
==== Front
Int J Colorectal Dis
Int J Colorectal Dis
International Journal of Colorectal Disease
0179-1958
1432-1262
Springer Berlin Heidelberg Berlin/Heidelberg

39292276
4717
10.1007/s00384-024-04717-5
Research
Lateral pelvic lymph node positivity (LPLNP) score: predictive clinic-radiological model of lateral pelvic lymph node involvement in rectal cancer patients
Tsarkov Petr 1
Balaban Vladimir balaban@kkmx.ru

1
Babajanyan Harutyun 1
Fingerhut Abe 23
Tulina Inna 1
He Mingze 4
1 https://ror.org/02yqqv993 grid.448878.f 0000 0001 2288 8774 Clinic of Colorectal and Minimally Invasive Surgery, Sechenov University, 1 Building 1 Pogodinskaya St, Moscow, Russia 119435
2 https://ror.org/0220qvk04 grid.16821.3c 0000 0004 0368 8293 Department of General Surgery, Ruijin Hospital Shanghai Jiao Tong University School of Medicine, Shanghai, China
3 grid.11598.34 0000 0000 8988 2476 Division for Surgical Research, Medical University of Graz, Graz, Austria
4 https://ror.org/02yqqv993 grid.448878.f 0000 0001 2288 8774 Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
18 9 2024
18 9 2024
2024
39 1 1455 9 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
Purpose

The population in Western countries differs significantly from that in Eastern countries, and the prevalence of lateral pelvic lymph node (LPLN) involvement in Western populations remains largely unknown due to the limited application of LPLN dissection (LPLND). This discrepancy is primarily attributed to the higher body mass index commonly observed in Western populations, which increases the risk of intraoperative complications. Consequently, the aim of this study is to describe a specific Western clinico-radiological selection tool for LPLND, namely, the lateral pelvic lymph node positivity (LPLNP) score.

Methods

This retrospective single center study was designed to elaborate the LPLNP score, which was further tested on a prospective cohort of patients. Clinical and MRI factors associated with LPLN involvement were identified, and logistic regression was used to establish the LPLNP score.

Results

In the retrospective series, 120 patients underwent lateral pelvic lymph node dissection. After stepwise logistic regression, five parameters were ultimately included in the LPLNP score. When tested on 66 prospectively selected patients, 40 with an LPLNP score > 0.23 (corresponding to the highest sensitivity and specificity) underwent LPLND: 22 patients (55%) had pathologically confirmed positive LPLN. The negative predictive value of the LPLNP score was 96%, with a sensitivity of 95.7% and a specificity of 58.1%.

Conclusion

The LPLNP score was developed based on the largest group of Western patients with locally advanced rectal cancer. This scoring system demonstrated high sensitivity and specificity during validation on the prospective series, correctly identifying LPLN involvement in 55% of cases.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00384-024-04717-5.

Keywords

Lateral pelvic lymph node
Rectal cancer
Lymph node dissection
issue-copyright-statement© Springer-Verlag GmbH Germany, part of Springer Nature 2024
==== Body
pmcIntroduction

Lateral pelvic lymph node (LPLN) involvement has become an increasing concern for multidisciplinary teams treating rectal cancer worldwide. However, little is known about the incidence of pathologically confirmed LPLN metastases and the pertinence of lateral pelvic lymph node dissection (LPLND) in patients with rectal cancer treated in Western medical systems. Of note, Japanese data, collected since the 1970s, suggest that low rectal adenocarcinoma with deep invasion and mesorectal lymph node (MLN) involvement is associated with an increased risk of LPLN involvement [1]. As a result, Japanese guidelines [2] recommend LPLND for T3–T4 tumors located distal to the peritoneal reflection. For many years, LPLND was performed in Japan solely for the clinical indications mentioned above. The prevalence of LPLN involvement with this prophylactic approach has been reported to range from 7 to 42% [1, 3–5]. Since the mid-2000s, when the era of precise preoperative diagnosis began thanks to magnetic resonance imaging (MRI) [6], it has become possible to predict the involvement of LPLNs and perform LPLND only for selected patients with suspected LPLN involvement. The rate of LPLN positivity in the Asian publications ranges from 34 to 65% [7, 8] while the prevalence in Western populations is largely unknown because LPLND is not widely performed.

However, even with the selective approach, this method still has a high morbidity rate, and it needs to be more restrictive to accurately identify the patients who would truly benefit from lymphadenectomy. Reliance only on clinical tumor characteristics or LPLN size on MRI for detecting LPLN invasion can result in high rates of false positives and false negatives, potentially leading to overtreatment or undertreatment of a significant proportion of rectal cancer patients. The cut-off values of short axis diameter of LPLNs on MRI, typically > 5 mm or > 8 mm, are among the most common criteria for assessing LPLN involvement [9, 10]. However, cancer deposits and metastatic cells can be present in patients with LPLNs smaller than 6 mm in short-axis diameter [11].

A recent Japanese nomogram is based on short-axis diameters of LPLNs and MLNs, the presence of extramural venous invasion (EMVI), and tumor distance from the anal verge [12]. However, it remains unclear whether this nomogram can effectively predict LPLN involvement in Western patients. Therefore, there is a pressing need for a more accurate clinico-radiological tool to assess the risk of LPLN involvement before surgery and be able to plan highly selective LPLND.

The objective of this study was to describe the clinical and pathological features of Western type rectal cancer patients who had undergone LPLND and to create a clinico-radiological tool for predicting LPLN involvement in this population.

