1) Anal cancer is uncommon, comprising 2.4% of digestive system cancers in the US, with an estimated 7,060 new cases and 880 deaths in 2013. 2) The median age at diagnosis of anal cancer is 60, younger than the median age of 66 for all cancers. 3) The majority of anal cancers are squamous cell carcinomas caused by HPV infection, while adenocarcinomas are rare. Treatment typically involves chemotherapy and radiation. 4) Five-year survival rates range from 71-78% for early stage anal cancer to 20-24% for late stage or metastatic disease. Combined chemoradiation provides local control in 85-90% of cases.

1. Anal Canal Cancer
Robert Miller MD
www.aboutcancer.com

2. Incidence of new cases in
2013
Site Men Women
Colon 50,090 52,390
Rectum 23,590 16,750
Anus 2,630 4,430
Anal cancer is uncommon. It comprises
only 2.4 percent of all digestive system
malignancies in the United States

3. Age and Anal Cancer
US Data 2005 - 2009
• Median age at diagnosis all
cancers was 66 for Anus was
60
• Median age at death was 72 for
all cancers and for anus was 64
In 2013 estimated 7,060 new cases and 880 deaths so crude death
rate was only 12%

4. Anal Cancer
• This is usually squamous cancer
(HPV infection) and is treated with
chemo-radiation.
• Rectal cancer is adenocarcinoma
(from a polyp) and is treated with
surgery +/- chemoradiation

5. Anal Cancer
Rectal bleeding is the most common initial
symptom of squamous-cell carcinoma of the
anus, occurring in 45 percent of patients.
Bleeding from a mass lesion just above the anal
sphincter may be ascribed erroneously to the
presence of hemorrhoids. Thirty percent of
patients have either pain or the sensation of a
rectal mass, whereas 20 percent have no rectal
symptoms whatsoever

6. Histology (what type of cancer
from the biopsy and pathology
report)
Cellular Classification of Anal Cancer
Squamous cell (epidermoid) carcinomas make up the
majority of all primary cancers of the anus. The important
subset of cloacogenic (basaloid transitional cell, non-
keratinizing) tumors constitutes the remainder. (about
25%). These two histologic variants are associated with
human papillomavirus infection.
Adenocarcinomas from anal glands or fistulae formation
and melanomas are rare

7. Histology
Treatment for
keratinizing
squamous cancers is
the same as non-
keratinizing (basaloid
or cloacogenic

8. HPV Cancers
Cancers Percent
Cervix > 99%
Anus 84%
Vagina 70%
Penis 47%
Vulva 44%
Oropharynx 36%
Oral Cavity 24%
JCO May 2011;29:1785

9. HPV Cancers 2004-2008
Cancer All Cases HPV Caused
Cervix 11,967 11,500
Vulva 3,136 1,600
Vagina 729 500
Penis 1,046 400
Anus (female)
Anus (male)
2,900
1,678
2,700
1,600
Oropharynx (female) 2,370 1,500
Oropharynx (male) 9,356 5,900

10. HPV Types

11. Prevalence of High Risk HPV
infection found in biopsy
Anus cancer: 84%
Rectal cancer: 0 %
N Eng J Med 1997;337:1350

12. The proximal end of the anal canal
begins anatomically at the junction of
the puborectalis portion of the levator
ani muscle and the external anal
sphincter, and extends distally to the
anal verge, a distance of
approximately 4 cm. The anal canal is
divided by the dentate line, which
overlies the transition from glandular
(columnar) to squamous mucosa that
is often referred to as the transitional
zone.
Anal Canal lower 4cm
tumors are classified as rectal cancers if their epicenter is located
more than 2 cm proximal to the dentate line or proximal to the
anorectal ring on digital examination, and as anal canal cancers if their
epicenter is 2 cm or less from the dentate line

13. Anal Canal and Anal Margin

14. Anal Canal Anatomy

15. Pelvic Anatomy (female)
colon
Anal canal
bowel
uterus
rectum
bladder

16. Pelvic Anatomy (male)
Anal canal

17. Lymph Nodes at Risk in Anal Cancer
• Cancers from the
distal region (below
dentate line) go to
superficial groin
(inguinal) nodes
• Cancers that arise ate
or proximal (above)
the dentate line are
directed to anorectal,
perirectal,
paravetebral and

18. para-aortic
peri-rectal
inguina
l
pelvic
inguinal
Lymph Nodes at Risk in Anal Cancer

19. Stage
Start with Tumor (T) stage

20. Stage
Then Nodes (N) or Metastases (M)

21. Stage
Then combine T, N, M

22. Cancer Imaging for Anal Cancer
in a study of 61 patients with anal cancer the sensitivity for nodal
regional disease by PET versus conventional imaging (CT and/or MRI)
was 89 and 62 percent, respectively

23. CT scan = large anal cancer

24. Since cancers use more glucose than normal
cells (hypermetabolic) they will ‘light up’ on a
PET Scan

25. CT and PET Imaging for Anal Cancer

26. PET scan showing small anal cancer

28. PET and Lymph Node
Metastases

29. PET and Lymph Node
Metastases

30. More
advanced
case of anal
cancer that
has spread on
PET scan to
para- aortic
lymph nodes
PET and Lymph Node
Metastases

