercourse, who have had more than 10 sexual partners, or who have sexually transmitted diseases such as genital warts, gonorrhoea, or Chlamydia trachomatis. Other aetiological risk factors are immunosuppression, human immunodeficiency virus (HIV) infection, and smoking. Women with anal cancer have a higher incidence of vulval, vaginal, cervical and lung cancers.

Histopathology

The anal canal below the dentate or pectinate line is lined with squamous mucosa. At the level of the dentate line there is a junctional area of squamous and non-squamous mucosa. Above the dentate line there is transitional (urothelial type) or rectal glandular mucosa. Cancers arising below the dentate line are predominantly keratinising squamous cell carcinomas. Cancers arising in the junctional zone at the level of, and just above the dentate line, are termed non-keratinising squamous cell carcinomas. This group includes the previously described sub-types of basaloid cloacogenic and transitional sub-types, terms that have now been abandoned. Biological behaviour, management strategies, and prognosis of the keratinising and non-keratinising types of squamous cell carcinoma are similar.

Uncommonly, small cell carcinoma, undifferentiated carcinoma and malignant melanoma can arise within the anal canal. Cancers arising in glandular mucosa of the upper anal canal behave like, and are managed in the same way, as rectal cancers.

Patterns of tumour spread

Carcinoma of the anus is an indolent disease, which usually becomes locally extensive before distant metastases occur. The pattern of lymph node metastatic spread depends on the site of origin of the tumour within the anal canal. Above the level of the dentate line drainage is to the perirectal, internal iliac and retroperitoneal nodes. Below the dentate line, drainage is to the inguinal nodes. The TNM staging classification for anal cancer is given in Table 10.1. At the time of presentation, approximately 50% of patients will have a superficial mass (T1 or T2 lesion) and approximately 25% will have regional lymph node involvement.

Prognostic indicators

The tumour size and depth of penetration at presentation are the most Important prognostic factors. Mobile lesions less than 2.0 cm in diameter are cured in approximately 80% of cases whereas the cure rate for lesions greater than 5.0 cm in diameter is less than 50%. Skin ulceration and nodal disease are other poor prognostic factors. The likelihood of loco-regional lymph node involvement is related to tumour size and location. Tumours at the anal verge are less likely to develop lymph node metastases than those of the anal canal, probably because of earlier clinical presentation. Women achieve better local control and longer survival than men.

Treatment

Until the 1980s, the treatment of choice for cancer arising within the anal canal was an abdomino-perineal resection (APR). In an attempt to reduce surgical failure rates, workers in the USA introduced preoperative 5 -fluorouracil (5-FU) and mitomycin, combined with radiotherapy. The first three patients treated in this way were found to have no residual tumour in the excised anus following APR. This unexpected finding led to a change in the approach to management of anal cancer. Primary treatment now employs chemoradiation, with APR reserved for patients with persistent tumour on post-radiation biopsy or those with locally recurrent disease.

Multi-centre studies in Europe (United Kingdom Coordinating Committee on Cancer Research (UKCCR) and European Organisation for Research and Treatment of Cancer (EORTC)) have confirmed the benefit of combined modality therapy over radiation therapy alone in reducing loco-regional recurrence, death from anal cancer, and producing a higher colostomy-free rate and improved progression-free survival. However, no overall survival benefit was demonstrated between the two modes of therapy. A 5-year survival rate of 67% has been achieved using combined radiotherapy, 5-FU and mitomycin. Current studies are investigating the role of cisplatin in combined modality therapy.

