Lymph node regression grade as a prognostic marker in rectal cancer after neoadjuvant therapy and radical resection

doi:10.3748/wjg.v32.i15.116026

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World Journal of Gastroenterology

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World J Gastroenterol. Apr 21, 2026; 32(15): 116026
Published online Apr 21, 2026. doi: 10.3748/wjg.v32.i15.116026

Lymph node regression grade as a prognostic marker in rectal cancer after neoadjuvant therapy and radical resection

Yun-Jie Shi, Pan-Pan Duan, Qian-Qian Liu, Hong-Yan Ru, Ya-Jun Huang, Wen Xia, Ling Chen, Xu Li

Yun-Jie Shi, Qian-Qian Liu, Hong-Yan Ru, Ya-Jun Huang, Wen Xia, Xu Li, Department of Colorectal Surgery, Changhai Hospital, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China

Pan-Pan Duan, Ling Chen, Department of Anesthesiology, Changhai Hospital, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China

Co-first authors: Yun-Jie Shi and Pan-Pan Duan.

Co-corresponding authors: Ling Chen and Xu Li.

Author contributions: Shi YJ and Duan PP are co-first authors and contributed equally to this work, including design of the study, acquiring and analyzing data from experiments, and writing of the manuscript; Liu QQ, Ru HY, Huang YJ, and Xia W designed the experiments and conducted clinical data collection; Shi YJ, Duan PP, Chen L, and Li X performed postoperative follow-up and recorded the data, conducted the collation and statistical analysis, wrote the original manuscript and revised the paper; Chen L and Li X made equal contributions as co-corresponding authors; all authors read and approved the final manuscript.

Supported by Shanghai Municipal Health Commission, No. 20244Y0186.

Institutional review board statement: This study was approved by the Ethics Committee of Changhai Hospital, Second Military Medical University.

Informed consent statement: This study obtained informed consent forms signed by all patients.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: All data generated or analyzed during this study are included in this published article.

Corresponding author: Xu Li, Department of Colorectal Surgery, Changhai Hospital, The First Affiliated Hospital of Naval Medical University, No. 168 Changhai Road, Yangpu District, Shanghai 200433, China. xuli_ch@163.com

Received: November 21, 2025
Revised: December 29, 2025
Accepted: February 4, 2026
Published online: April 21, 2026
Processing time: 144 Days and 22.3 Hours

Abstract

BACKGROUND

Neoadjuvant chemoradiotherapy (nCRT) followed by radical resection is the standard for locally advanced rectal cancer (LARC). The tumor regression grade (TRG) of the primary tumor is a known prognostic marker, but its value may be limited by lymph node (LN) status. Assessment of treatment response in LNs is not standardized.

AIM

To determine the prognostic significance of both primary TRG and a novel LN regression grade (LRG) in patients with LARC after nCRT and surgery.

METHODS

The study cohort included patients with LARC who received nCRT and subsequent radical resection from January 2022 to March 2025. The impacts of TRG and LRG scores were assessed.

RESULTS

During the study period, 155 patients underwent long-course nCRT followed by radical rectal resection. Overall, 51 (32.9%) patients developed recurrence, and 34 (21.9%) patients died over the follow-up period. The 5-year overall survival (OS) was 66.1%, and the 5-year disease-free survival (DFS) was 59.5%. With all patients taken into consideration, TRG had no significant correlation with OS (P = 0.11) and DFS (P = 0.18). Conversely, TRG was significantly associated with DFS (P = 0.01) in the 92 patients with ypN0. After excluding patients without LN metastasis, LRG was significantly associated with OS (P = 0.001) and DFS (P = 0.04). Furthermore, LRG was an independent predictor for mortality (hazard ratio = 1.533, P = 0.0002) and recurrence (hazard ratio = 1.278, P = 0.01).

CONCLUSION

Among patients with advanced rectal cancer after nCRT, TRG emerged as a predictive factor solely limited to patients with ypN0. In patients with LN metastasis, LRG could have independent prognostic significance.

Keywords: Rectal cancer; Lymph node regression grade; Tumor regression grade; Neoadjuvant chemoradiotherapy; Prognostic marker

Core Tip: In locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy, the prognostic value of the primary tumor regression grade is limited to patients without lymph node (LN) metastasis (ypN0). Importantly, we demonstrate that a novel LN regression grade, assessing residual cancer in treated LNs, serves as a powerful and independent prognostic marker for both survival and recurrence in patients with residual nodal disease (ypN+). Integrating LN regression grade into postoperative evaluation refines risk stratification beyond current tumor-node-metastasis staging.