Predictors of lateral lymph node metastasis and prognostic factors in patients with low rectal cancer who underwent lateral lymph node dissection without preoperative treatment

Riki Ohno; Haruka Oi; Soichiro Natsume; Kazuki Kawasaki; Yuichiro Yoshioka; Nao Kakizawa; Junko Kishikawa; Toshiya Nagasaki

doi:10.3393/ac.2025.00675.0096

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Original Article Colorectal cancer Predictors of lateral lymph node metastasis and prognostic factors in patients with low rectal cancer who underwent lateral lymph node dissection without preoperative treatment: Riki Ohno, Haruka Oi, Soichiro Natsume, Kazuki Kawasaki, Yuichiro Yoshioka, Nao Kakizawa, Junko Kishikawa, Toshiya Nagasaki; Annals of Coloproctology 2025;41(6):545-553.
DOI: https://doi.org/10.3393/ac.2025.00675.0096
Published online: December 29, 2025

Department of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan

Correspondence to: Toshiya Nagasaki, MD, PhD Department of Gastroenterological Surgery, Saitama Cancer Center, 780 Komuro, Ina, Saitama 362-0806, Japan Email: nagasaki.toshiya@saitama-pho.jp

• Received: May 23, 2025 • Revised: July 7, 2025 • Accepted: August 3, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Abstract
INTRODUCTION
METHODS
RESULTS
DISCUSSION
ARTICLE INFORMATION
REFERENCES

Abstract

Purpose
This study aimed to identify predictors of lateral lymph node metastasis (LLNM) and assess prognostic factors in patients with locally advanced low rectal cancer (LALRC), with the goal of informing optimal treatment strategies for LALRC.
Methods
We retrospectively analyzed clinicopathological data from patients with LALRC who underwent lateral lymph node dissection without preoperative treatment between 2014 and 2023. The radiological criterion for LLNM was a short-axis diameter of ≥6 mm on magnetic resonance imaging (MRI).
Results
Of 163 patients, 27 (16.6%) had pathological LLNM (pLLNM). Among 130 patients preoperatively classified as LLNM-negative, 5 (3.8%) were found to have pLLNM. Univariate and multivariate analyses showed that meeting the radiological LLNM criterion independently predicted pLLNM (odds ratio, 53.000; P<0.001). The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of this criterion were 90.2%, 81.5%, 91.9%, 66.7%, and 96.2%, respectively. In multivariate analyses, pLLNM was an independent risk factor for 3‑year relapse‑free survival. MRI‑detected extramural vascular invasion (mrEMVI) was independently associated with 3‑year relapse‑free survival, local recurrence‑free survival, and distant recurrence‑free survival.
Conclusion
These radiological criteria may help clinicians develop personalized treatment plans for patients with LALRC. The high negative predictive value and specificity of LLNM assessment can assist in avoiding overtreatment in appropriate patients. Further evaluation is needed to define optimal management for mrEMVI‑positive cases.
Keywords: Rectal cancer; Both lateral lymph node dissection; Lateral lymph node metastasis

INTRODUCTION

The treatment strategies for patients with locally advanced low rectal cancer (LALRC) are quite different between Japan and other countries. Preoperative treatment for LALRC is not common in Japan. Japanese guidelines recommend total mesorectal excision (TME) and bilateral lateral lymph node dissection (LLND) without preoperative treatment, given the reported 15% to 25% incidence of LLN metastasis (LLNM) in LALRC and the poor prognosis of patients with pathological LLNM (pLLNM) [1–6].

In Western countries, preoperative treatment (radiotherapy, chemoradiotherapy [CRT], and total neoadjuvant therapy [TNT]) followed by TME is the standard of care for rectal cancer. LLND is not regarded as a routine surgical procedure because it has been reported to be associated with higher postoperative complication rates and not to improve overall survival or distant recurrence‑free survival (DRFS). However, a high rate of lateral local recurrence (LR) has been demonstrated in patients with enlarged LLNs after CRT [7–10].

