Tumour- and treatment-related colostomy rates following mitomycin C or cisplatin chemoradiation with or without maintenance chemotherapy in squamous cell carcinoma of the anus in the ACT II trial.
BACKGROUND
Squamous cell carcinoma of the anus (SCCA) is highly sensitive to chemoradiation (CRT) which achieves good loco-regional control and preserves anal function. However, some patients require permanent stoma formation either as a result of surgery on relapse, poor anal function or treatment-related symptoms. Our aim was to determine patient, tumour and treatment-related colostomy rates following CRT and maintenance chemotherapy in the ACT II trial.


METHODS
The ACT II trial recruited 940 patients comparing 5FU-based CRT using cisplatin (CisP) or mitomycin C (MMC) with or without additional maintenance chemotherapy. We investigated the association between colostomy-free survival (CFS) and progression-free survival (PFS) with age, gender, T-stage, N-stage, treatment and baseline haemoglobin.


RESULTS
The median follow-up was 5.1 years (n = 884 evaluable/940); tumour site canal (84%), margin (14%); stage T1/T2 (52%), T3/T4 (46%); N+ (32%), N0 (62%). Twenty out of 118 (17%) colostomies fashioned before CRT were reversed within 8 months. One hundred and twelve patients had a post-treatment colostomy due to persistent disease (98) or morbidity (14). Fifty-two per cent (61/118) of all pre-treatment colostomies were never reversed. The 5-year CFS rates were 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint. CRT with CisP did not improve CFS when compared with MMC (hazard ratio: 1.04, 95% confidence interval: 0.82-1.31, P = 0.74). The 5-year CFS rates were higher for T1/T2 (79%) than T3/T4 (54%) tumours and higher for node-negative (72%) than node-positive (60%) patients. Significant predictors of CFS were gender, T-stage and haemoglobin, while treatment factors had no impact on outcome. Similar associations were found between PFS and tumour/treatment-related factors.


CONCLUSIONS
The majority (52%) of pre-treatment colostomies were never reversed. Neither CRT with 5FU/CisP nor maintenance chemotherapy impacted on CFS. The low risk of colostomy for late effects (1.7%) is likely to be associated with the modest total radiotherapy dose. The predictive factors for CFS were T-stage, gender and baseline haemoglobin.


BACKGROUND
ISRCTN 26715889.
Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, Northwood rob.glynnejones@nhs.net.
R
R
Glynne-Jones
Cancer Research UK and University College London Cancer Trials Centre, London.
L
L
Kadalayil
Cancer Research UK and University College London Cancer Trials Centre, London.
H M
HM
Meadows
Royal Marsden Hospital, London.
D
D
Cunningham
Department of Clinical Oncology, Aberdeen Royal Infirmary, Aberdeen.
L
L
Samuel
Department of Oncology, Queen Elizabeth Hospital, Birmingham.
J I
JI
Geh
Department of Oncology, Imperial College Healthcare NHS Trust, London.
C
C
Lowdell
The Kent Cancer Centre, Tonbridge, Maidstone.
R
R
James
Cancer Research UK and University College London Cancer Trials Centre, London.
S
S
Beare
Cancer Research UK and University College London Cancer Trials Centre, London.
R
R
Begum
Cancer Research UK and University College London Cancer Trials Centre, London.
J A
JA
Ledermann
University of Leeds, St James's Institute of Oncology, Leeds, UK.
D
D
Sebag-Montefiore
D001003:Anal Canal / Q000473:pathology / Q000601:surgery; D001005:Anus Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage*; D003125:Colostomy / Q000706:statistics & numerical data*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D060046:Maintenance Chemotherapy / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology / Q000628:therapy; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000601:surgery
D016685:Mitomycin; D002945:Cisplatin
anal cancer; chemoradiation; colostomy-free survival; loco-regional control; risk factors; squamous cell carcinoma