eP204 - Real-World Clinical Outcomes of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer – a Retrospective Analysis

Purpose/Background: There is a paucity of real-world data pertaining to the safety and clinical efficacy of total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC). The objective of this study is to demonstrate the clinical outcomes of patients undergoing TNT at a high-volume center providing multi-disciplinary rectal cancer care.Methods/Interventions: Clinicodemographic and pathologic data from patients with LARC (clinical stage II or III) treated with consolidation or induction TNT between 2018-2023 were retrospectively collected. Nonparametric data was reported as median and range. Categorical data was analyzed using Fisher’s exact test and reported as percentages. An interim analysis was performed.Results/Outcomes: A total of 63 patients were treated with TNT in the study period. 41% (n=26), 48% (n=30), and 11% (n=7) had low, mid, and high-rectal cancer, respectively. Majority of the patients had cT3 node-positive disease (n=35, 56%), and 25% (n=16) had cT4 node-positive disease. 95% of patients were treated with consolidation TNT, composed of long-course chemoradiation therapy followed by FOLFOX (n=42), CAPEOX (n=15), or capecitabine (n=3). 3 patients (5%) received induction TNT with FOLFOX. Chemotherapy interruptions were seen in 33% of patients, and 59% underwent dose reduction. Three patients are currently undergoing TNT. 42% (n=25) achieved clinical complete response after TNT, all of whom proceeded with a watch-and-wait (WW) protocol. 58% (n=35) underwent total mesorectal excision (TME) after TNT. Of this group, 77% (n=27) underwent a sphincter-sparing surgery. A pathological complete response was seen in 5 patients (15%). During a median follow-up of 13 months [0, 46], three patients treated with TNT + TME developed a locoregional recurrence (median time of 19 months [9, 21]) and 7 patients developed distant metastasis (median time of 12 months [2, 26]). 4 patients (16%) under the WW protocol developed luminal regrowth (median time of 9 months [5, 21]). 3 patients underwent salvage surgery, in the form of low-anterior resection (n=1), abdominoperineal resection (n=1), and pelvic exenteration (n=1). 4 patients under the WW protocol developed distant metastasis (median time of 14 months [5, 38]). Non-regrowth event rates were comparable between the TNT + TME and TNT + WW groups (20% vs. 16%).Conclusion/

Discussion: Real-world data from LARC patients treated with TNT demonstrates comparable clinical efficacy in the short-term to that reported in recent RCTs, despite variable tolerability and chemotherapy regimens. This interim analysis supports the safety and feasibility of a WW protocol in patients who achieve clinical complete response after consolidation TNT under an intensive surveillance regimen."Flowchart illustrating clinical outcomes in TNT + WW vs. TNT+ TME

Characteristics of patients with clinical complete response after TNT

Characteristics of patients with pathological complete response after TNT
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