Nodal Downstaging in Rectal Cancer Patients: Survival is Promising if YpN0 is Achieved.

Abstract

Background: Locally advanced rectal cancer is a critical health concern, with neoadjuvant therapy emerging as a pivotal strategy to enhance survival rates.

Objective: This study aims to evaluate the prognostic value of achieving ypN0 status following neoadjuvant therapy patients with locally advanced rectal cancer, comparing survival outcomes among natural N0, downstaged N0, and ypN + groups.

Design: We conducted a post hoc analysis of the FOWARC trial, employing Kaplan-Meier survival analysis and Cox regression models to assess overall survival, disease-free survival, and locoregional recurrence-free survival.

Settings: The multicenter, randomized phase III FOWARC trial was conducted across 15 hospitals in China, adhering to ethical standards.

Patients: Our cohort included 449 patients with locally advanced rectal cancer who underwent neoadjuvant chemoradiotherapy followed by total mesorectal excision.

Interventions: Neoadjuvant chemoradiotherapy followed by total mesorectal excision.

Main outcome measures: The primary endpoint was 5-year overall survival, with secondary endpoints being 3-year disease-free survival and 3-year locoregional recurrence-free survival.

Results: The 5-year overall survival for natural N0 and downstaged N0 groups were 88% and 89%, respectively, significantly higher than the 73% observed in the ypN+ group (p = 0.0034). The complete pathological response rate was markedly lower in the ypN+ group. Multivariable analysis showed the ypN stage as an independent prognostic factor for overall survival.

Limitations: The study's retrospective design may introduce potential biases in patient selection and preoperative staging.

Conclusions: Achieving ypN0 status via neoadjuvant chemoradiotherapy significantly improves survival in patients with locally advanced rectal cancer, regardless of ypT or cN status. This status not only serves as an independent prognostic factor, but may also help to guide hypothesis-driven, individualized postoperative-treatment strategies. See Video Abstract.ClinicalTrials.gov identifier: NCT01211210.