In contrast to international practice, LLND is performed for patients with LALRC without preoperative treatment at our institution. Although we could not evaluate outcomes in patients with LALRC who underwent preoperative treatment, we were able to determine the presence or absence of pLLNM in these cases. The aim of this study was to investigate clinical predictors of pLLNM and other prognostic factors in patients with LALRC.

METHODS

Ethics statement

This study was approved by the Institutional Review Board of Saitama Cancer Center (No. 1969). All patients provided written informed consent.

Study design

Our standard treatment strategy for LALRC was TME with bilateral LLND without preoperative therapy. LALRC was defined as pathological stage II (T3–4, N0) or stage III (any T, N1–2) rectal adenocarcinoma with the lower tumor margin located below the peritoneal reflection. Preoperative CRT or systemic chemotherapy was reserved for patients with circumferential resection margin (CRM) involvement. CRM involvement, including mesorectal fascia involvement and tumor invasion into adjacent structures, was assessed using magnetic resonance imaging (MRI). Patients who received preoperative treatment and those with multiple synchronous or metachronous cancers, familial adenomatous polyposis, or anal fistula cancer were excluded from analysis.

The following variables were retrospectively analyzed: sex, age at surgery, tumor distance from the anal verge (AV), preoperative serum carcinoembryonic antigen (CEA) level, preoperative serum carbohydrate antigen 19‑9 (CA19‑9) level, clinical T category, clinical mesorectal lymph node metastasis (cMLNM), clinical LLNM (cLLNM), clinical stage, clinical CRM status, tumor size, histological type, MRI‑detected extramural vascular invasion (mrEMVI), pathological T category, pathological MLNM (pMLNM), pLLNM, pathological stage, pathological CRM status, and whether postoperative treatment was administered. The depth of tumor invasion and lymph node size were determined by MRI. In line with a previous report, the radiological criterion for cMLNM and cLLNM was a short‑axis diameter of ≥6 mm (Fig. 1A) [11]. mrEMVI was classified according to the MRI‑EMVI scoring system [12], with scores of 0–2 defined as mrEMVI‑negative and scores of 3–4 defined as mrEMVI‑positive (Fig. 1B). Predictors of pLLNM were evaluated by univariate and multivariate analyses.

Postoperative surveillance included measurement of serum CEA and CA19‑9 levels every 3 months for the first 3 years and every 6 months thereafter. Computed tomography of the chest, abdomen, and pelvis was performed every 6 months, and total colonoscopy was performed annually. Long‑term outcomes were assessed as RFS, LR‑free survival (LRFS), and DRFS. RFS was defined as the interval from the date of operation to any relapse. LR was defined as recurrence within the pelvis, and distant recurrence (DR) as recurrence outside the pelvis. For LRFS, events included LR even when DR occurred simultaneously or earlier.

Statistical analysis

The proportion of patients with pLLNM was analyzed using the chi‑square or Fisher exact tests, as appropriate. Survival analyses for RFS, LRFS, and DRFS were performed using the Kaplan-Meier method and compared with the log‑rank test. A P-value of <0.05 was considered statistically significant. Variables with P<0.10 in univariate analyses were subsequently entered into multivariate models. Multivariate logistic regression was used to identify predictors of pLLNM. To assess predictors of long‑term survival, multivariate analyses using the Cox proportional hazards model were conducted, with results reported as hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical analyses were performed using EZR (Saitama Medical Center, Jichi Medical University).

RESULTS

Between January 2014 and December 2023, a total of 233 patients with LALRC underwent TME plus bilateral LLND and were diagnosed with pathological stage II or III disease. Preoperative treatment was performed in 48 patients, who were excluded from this analysis. In addition, 18 patients with multiple primary cancers, 3 with anal fistula cancer, and 1 with familial adenomatous polyposis were excluded. Consequently, 163 patients with LALRC who underwent LLND without preoperative treatment were analyzed (Fig. 2). Patient demographics and tumor characteristics are summarized in Table 1. The mean tumor distance from the AV was 47.3 mm. Because of advanced age, severe comorbidity, or patient refusal, 31 patients with clinically positive CRM status did not receive preoperative treatment. pLLNM was confirmed in 27 patients (16.6%). Unilateral and bilateral pLLNM were identified in 19 and 8 patients, respectively. Nineteen patients had both pLLNM and pMLNM, whereas the remaining 8 did not have pMLNM. mrEMVI was observed in 48 patients (29.4%). A total of 93 patients had pathological stage III disease, of whom 71 (76.3%) received postoperative treatment; 2 of 70 patients with pathological stage II disease received postoperative treatment.

