Extensive multimodal treatments with Total Neoadjuvant Therapy followed by Total Mesorectal Excision for locally advanced rectal cancer allows fit older patients to achieve good oncologic and functional outcomes. Real world data and proof of concept

Abstract

Abstract Introduction Rectal cancer (RC) commonly affects older patients, a heterogeneous population whose general status may vary from fit to frail. Total Neoadjuvant Therapy (TNT) has been introduced to improve local and systemic control of RC. The aim was to present real-world data of older patients receiving TNT followed by minimally invasive surgery after a multidimensional frailty assessment and verify whether this approach would be feasible and safe. Methods This was a single-center retrospective study which enrolled all patients ≥ 70 years of age with RC who underwent TNT followed by surgery between November 2017 and April 2022. Data regarding cancer characteristics, the duration of neoadjuvant chemoradiotherapy, toxicity and the need for dose reduction were recorded. All patients underwent minimally invasive surgery 12 to 16 weeks after the end of therapy. Intra- and postoperative outcomes were recorded. Pre- and postoperative functional evaluation was carried out in all patients. Results Fifteen patients were enrolled. Mean age was 74 (70-81) years. The median BMI was 26.2 (22-32) kg/m2. The mean distance of the tumor from the anal verge was 5.2 cm. At diagnosis, 14 patients had positive nodes (93.3%), 11 (73.3%) showed involvement of the circumferential margin (CRM+) and 10 (66.6%) had extramural vascular invasion (EMVI+). Ten patients (66.6%) received mFOLFOX-6 and 5 CAPOX (33.3%) followed by chemoradiation (CRT). After CRT, positive nodes were reported in 4 cases (26.6%), CRM+ in 4 (26.6%), and EMVI+ in 1 (6.6%). A laparoscopic transanal total mesorectal excision (taTME) was performed in all cases. Median operative time was 280 minutes (110-420). Median length of stay was 4 days (3-29). One Clavien-Dindo grade 4 complication, no readmissions, and no variations in pre- and postoperative functional status within 30 days from surgery were reported. No patient died within 90 days. No positive distal or CRMs were detected at final pathology. Three pathologic complete responses were reported (20%). Conclusions Total neoadjuvant therapy followed by TME is feasible and safe, even for older patients, with good short-term clinical and oncologic outcomes. Patient evaluation is crucial for maximizing cancer care as fit older patients can tolerate extended treatment to overcome the threat of advanced rectal cancer.