Multimodal assessment after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer accurately predicts complete responders

Purpose This study aimed to compare local regrowth rates after total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy (SNCRT) in locally advanced rectal cancer (LARC) patients that were strictly selected and assessed with a multimodal approach. Secondary outcomes were 4-year disease-free (DFS) and overall survival (OS) rates. Methods Locally advanced rectal cancer patients without distant metastases treated at Koç Healthcare Group between January 2014 and January 2021 were included. Patients were assessed for complete response with a combination of digital rectal exam, endoscopy, and magnetic resonance imaging with a dedicated rectum protocol. The systemic evaluation was performed with an upper abdomen MRI using intravenous hepatobiliary contrast agent and a thorax CT. Results Of the 270 patients with LARC, 182 fulfilled the inclusion criteria. Ninety-seven (53.3%) underwent TNT, while 85 (46.7%) underwent SNCRT. A cumulative combination of pathological and sustained clinical complete response was significantly higher in the TNT group than in the SNCRT (45.4% vs. 20.0%, p < 0.0001). After a median follow-up of 48 months, seven patients in the W&W group had regrowth [TNT: 4 (10.8%) vs. SNCRT: 3 (23.1%), p = 0.357]. Based on pathological examination, complete/near complete mesorectum rates ( p = 1.000) and circumferential resection margin positivity rates ( p = 1.000) were similar between the groups. The 4-year DFS and OS rates were comparable. The patients with clinical or pathological complete response had significantly longer overall survival ( p = 0.017) regardless of the type of neoadjuvant treatment. Conclusions Multimodal assessment after TNT effectively detects complete responders, resulting in low local recurrence and increased cumulative complete response rates. However, these outcomes did not translate into a survival advantage.