Table 2 shows the association between preoperative clinical factors and pLLNM. In univariate analysis, cMLNM‑positive and cLLNM‑positive status were significantly associated with pLLNM. Multivariate analysis revealed that cLLNM‑positive status was an independent predictor of pLLNM (odds ratio, 53.000; 95% CI, 15.100–185.00; P<0.001). Using our radiological criterion, 33 patients were classified as cLLNM‑positive, and of these patients, pLLNM was confirmed in 22 (66.7%). Among 130 patients classified as cLLNM‑negative, 5 (3.8%) were found to have pLLNM. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the cLLNM criterion were 90.2%, 81.5%, 91.9%, 66.7%, and 96.2%, respectively (Fig. 3). Moreover, among 71 patients who were both cLLNM‑negative and cMLNM‑negative, pLLNM was confirmed in 2 (2.8%). Of 59 patients with cMLNM‑positive and cLLNM‑negative status, 3 (5.1%) were diagnosed with pLLNM.

With a median follow‑up of 46.6 months (range, 0.5–124.9 months), 36 patients developed DR and 12 developed LR. Of the 12 patients with LR, 7 recurred in the lateral pelvic region, 3 in the presacral area, and 2 at the anastomotic site. Among the 27 patients with pLLNM, 3 had LR in the lateral pelvic area and 1 in the presacral area. Among the 5 patients who were cLLNM‑negative but had pLLNM, none developed LR and 4 developed DR. The 3‑year RFS, LRFS, and DRFS were 72.7%, 91.2%, and 77.6%, respectively. Table 3 shows correlations between clinicopathological factors and 3‑year outcomes. In univariate analyses, sex and age were not associated with prognosis. Tumor distance from the AV, pathological T category, pMLNM, pLLNM, pathological CRM‑positivity, and histological type were significantly associated with 3‑year RFS and DRFS. Preoperative serum CEA level was significantly associated with RFS and LRFS. mrEMVI was significantly associated with 3‑year RFS, LRFS, and DRFS. Table 4 presents the multivariate analyses of prognostic factors. Tumor distance from the AV was an independent predictor of 3‑year RFS and DRFS. pLLNM was independently associated with RFS. mrEMVI was an independent predictor of RFS, LRFS, and DRFS. Histological type was independently associated with DRFS.

DISCUSSION

Our data indicated that an LLN short‑axis diameter ≥6 mm on MRI was strongly associated with pLLNM and yielded high NPV and specificity. Patients with LALRC who had pLLNM experienced poorer prognosis than those without pLLNM. Therefore, elucidating predictors of pLLNM is important. A strength of this study is that the accuracy of cLLNM was verified histopathologically in all cases.

In our cohort, pLLNM was confirmed in 16.6% of patients with LALRC who underwent TME plus LLND without preoperative treatment, and this incidence is comparable to previous reports [1–5]. Multiple studies have shown that LLN short‑axis diameter is a valuable predictor of LLNM [13]. A recent Japanese multicenter prospective study identified ≥6 mm as the optimal cutoff by receiver operating characteristic analysis and confirmed it as an independent risk factor for LLNM [11]. Our results corroborate the diagnostic performance of this cutoff. Notably, the NPV (96.2%) and specificity (91.9%) were very high. Thus, the current radiological criterion for cLLNM may help prevent overtreatment in patients unlikely to harbor LLNM. However, LLN size alone may be insufficient for maximal accuracy. Morphologic MRI features, such as irregular borders and mixed signal intensity, can improve diagnostic accuracy [14]. Some studies have also shown that combining mrEMVI status with LLN size enhances performance [15, 16], and a validated nomogram has been developed incorporating LLN and perirectal lymph node short‑axis diameters, EMVI status, and other variables [17]. As noted in our study, pLLNM occurred in 2.8% of patients with both negative cLLNM and cMLNM, suggesting that the absence of enlarged MLNs may aid pLLNM prediction. These findings are useful for refining preoperative risk stratification.

