Chemoradiotherapy

Dr Mark Saunders, Christie Hospital, Manchester

Powerpoint File

For many years, epidermoid anal cancer was treated primarily by surgical resection, namely abdomino-perineal resection, which yielded 5-year survival rates ranging from 40-70%. Over the last decade, primary treatment by radical surgery has been largely superseded by sphincter-preserving therapy using radiotherapy with or without chemo-induction. Two randomised trials (UKCCCR, 1996; Bartelink et al. 1997) comparing chemoradiotherapy to radiotherapy alone, showed a significant gain in terms of local control and a reduction in the need for colostomy, with the combined therapy.

The former of the two studies, known as the ACT1 trial, randomised patients to radiotherapy alone or a combination of radiotherapy with Mitomycin C and 5-Fluorouracil. They demonstrated a 46% reduction in the risk of local treatment failure after a median follow-up of 42 months. There was also a significantly reduced risk of death from anal cancer and the combined treatment did not seem to impair the patient's quality of life (QoL). Because of the impact of these trials, sphincter sacrificing radical surgery is reserved for patients with residual or recurrent cancer after chemoradiotherapy, and in a few patients in whom chemoradiotherapy is considered inappropriate for medical or social reasons. However, the ACT1 trial also showed that 46% of patients had local treatment failure and only 58% of these were considered suitable for salvage surgery. The remaining patients had disease that was too extensive to resect.

Some patients have a poor response to initial treatment and should be considered for surgery earlier in the treatment pathway. It is also possible that some patients with advanced local disease may benefit from primary radical surgery rather than chemoradiotherapy and in a proportion of cases, planned surgery after chemoradiotherapy may be the optimum approach (Renehan et al. 2005). What is essential is that patients with anal cancer are treated by a dedicated team of surgeons, oncologists, pathologists and radiologists that are experienced in the management of this disease. It is not only the treatment that is important, it is the initial staging and decision making, together with the long term follow-up of these patients. Obviously, the detection of recurrent disease is important, however, the management of the treatment related complications is also essential. This is emphasised by the thirty-seven patients in the ACT1 study that required a colostomy for treatment-related morbidity.

The ongoing trial in the UK is the ACT2 study. This study randomises patients into four arms and aims to evaluate whether the replacement of mitomycin C (from the ACT1 study), with cisplatin is advantageous. It also aims to determine whether two additional cycles of cisplatin and 5-Fluorouracil after completion of chemoradiotherapy is beneficial. This trial is recruiting well and aims to enter 600 patients over the study period. The Manchester and Cheshire network of surgeons and oncologists was the highest recruiter into the ACT1 study and presently we have entered the largest number of patients into the ACT2 trial.

Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 1996;348:1049-54.

Bartelink H, Roelofsen F, Eschwege F, et al. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative Groups. J Clin Oncol 1997;15:2040-9.

Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer. Renehan A G, Saunders M P, Schofield P F, O'Dwyer S T. Accepted by British J Surgery, 2005.