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UEG Presentation

HISTOLOGICAL RISK STRATIFICATION FOR LYMPH NODE METASTASIS IN PT2 RECTAL CANCER AFTER LOCAL EXCISION: A MULTICENTRE INTERNATIONAL STUDY

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HISTOLOGICAL RISK STRATIFICATION FOR LYMPH NODE METASTASIS IN PT2 RECTAL CANCER AFTER LOCAL EXCISION: A MULTICENTRE INTERNATIONAL STUDY

Affiliations

1 Amsterdam University Medical Center, Amsterdam, Netherlands

2 University Medical Center Utrecht, Utrecht, Netherlands

3 IJsselland Hospital, Capelle aan de IJssel, Netherlands

4 Flevo Hospital, Almere, Netherlands

5 OLVG, Amsterdam, Netherlands

6 Elisabeth-TweeSteden Hospital, Tilburg, Netherlands

7 IRCCS Humanitas Research Hospital, Milan, Italy

8 University Hospital Leuven, Leuven, Belgium

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Abstract

Introduction

Local excision (LE) is increasingly used to treat early rectal cancer (cT1-2N0M0), but its role in pT2 cancer remains controversial due to a reported 20–30% risk of lymph node metastasis (LNM). Since this risk is largely linked to adverse histological features, patients without these risk factors may safely avoid completion total mesorectal excision (cTME). We aimed to refine LNM risk in pT2 rectal cancer following LE to better guide decisions on rectal-preserving treatment strategies.

Aims & Methods

Patients with pT2 rectal cancer who underwent en bloc LE for cT1-2N0M0 lesions were retrospectivelly enrolled from seven international centres (2015-2025). Eligible patients received either cTME or active surveillance with MRI follow-up for at least two years. Exclusion criteria were positive resection margins (<0.1mm), synchronous or recurrent colorectal cancer and (neo)adjuvant therapy. LNM were confirmed through TME histology or considered absent when no suspicious lymph nodes appeared on follow-up MRI. A detailed histological review of LE specimens was conducted by specialised pathologists at each participating centre using a standardised protocol. Assessed risk factors included high-grade differentiation and/or mucinous subtype, lymphovascular invasion (small and/or large vessels), tumour budding grade 2-3 and/or poorly differentiated clusters grade 2-3, and perineural invasion. Primary endpoint was LNM rate in patients without histological risk factors. Secondary endpoints included the association between individual risk factors and LNM, as well as locoregional recurrences during active surveillance.

Results

A total of 103 patients (mean age 66 (SD 10), 56% male) with a median lesion size of 25mm (IQR 15) were included. Endoscopic LE was performed in 31 patients (30%) and surgical LE in 72 (70%). After LE, 76 patients (74%) underwent cTME while 27 (26%) opted for active surveillance. The overall LNM rate was 17.5% (18/103). Among the 36 patients (35%) without histological risk factors, the LNM rate was 5.6% (2/36; OR 0.19, 95% CI 0.04-0.87, p=0.032). Both LNM cases were detected in the cTME group. LNM rates per individual risk factor are presented in Table 1.
In the active surveillance group, no locoregional recurrences occurred in the ten patients without risk factors during a median follow-up of 53 months (IQR 26). Among patients with risk factors, two of 14 patients with one risk factor developed a locoregional recurrence and one of two patients with two risk factors. All recurrences occurred intramurally following prior surgical LE. The only patient with three risk factors had no locoregional recurrence but died from unrelated cause at 24 months.

Table 1. Univariate analyses of histological risk factors for lymph node metastasis

Risk factor	n/N (%)	Lymph node metastasis rate (%)	Odds ratio (95% CI)	P-value
No histological risk factors	36/103 (35.0)	2/36 (5.6)	0.19 (0.04-0.87)	0.032
Lymphovascular invasion Small vessel invasion Large vessel invasion	47/103 (45.6) 32/103 (31.1) 28/103 (27.2)	12/47 (25.5) 11/32 (34.4) 4/28 (14.3)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	0.055 0.004 0.604
Tumour budding and/or poorly differentiated clusters grade 2-3 Tumour budding grade 2-3 Poorly differentiated clusters grade 2-3	36/103 (35.0) 29/103 (28.2) 19/103 (18.4)	13/36 (36.1) 10/29 (34.5) 9/19 (47.4)	7.0 (2.2-21.8) 4.3 (1.5-12.5) 7.5 (2.4-23.3)	<0.001 0.007 <0.001
Adverse histology Poor tumour differentiation Mucinous subtype	13/103 (12.6) 7/103 (6.8) 6/103 (5.8)	6/13 (46.2) 3/7 (42.9) 3/6 (50.0)	5.6 (1.6-19.4) 4.1 (0.8-20.0) 5.5 (1.0-29.7)	0.007 0.086 0.049
Perineural invasion	11/103 (10.7)	5/11 (45.5)	5.1 (1.3-19.0)	0.016

Conclusion

In this group of pT2 rectal cancer patients treated with LE, detailed histological analysis suggests a low LNM risk (5.6%) in patients without histological risk factors. No locoregional recurrences occurred in this low-risk group during active surveillance. As 35% of pT2 rectal cancers lacked histological risk factors, a risk-stratified approach could potentially allow a substantial proportion of patients to avoid cTME. Prospective validation in larger cohorts is needed before clinical implementation.

Event

UEG Week Berlin 2025

Topics

Colorectal Digestive Oncology Endoscopy Histopathology

Submission format

Late-Breaking Abstract

Session

Colorectal ESD: The better way?

Citation

United European Gastroenterology Journal 2025; 13 (Supplement 8)

Published

2025

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	Univariate analysis		Multivariate analysis
	OR	P-value	OR	P-value
Lymphatic		0.000		0.025
Lv 0: LV 1	1:10.557 (4.188-26.712)		1:3.843 (1.181-12.510)
Perineural		0.000		0.000
Pn 0: Pn 1	1:31.167(8.073-120.328)		1: 35.774 (6.655-192.317)
Tumor budding		0.000		0.000
BD 0	1	0.232	1	0.799
BD 1	2.226 (0.592-8.675)	0.000	0.817 (0.173-2.471)	0.001
BD 2,3	19.880 (5.457-72.418)		9.794 (2.471-38.815)