Method

Study design and patient selection

The first part of this study consisted of a retrospective observational analysis based on prospectively collected data from patients treated at our clinic between 2009 and 2019. The inclusion criteria included age over 18, pathologically confirmed rectal adenocarcinoma, the absence of distant metastases on pre-operative chest and abdominal computed tomography (CT), availability of pre-operative pelvic MRI, and curative rectal resection with LPLND. Patients with synchronous or metachronous tumors or recurrent rectal cancer were excluded. Logistic regression analysis of this retrospective group led to the development of the lateral pelvic lymph node positivity (LPLNP) score.

The second part involved a prospective evaluation of the LPLNP score between 2020 and 2022. The LPLNP score was prospectively tested on 66 patients. The selection criteria for participants included age over 18, pathologically confirmed lower and middle rectal adenocarcinoma staged II–III, located less than 12 cm from the anal verge, availability of preoperative pelvic MRI, and patients scheduled for curative rectal resection. The study adhered to the TRIPOD reporting recommendations.

Preoperative workup

Our institutional policy demands that all the patients diagnosed with rectal cancer undergo chest, abdominal and pelvic CT, and pelvic MRI for tumor stage assessment. The following parameters were evaluated on initial pelvic MRI scans: depth of primary tumor invasion (mrT stage), extramural vascular invasion (mrEMVI), mesorectal fascia involvement (MRF+), mucinous appearance of the tumor, and number and location of suspicious mesorectal and lateral lymph nodes (MLNs and LPLNs). We classified mesorectal lymph nodes (mrMLN+) and lateral lymph nodes (mrLPLN+) as suspicious if, based on MRI, they exhibited a short-axis diameter greater than 6 mm and/or characteristics such as irregular borders, heterogeneous signal intensity, and a round shape. The mrN stage was assessed considering only the number of suspicious lymph nodes, regardless of their location (MLN or LPLN). MRF involvement on MRI, stated as mrMRF+ , was defined as primary tumor being within 1 mm from mesorectal fascia, metastatic lymph node, or tumor deposit.

Multidisciplinary team recommendations included preoperative long-course chemoradiotherapy for patients with mrMRF+ , less than 2 cm from the lower edge of the tumor to the dentate line, multiple suspicious mesorectal lymph nodes, and/or mrEMVI+. After completion of preoperative chemoradiotherapy, clinical stage reassessment with CT and MRI was performed at 6–8 weeks, and surgery was planned at 10–12 weeks post-treatment.

Operative details

Either open, laparoscopic, or robotic procedures were performed. For patients with the lower edge of the tumor located between 7 and 12 cm from the dentate line, anterior resection with partial mesorectal excision and colorectal anastomosis was conducted. Tumors below 7 cm from the anal verge were treated with total mesorectal excision, which could involve sphincter-preserving low anterior resection, intersphincteric resection, or extralevator abdomino-perineal excision. Pelvic exenteration was performed when necessary.

Each procedure started with the removal of lymphatic tissue around the root and trunk of the inferior mesenteric artery down to the origin of the left colic artery with careful preservation of left and right splanchnic nerves [13].

Indications and technique of LPLND

In the initial retrospective phase of the study, the indications for selective LPLND were based exclusively on the presence of suspicious lateral pelvic lymph nodes (mrLPLN+) identified on pretreatment pelvic MRI, conducted prior to chemoradiotherapy (if indicated). However, several patients without suspicious LPLNs on pelvic MRI still underwent prophylactic LPLND. The primary indication for this was a positive circumferential resection margin (CRM) at the level of the pelvic plexus, identified either on MRI or intraoperatively, which could facilitate direct cancer spread to the lateral pelvic fossae via lymphatic vessels. All patients underwent bilateral pelvic lymph node dissection, even when suspicious LPLNs or CRM involvement were detected on only one side.

In the second, prospective part of the study, the LPLNP score, and the LPLN short-axis diameter on pre-treatment MRI were used to select patients for selective LPLND.

The LPLND included the removal of obturator, internal iliac lymph nodes, and the medial semicircumference of external iliac lymph nodes. The proximal LPLND margin was the bifurcation of the common iliac artery; the lateral margin was the obturator internus muscle and medial circumference of external iliac vessels; the medial margin was the pelvic plexus and the hypogastric nerve; the distal margin was Alcock’s canal; and the posterior margin of LLND was the sciatic nerve [14].

Statistical analysis

Quantitative variables were checked for normality using the Shapiro-Wilk test and presented as means with standard deviations or medians with ranges, as appropriate. Quantitative variables were compared using the t-test for normally distributed data or the Mann-Whitney U test for non-parametric distributions. Categorical and ordinal variables were presented as raw numbers and percentages and compared using either the chi-square test or Fisher’s exact test (if any of the expected frequencies were less than 5).

A logistic regression with stepwise factor inclusion was used to identify risk factors for LPLN involvement. For the LPLN involvement prediction model, factors were stratified into several groups and then nominally designated with numbers (nominal scale). Each factor’s stratification was based on the optimal specificity and sensitivity of the model in general. The optimal value of the cut-off logistic regression equation was determined during ROC analysis. The statistical analysis was conducted using SPSS (Version 26, USA).

Ethical considerations

The study was approved by the Local Ethics Committee of Sechenov University (04–20) based on ethical principles of the 1975 Helsinki Declaration.

