anal cancer 2008
DESCRIPTION
Anal cancer 2008. John Northover St Mark’s Hospital M62 course, 2008. The disease. Rare - 1% of bowel cancers First GI tumour to become ‘non-surgical’ II. Peak of development activity - 1990s. Viral aetiology and treatment. The development of therapy. Surgery alone Radiotherapy alone - PowerPoint PPT PresentationTRANSCRIPT
Anal cancerAnal cancer20082008
Anal cancerAnal cancer20082008
John Northover
St Mark’s Hospital
M62 course, 2008
John Northover
St Mark’s Hospital
M62 course, 2008
Anal cancer update
The disease
• Rare - 1% of bowel cancers
• First GI tumour to become ‘non-surgical’ II
Anal cancer update
Peak of development activity - 1990s
Viral aetiology and treatment
Anal cancer update
The development of therapy
• Surgery alone
• Radiotherapy alone
• Combined modality therapy
Anal cancer update
Surgical results, St Mark’s
Abdominoperineal excision:
• Margin, 72 cases, 5YS = 55%• Canal, 123 cases, 5YS = 58%
Pinna-Pintor et al, 1989
Anal cancer update
Radiotherapy results
• 72 patients:
• 67% 5 year survival
• 75% anal function retained
Papillon et al, 1985
Anal cancer update
The coming of combined therapy
• Nigro began in 1974
• Three inoperable cases
• Complete remissions
Anal cancer update
Optimum non-surgical therapy?
RADIOTHERAPY ALONE
or
CHEMO plus RADIOTHERAPY
Anal cancer update
ACT I trial - patient entry
Randomised 577 patients
331 surgeons, 162 radiotherapists
Anal cancer update
UKCCCR trial - side effects
Radiotherapy alone Chemoradiotherapy
62% 65%
Anal cancer update
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
% e
ven
t fr
ee
CMTRadiotherapy
ACT I - Local treatment failure
111/285125/283
P<0.001, RR=0.57 (0.45, 0.73)
Anal cancer update
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
Cau
se-s
pecifi
c s
urv
ival
CMTRadiotherapy
ACT I - Deaths from anal cancer
P=0.02, RR=0.71 (0.53, 0.95)
77/285105/283
Anal cancer update
ACT I - Disease at death
RT CM
Locoregional only 48 38
Distant ± LR 48 29
Other 7 4
TOTAL 105 77
Anal cancer updateSurgical salvage ACT I
Anal cancer updateSurgical salvage ACT I
• 265/577 (46%) local failures
• 143/265 (54%) radical surgery
• 10/143 (7%) no cancer in specimen
Anal cancer updateSurgical salvage ACT I
• 67/133 (50%) alive at 2.1 years
• 58/133 (44%) further pelvic rec.
• Perineal wound healing -median 2 m.
Anal cancer updateSurgical salvage ACT I - ARE
0%
20%
40%
60%
80%
100%
0 1 2 3 4 5 6time (yrs)
% e
ven
t fr
ee
CMTRadiotherapy
P>0.5 , RR=0.89 (0.54, 1.47)
22/4051/89
Anal cancer updateLessons from ACT I
• CMT established
• High local failure rate (33%)
• Less distant spread with CMT
• Surgical salvage disappointing
Anal cancer updateACT II - the questions
• Better primary chemotherapy?
• 5FU + MMC
• 5FU + CDDP
• “Adjuvant” therapy?
Anal cancer updateACT II Trial - Protocol
No maintenance
5FU & MMCRADIOTHERAPY
Maintenance5fu & CDDP
5FU & MMC RADIOTHERAPY
No Maintenance
5FU & CDDPRADIOTHERAPY
Maintenance5FU & CDDP
5FU & CDDPRADIOTHERAPY
Confimed anal cancer
Anal cancer update
Intra-epithelial neoplasia
Normal AIN I AIN II AIN III
Anal cancer update
The main target
AIN III
Anal cancer update
AIN - why does it matter?
• Premalignant
• Multifocal
• High risk groups
• Increasing incidence
• Anal ca. incidence rising
Anal cancer update
Aetiology of AIN
• HPV infection
• Mainly types 16, 18, 32, 33
• Integrates into genome
• Genetic instability
Anal cancer update
High risk groups
• Immune deficiency
• Pathological - HIV
• Therapeutic - transplant recipients
• MSM
Anal cancer update
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
• ± universal HPV infection (95%)
• Majority have AIN (81%)
• HAART does not protectPalefsky 2005
Anal cancer update
Risks in other groups
MSW
MSS
WSN
Anal cancer update
Men who have Sex with Women
Anal cancer update
Men who have Sex with Sheep
Anal cancer update
Women who have Sex with Nobody
Anal cancer updateSymptoms
• None
• Pruritus
• Bleeding
Anal cancer updateAnoscopy
Anal cancer update
Aceto-white lesions
Anal cancer update
Diagnosis of AIN III
Corkscrew vessels (AIN III)Corkscrew vessels (AIN III)
Anal cancer update
Risk of progression
Nottingham study
• 35 patients AIN III
• FU 63m (14-120)
• 28 immune competent - no Ca
• 6 immune deficient - 3 (50%) CaScholefield et al 2005
Anal cancer update
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?
Anal cancer update
Should there be screening?
• High risk groups• MSM, HIV+ ??
• What marker lesion?• HPV type, AIN stage?
• What tests?• Anoscopy, HPV type, histology?
• What intervention?
Anal cancer update
Should there be screening?
• x20 anal cancer in MSM
• AIN highly prevalent
• ? Natural history
• ? Improved outcomes
• Rx morbidity and recurrence
CASE NOT MADE
Anal cancer update
Medical management
Surgery:• may be difficult (cf cervix)• high recurrence rate
Medical:• Imiquimod• Vaccination
Anal cancer update
Medical management
Imiquimod
• Introduced 1997• Cytokine induction• Stimulates cellular immunity• Approved for anogenital warts• ? Role in neoplasia (VIN)
Anal cancer update
Surgical options
• LE ± graft ± faecal diversion
Anal cancer update
Surgical options
• LE ± graft ± faecal diversion
• Recurrence rates
• Surgical morbidity
Anal cancer update
Excision and Thiersch graft
Anal cancer update
Excision and Thiersch graft
Anal cancer update
Excision and Thiersch graft
Anal cancer update
Excision and advancement flaps
Anal cancerAnal cancer20082008
Anal cancerAnal cancer20082008
John Northover
St Mark’s Hospital
M62 course, 2008
John Northover
St Mark’s Hospital
M62 course, 2008