34. Treatment of Anal Cancer
• Anal canal Stages I – III : radiation
+ chemotherapy (5FU + Mitomycin)
• Anal margin Stage I : wide local
excision
• Anal margin Stage II – III: radiation
+ chemotherapy (5FU + Mitomycin)
• Stage IV: Cisplatin based
chemotherapy +/- radiation

35. CT scan is obtained at the
time of simulation
CT images are then
imported into the
treatment planning
computer

36. In the
simulation
process the
CT and PET
scan images
are used to
create a
computer
plan

37. Computer generated
images of anal cancer

38. Tomotherapy for
Anal Cancer

39. Tomotherapy for anal cancer, high dose to anus
and groin nodes, while avoiding the bladder
and femurs

40. Radiation Dose and
Technique
• Radiation is daily, Monday through Friday for
5 to 6 weeks
• Radiation works best when combined with
chemotherapy
• Minimal dose of 45Gy (1.8Gy X 25) up to 54
to 59Gy for more advanced cancers
• The radiation should include the lymph node
regions for at least part of the treatment

42. Target Volumes for Anal Carcinoma For RTOG 0529
Radiation
Dose and
Techniqu
e

43. RTOG 0529: A Phase 2 Evaluation of Dose-Painted Intensity
Modulated Radiation Therapy in Combination With 5-Fluorouracil and
Mitomycin-C for the Reduction of Acute Morbidity in Carcinoma of the
Anal Canal
DP-IMRT was associated with significant sparing of acute grade
2+ hematologic and grade 3+ dermatologic and gastrointestinal
toxicity.
IJROBP 2013;86:27
Anus cancer
Nodes
High Risk
Node

44. Side Effects of Pelvic
Radiation
Radiation fields
Radiation may hit the
small bowel causing
some cramps, diarrhea
and fatigue
High dose
area

45. Side Effects of Pelvic
Radiation
Radiation fields
Radiation may hit the bladder
and rectum causing urinary
burning or frequency and ano-
rectal irritation and skin burning
High dose area
In pre-menopausal women, radiation is likely to
effect ovarian function and should not be used if
the woman is pregnant

46. Results with combined chemo-
radiation for anal cancer
• Local failure rates of 14 to 37
percent
• Five-year overall survival rates of
72 to 89 percent
• Five-year colostomy-free survival
rates of 70 to 86 percent

47. Long-Term Update of US GI Intergroup RTOG 98-11 Phase III Trial for
Anal Carcinoma
JCO December 10, 2012 vol. 30 no. 35 4344-4351
Survival
78%
71%

48. 5 Year Survival with Anal
Cancer
Stage Squamous Non-
squamous
I 71.4 59.2
II 63.5 52.9
IIIA 48.1 37.7
IIIB 43.2 24.4
IV 20.9 7.4
NCDB 1998-99, n = 3598

49. 5 Year Survival with Anal
Cancer
NCDB 1985 - 2000
Stage Survival
I 70%
II 59%
III 41%
IV 19%

50. 5 Year Survival with Anal
Cancer (SEER Data Base)
SEER 1999-2006
Stage Incidence Survival
Local 50% 80%
Regional 29% 60%
Distant 12% 30.5%

51. Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin,
and radiotherapy for carcinoma of the anal canal: a randomized
controlled trial. US Gastrointestinal Intergroup trial RTOG 98-11,
The 5-year overall survival rate was 75% in the
mitomycin-based group and 70% in the cisplatin-
based group.
The 5-year local-regional recurrence and distant
metastasis rates were 25% and 15%, respectively, for
mitomycin-based treatment and 33% and 19%,
respectively, for cisplatin-based treatment.
The cumulative rate of colostomy was significantly
better for mitomycin-based than cisplatin-based
treatment (10% vs 19%)
JAMA. 2008 Apr 23;299(16):1914-21.

52. Survival by Stage in a series of
270 patients with anal cancer
5 Year Survival by Stage
T1: 86% N0: 76%
T2: 86% N1: 54%
T3: 60%
T4: 45%

53. Odds of Requiring a
Colostomy
• In large series the odds were 10 to 30%
• 235 patients diagnosed with anal cancer between 1995 and 2003
the five-year cumulative incidences of tumor-related and
treatment related colostomy were 26 and 8 percent, respectively.
Large tumor size (>6 cm) was associated with a higher risk of
tumor-related colostomy, while a history of prior excision was a
risk factor for therapy-related colostomy.
• RTOG trial 98-11 five-year colostomy rates among patients
treated initially with Chemoradiotherapy were 9 percent for those
with node-positive disease, and 19 percent for tumors >5 cm in
diameter, regardless of nodal status. Overall, 78 percent of the
colostomies were performed for persistent or recurrent disease.

54. Anal Cancer
Robert Miller MD
www.aboutcancer.com