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CLINICAL PRACTICE GUIDELINE GI-001
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ANAL CANAL CANCER
Effective Date: October, 2013
The recommendations contained in this guideline are a consensus
of the Alberta Provincial Gastrointestinal Tumour Team synthesis of
currently accepted approaches to management, derived from a review
of relevant scientific literature. Clinicians applying these
guidelines should, in consultation with the patient, use
independent medical
judgment in the context of individual clinical circumstances to
direct care.
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BACKGROUND The anal canal is delimited superiorly by the
proximal extent of the levator-external anal sphincter complex and
inferiorly by the anal verge (the junction between the anal mucosa
and the hair-bearing skin). Lesions that involve the hair-bearing
skin (peri-anal skin within 5 cm of the anal verge) are considered
cancers of the anal margin and should also be treated as anal
cancers.
This guideline was developed to outline the management
recommendations for patients with squamous cell carcinomas that
arise within the anal canal. Adenocarcinomas of the anal canal
should be treated like rectal cancers (see the Early-Stage Rectal
Cancer Clinical Practice Guideline).
http://www.albertahealthservices.ca/hp/if-hp-cancer-guide-gi005-early-stage-rectal.pdf
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GUIDELINE QUESTIONS What are the goals of therapy and
recommendations for the treatment of adult patients with
potentially
curable cancer of the anal canal? What are the recommendations
for management of adult patients who have undergone curative
therapy for cancer of the anal canal? What are the
recommendations for management of adult patients with locally
recurrent cancer of the
anal canal? What are the recommendations for management of adult
patients with metastatic cancer of the anal
canal? DEVELOPMENT AND REVISION HISTORY This guideline was
reviewed and endorsed by the Alberta Provincial Gastrointestinal
Tumour Team. Members of the Alberta Provincial Gastrointestinal
Tumour Team include medical oncologists, radiation oncologists,
surgical oncologists, hepatologists, gastroenterologists,
interventional radiologists, nurses, nurse practitioners,
pathologists, and pharmacists. This guideline was originally
developed in January, 2008. This guideline was revised in March,
2011, June, 2011 and October, 2013. SEARCH STRATEGY This guideline
was developed to promote evidence-based practice in Alberta. It was
compiled from the results of randomized controlled trials and
systematic reviews, derived from an English language and relevant
term search of PubMed and MEDLINE from 1990 forward. It takes into
consideration related information presented at local, national, and
international meetings as well as the Alberta Provincial
Gastrointestinal Tumour Teams interpretation of the data. TARGET
POPULATION The recommendations outlined in this guideline apply to
adults over the age of 18 years with squamous cell carcinomas that
arise within the anal canal. Different principles may apply to
pediatric patients. RECOMMENDATIONS AND DISCUSSION Suggested
Diagnostic Work-Up The incidence of squamous cell carcinomas that
arise within the anal canal has increased with the prevalence of
Human Papilloma Virus (HPV) infection, Human Immunodeficiency Virus
(HIV) infection, and immunosuppression required for organ
transplantation. If the use of chemotherapy or radiotherapy is
considered and HIV infection is suspected, HIV serology and an
evaluation of the CD4 count are suggested in addition to the
complete blood count and both liver and renal function tests.
Because prognosis depends upon the stage of disease, an anatomic
assessment with digital rectal examination, anoscopy or
sigmoidoscopy (with biopsy), and a CT scan of the abdomen and
pelvis (and/or MR or transrectal ultrasound) plus chest x-ray are
recommended. Suspicious lymph nodes should be
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evaluated with a biopsy by fine-needle aspirate. Female patients
should have a gynecological assessment (including a Pap smear) to
exclude a synchronous cervical cancer. A colonoscopy should be
performed to detect synchronous lesions. Stage Information Table 1.