Treatment strategies for LALRC should be individualized according to LLN status, since LLND is associated with longer operative time, greater blood loss, male sexual dysfunction, and urinary dysfunction compared with TME alone [18, 19]. LLND is not commonly performed outside Japan. Worldwide, the standard of care for rectal cancer is neoadjuvant CRT followed by TME without LLND. Patients with LALRC and enlarged LLNs who undergo neoadjuvant CRT followed by TME alone have been reported to experience significantly higher lateral LR rates [7–10], likely because pLLNM is identified in 24.6% to 65.8% of patients with enlarged LLNs after CRT [20–22]. LLN metastases may not be completely eradicated by preoperative CRT. Our results showed that 3‑year RFS and DRFS were significantly worse in patients with pLLNM than in those without pLLNM despite LLND. In this study, LR also occurred in regions outside the LLN area. Moreover, 11.1% of patients with pLLNM had LR in the lateral pelvic area, a rate higher than in patients without pLLNM. These findings suggest that LLND alone is insufficient to prevent pelvic recurrence and may not fully eliminate LLN recurrence in patients with pLLNM. A previous report showed that LR rates were similar between Japanese patients who underwent TME plus LLND and Western patients who underwent preoperative CRT followed by TME without LLND [23]. Although our data do not include outcomes for patients who received preoperative CRT, long‑term results, including overall survival, RFS, LRFS, and lateral LR, reportedly improve in pLLNM when neoadjuvant CRT is followed by TME plus LLND [22, 24, 25]. Collectively, these reports indicate that combining neoadjuvant CRT with LLND could be a promising strategy for LALRC with enlarged LLNs.

The necessity of LLND for LALRC without enlarged LLNs remains unclear. A Japanese multicenter randomized controlled trial (JCOG0212) tested the noninferiority of TME alone versus TME with LLND in patients without enlarged LLNs. Although noninferiority was not proven, 5‑year overall survival, RFS, and LRFS were similar between the groups [26, 27]. In our series, using the present radiological criterion, 5 of 130 cLLNM‑negative patients (3.8%) had pLLNM. Given the adverse short‑term effects of LLND, the procedure can be omitted in cLLNM‑negative LALRC.

Our study also showed that mrEMVI was an independent prognostic factor in multivariate analysis. By Kaplan-Meier estimates, 3‑year RFS, LRFS, and DRFS were significantly worse in mrEMVI‑positive than in mrEMVI‑negative patients (29.1% vs. 83.0%, 75.8% vs. 95.8%, and 50.8% vs. 85.3%, respectively). The presence of EMVI is mechanistically linked to a higher risk of DR due to hematogenous spread [11, 28], and mrEMVI has been associated with increased CRM involvement and pelvic sidewall dissemination [29,30]. A previous report demonstrated that regression of mrEMVI after CRT is associated with improved outcomes [31]. Therefore, even in cLLNM‑negative patients, multimodal therapy should be considered for those who are mrEMVI‑positive. In this study, 71 of 93 patients (76.3%) with pathological stage III disease received postoperative chemotherapy after bilateral LLND, and postoperative chemotherapy was not associated with improved prognosis. Recently, TNT has been reported to increase chemotherapy completion and improve outcomes in rectal cancer [32–35]. Further research is needed to define optimal strategies for LALRC with this prognostic risk factor.

In addition to mrEMVI and pLLNM, tumor distance from the AV (within 50 mm) and poor histological type were independently associated with poor prognosis in multivariate analyses. In the total cohort, 41 patients had none of these risk factors and experienced neither LR nor DR. These patients might not require preoperative therapy or LLND.

