Organ Preservation in Patients with Rectal Cancer Treated with Total Neoadjuvant Therapy

BACKGROUND: Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy. OBJECTIVE: This study aimed to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait. DESIGN: This study is a retrospective analysis of data from prospectively maintained databases. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included. INTERVENTION: Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision. MAIN OUTCOMES AND MEASURES: Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group. RESULTS: A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group. LIMITATIONS: Generalizability, sample size, and follow-up duration were limitations of this study. CONCLUSIONS: Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team.