ABSTRACT Aim: Intensified preoperative treatment regimens have been increasingly investigated in locally advanced rectal cancer. However, there are very limited data on the impact of these regimens on patient quality of life (QoL) and bowel function. We assessed patient QoL and bowel function in EXPERT-C, a randomised, phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy (CRT), total mesorectal excision and adjuvant CAPOX ± cetuximab in MRI-defined, high-risk, locally advanced rectal cancer. Methods: Patient reported QoL was assessed using the EORTC QLQ-C30 and the colorectal cancer EORTC QLQ-CR29 questionnaire. Scores which differed by ≥10 percent points were considered clinically significant. Bowel incontinence was assessed using a modified Cleveland Clinic Incontinence Score (mCCIS) questionnaire. Results: Of 164 study patients, 157 (95.1%) completed a QLQ-C30 and a QLQ-CR29 questionnaire and 147 (89.6%) a mCCIS questionnaire, at baseline. Compared to baseline, QoL scores were worse for role functioning, fatigue, appetite loss, taste, hair loss, throughout neoadjuvant treatment, for nausea/vomiting and dry mouth during and/or after neoadjuvant chemotherapy (NACT), and for sore skin and impotence after CRT. QoL scores were better for blood and mucus in stool throughout neoadjuvant treatment, and for diarrhoea, stool frequency, faecal incontinence and buttock pain during NACT. A significant difference was observed between QoL scores after NACT and those after CRT for sexual interest in women, diarrhoea, sore skin and buttock pain (all worse after CRT). When the two treatment groups were analysed separately, patients who received cetuximab had worse QoL scores for body image, dry mouth and taste throughout neoadjuvant treatment and sexual interest in women after CRT compared to patients treated without cetuximab. Long-term QoL data and data on bowel function will be presented at the meeting. Conclusions: This is the first study reporting on QoL and bowel function in locally advanced rectal cancer patients treated with NACT followed by CRT. QoL and functional outcome should be important endpoints to use in clinical trials investigating intensified neoadjuvant treatment strategies. Disclosure: D. Cunningham: has received research funding from Amgen, Roche, Sanofi-Aventis, and Merck- Serono; A. Cervantes Ruiperez: has had advisory roles with Merck-Serono and Roche. He has received research funding from Roche and honoraria from Roche and Merck-Serono; I. Chau: has had advisory roles with Merck Serono, Roche, and Sanofi-Aventis. He has received research funding from Merck and Roche, and honoraria from Roche and Sanofi-Aventis. All other authors have declared no conflicts of interest.