Limitations

This study has limitations. First, it was a retrospective, single‑center analysis with a limited sample size; thus, selection bias is possible. Second, 14 patients (8.6%) had less than 1 year of follow‑up; longer observation is needed to fully evaluate the prognostic factors identified here. Third, detailed morphologic MRI findings of LLNs and pathological confirmation of EMVI were not evaluated. We focused on LLN size and EMVI findings on MRI, and these simple features were clearly associated with prognosis. Fourth, because our treatment strategy differs from international standards, the results should be interpreted with caution. Despite these limitations, we believe our findings may assist with treatment selection for patients with LALRC.

Conclusions

Our radiological criterion for cLLNM was independently associated with pLLNM, with very high NPV and specificity. Accurate pretreatment diagnosis is essential to determine appropriate treatment strategies for patients with LALRC.

ARTICLE INFORMATION

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Funding

None.

Author contributions

Conceptualization: all authors; Data curation: all authors; Formal analysis: all authors; Investigation: all authors; Methodology: all authors; Writing–original draft: all authors; Writing–review & editing: all authors. All authors read and approved the final manuscript.

Fig. 1.

Preoperative magnetic resonance imaging findings. (A) Clinical lateral lymph node metastasis positive (arrow). (B) Magnetic resonance imaging–detected extramural vascular invasion positive (arrow).

Fig. 2.

Patient inclusion flowchart. TME, total mesorectal excision; LLND, lateral lymph node dissection.

Fig. 3.

Prediction of lateral lymph node metastasis based on lymph node size. cLLNM, clinical lateral lymph node metastasis; pLLNM, pathological lateral lymph node metastasis; TP, true positive; FP, false positive; FN, false negative; TN, true negative.

Table 1.

Patient demographics and tumor characteristics (n=163)

Characteristic	Value
Sex
Female	45 (27.6)
Male	118 (72.4)
Age (yr)	64.8±10.7
Tumor distance from AV (mm)	47.3±18.2
Preoperative serum CEA (ng/mL)	15.6±37.3
Preoperative serum CA19-9 (U/mL)	27.4±82.2
Clinical T category
T2	3 (1.8)
T3	134 (82.2)
T4	26 (16.0)
cMLNM
Negative	79 (48.5)
Positive	84 (51.5)
cLLNM
Negative	130 (79.8)
Positive	33 (20.2)
Clinical stage
II	72 (44.2)
III	91 (55.8)
Clinical CRM
Negative	128 (78.5)
Positive	35 (21.5)
Tumor size (mm)	52.8±19.9
Histological type
Well/moderately differentiated	154 (94.5)
Poorly differentiated, mucinous, signet ring cell	9 (5.5)
mrEMVI
Negative	115 (70.6)
Positive	48 (29.4)
Pathological T category
T1b, T2	11 (6.7)
T3	138 (84.7)
T4	14 (8.6)
pMLNM
Negative	80 (49.1)
Positive	83 (50.9)
pLLNM
Negative	136 (83.4)
Positive	27 (16.6)
Pathological stage
II	70 (42.9)
III	93 (57.1)
Pathological CRM
Negative	149 (91.4)
Positive	14 (8.6)
Postoperative chemotherapy
Yes	73 (44.8)
No	90 (55.2)

Values are presented as number (%) or mean±standard deviation.

AV, anal verge; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; cMLNM, clinical mesorectal lymph node metastasis; cLLNM, clinical lateral lymph node metastasis; CRM, circumferential resection margin; mrEMVI, magnetic resonance imaging–detected extramural vascular invasion; pMLNM, pathological mesorectal lymph node metastasis; pLLNM, pathological lateral lymph node metastasis.

Table 2.

The association between pLLNM and preoperative clinical factors (n=163)

Factor	pLLNM		Univariate analysis	Multivariate analysis
Factor	Negative (n=136)	Positive (n=27)	P-value	OR (95% CI)	P-value
Sex			0.816
Female	37	8
Male	99	19
Age (yr)			0.531
<65	60	10
≥65	76	17
Tumor distance from AV (mm)			0.184
>50	51	6
≤50	85	21
Preoperative serum CEA (ng/mL)			0.294
<5	67	10
≥5	69	17
Preoperative serum CA19–9 (U/mL)			0.084		0.257
<37	124	21		1 (Reference)
≥37	12	6		2.618 (0.495–13.889)
Clinical T category			0.294
T2	2	1
T3	114	20
T4	20	6
cMLNM			0.036		0.643
Negative	71	8		1 (Reference)
Positive	65	19		1.371 (0.361–5.208)
cLLNM			<0.001		<0.001
Negative	125	5		1 (Reference)
Positive	11	22		53.000 (15.100–185.000)
Clinical CRM			0.305
Negative	109	19
Positive	27	8
mrEMVI			0.069		0.242
Negative	100	15		1 (Reference)
Positive	36	12		2.170 (0.593–7.950)
Histological type			0.645
Well/moderately differentiated	129	25
Poorly differentiated, mucinous, signet ring cell	7	2