Results

Among 1091 male and female patients who underwent curative rectal resection for primary adenocarcinoma without distant metastases, 120 had LPLND (Fig. 1, observational study flow diagram). Baseline patient characteristics can be found in Table 1. On pre-treatment MRI, 32 patients (26.7%) either had no visible LPLNs (25 patients) or small (short axis < 6 mm) LPLNs (7 patients).Fig. 1 Observational study flow diagram. TME, total mesorectal excision; LLND, lateral lymph nodes dissection; LPLND, lateral pelvic lymph node dissection; LN, lymph node; MRI, magnetic resonance imaging

Table 1 Clinico-pathological characteristics of patients who underwent LPLND

Parameter	N = 120	
Age, years, (mean ± SD)	55.6 ± 12.3	
Male gender, n (%)	62 (51.2)	
Body mass index (BMI), kg/m2, median (range)	26 (21–40)	
mrT stage, n (%)		
  mrT2

  mrT3

  mrT4

	10 (8.3)

47 (39.2)

63 (52.5)

	
mrN stage, n (%)		
  mrN0

  mrN1

  mrN2

	7 (5.8)

58 (48.3)

55 (45.9)

	
LPLN short axis diameter on preoperative MRI, n (%)		
  no visible LPLN

  0.1–6.0 mm

  6.1–10.0 mm

  10.1–20.0 mm

  > 20.0 mm

	25 (20.8)

7 (5.8)

35 (29.2)

41 (34.2)

12 (10.0)

	
mrLPLN status, n (%)		
  Suspicious (+)

  Negative (−)

	89 (74.2)

31 (25.8)

	
mrEMVI, n (%)		
  Positive (+)

  Negative

	55 (45.8)

65 (54.2)

	
Pretreatment clinical TNM stage, n (%)		
  II

  III

	7 (5.8)

113 (94.2)

	
Tumor differentiation, n (%)		
  G1 well differentiated

  G2 moderately differentiated

  G3 poorly differentiated

  Mucinous

  Signet cell

	30 (25.0)

46 (38.3)

10 (8.3)

31 (25.8)

3 (2.6)

	
Resection margins, n (%)		
  R0

  R1

  R2

	103 (85.8)

15 (12.4)

2 (1.6)

	
pT-stage, n (%)		
  T0

  T1

  T2

  T3

  T4

	2 (1.6)

0 (0)

26 (21.6)

57 (47.5)

35 (29.3)

	
pN-stage, n (%)		
  N0

  N1

  N2

	40 (33.3)

33 (27.5)

37 (39.2)

	
pLPLN-status, n (%)		
  Positive

  Negative

	35 (29.2)

85 (70.8)

	
pEMVI-status, n (%)		
  Positive

  Negative

	57 (47.5)

63 (52.5)

	
Pathologic TNM stage, n (%)		
  0

  I

  II

  III

  IV

	1 (0.8)

16 (13.4)

15 (12.5)

85 (70.8)

3 (2.5)

	

According to the indications mentioned above, the selective LPLND was performed in 91 (76.8%) patients. Among them, 88 patients had lymph nodes with a short-axis diameter greater than 6 mm, while 3 patients had lymph nodes with a short-axis diameter less than 6 mm but exhibited other suspicious features. According to the indications for prophylactic LPLND, it was performed in 29 (24.2%) patients who either had no visible LPLNs (25 patients) or LPLNs with a short-axis diameter of less than 6 mm (4 patients) on the pretreatment MRI. Metastatic LPLNs were identified in 35 patients, resulting in a 29.2% overall prevalence of LPLN involvement. Of note, metastases in LPLNs or extra-lymph node tumor deposits in the removed obturator fossa fatty tissue were detected on pathology in four out of 25 patients (16%) who did not have any visible LPLNs on MRI and thus were considered for prophylactic LPLND. Of the seven patients (three in the selective group and four in the prophylactic group) with small LPLNs on pretreatment MRI (short-axis diameter < 6 mm), one patient from the prophylactic group (14.3%) was found to have positive LPLNs.

Metastatic LPLNs were most often found in patients who had synchronous metastatic MLNs (30/35, 86%). Finally, five patients were diagnosed with skip metastases to LPLN, having no metastatic MLNs. One patient had apical inferior mesenteric artery metastasis without any LPLN involvement.

Five out of 25 patients (20%) with pT2 tumors, 17 out of 54 (31%) patients with pT3 tumors and 13 out of 35 (37%) patients with pT4 tumors had metastatic LPLNs.

Neoadjuvant chemoradiotherapy was administered in 32 (26.7%) patients. Two patients had a pathological complete response (pCR) (6%). One of them, who was diagnosed with mrT3 cancer before chemoradiotherapy, had pathologically proven LPLN metastases, which was removed during LPLND.

Most of the tumors were moderately differentiated, while three patients had colloid tumors (two with LPLN metastases), and 31 had mucinous carcinomas, among whom 15 (48%) had LPLN metastases. Although preoperative pelvic MRI demonstrated high sensitivity in determining the status of MLNs and LPLNs, its specificity was low. The value of pelvic MRI in defining T-stage and EMVI status was much higher (Table 2).Table 2 Sensitivity and specificity of preoperative MRI variable

	Sensitivity (95% CI)	Specificity (95% CI)	
EMVI status	64.9% (51.1–77.0)	73.0% (60.4–83.4)	
T-stage	95.8% (88.3–99.1)	59.0% (49.5–67.0)	
MLN status	84.0% (73.2–91.45)	11.0% (3.71–24.1)	
LPLN status	88.6% (73.3–96.8)	12.9% (6.6–21.0)	

To develop a statistical prognostic model of LPLN involvement, various clinical pretreatment parameters were analyzed to identify factors associated with LPLN metastases. Each parameter was stepwise included and tested in the statistical prognostic model of LPLN involvement. Gender, age, and mrMLN status were subsequently excluded from the model. Additionally, the mrMRF status, which had a strong multicollinearity with mrT stage, was also excluded. Through step-by-step reduction, the following parameters were ultimately included in the model: tumor distance from the anal verge, mrEMVI status, LPLN short-axis diameter on pretreatment pelvic MRI, mrT stage, and tumor histological differentiation on pretreatment biopsy (Table 3).Table 3 Value of coefficients in the prognostic model of LPLN involvement

