MRI-defined high-risk rectal cancer patients: comparison of treatment response and survival outcomes between total neoadjuvant therapy and neoadjuvant chemoradiotherapy-a propensity score matched analysis.

PURPOSE: This study evaluated whether total neoadjuvant therapy (TNT), compared to neoadjuvant chemoradiotherapy (nCRT), improves response and prognosis in magnetic resonance imaging (MRI)-defined high-risk patients with locally advanced rectal cancer (LARC).

METHODS: This retrospective cohort study ultimately included 791 patients with pathologically confirmed rectal cancer who underwent baseline rectal MRI at our institution between 2015 and 2022. Independent MRI-based prognostic risk factors were identified through multivariable Cox regression analysis. Propensity score matching (PSM) was employed to control for confounding variables, followed by survival and treatment response analyses between groups.

RESULTS: The Cox model revealed that MR-based T4 stage and extramural venous invasion (EMVI) status significantly impacted overall survival (OS), whereas tumor location and mesorectal fascia invasion (MRF) status served as important predictors of disease-free survival (DFS). After PSM, the MRI-defined TNT group exhibited a significantly higher clinical complete response (cCR) rate (25.8% vs. 4.0%, p < 0.001), thus leading to more frequent adoption of the watch and wait (W&W) strategy. Furthermore, Kaplan-Meier (KM) curve analysis ultimately confirmed that, compared with the nCRT group, the TNT group exhibited superior OS (HR = 0.48, 95% CI 0.27-0.86) and DFS (HR = 0.62, 95% CI 0.39-1).

CONCLUSION: In MRI-defined high-risk LARC patients, TNT could improve the survival trend while increasing the likelihood of organ preservation without exacerbating surgical complexity. These findings emphasize the fact that TNT should be prioritized for the high-risk MRI-defined population to achieve enhanced local tumor control, sustained therapeutic efficacy, and prolonged survival.