Table 10.1. Analcancer staging system

Primary tumour (T) Lymph node (N) Distant metastasis Stage grouping

Table 10.1. Analcancer staging system

Primary tumour (T) Lymph node (N) Distant metastasis Stage grouping

TX Primary tumour cannot be assessed

Nx

Regional lymph nodes cannot be

Mx Presence of distant

Stage

Tis

N0

M0

assessed

metastasis cannot

0

be assessed

T0 No evidence of primary tumour

Stage I

T1

N0

M0

Tis Carcinoma in situ

N0

No regional lymph node

Stage

T2

N0

M0

metastasis

II

T1 Tumour 2.0 cm or less in greatest dimension

N1

Metastasis in perirectal lymph

M0 No distant

T3

N0

M0

node(s)

metastasis

Ml Distant metastasis

Stage

T1

N1

M0

IIIA

T2 Tumour more than 2.0 cm but not more than

N2

Metastasis in unilateral internal

T2

N1

M0

5.0 cm in greatest dimension

iliac and/or inguinal lymph node

(s)

T3

N1

M0

T3 Tumour more than 5.0 cm in greatest

T4

N0

M0

dimension

Stage

T4

N1

M0

IIIB

T4 Tumour of any size invades adjacent organ

N3

Metastasis in perirectal and

any

N2

M0

(s), e.g. vagina, urethra, bladder

inguinal lymph nodes and/or

T

(involvement of sphincter muscle(s) alone is

bilateral internal iliac and/or

N3

M0

not classified as T4)

inguinal lymph nodes

any T

Stage

any

any

M1

IV

T

N

From guidelines of the American Joint Committee on Cancer, 2002

MR IMAGING OF ANAL CANCER Current indications

Imaging has yet to find a place in the routine evaluation of primary anal cancer. Determination of the extent and nature of lesions is currently made at examination under anaesthetic and biopsy. CT of the abdomen and pelvis is routinely used to establish lymph node or visceral metastatic disease. Transrectal sonography of cancers of the lower third of the rectum has been shown to be useful in determining the extent of longitudinal tumour spread and infiltration of the anal sphincters, with a reported accuracy of 92%. Since MRI using phased array or endoluminal coils is effective in depicting the structure of the anal canal and its diseases, MRI does have a potential role in the local staging of primary anal cancer.

The principal current indication for MRI in anal cancer is the evaluation and staging of large primary masses, particularly when the craniocaudal dimension is the maximum diameter, as endoscopy is inadequate in these cases due to the size of the mass. MRI is also useful for the evaluation of residual or recurrent tumour prior to biopsy or salvage surgery. MRI has the drawback of being poor in differentiating between tumour and post treatment fibrosis, which is usually extensive following primary chemoradiotherapy. Endo-anal MRI performed after chemoradiotherapy or local excision of anal canal tumours only had an accuracy of 50%. Therefore, biopsy confirmation of residual or recurrent tumour is required.

MRI staging accuracy

There are no published results for the staging accuracy of primary or recurrent anal cancer using MRI.

Technique

A standard technique is employed with body coil transaxial T1W1 to cover the abdomen and pelvis and high-resolution thin section T2W1 in the three orthogonal planes. Fat suppressed imaging can help to improve the conspicuity of the primary tumour mass. Endoluminal coil imaging suffers from near field artifact and may not be tolerated by patients with anal cancer.

Imaging features

Usually anal cancer is of intermediate to low signal intensity on T1W1 and intermediate to high signal intensity on T2W1 and fat suppressed imaging. Mucinous adenocarcinoma displays characteristic high signal intensity on T2W1. Tumour usually spreads circumferentially around the anal wall and may form a lobulated intra-luminal or extra-mural mass. Fistulation into adjacent organs and tissues may occur.

Nodal disease

Metastatic spread occurs to the inguinal, iliac, perirectal and retroperitoneal nodes. As with other pelvic malignancy, lymph nodes with a short axis diameter greater than 1.0 cm in the pelvis and 1.5 cm in the inguinal regions are considered pathological. Lymph nodes are not normally identified in the perirectal fat and should be regarded as pathological (hyperplastic or metastatic) when seen.

Metastatic disease

Distant metastatic spread is primarily to the liver in advanced disease.

Post treatment—chemoradiotherapy

Residual mixed, predominantly low signal intensity foci are usually seen at the site of the primary tumour. Changes in normal tissues are mainly attributable to radiotherapy. An acute reaction occurs up to 3 months following treatment and is characterised by mucosal oedema and high signal on T2W1 of the anal musculature. Chronic changes develop up to 5 years following treatment and are predominantly fibrotic change with low signal on T2W1 and consequent morphological distortion of the pelvic viscera and soft tissues. Affected bone marrow shows fatty change seen as high signal on T1W1.