Variable	Coefficient	95% CI	p-value	
Lower	Upper		
Distance from the anal verge	 − 1.088	 − 2.353	0.661	0.114	
mrEMVI status	1.490	0.750	2.032	0.002	
LPLN short-axis diameter on MRI	0.422	0.072	1.243	0.035	
mrT stage	0.358	 − 2.113	3.154	0.396	
Tumor differentiation	0.420	0.061	0.122	0.037	
Intercept	 − 3.297	 − 5.241	0.562	0.070	

All of these parameters demonstrated a high ROC area (not shown). Further logistic regression analysis demonstrated that mr-EMVI status, LPLN short-axis diameter on pretreatment pelvic MRI, and histological tumor type were significantly associated with LPLN involvement. Although tumor distance from the anal verge and mrT stage were not statistically significant, they generally enhanced the predictive value of the model. Each factor was further subdivided, and a numeric value was assigned to each variant. The optimal nominal designations of each factor stratification for the prediction model are presented in Table 4.Table 4 Stratification of the risk factors in LPNLP score

	Variable	Nominal designations	
k1	Distance (cm) from the anal verge		
	  0–6	1	
	  6.1–12.0	2	
	  12.1 or more	3	
k2	mrEMVI status		
	  Positive	1	
	  Negative	0	
k3	Size (mm) of LPLN on MRI		
	  None	0	
	  0.1–6	1	
	  6.1–10	2	
	  10.1–20	3	
	  20 or more	4	
k4	mrT-stage		
	  T1	1	
	  T2	2	
	  T3	3	
	  T4	4	
k5	Tumor differentiation before surgery	
	  G1	0	
	  G2	1	
	  G3	2	
	  Mucinous	3	
	  Signet cell	4	

Logistic regression analysis demonstrated that mr-EMVI status, LPLN short-axis diameter on pretreatment pelvic MRI, and histological tumor type were statistically significantly associated with LPLN involvement. The AUC was 0.81 (95% CI 0.73–0.89) (Fig. 2). The cut-off value of 0.23 corresponded to the highest sensitivity and specificity at 82.9% (95% CI 75.43–89.24) and 69.4% (95% CI 60.12–77.32), respectively.Fig. 2 Receiver operating characteristic curves of LPLNP score

In the second phase of the study (2020–2022), of the 66 prospectively tested patients, 40 with a LPLNP score ≥ 0.23 were considered at high risk for LPLN metastases and were recommended for LPLND. Patients with a LPLNP score < 0.23 were considered at low risk for LPLN metastases and could be advised to forgo LPLND. However, as the published indication for LPLND is a LPLN short-axis diameter ≥ 7 mm [20], patients with a LPLNP score < 0.23 but enlarged LPLNs (≥ 7 mm) were still advised to undergo LPLND for ethical reasons. Consequently, the efficacy of two prediction models, LPLNP score and LPLN short-axis diameter on MRI, was analyzed (Table 5). Our LPLNP score outperformed the three traditional cut-off values: the sensitivity (95.7%) and specificity (58.1%) of our LPLNP score were higher compared with predicting LPLN metastases based solely on the short-axis diameter of LPLN on MRI. Of note, the overall accuracy of the model was high (72.2%), and its ability to predict the absence of LPLN metastases (negative predicative value, NPV) was 96.1%, and the estimation of LPLN involvement (positive predictive value, PPV) was 55.0%.Table 5 Comparison of LPLNP score and short-axis of LPLN on MRI as prediction models of LPLN metastases

Statistic	LPLNP score	MRI ≥ 5 mm	MRI ≥ 6 mm	MRI ≥ 7 mm	
Sensitivity

(95% CI)

	95.7%

(78.1–99.9)

	84.2%

(60.4–96.6)

	73.7%

(48.8–90.9)

	68.4%

(43.5–87.4)

	
Specificity

(95% CI)

	58.1%

(42.1–73.0)

	9.7%

(2.0–25.8)

	25.8%

(11.9–44.6)

	35.5%

(19.2–54.6)

	
Positive predictive value (95% CI)	55.0%

(46.0–63.7)

	36.4%

(22.4–52.2)

	37.8%

(22.5–55.2)

	39.4%

(22.9–57.9)

	
Negative predictive value (95% CI)	96.1%

(78.3–99.4)

	50%

(11.8–88.2)

	61.5%

(31.6–86.1)

	64.7%

(38.3–85.8)

	
Accuracy

(95% CI)

	72.2%

(58.8–81.7)

	38.0%

(24.7–52.8)

	44.0%

(30.0–58.8)

	48.0%

(33.6–62.6)

	

Discussion

In presented Western population of 120 patients undergoing LPLND, the LPLNP score, based on five preoperative parameters (short-axis diameter of LLNs, mr-EMVI status, mr-T stage, histological structure, and tumor distance from the anal verge), can serve as an indication for selective LPLND with an accuracy of 72.2% (95% CI 58.8–81.7), a sensitivity of 95.7% (95% CI 78.1–99.9), and a specificity of 58.1% (95% CI 42.1–73.0) when planning surgery for low rectal cancer. Its 96.1% NPV can be used to better target those patients who might not benefit from LPLND, while its 55% PPV can more accurately detect LPLN involvement, achieving the highest value reported in recent publications [11, 12]. Our 29.2% incidence of LPLN involvement falls well within the reported range of 7–42% following prophylactic LPLND [1, 3–5], although it is lower than the overall 34%-65% incidence reported in Eastern series that include both prophylactic and selective LPLND [7, 8].