pLLNM, pathological lateral lymph node metastasis; OR, odds ratio; CI, confidence interval; AV, anal verge; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; cMLNM, clinical mesorectal lymph node metastasis; cLLNM, clinical lateral lymph node metastasis; CRM, circumferential resection margin; mrEMVI, magnetic resonance imaging–detected extramural vascular invasion.

Table 3.

The correlation between clinicopathological factors and 3-year prognosis (n=163)

Factor	No. of patients	RFS (%)	P-value	LRFS (%)	P-value	DRFS (%)	P-value
Sex			0.547		0.638		0.640
Female	45	71.5		91.4		76.5
Male	118	68.7		88.8		75.9
Age (yr)			0.107		0.838		0.095
<65	70	76.4		89.7		82.6
≥65	93	63.9		91.8		70.5
Tumor distance from AV (mm)			<0.001		0.149		<0.001
>50	57	93.2		95.2		93.5
≤50	106	57.1		88.4		67.2
Preoperative serum CEA (ng/mL)			0.024		0.036		0.202
<5	77	80.6		96.5		81.4
≥5	86	60.9		85.8		71.7
Preoperative serum CA19–9 (U/mL)			0.054		0.424		0.141
<37	145	71.0		91.1		77.0
≥37	18	56.7		86.7		66.6
Pathological T category			0.038		0.187		0.009
T1b–3	149	71.6		91.3		78.5
T4	14	43.1		71.8		43.1
pMLNM			0.017		0.332		0.004
Negative	80	79.6		88.4		87.0
Positive	83	61.2		92.4		61.7
pLLNM			<0.001		0.056		<0.001
Negative	136	75.8		92.4		81.1
Positive	27	28.2		80.7		49.0
Pathological CRM			<0.001		0.348		<0.001
Negative	149	72.5		90.0		79.4
Positive	14	30.5		100		32.5
mrEMVI			<0.001		<0.001		<0.001
Negative	115	83.0		95.8		85.3
Positive	48	29.1		75.8		50.8
Histological type			<0.001		0.484		<0.001
Well/moderately differentiated	154	71.9		91.0		78.8
Poorly differentiated, mucinous, signet ring cell	9	33.3		80.0		33.3
Postoperative treatment			0.852		0.973		0.625
No	90	70.2		91.5		75.2
Yes	73	69.2		90.1		77.6

RFS, recurrence-free survival; LRFS, local recurrence-free survival; DRFS, distant recurrence-free survival; AV, anal verge; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; pMLNM, pathological mesorectal lymph node metastasis; pLLNM, pathological lateral lymph node metastasis; CRM, circumferential resection margin; mrEMVI, magnetic resonance imaging–detected extramural vascular invasion.

Table 4.

Multivariate analyses of the predictive factors for 3-year prognosis

Factor	Recurrence-free survival		Local recurrence-free survival		Distant recurrence-free survival
Factor	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Tumor distance from AV (mm)		0.009				0.037
>50	1 (Reference)				1 (Reference)
≤50	4.196 (1.437–12.250)				3.172 (1.071–9.395)
pLLNM		0.047		0.120		0.224
Negative	1 (Reference)		1 (Reference)		1 (Reference)
Positive	2.086 (1.010–4.308)		2.614 (0.779–8.772)		1.626 (0.743–3.562)
mrEMVI		<0.001		0.007		0.012
Negative	1 (Reference)		1 (Reference)		1 (Reference)
Positive	3.838 (1.939–7.600)		5.225 (1.561–17.490)		2.601 (1.230–5.502)
Histological type						0.039
Well/moderately differentiated					1 (Reference)
Poorly differentiated, mucinous, signet ring cell					2.604 (1.048–6.494)

The table includes significant risk factors alone, apart from pLLNM.

