Anal Cancer - Treatment and Results

John Northover, St Mark’s Hospital, London

Powerpoint File

Ana cancer is a rare tumour, though it has become more common in recent decades, almost certainly related to changing patterns of sexual activity and the HIV/AIDS epidemic. Incidence doubled in the US in the 1990s compared to the 1970s; although survival improved the US white population, it fell markedly in the US black male population .

Anal epidermoid cancer has not been primarily a ‘surgical’ disease in the UK since the publication of the UKCCCR ACT I trial in 1996, when it was established that 60+% of tumours entered full remission after radical chemoradiation . This influential trial showed in subsequent analyses that the addition of chemo to radiotherapy improved outcomes in all T and N stages; tumours at both the verge and in the canal; in men and women; and in all age groups. Thereafter the key questions and issues were:

Can local control be improved using alternative regimens?
Can the risk of distant metastasis be decreased?
What is the role of surgery in the ‘post-surgical era’?
The ACT II Trial was launched in 2001 to address questions 1 and 2 above. The randomisations were as follows:

The Trial will determine whether Cisplatin has advantages over Mitomycin in primary treatment in achieving local control, and whether repeated courses of chemotherapy subsequently diminish distant spread . Trial accrual finished in 2006. US and French Trials are examining other aspects of primary treatment, including radiotherapy dose. Further UK studies include an investigation of oral capecitebine in primary treatment (EXTRA trial), and in relapsed disease (SCENE I trial).
The role of surgery has become both less prevalent but more challenging. The surgeon has a role today as follows:

• Initial diagnosis, including EUA and biopsy
• Faecal diversion in selected cases prior to primary chemoradiation
• Primary treatment in patients with malignant anovaginal fistula or gross sphincter destruction
• Salvage after incomplete primary remission or in subsequent relapse.

Data from analysis of surgical outcomes in the ACT I Trial cohort of patients with residual or relapsing disease indicates that a significant proportion of patients can be salvaged, though the surgery is very demanding, and carries a high risk of surgical morbidity and distressing symptomatic relapse.

LG Johnson, MM Madeleine, et al. Anal cancer incidence and survival, 1973-2000. Cancer 2004; 101: 281-288.
UKCCCR Anal Cancer Trial Working Party. Epidermoid anal cancer: resuts form the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil and Mitomycin C. Lancet 1996; 348: 1049-1054.

R James, H Meadows, S Wan. ACT II: The second UK Phase III Anal Cancer Trial. Clinical Oncology 2005; 17: 364-366

LG Johnson, MM Madeleine, et al. Anal cancer incidence and survival, 1973-2000. Cancer 2004; 101: 281-288.