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