HR, hazard ratio; CI, confidence interval; AV, anal verge; pLLNM, pathological lateral lymph node metastasis; mrEMVI, magnetic resonance imaging–detected extramural vascular invasion.

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Clinical implications of radiologic criteria and prognostic factors for lateral lymph node metastasis in low rectal cancer
Gyung Mo Son
Annals of Coloproctology.2025; 41(6): 489. CrossRef

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Predictors of lateral lymph node metastasis and prognostic factors in patients with low rectal cancer who underwent lateral lymph node dissection without preoperative treatment

Ann Coloproctol. 2025;41(6):545-553. Published online December 29, 2025

DOI: https://doi.org/10.3393/ac.2025.00675.0096

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Predictors of lateral lymph node metastasis and prognostic factors in patients with low rectal cancer who underwent lateral lymph node dissection without preoperative treatment

Fig. 1. Preoperative magnetic resonance imaging findings. (A) Clinical lateral lymph node metastasis positive (arrow). (B) Magnetic resonance imaging–detected extramural vascular invasion positive (arrow).

Fig. 2. Patient inclusion flowchart. TME, total mesorectal excision; LLND, lateral lymph node dissection.

Fig. 3. Prediction of lateral lymph node metastasis based on lymph node size. cLLNM, clinical lateral lymph node metastasis; pLLNM, pathological lateral lymph node metastasis; TP, true positive; FP, false positive; FN, false negative; TN, true negative.

Fig. 1.

Fig. 2.

Fig. 3.

Predictors of lateral lymph node metastasis and prognostic factors in patients with low rectal cancer who underwent lateral lymph node dissection without preoperative treatment

Characteristic	Value
Sex
Female	45 (27.6)
Male	118 (72.4)
Age (yr)	64.8±10.7
Tumor distance from AV (mm)	47.3±18.2
Preoperative serum CEA (ng/mL)	15.6±37.3
Preoperative serum CA19-9 (U/mL)	27.4±82.2
Clinical T category
T2	3 (1.8)
T3	134 (82.2)
T4	26 (16.0)
cMLNM
Negative	79 (48.5)
Positive	84 (51.5)
cLLNM
Negative	130 (79.8)
Positive	33 (20.2)
Clinical stage
II	72 (44.2)
III	91 (55.8)
Clinical CRM
Negative	128 (78.5)
Positive	35 (21.5)
Tumor size (mm)	52.8±19.9
Histological type
Well/moderately differentiated	154 (94.5)
Poorly differentiated, mucinous, signet ring cell	9 (5.5)
mrEMVI
Negative	115 (70.6)
Positive	48 (29.4)
Pathological T category
T1b, T2	11 (6.7)
T3	138 (84.7)
T4	14 (8.6)
pMLNM
Negative	80 (49.1)
Positive	83 (50.9)
pLLNM
Negative	136 (83.4)
Positive	27 (16.6)
Pathological stage
II	70 (42.9)
III	93 (57.1)
Pathological CRM
Negative	149 (91.4)
Positive	14 (8.6)
Postoperative chemotherapy
Yes	73 (44.8)
No	90 (55.2)

Factor	pLLNM		Univariate analysis	Multivariate analysis
Factor	Negative (n=136)	Positive (n=27)	P-value	OR (95% CI)	P-value
Sex			0.816
Female	37	8
Male	99	19
Age (yr)			0.531
<65	60	10
≥65	76	17
Tumor distance from AV (mm)			0.184
>50	51	6
≤50	85	21
Preoperative serum CEA (ng/mL)			0.294
<5	67	10
≥5	69	17
Preoperative serum CA19–9 (U/mL)			0.084		0.257
<37	124	21		1 (Reference)
≥37	12	6		2.618 (0.495–13.889)
Clinical T category			0.294
T2	2	1
T3	114	20
T4	20	6
cMLNM			0.036		0.643
Negative	71	8		1 (Reference)
Positive	65	19		1.371 (0.361–5.208)
cLLNM			<0.001		<0.001
Negative	125	5		1 (Reference)
Positive	11	22		53.000 (15.100–185.000)
Clinical CRM			0.305
Negative	109	19
Positive	27	8
mrEMVI			0.069		0.242
Negative	100	15		1 (Reference)
Positive	36	12		2.170 (0.593–7.950)
Histological type			0.645
Well/moderately differentiated	129	25
Poorly differentiated, mucinous, signet ring cell	7	2