Removal of MLN as described by the total mesorectal excision (TME) principle [15, 16], as well as lymph nodes along the inferior mesenteric artery, is an integral part of radical lymph node dissection for rectal cancer. However, LPLN spread is frequent in low and ultra-low rectal cancer [1, 3–5] leading to the principle of prophylactic or selective LPLND. Despite the extensive research dedicated to LPLND in the Eastern world, LPLND is still not routinely included in western treatment protocols because of its technical difficulty, uncertain indications, and relatively high morbidity [17], which has led some to consider chemoradiotherapy as a substitute [18].

Identification of lymph node metastasis by size alone, whether by CT, MRI, or nuclear medicine imaging, is misleading because none of these modalities can detect small or micro-metastases. Moreover, enlarged lymph nodes do not necessarily harbor metastases. We conclude that visible and MRI-detected enlargement of LPLNs should not be considered the only reliable indication for performing LPLND.

The short axis diameter of LPLNs is the most universally used parameter as an indication for LPLND. Published cut-offs have been > 8 mm, > 7 mm or > 5 mm [9, 20, 21]. The Japanese nomogram [12] cited the LPLN short-axis diameter of 5 mm. Selecting a threshold obviously creates a tradeoff between sensitivity and specificity: a low size threshold is associated with high sensitivity but poor specificity, while a high size threshold increases the specificity at the expense of diminished sensitivity. Low sensitivity may lead to worse long-term outcomes and low specificity to worse functional results. In our series, among the patients without any visible LPLNs on MRI who underwent prophylactic LPLND, 16% had pathologically proven extra-lymph node tumor deposits. In addition, 14.3% of patients with lymph nodes having a short-axis diameter of less than 6 mm on the pretreatment MRI were identified as having metastatic lymph nodes. This highlights the results of two Japanese studies [1, 3] where the prevalence of LPLN metastases in patients without initially enlarged LPLNs ranged from 7 to 15%. Of note, as LPLND was not performed routinely in these studies, the true prevalence might even be higher. The prospective part of our study also suggested that the LPLNP score possesses higher accuracy in predicting the presence and absence of LPLN metastases than MRI-detected enlargement of LPLN alone.

In the development of LPLNP score, mrEMVI status was one of the most important predictors of LPLN involvement. Previously, EMVI had been suggested as a strong negative prognostic factor for survival and remote metastases [22] as well as a predictive factor of LPLN metastases [9, 12].

The depth of primary tumor invasion can be assessed on MRI with high sensitivity and specificity [22]. In most prediction models, T3 stage or higher strongly affected the risk of LPLN involvement [23–25]. In our study, mrT stage did not influence the result as much as other risk factors, but together with other parameters improved the overall sensitivity and specificity of the LPLNP score.

Tumor histological structure was one of the first risk factors for LPLN involvement described in the literature [5]. Poorly differentiated tumors do not only have a higher risk of LPLN metastases, but also are associated with lower survival [9]. In LPNLP-score, colloid and mucinous carcinomas had the greatest risk of LPLN involvement.

With respect to tumor height, current JSCCR recommendations [2] suggest that LPLND should be performed in all rectal cancer patients with tumors below the pelvic peritoneal fold. Indeed, the lower the tumor, the greater the risk of LPLN involvement [5]. In our study, specificity and sensitivity with two cut-off levels of 6 cm and 12 cm from the lower tumor border to the anal verge were higher as compared with the Japanese nomogram [12] with 6 cm as the maximum distance from the anal verge, but the proportion of patients where MRI was evaluated after neoadjuvant chemo(radio)therapy in the Japanese study was unknown.

Involvement of regional (mesorectal) lymph nodes is considered to be a predictor of LPLN involvement in many studies [5, 9, 23]. Several groups have proposed that suspicious MLN on MRI can be considered as a predictor of LPLN metastases [12, 25]. However, in our study, this variable was not included in our analysis because of its low MRI specificity to detect MLN metastases. Another reason for non-inclusion of this factor in the prediction model was the high rate (25%) of skip metastases [26].

Compared with the Japanese methodology, where a combination of the short axis of LPN, tumor location, EMVI, and short axis of PRLN was most effective in predicting potential LPN metastasis (backward stepwise multivariable logistic regression), the AUC of their nomogram was 0.74, the positive predictive value was 25.4%, and the negative predictive value was 93.4%. Our corresponding numbers were 0.81, 96%, and 96.1%, respectively. Possible reasons might be that the MRI values used in the Japanese study were the means of the interpretation of six radiologists who did not always use the MERCURY criteria, whereas in our study, all interpretations were in accordance with the MERCURY criteria [6].

Reliance on a score such as ours might be preferable to node picking techniques that result in high lateral local recurrence rates as high as 20% [27].

All the necessary clinic-radiological data can be easily obtained during routine diagnostic procedures without the need for additional checkups. Furthermore, the scoring system has been updated on the website of the Russian Society of Colorectal Surgeons (RSCS) for internal use (https://siterscs.com/en/calc).

There are several limitations to our study. Firstly, it is based on a single-center retrospective series, which increases the likelihood of systemic error and limits the generalizability of the findings. Secondly, the impact of risk factors on LPLN involvement may vary with a larger number of patients studied. Thirdly, long-term results are necessary to evaluate the local recurrence rate after using the score. Fourth, definitions used for inclusion into the score may vary from one institution to another [27]. Lastly, only 26.7% of the patients received neoadjuvant chemoradiation, which may limit the applicability of LPLNP score in irradiated patients.

