Patients with a tumor regression grade of 0 or 1 (CAP), are classified as well-responders after neoadjuvant chemoradiotherapy (NCRT). Although well-responders are expected to have superior prognosis, occurrences of recurrence and metastasis still exist.

Clinical data of patients from January 2017 to 2022 were analyzed. Inclusion criteria: adenocarcinoma, cT3-4N0 or cTanyN+, receiving NCRT and surgery, CAP 0 ~ 1. The primary endpoint was three-year disease-free survival (3y-DFS). According to occurrence of DFS events, patients were divided into DFS (470, 91.8%) and non-DFS group (42, 8.2%). Cox regression analysis was applied to identify risk factors affecting prognosis of well-responders.

A total of 512 well-responders were included, with mean age of 59.1 ± 10.6 years. Compared to DFS group, patients in non-DFS group had advanced mrT4 stage (33.3% vs. 18.1%, P = 0.017), higher positive rates of mesorectal fascia (52.4% vs. 35.1%, P = 0.026) and extramural vascular invasion (59.5% vs. 36.6%, P = 0.003), advanced ypT4 stage (56.2% vs. 23.8%, P < 0.001), ypN+ (23.8% vs. 9.4%, P = 0.014), and tumor deposits (14.3% vs. 3.6%, P = 0.005). The follow-up was end up to May 2024, with a duration of 36 (18 to 53) months. The tumor recurrence and metastasis rates were 0.8% (4) and 7.0% (36). The estimated 3y-DFS and overall survival in well-responders were 90.1% and 97.4%. Cox analysis identified ypT3 ~ 4 stage as independent risk factor resulting inferior DFS.

Well-responders are expected to have superior prognosis. Special attention should be given to patients with advanced stages or those exhibiting positive mesorectal fascia or extramural vascular invasion, or adverse pathological features.