Post treatment—surgery

Following APR there are characteristic MR appearances.

• A band of pre-sacral fibrosis occurs, seen as intermediate signal on T1W1 and low signal on T2W1.

• The levator ani muscles are sutured together with a consequent irregular contour to the central pelvic floor.

• The pelvic viscera prolapse posteriorly into the void left by the excised ano-rectum.

Residual/recurrent disease

Differentiation between residual/recurrent tumour and post treatment effect can be difficult. Persistent increased signal on T2W1 in the primary tumour site more than 6 months following treatment, although a nonspecific finding, is suspicious of residual disease and warrants biopsy assessment. Recurrent disease occurs at the site of the primary tumour mass, in the loco-regional lymph nodes or outside of the radiation field. It has similar signal characteristics to the original disease.

Pitfalls of MRI

Identifying the location and extent of the primary tumour can be problematical in anal cancer especially when the tumour is small.

• Reference to the clinical findings and findings at examination under anaesthetic can guide the radiologist to the site of the primary tumour.

• Fat suppressed imaging can increase tumour conspicuity.

• Describing the relationship of the tumour to the ano-rectal junction, located at the indentation of the pubo-rectalis muscle, helps differentiate between tumours of rectal and anal origin.

• Measurement of tumour volume is difficult with infiltrative anal cancers that have circumferential spread. Measurement of the radial diameter of the anal canal wall at the site of tumour is useful for comparison with subsequent examinations.

Prediction of metastatic disease in inguinal lymph nodes is particularly difficult. Inguinal nodes can normally measure up to 1.5 cm in short axis diameter. However, use of this measurement probably reduces the sensitivity for the identification of metastatic disease. Features suggestive of metastatic disease in nonenlarged and enlarged nodes are:

• asymmetrical clustering in the groin or on the pelvic sidewall;

• signal intensity on T2W1 similar to the primary tumour mass;

• central nodal necrosis, which is a strong indicator of metastatic disease in squamous cell tumours.

FURTHER READING

1. Ryan DP, Compton CC and Mayer RJ. (2000) Carcinoma of the anal canal. N. Engl.J.Med. 342:792-800. Informative Review.

2. Ryan DP and Mayer RJ. (2000) Anal carcinoma 'histology, staging, epidemiology and treatment.' Curr. Opin. Oncol. 12:345-352. Detailed review by same authors as above.

3. Spratt JS. (2000) Cancer of the anus. J. Surg. Oncol. 74:173-174. Surgically orientated summary.

4. Myerson RJ, Karnell LH and Menck HR. (1997) The national cancer database report on carcinoma of the anus. Cancer 80(4): 805-815 Comprehensive epidemiological study of anal cancer in the USA.

5. Stoker J, Rocio E, Wiersma TG and Lameris JS. (2000) Imaging of anorectal disease. Br.J. Surg. 87:10-27. Useful review of anorectal imaging but concentrating on benign disease of the anal canal and malignant disease of the rectum.

6. Indinnimeo M, Cicchini C, Stazi A et al. (2000) Magnetic resonance imaging using endoanal coil in anal canal tumours after radiochemotherapy or local excision. Int. Surg. 85:143-146. Study illustrating difficulty in differentiating tumour from benign change following treatment

7. Grey AC, Carrington BM, Hulse PA etal. (2000). Magnetic resonance appearance of normal inguinal nodes. Clin. Radiol. 55: 124-130. Describes 1.5cm as the upper limit of normal for inguinal lymph node size.

8. Sugimura K, Carrington BM, Quivey JM and Hricak H. (1990) Post irradiation changes in the Pelvis: Assessment with MRI. Radiology 175:805-813. Correlates clinical and MR findings of pelvic radiation change.

Anus Levator Muscle

Figure 10.1. Normal anatomy.

Transaxial T2W1 of male perineum showing normal anatomy of anus. Anal canal (AC), internal sphincter (IS), longitudinal muscle layer in intersphincteric space (LM), external sphincter (ES), anococcygeal body (AB), perineal body (PB), ischioanal fossa (IAF).

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