Conclusions

Our LPLNP score showed high predictive values in detecting and excluding potential LPLN metastases in patients with rectal cancer, enabling further refinement of an individualized approach by narrowing down the group of patients who may most benefit from LPLND. In the future, radiomics, combining MRI and clinical characteristics, may increase the predictive values and enhance the detection of high-risk patients [28].

Supplementary Information

Below is the link to the electronic supplementary material.Supplementary file1 (DOCX 29 KB)

Author contributions

All authors listed have significantly contributed to the development and the writing of this article. Material preparation, data collection and analysis were performed by P.T., V.B., H.B. and A.F.. The first draft of the manuscript was written by I.T.and all authors commented on previous versions of the manuscript. The manuscript was reviewed and edited by M. H.. All authors read and approved the final manuscript.

Data availability

The data presented in this study are available on request from the corresponding author.

Declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The approval was granted by the Local Ethics Committee of Sechenov University with the reference number 04-20.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Competing interests

The authors declare no competing interests.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
==== Refs
References

1. Sugihara K Kobayashi H Kato T Mori T Mochizuki H Kameoka S Indication and benefit of pelvic sidewall dissection for rectal cancer Dis Colon Rectum 2006 49 11 1663 1672 10.1007/s10350-006-0714-z 17041749
Sugihara K, Kobayashi H, Kato T, Mori T, Mochizuki H, Kameoka S et al (2006) Indication and benefit of pelvic sidewall dissection for rectal cancer. Dis Colon Rectum 49(11):1663–1672. 10.1007/s10350-006-0714-z17041749
2. Hashiguchi Y Muro K Saito Y Ito Y Ajioka Y Hamaguchi T Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer Int J Clin Oncol 2020 25 3 1 42 10.1007/s10147-019-01485-z 31203527
Hashiguchi Y, Muro K, Saito Y, Ito Y, Ajioka Y, Hamaguchi T et al (2020) Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2019 for the treatment of colorectal cancer. Int J Clin Oncol 25(3):1–42. 10.1007/s10147-019-01485-z31203527
3. Fujita S Akasu T Mizusawa J Saito N Kinugasa Y Kanemitsu Y Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer(JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial Lancet Oncol 2012 13 6 616 621 10.1016/S1470-2045(12)70158-4 22591948
Fujita S, Akasu T, Mizusawa J, Saito N, Kinugasa Y, Kanemitsu Y et al (2012) Postoperative morbidity and mortality after mesorectal excision with and without lateral lymph node dissection for clinical stage II or stage III lower rectal cancer(JCOG0212): results from a multicentre, randomised controlled, non-inferiority trial. Lancet Oncol 13(6):616–621. 10.1016/S1470-2045(12)70158-422591948
4. Takahashi T Ueno M Azekura K Ohta H Lateral node dissection and total mesorectal excision for rectal cancer Dis Colon Rectum 2000 43 10 Suppl S59 68 10.1007/BF02237228 11052480
Takahashi T, Ueno M, Azekura K, Ohta H (2000) Lateral node dissection and total mesorectal excision for rectal cancer. Dis Colon Rectum 43(10 Suppl):S59-68. 10.1007/BF0223722811052480
5. Ueno M Oya M Azekura K Yamaguchi T Muto T Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer Br J Surg 2005 92 6 756 763 10.1002/bjs.4975 15838895
Ueno M, Oya M, Azekura K, Yamaguchi T, Muto T (2005) Incidence and prognostic significance of lateral lymph node metastasis in patients with advanced low rectal cancer. Br J Surg 92(6):756–763. 10.1002/bjs.497515838895
6. Taylor FG Quirke P Heald RJ Moran BJ Blomqvist L Swift IR Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study J Clin Oncol 2014 32 34 43 10.1200/JCO.2012.45.3258 24276776
Taylor FG, Quirke P, Heald RJ, Moran BJ, Blomqvist L, Swift IR et al (2014) Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study. J Clin Oncol 32:34–4324276776
7. Kim MC Oh JH Lateral pelvic lymph node dissection after neoadjuvant chemoradiotherapy in patients with rectal cancer: a single-center experience and literature review Ann Coloproctol 2021 37 6 382 394 10.3393/ac.2021.00913.0130 34961302
Kim MC, Oh JH (2021) Lateral pelvic lymph node dissection after neoadjuvant chemoradiotherapy in patients with rectal cancer: a single-center experience and literature review. Ann Coloproctol 37(6):382–394. 10.3393/ac.2021.00913.0130. (Epub 2021 Dec 22)34961302
8. Akiyoshi T Ueno M Matsueda K Konishi T Fujimoto Y Nagayama S Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on pretreatment imaging Ann Surg Oncol 2014 21 189 196 10.1245/s10434-013-3216-y 23963871
Akiyoshi T, Ueno M, Matsueda K, Konishi T, Fujimoto Y, Nagayama S et al (2014) Selective lateral pelvic lymph node dissection in patients with advanced low rectal cancer treated with preoperative chemoradiotherapy based on pretreatment imaging. Ann Surg Oncol 21:189–19623963871
