BACKGROUND: Perineal wound complications (PWCs) occur in 15-30% of patients after abdominoperineal excision (APE) and are associated with adverse events, such as delayed wound healing, prolonged hospitalization, a delay in initiating postoperative chemotherapy, and decreased quality of life. Preoperative radiotherapy and chemotherapy are risk factors for wound complications. It is unknown whether total neoadjuvant treatment (TNT) affects the risk of PWCs compared with chemoradiotherapy (CRT). METHODS: This study compared patients from the experimental (EXP
short-course radiotherapy, chemotherapy, and surgery as TNT) and standard-of-care (STD
CRT, surgery, and postoperative chemotherapy depending on hospital policy) treatment arms of the RAPIDO trial who underwent APE within 6 months after preoperative treatment. The primary outcome was the incidence of PWCs (infection, abscess, dehiscence, wound discharge, presacral abscess affecting the perineum) of any grade ≤ 30 days after APE. Secondary outcomes were the incidence of PWCs >
30 days after APE, length of hospital stay, characteristics associated with PWCs, and oncological outcomes in patients with versus without PWC. RESULTS: Of the 901 patients who started treatment (460 in EXP arm, 441 in STD arm), 153 (33%) and 160 (36%) underwent APE after TNT and CRT, respectively. After TNT and CRT, the incidence of PWCs ≤30 days after APE, readmission, and reoperation was 54 of 153 (35%) versus 53 of 160 (33%) (P = 0.69), 9% versus 12% (P = 0.54), and 7% versus 8% (P = 0.75), respectively. The median length of hospital stay was 2-3 days longer for patients with PWC. Univariable analysis revealed that pretreatment albumin <
35 g/l, hypertension, and haemoglobin ≤ 8.0 mmol/l were associated with PWC. Oncological outcomes were similar between patients with and without PWCs. CONCLUSION: In the RAPIDO trial, TNT and CRT resulted in a similar incidence of PWCs among patients with high-risk locally advanced rectal cancer who underwent APE.