1. John Northover St Mark’s Hospital M62 course, 2008
Anal cancer 2008
John Northover
St Mark’s Hospital
M62 course, 2008

2. The disease Rare - 1% of bowel cancers
First GI tumour to become ‘non-surgical’ II

3. Peak of development activity - 1990s
Viral aetiology and treatment

4. The development of therapy
Surgery alone
Radiotherapy alone
Combined modality therapy

5. Surgical results, St Mark’s
Abdominoperineal excision:
Margin, 72 cases, 5YS = 55%
Canal, 123 cases, 5YS = 58%
Pinna-Pintor et al, 1989

6. Radiotherapy results 72 patients: 67% 5 year survival
75% anal function retained
Papillon et al, 1985

7. The coming of combined therapy
Nigro began in 1974
Three inoperable cases
Complete remissions

8. Optimum non-surgical therapy?
RADIOTHERAPY ALONE or
CHEMO plus RADIOTHERAPY

9. ACT I trial - patient entry
Randomised 577 patients
331 surgeons, 162 radiotherapists

10. UKCCCR trial - side effects
Radiotherapy alone Chemoradiotherapy
62% 65%

11. ACT I - Local treatment failure
111/285
125/283
P<0.001, RR=0.57 (0.45, 0.73)

12. ACT I - Deaths from anal cancer
77/285
105/283
P=0.02, RR=0.71 (0.53, 0.95)

13. ACT I - Disease at death RT CM Locoregional only 48 38
Distant ± LR 48 29
Other
TOTAL

14. Surgical salvage ACT I

15. Surgical salvage ACT I 265/577 (46%) local failures
143/265 (54%) radical surgery
10/143 (7%) no cancer in specimen

16. Surgical salvage ACT I 67/133 (50%) alive at 2.1 years
58/133 (44%) further pelvic rec.
Perineal wound healing -median 2 m.

17. Surgical salvage ACT I - ARE
22/40
51/89
P>0.5 , RR=0.89 (0.54, 1.47)

18. Lessons from ACT I CMT established High local failure rate (33%)
Less distant spread with CMT
Surgical salvage disappointing

19. ACT II - the questions Better primary chemotherapy?
5FU + MMC
5FU + CDDP
“Adjuvant” therapy?

20. ACT II Trial - Protocol

21. Intra-epithelial neoplasia
Normal
AIN I
AIN II
AIN III

22. The main target
AIN III

23. AIN - why does it matter? Premalignant Multifocal High risk groups
Increasing incidence
Anal ca. incidence rising

24. Aetiology of AIN HPV infection Mainly types 16, 18, 32, 33
Integrates into genome
Genetic instability

25. High risk groups Immune deficiency MSM Pathological - HIV
Therapeutic - transplant recipients
MSM

26. Relative prevalence of AIN
‘Normal’ haemorrhoidectomy:
3 in 8153 specimens (0.04%) Lemarchand 2004
HIV+ men:
20 in 103 men (19.4%) Kreuter 2005
x500 INCIDENCE

27. ± universal HPV infection (95%) Majority have AIN (81%)
HAART does not protect
Palefsky 2005

28. Risks in other groups
MSW
MSS
WSN

29. Men who have Sex with Women

30. Men who have Sex with Sheep

31. Women who have Sex with Nobody

32. Symptoms
None
Pruritus
Bleeding

33. Anoscopy

34. Aceto-white lesions

35. Diagnosis of AIN III
Corkscrew vessels (AIN III)

36. Risk of progression Nottingham study 35 patients AIN III
FU 63m (14-120)
28 immune competent - no Ca
6 immune deficient - 3 (50%) Ca
Scholefield et al 2005

37. Surveillance - in known cases?
AIN I/II
None in immune competent
6-12m in immune deficient?
AIN III
6-12m in all - or immune def. only?

38. Should there be screening?
High risk groups
MSM, HIV+ ??
What marker lesion?
HPV type, AIN stage?
What tests?
Anoscopy, HPV type, histology?
What intervention?

39. Should there be screening?
x20 anal cancer in MSM
AIN highly prevalent
? Natural history
? Improved outcomes
Rx morbidity and recurrence
CASE NOT MADE

40. Medical management Surgery: Medical: may be difficult (cf cervix)
high recurrence rate
Medical:
Imiquimod
Vaccination

41. Medical management Imiquimod Cytokine induction
Introduced 1997
Cytokine induction
Stimulates cellular immunity
Approved for anogenital warts
? Role in neoplasia (VIN)

42. Surgical options
LE ± graft ± faecal diversion

43. Surgical options LE ± graft ± faecal diversion Recurrence rates
Surgical morbidity

44. Excision and Thiersch graft

45. Excision and Thiersch graft

46. Excision and Thiersch graft

47. Excision and advancement flaps

48. John Northover St Mark’s Hospital M62 course, 2008
Anal cancer 2008
John Northover
St Mark’s Hospital
M62 course, 2008