American Joint Committee on Cancer Staging Information, Seventh
Edition. Stage Tumour Stage Regional Lymph Node Involvement
Metastases Stage 0 Tis Carcinoma in situ N0 None M0 Absent Stage I
T1 Tumour 2 cm in size N0 None M0 Absent Stage II T2 Tumour between
2 cm and 5 cm N0 None M0 Absent
T3 Tumour > 5 cm in size N0 None M0 Absent Stage IIIA
T1 Tumour 2 cm in size N1 Perirectal lymph nodes M0 Absent T2
Tumour between 2 cm and 5 cm N1 Perirectal lymph nodes M0 Absent T3
Tumour > 5 cm in size N1 Perirectal lymph nodes M0 Absent T4
Invasion into adjacent organs
(e.g.: vagina, urethra, bladder) N0 None M0 Absent
Stage IIIB
T4 Invasion into adjacent organs (e.g.: vagina, urethra,
bladder)
N1 Perirectal lymph nodes M0 Absent
Tany As described above N2 Unilateral internal iliac and/or
inguinal lymph nodes
M0 Absent
Tany As described above N3 Perirectal and inguinal lymph nodes
Bilateral internal iliac lymph nodes Bilateral inguinal lymph
nodes
M0 Absent
Stage IV Tany As described above Nany As described above M1
Present Goals of Therapy and Recommendations for Potentially
Curable Cancer of the Anal Canal 1. To render the patient free of
disease and to delay or prevent recurrence. 2. To improve the
patients quality of life (to eliminate tumour-related symptoms) and
to preserve
continence. Consider treatment on a clinical trial, if
available. Table 2. Recommendations for Potentially Curable Cancer
of the Anal Canal. Stage Recommendations Stage 0 Consider a wide
local excision provided that surgical resection can be completed to
achieve
negative margins and to preserve continence (no involvement of
the anal sphincter). Stage I Consider a wide local excision
provided that surgical resection can be completed to achieve
negative margins and to preserve continence (no involvement of
the anal sphincter). Consider primary chemoradiotherapy (as
described for stage II and IIIA disease) if sphincter
preservation (maintenance of continence) is not possible with a
wide local excision. Consider an abdominoperineal resection for
residual or recurrent disease.
Stage II Stage IIIA
Primary chemoradiotherapy1-6 involves the sequential
administration of Mitomycin C (10 to 12 mg/m2 IV) followed by a
continuous intravenous infusion of 5-Fluorouracil (4,000 mg/m2 over
ninety-six hours) during week one (and, possibly, week five) of a
course of radiation (4,500 to 5,400 cGy to the perineum and
regional lymph nodes). This regimen requires placement of a central
venous catheter (CVC) or a peripherally inserted central catheter
(PICC line).
Consider an abdominoperineal resection for residual or recurrent
disease. Stage IIIB Primary chemoradiotherapy (as described for
stage II and IIIA disease). Consider a boost, if
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Stage Recommendations indicated.
Consultation with the multidisciplinary and surgical team should
be sought to determine the role of further surgery.
Post-Curative Therapy Guidelines
Perform a digital rectal examination and consider anoscopy at
six to eight weeks after completion
of the therapy. Consider biopsy of any suspicious lesions at
three months after completion of therapy, but recognize that tumors
may continue to respond up to six months after the radiation.7
Perform salvage surgery for biopsy-proven persistent,
progressive, or recurrent disease. After achieving a complete
response, repeat digital rectal examination, anoscopy, and
examination of the inguinal lymph nodes every four months for
two years then every six months for the balance of five years.
Female patients should have a gynecological assessment
(including a Pap smear) due to the increased risk of cervical
cancer. A colonoscopy should be obtained as outlined in the
colorectal cancer screening guidelines.
Recommendations for Locally Recurrent Cancer of the Anal Canal
1. For patients whose disease recurs despite prior radical
chemoradiotherapy, consider surgical
resection, if possible. Consider palliative therapy (see below)
if surgical resection is not possible. 2. For patients whose
disease recurs after not having received prior chemoradiotherapy,
consider radical
chemoradiotherapy (see above) with or without surgery. Goals of
Therapy and Recommendations for Metastatic Cancer of the Anal Canal
1. To maintain or to improve the patients quality of life (to
control or to delay the onset of tumor-related
symptoms). 2. To prolong life, if possible. Metastatic anal
canal cancer describes the situation where a cancer that originated
within the anal canal has spread beyond the regional lymph nodes to
other organs. This represents an incurable situation for which
palliative options (e.g.: best supportive care, palliative
chemotherapy) may be considered. Palliative chemotherapy regimens
are generally continued as long as tumor shrinkage or stability is
confirmed, as long as the side effects remain manageable, as long
as the patient wishes to continue, and as long as the treatment
remains medically reasonable. Palliative chemotherapy may involve
the sequential administration of anti-emetics, adequate
prehydration, and Cisplatin (75 mg/m2 in 250 mL of normal saline IV
over one hour) followed by a continuous intravenous infusion of
5-Fluorouracil (4,000 mg/m2 over ninety-six hours) every
twenty-eight days. This regimen requires placement of a central
venous catheter (CVC), peripherally inserted central catheter (PICC
line), or port.
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GLOSSARY OF ABBREVIATIONS Acronym Description AJCC American
Joint Committee on Cancer CT computed tomography CVC central venous
catheter HIV human immunodeficiency virus HPV human papilloma virus
IV intravenous PICC peripherally inserted central catheter TNM
tumour-node-metastasis
DISSEMINATION Present the guideline at the local and provincial
tumour team meetings and weekly rounds. Post the guideline on the
Alberta Health Services website. Send an electronic notification of
the new guideline to all members of CancerControl Alberta.
