Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I)

Abstract

Background: The first UKCCCR Anal Cancer Trial (1996) demonstrated the benefit of chemoradiation over radiotherapy (RT) alone for treating epidermoid anal cancer, and it became the standard treatment. Patients in this trial have now been followed up for a median of 13 years.

Methods: A total of 577 patients were randomised to receive RT alone or combined modality therapy using 5-fluorouracil and mitomycin C. All patients were scheduled to receive 45 Gy by external beam irradiation. Patients who responded to treatment were recommended to have boost RT, with either an iridium implant or external beam irradiation. Data on relapse and deaths were obtained until October 2007.

Results: Twelve years after treatment, for every 100 patients treated with chemoradiation, there are an expected 25.3 fewer patients with locoregional relapse (95% confidence interval (CI): 17.5-32.0 fewer) and 12.5 fewer anal cancer deaths (95% CI: 4.3-19.7 fewer), compared with 100 patients given RT alone. There was a 9.1% increase in non-anal cancer deaths in the first 5 years of chemoradiation (95% CI +3.6 to +14.6), which disappeared by 10 years.

Conclusions: The clear benefit of chemoradiation outweighs an early excess risk of non-anal cancer deaths, and can still be seen 12 years after treatment. Only 11 patients suffered a locoregional relapse as a first event after 5 years, which may influence the choice of end points in future studies.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1

(A) Risk of locoregional relapse, by treatment. Estimates shown are the absolute risk differences: combined modality therapy (CMT) minus radiotherapy (RT) alone (95% confidence interval (CI)). Number of locoregional relapses: RT alone: 151; CMT: 84 (excludes deaths and relapses within 6 weeks from the end of initial treatment). Hazard ratio (HR): 0.46 (95% CI: 0.35–0.60). (B) Relapse-free survival, by treatment. Estimates shown are the absolute risk differences: CMT minus RT alone (95% CI). Median: RT alone: 1.3 years; CMT: 4.6 years. HR: 0.70 (95% CI: 0.58–0.84).

Figure 2

Overall survival, by treatment. The estimates shown are the absolute risk differences: combined modality therapy (CMT) minus RT alone (95% confidence interval (CI)). Median: RT alone: 5.4 years; CMT: 7.6 years. Hazard ratio (HR): 0.86 (95% CI: 0.70–1.04).

Figure 3

Risk of death due to anal cancer, by treatment. Estimates shown are the absolute risk differences: combined modality therapy (CMT) minus RT alone (95% confidence interval (CI)). Hazard ratio (HR): 0.67 (95% CI: 0.51–0.88).

Figure 4

Risk of death due to causes other than anal cancer, by treatment. Estimates shown are the absolute risk differences: combined modality therapy (CMT) minus RT alone (95% confidence interval (CI)).

Figure A1

Colostomy-free survival, by treatment. Estimates shown are the absolute risk differences: combined modality therapy (CMT) minus RT alone (95% confidence interval (CI)). Median: RT alone: 1.8 years; CMT: 4.7 years. Hazard ratio (HR): 0.76 (95% CI: 0.63–0.91).