Real-world clinical outcomes of total neoadjuvant therapy followed by total mesorectal excision for locally advanced rectal cancer at a high-volume institution.

Background: While total neoadjuvant therapy (TNT) has become the gold standard for locally advanced rectal cancer (LARC) based on phase III trials, comprehensive real-world data are essential to understanding its impact on a diverse patient population.

Methods: Adult patients with cTNM stage II/III microsatellite-stable primary rectal adenocarcinoma who underwent TNT (2018-2023) followed by curative total mesorectal excision (TME) were included. Primary outcomes were pathological complete response (pCR), local/distant recurrence rates, disease-free survival (DFS), and cancer-specific survival (CSS).

Results: Three-hundred and eleven patients were analyzed: 92.9 % presenting with cT3-4 tumors, 86.5 % with clinically positive nodes, 34.7 % exhibiting extramural venous invasion (EMVI), and 63.1 % having threatened/involved mesorectal fascia on pre-treatment magnetic resonance imaging (MRI). There were 71.7 % of patients that received FOLFOX, 85.5 % had induction chemotherapy, and 76.5 % underwent long-course chemoradiation. Robotic surgery was performed in 71.1 %, with 68.5 % having sphincter-sparing surgery. The pCR rate was 26.4 %, with 75.2 % showing downstaging. Positive margins occurred in 0.6 %, and incomplete mesorectal resection in 3.6 %. At a median follow-up of 36 months, local and distant recurrence rates were 5.7 % and 12.5 %, respectively. The estimated 5-year CSS and DFS were 88.8 % and 80.5 %, with significantly better outcomes in downstaged patients (CSS: 94.8 % vs. 68.8 %, p < 0.001; DFS: 84.4 % vs. 68.0 %, p = 0.001). Pretreatment tumor size, extramural venous invasion (EMVI), and cT4 were identified as risk factors of non-downstaging.

Conclusions: TNT, followed by TME, provides excellent outcomes for LARC, with pCR and survival rates comparable to clinical trials. Our results support TNT as a robust standard of care despite variations in treatment protocols and patient populations.