Background: Concurrent CRT is standard treatment for patients (pts) with SCCA. We explore tumor- and treatment-related CFS in a phase III trial (ACT II), which mandated standardised radiation fields and a uniform dose (50.4Gy in 28 daily fractions of 1.8Gy). Methods: The ACT II trial (940 pts) compared both CisP (n=468) versus MMC (n=472) combined with 5-FU/CRT, and 2 cycles of maintenance CT (Maint, n=448) versus none (No-maint, n=446). We investigated the association between CFS and baseline factors (age, sex, T stage, size of tumour, nodal status) and treatment using Cox regression. CFS events included baseline colostomies not reversed at first follow up after treatment and post-treatment colostomies. Results: Median follow-up (all pts) was 5.1 years. Median age: 58 years; tumour site – canal (84%), margin (14%); stage T1-T2 (52%), T3-T4 (46%); N+ (32%), N0 (62%). Of 884 evaluable patients only 20/118 (17%) baseline colostomies were reversed within 8 months, and 37 later. 112 pts had a post-treatment colostomy due to persistent disease (98) or morbidity (14). The 5-year CFS rates by stage were 86% T1, 77% T2, 57% T3 and 47% T4; 72% N0, 60% N+; by treatment arm 68% MMC/Maint, 70% CisP/Maint, 68% MMC/No-maint and 65% CisP/No-maint respectively. The 5-year CFS rates were 72% and 60% for N0 and N+ respectively. The most significant predictors of colostomy in multivariable Cox regression analyses were T stage, sex and baseline haemoglobin (p<0.001 for all). Men were more at risk than women (adjusted HR 1.64; 95% CI: 1.26, 2.14). Age, site of primary or treatment did not impact on CFS. Although significant in univariate analysis, nodal status did not influence CFS when adjusted for other baseline factors. Conclusions: In the largest trial in anal cancer, neither the type of CRT (5FU/CisP vs. 5FU/MMC) nor maintenance chemotherapy improved CFS. 34% (61/177) of all colostomies were baseline fashioned prior to treatment and never reversed after all treatments. The major predictive factors for CFS were T stage, sex and haemoglobin levels. Clinical trial information: NCT00025090.