Outcomes Associated with Total Neoadjuvant Therapy (TNT) with Non-Operative Intent for Rectal Adenocarcinoma

Abstract

<h3>Purpose/Objective(s)</h3> To evaluate surgery- and permanent ostomy-free survival in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. <h3>Materials/Methods</h3> A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013-2021. All patients received radiation with concurrent capecitabine or 5-fluorouracil and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Clinical complete response rates were determined based on post-treatment MRI or endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression analysis was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Institutional results on patient outcomes treated from 2013-2018 (n=28) has been reported previously, which have been updated with more patients and longer-term follow-up. <h3>Results</h3> 45 patients were identified with a median follow up of 28 months. 66.7% (n=30) achieved a clinical complete response (cCR). 17 patients (37.8%) underwent surgical resection while only 13.3% (n=4) of patients who achieved a cCR ultimately required surgery. 2 clinical incomplete responders did not have surgery; one patient refused APR and has been stable on maintenance chemotherapy, and one patient continued on surveillance and failed distantly. At 12 months, permanent ostomy free survival was 90.8% and 80.3% at 24 months. Surgery free survival was 76.9% and 65.7%, at 12 and 24 months, respectively. On Cox regression multivariate analysis, 6-month, but not 1-month, post treatment endoscopy was associated with surgery free survival (p=0.006) and permanent ostomy free survival (p=0.033). <h3>Conclusion</h3> Our institutional results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma. 6-month, but not 1-month post treatment endoscopy was associated with surgery- and permanent ostomy-free survival suggesting continued tumor regression after 1 month. This is consistent with National Comprehensive Cancer Network (NCCN) guidelines to restage rectal cancer patients after at least 8 weeks following RT. Identification of reliable predictors of tumor regression after TNT for patient treatment planning is warranted.