It is accepted that tumor stage and size can influence response to neoadjuvant therapy in locally advanced rectal cancer (LARC). Studies on organ preservation to date have included a wide variety of size and TNM stage tumors. The aim of this study was to report tumor response based on each relevant TNM stage and tumor size. Patients treated with LARC from 2014 to 2021 with cT2-3NxM0 tumors who received neoadjuvant chemoradiotherapy with or without induction chemotherapy were included. Tumors were staged and tumor size calculated on pelvic MRI at the time of diagnosis (cTNM). Tumor size was based on the largest dimension taken on the longest axis of each tumor. Clinical response was defined on the basis of post-treatment pelvic MRI and pathological response following surgery, when performed. Statistical analysis was performed using IBM SPSS Statistics™, version20. Data from 432 patients were analyzed as follows: cT2N0 (n = 51), cT2N+ (n = 36), cT3N0 (n = 76), cT3N+ (n = 270). The rate of complete or near-complete response (cCR or nCR) varied from 77% in cT2N0 ≤ 3cm to 20% in cT3N+ > 4cm. Organ preservation without recurrence at 2years was achieved in 86% of patients with cT2N0, 50% in cT2N+, 39% in cT3N0, and 12% in cT3N+. There is significant variation in tumor response according to tumor stage and size. Tumor response appears inversely proportional to increasing TNM stage and tumor size. This data can support both refinement of selective patient recruitment to organ preservation programs and shared decision-making.