9. Akiyoshi T Matsueda K Hiratsuka M Unno T Nagata J Nagasaki T Indications for lateral pelvic lymph node dissection based on magnetic resonance imaging before and after preoperative chemoradiotherapy in patients with advanced low-rectal cancer Ann Surg Oncol 2015 22 Suppl 3 S614 S620 10.1245/s10434-015-4565-5 25896145
Akiyoshi T, Matsueda K, Hiratsuka M, Unno T, Nagata J, Nagasaki T et al (2015) Indications for lateral pelvic lymph node dissection based on magnetic resonance imaging before and after preoperative chemoradiotherapy in patients with advanced low-rectal cancer. Ann Surg Oncol 22(Suppl 3):S614–S620. 10.1245/s10434-015-4565-525896145
10. Oh HK Kang SB Lee SM Lee SY Ihn MH Kim DW Neoadjuvant chemoradiotherapy affects the indications for lateral pelvic node dissection in mid/low rectal cancer with clinically suspected lateral node involvement: a multicenter retrospective cohort study Ann Surg Oncol 2014 21 7 2280 2287 10.1245/s10434-014-3559-z 24604580
Oh HK, Kang SB, Lee SM, Lee SY, Ihn MH, Kim DW et al (2014) Neoadjuvant chemoradiotherapy affects the indications for lateral pelvic node dissection in mid/low rectal cancer with clinically suspected lateral node involvement: a multicenter retrospective cohort study. Ann Surg Oncol 21(7):2280–2287. 10.1245/s10434-014-3559-z24604580
11. Komori K Fujita S Mizusawa J Kanemitsu Y Ito M Shiomi A Predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis (clinical stage II/III): The analysis of data from the clinical trial (JCOG0212) Eur J Surg Oncol 2019 45 3 336 340 10.1016/J.EJSO.2018.11.016 30477950
Komori K, Fujita S, Mizusawa J, Kanemitsu Y, Ito M, Shiomi A et al (2019) Predictive factors of pathological lateral pelvic lymph node metastasis in patients without clinical lateral pelvic lymph node metastasis (clinical stage II/III): The analysis of data from the clinical trial (JCOG0212). Eur J Surg Oncol 45(3):336–340. 10.1016/J.EJSO.2018.11.01630477950
12. Sumii A Hida K Sakai Y Hoshino N Nishizaki D Akagi T Establishment and validation of a nomogram for predicting potential lateral pelvic lymph node metastasis in low rectal cancer Int J Clin Oncol 2022 27 7 1173 1179 10.1007/S10147-022-02157-1 35415787
Sumii A, Hida K, Sakai Y, Hoshino N, Nishizaki D, Akagi T et al (2022) Establishment and validation of a nomogram for predicting potential lateral pelvic lymph node metastasis in low rectal cancer. Int J Clin Oncol 27(7):1173–1179. 10.1007/S10147-022-02157-135415787
13. Hompes R Efetov SK Tulina IA Kitsenko YE Pokshubina AA Kochneva KA Transanal total mesorectal excision with D3 para-aortic lymph node dissection for low rectal cancer - a video vignette Colorectal Dis 2020 22 2 230 231 10.1111/codi.14878 31621159
Hompes R, Efetov SK, Tulina IA, Kitsenko YE, Pokshubina AA, Kochneva KA et al (2020) Transanal total mesorectal excision with D3 para-aortic lymph node dissection for low rectal cancer - a video vignette. Colorectal Dis 22(2):230–231. 10.1111/codi.1487831621159
14. Tsarkov P Babajanyan H Shershneva A Barskaya K Kitsenko Y Efetov S Step-by- step robotic lateral lymph node dissection for rectal cancer - a video vignette Color Dis 2021 10.1111/codi.15909
Tsarkov P, Babajanyan H, Shershneva A, Barskaya K, Kitsenko Y, Efetov S (2021) Step-by- step robotic lateral lymph node dissection for rectal cancer - a video vignette. Color Dis. 10.1111/codi.15909
15. Wibe A Rendedal PR Svensson E Norstein J Eide TJ Myrvold HE Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer Br J Surg 2002 89 327 334 10.1046/j.0007-1323.2001.02024.x 11872058
Wibe A, Rendedal PR, Svensson E, Norstein J, Eide TJ, Myrvold HE et al (2002) Prognostic significance of the circumferential resection margin following total mesorectal excision for rectal cancer. Br J Surg 89:327–33411872058
16. Heald RJ Ryall RD Recurrence and survival after total mesorectal excision for rectal cancer Lancet 1986 1 1479 1482 10.1016/S0140-6736(86)91510-2 2425199
Heald RJ, Ryall RD (1986) Recurrence and survival after total mesorectal excision for rectal cancer. Lancet 1:1479–14822425199
17. Georgiou P Tan E Gouvas N Antoniou A Brown G Nicholls RJ Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis Lancet Oncol 2009 10 11 1053 1062 10.1016/S1470-2045(09)70224-4 19767239
Georgiou P, Tan E, Gouvas N, Antoniou A, Brown G, Nicholls RJ et al (2009) Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis. Lancet Oncol 10(11):1053–106219767239
18. Malakorn S Yang Y Bednarski BK Kaur H You YN Holliday EB Who should get lateral pelvic lymph node dissection after neoadjuvant chemoradiation? Dis Colon Rectum 2019 62 10 1158 1166 10.1097/DCR.0000000000001465 31490825
Malakorn S, Yang Y, Bednarski BK, Kaur H, You YN, Holliday EB et al (2019) Who should get lateral pelvic lymph node dissection after neoadjuvant chemoradiation? Dis Colon Rectum 62(10):1158–1166. 10.1097/DCR.000000000000146531490825