MAINTENANCE A formal review of the guideline will be conducted at
the Annual Provincial Meeting in 2015. If critical new evidence is
brought forward before that time, however, the guideline working
group members will revise and update the document accordingly.
CONFLICT OF INTEREST Participation of members of the Alberta
Provincial Gastrointestinal Tumour Team in the development of this
guideline has been voluntary and the authors have not been
remunerated for their contributions. There was no direct industry
involvement in the development or dissemination of this guideline.
CancerControl Alberta recognizes that although industry support of
research, education and other areas is necessary in order to
advance patient care, such support may lead to potential conflicts
of interest. Some members of the Alberta Provincial
Gastrointestinal Tumour Team are involved in research funded by
industry or have other such potential conflicts of interest.
However the developers of this guideline are satisfied it was
developed in an unbiased manner. REFERENCES 1. Epidermoid anal
cancer: results from the UKCCCR randomised trial of radiotherapy
alone versus radiotherapy,
5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working
Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996
Oct 19;348(9034):1049-1054. Level of Evidence: 1b
2. Ajani JA, Winter KA, Gunderson LL, Pedersen J, Benson AB,3rd,
Thomas CR,Jr, et al. Fluorouracil, mitomycin, and radiotherapy vs
fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal
canal: a randomized controlled trial. JAMA 2008 Apr
23;299(16):1914-1921. [Updated as J Clin Oncol 2012; 30(35):
4344-4351] Level of Evidence: 1b
3. Bartelink H, Roelofsen F, Eschwege F, Rougier P, Bosset JF,
Gonzalez DG, et al. Concomitant radiotherapy and chemotherapy is
superior to radiotherapy alone in the treatment of locally advanced
anal cancer: results of a
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phase III randomized trial of the European Organization for
Research and Treatment of Cancer Radiotherapy and Gastrointestinal
Cooperative Groups. J Clin Oncol 1997 May;15(5):2040-2049. Level of
Evidence: 1b
4. Flam M, John M, Pajak TF, Petrelli N, Myerson R, Doggett S,
et al. Role of mitomycin in combination with fluorouracil and
radiotherapy, and of salvage chemoradiation in the definitive
nonsurgical treatment of epidermoid carcinoma of the anal canal:
results of a phase III randomized intergroup study. J Clin Oncol
1996 Sep;14(9):2527-2539. Level of Evidence: 1b
5. James RD, Glynne-Jones R, Meadows HM, Cunningham D, Myint AS,
Saunders MP, et al. Mitomycin or cisplatin chemoradiation with or
without maintenance chemotherapy for treatment of squamous-cell
carcinoma of the anus (ACT II): a randomised, phase 3, open-label,
2 x 2 factorial trial. Lancet Oncol 2013 May;14(6):516-524. Level
of Evidence: 1b
6. Peiffert D, Tournier-Rangeard L, Gerard JP, Lemanski C,
Francois E, Giovannini M, et al. Induction chemotherapy and dose
intensification of the radiation boost in locally advanced anal
canal carcinoma: final analysis of the randomized UNICANCER ACCORD
03 trial. J Clin Oncol 2012 Jun 1;30(16):1941-1948. Level of
Evidence: 1b
7. Glynne-Jones R, James R, Meadows H, Begum R, Cunningham D,
Northover J, et al. Optimum time to assess complete clinical
response (CR) following chemoradiation (CRT) using mitomycin (MMC)
or cisplatin (CisP), with or without maintenance CisP/5FU in
squamous cell carcinoma of the anus: results of ACT II. J Clin
Oncol 2012 ASCO Annual Meeting Proceedings 2012;30(suppl; abstr
4004). Level of Evidence: 1b
Useful Review Articles: 8. Glynne-Jones R, Renehan A. Current
treatment of anal squamous cell carcinoma. Hematol Oncol Clin North
Am
2012 Dec;26(6):1315-1350. 9. Wietfeldt ED, Thiele J.
Malignancies of the anal margin and perianal skin. Clin Colon
Rectal Surg 2009
May;22(2):127-135.
Level Description of Evidence 1a Systematic reviews of
randomized controlled trials 1b Individual randomized controlled
trials 1c All or none randomized controlled trials 2a Systematic
reviews of cohort studies 2b Individual cohort study or low quality
randomized controlled trial 2c Outcomes research 3a Systematic
review of case-control studies 3b Individual case-control study 4
Case series 5 Expert opinion without explicit critical appraisal or
based on physiology, bench research, or
first principles