Factor	No. of patients	RFS (%)	P-value	LRFS (%)	P-value	DRFS (%)	P-value
Sex			0.547		0.638		0.640
Female	45	71.5		91.4		76.5
Male	118	68.7		88.8		75.9
Age (yr)			0.107		0.838		0.095
<65	70	76.4		89.7		82.6
≥65	93	63.9		91.8		70.5
Tumor distance from AV (mm)			<0.001		0.149		<0.001
>50	57	93.2		95.2		93.5
≤50	106	57.1		88.4		67.2
Preoperative serum CEA (ng/mL)			0.024		0.036		0.202
<5	77	80.6		96.5		81.4
≥5	86	60.9		85.8		71.7
Preoperative serum CA19–9 (U/mL)			0.054		0.424		0.141
<37	145	71.0		91.1		77.0
≥37	18	56.7		86.7		66.6
Pathological T category			0.038		0.187		0.009
T1b–3	149	71.6		91.3		78.5
T4	14	43.1		71.8		43.1
pMLNM			0.017		0.332		0.004
Negative	80	79.6		88.4		87.0
Positive	83	61.2		92.4		61.7
pLLNM			<0.001		0.056		<0.001
Negative	136	75.8		92.4		81.1
Positive	27	28.2		80.7		49.0
Pathological CRM			<0.001		0.348		<0.001
Negative	149	72.5		90.0		79.4
Positive	14	30.5		100		32.5
mrEMVI			<0.001		<0.001		<0.001
Negative	115	83.0		95.8		85.3
Positive	48	29.1		75.8		50.8
Histological type			<0.001		0.484		<0.001
Well/moderately differentiated	154	71.9		91.0		78.8
Poorly differentiated, mucinous, signet ring cell	9	33.3		80.0		33.3
Postoperative treatment			0.852		0.973		0.625
No	90	70.2		91.5		75.2
Yes	73	69.2		90.1		77.6

Factor	Recurrence-free survival		Local recurrence-free survival		Distant recurrence-free survival
Factor	HR (95% CI)	P-value	HR (95% CI)	P-value	HR (95% CI)	P-value
Tumor distance from AV (mm)		0.009				0.037
>50	1 (Reference)				1 (Reference)
≤50	4.196 (1.437–12.250)				3.172 (1.071–9.395)
pLLNM		0.047		0.120		0.224
Negative	1 (Reference)		1 (Reference)		1 (Reference)
Positive	2.086 (1.010–4.308)		2.614 (0.779–8.772)		1.626 (0.743–3.562)
mrEMVI		<0.001		0.007		0.012
Negative	1 (Reference)		1 (Reference)		1 (Reference)
Positive	3.838 (1.939–7.600)		5.225 (1.561–17.490)		2.601 (1.230–5.502)
Histological type						0.039
Well/moderately differentiated					1 (Reference)
Poorly differentiated, mucinous, signet ring cell					2.604 (1.048–6.494)

Table 1. Patient demographics and tumor characteristics (n=163)

Values are presented as number (%) or mean±standard deviation.

Table 2. The association between pLLNM and preoperative clinical factors (n=163)

Table 3. The correlation between clinicopathological factors and 3-year prognosis (n=163)

Table 4. Multivariate analyses of the predictive factors for 3-year prognosis

The table includes significant risk factors alone, apart from pLLNM.

HR, hazard ratio; CI, confidence interval; AV, anal verge; pLLNM, pathological lateral lymph node metastasis; mrEMVI, magnetic resonance imaging–detected extramural vascular invasion.