19. Hoshino N Murakami K Hida K Sakamoto T Sakai Y Diagnostic accuracy of magnetic resonance imaging and computed tomography for lateral lymph node metastasis in rectal cancer: a systematic review and meta-analysis Int J Clin Oncol 2019 24 1 46 52 10.1007/s10147-018-1349-5 30259217
Hoshino N, Murakami K, Hida K, Sakamoto T, Sakai Y (2019) Diagnostic accuracy of magnetic resonance imaging and computed tomography for lateral lymph node metastasis in rectal cancer: a systematic review and meta-analysis. Int J Clin Oncol 24(1):46–52. 10.1007/s10147-018-1349-530259217
20. Kasai S Shiomi A Kagawa H Hino H Manabe S Yamaoka Y The effectiveness of machine learning in predicting lateral lymph node metastasis from lower rectal cancer: a single center development and validation study Ann Gastroenterol Surg 2022 6 1 92 100 10.1002/ags3.12504 35106419
Kasai S, Shiomi A, Kagawa H, Hino H, Manabe S, Yamaoka Y et al (2022) The effectiveness of machine learning in predicting lateral lymph node metastasis from lower rectal cancer: a single center development and validation study. Ann Gastroenterol Surg 6(1):92–100. 10.1002/ags3.1250435106419
21. Ogawa S Hida JI Ike H Kinugasa T Ota M Shinto E Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using magnetic resonance imaging and risk factors for metastasis: Multicenter study of the Lymph Node Committee of the Japanese Society for Cancer of the Colon and Rectum Int J Colorectal Dis 2017 32 10 1479 1487 10.1007/s00384-017-2874-9 28762189
Ogawa S, Hida JI, Ike H, Kinugasa T, Ota M, Shinto E et al (2017) Prediction of lateral pelvic lymph node metastasis from lower rectal cancer using magnetic resonance imaging and risk factors for metastasis: Multicenter study of the Lymph Node Committee of the Japanese Society for Cancer of the Colon and Rectum. Int J Colorectal Dis 32(10):1479–1487. 10.1007/s00384-017-2874-928762189
22. Brown G Radcliffe AG Newcombe RG Dallimore NS Bourne MW Williams GT Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging Br J Surg 2003 90 3 355 364 10.1002/bjs.4034 12594673
Brown G, Radcliffe AG, Newcombe RG, Dallimore NS, Bourne MW, Williams GT (2003) Preoperative assessment of prognostic factors in rectal cancer using high-resolution magnetic resonance imaging. Br J Surg 90(3):355–364. 10.1002/bjs.403412594673
23. Tan KY Yamamoto S Fujita S Akasu T Moriya Y Improving prediction of lateral node spread in low rectal cancers - multivariate analysis of clinicopathological factors in 1,046 cases Langenbeck’s Arch Surg 2010 10.1007/s00423-010-0642-1
Tan KY, Yamamoto S, Fujita S, Akasu T, Moriya Y (2010) Improving prediction of lateral node spread in low rectal cancers - multivariate analysis of clinicopathological factors in 1,046 cases. Langenbeck’s Arch Surg. 10.1007/s00423-010-0642-1
24. Kobayashi H Mochizuki H Kato T Mori T Kameoka S Shirouzu K Outcomes of surgery alone for lower rectal cancer with and without pelvic sidewall dissection Dis Colon Rectum 2009 10.1007/DCR.0b013e3181a1d994 19502860
Kobayashi H, Mochizuki H, Kato T, Mori T, Kameoka S, Shirouzu K et al (2009) Outcomes of surgery alone for lower rectal cancer with and without pelvic sidewall dissection. Dis Colon Rectum. 10.1007/DCR.0b013e3181a1d99419502860
25. Dev K Veerenderkumar KV Krishnamurthy S Incidence and predictive model for lateral pelvic lymph node metastasis in lower rectal cancer Indian J Surg Oncol 2018 10.1007/s13193-017-0719-1 29887692
Dev K, Veerenderkumar KV, Krishnamurthy S (2018) Incidence and predictive model for lateral pelvic lymph node metastasis in lower rectal cancer. Indian J Surg Oncol. 10.1007/s13193-017-0719-129887692
26. Sekido Y Nishimura J Fujino S Ogino T Miyoshi N Takahashi H Predicting lateral pelvic lymph node metastasis based on magnetic resonance imaging before and after neoadjuvant chemotherapy for patients with locally advanced lower rectal cancer Surg Today 2020 10.1007/s00595-019-01886-7 31595366
Sekido Y, Nishimura J, Fujino S, Ogino T, Miyoshi N, Takahashi H et al (2020) Predicting lateral pelvic lymph node metastasis based on magnetic resonance imaging before and after neoadjuvant chemotherapy for patients with locally advanced lower rectal cancer. Surg Today. 10.1007/s00595-019-01886-731595366
27. Sluckin TC Hazen SJA Horsthuis K Beets-Tan RGH Aalbers AGJ Beets GL ASO visual abstract: evaluation of national surgical practice for lateral lymph nodes in rectal cancer in an untrained setting Ann Surg Oncol 2023 30 9 5486 5548 10.1245/s10434-023-13666-2
Sluckin TC, Hazen SJA, Horsthuis K, Beets-Tan RGH, Aalbers AGJ, Beets GL et al (2023) ASO visual abstract: evaluation of national surgical practice for lateral lymph nodes in rectal cancer in an untrained setting. Ann Surg Oncol 30(9):5486–5548
28. Inchingolo R Maino C Cannella R Vernuccio F Cortese F Dezio M Radiomics in colorectal cancer patients World J Gastroenterol 2023 29 19 2888 2904 10.3748/wjg.v29.i19.2888 37274803
Inchingolo R, Maino C, Cannella R, Vernuccio F, Cortese F, Dezio M et al (2023) Radiomics in colorectal cancer patients. World J Gastroenterol 29(19):2888–290437274803
