Exploring the prognostic value of positive lymph node ratio in stage Ⅲ colorectal cancer patients and establishing a predictive model

Wen WU; Ruoxin ZHANG; Junyong WENG; Yanlei MA; Guoxiang CAI; Xinxiang LI; Yongzhi YANG

doi:10.19401/j.cnki.1007-3639.2024.09.007

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Exploring the prognostic value of positive lymph node ratio in stage Ⅲ colorectal cancer patients and establishing a predictive model

Article | 更新时间：2025-12-31

- Exploring the prognostic value of positive lymph node ratio in stage Ⅲ colorectal cancer patients and establishing a predictive model
- China Oncology Vol. 34, Issue 9, Pages: 873-880(2024)
- 作者机构：
  
  复旦大学附属肿瘤医院大肠外科，复旦大学上海医学院肿瘤学系，上海 200032
- 作者简介：
  
  YANG Yongzhi
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2024.09.007
  CLC： R735.3+5；R735.3+7
- Received：24 June 2024，
  
  Revised：2024-09-02，
  
  Published：30 September 2024
- 稿件说明：
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Wen WU, Ruoxin ZHANG, Junyong WENG, et al. Exploring the prognostic value of positive lymph node ratio in stage Ⅲ colorectal cancer patients and establishing a predictive model[J]. China Oncology, 2024, 34(9): 873-880.
DOI：

Wen WU, Ruoxin ZHANG, Junyong WENG, et al. Exploring the prognostic value of positive lymph node ratio in stage Ⅲ colorectal cancer patients and establishing a predictive model[J]. China Oncology, 2024, 34(9): 873-880. DOI： 10.19401/j.cnki.1007-3639.2024.09.007.

摘要

背景与目的：

当前，对于中低位局部晚期直肠癌和T4bM0的潜在可切除结肠癌患者，指南均推荐新辅助治疗策略，以提高治疗的缓解率和增加转化性切除的可能性。其中对于ypⅢ期的结直肠癌（colorectal cancer，CRC）患者，均使用国际抗癌联盟（Union for International Cancer Control，UICC）/美国癌症联合会（American Joint Committee on Cancer，AJCC）TNM分期系统评估术后病理学特征。然而，新辅助治疗会导致术区淋巴结退缩，检出淋巴结数不足12枚的患者无法按照常规的TNM分期进行划分，因此TNM分期常无法预测接受过新辅助治疗的ypⅢ期患者的预后。本研究旨在评估阳性淋巴结比率（positive lymph node ratio，LNR）在接受新辅助治疗的ypⅢ期CRC患者中的预后价值。

方法：

回顾性分析2008—2018年在复旦大学附属肿瘤医院接受新辅助治疗且行根治性手术的ypⅢ期CRC患者。收集患者手术时的年龄、性别、原发肿瘤位置、肿瘤分化等级、病理学分期以及随访期间患者是否复发或死亡等临床病理学特征。纳入标准：接受新辅助治疗和手术且术后病理学检查证实为Ⅲ期的CRC患者。排除标准：① 术前影像学检查或术中探查发现已有远处脏器转移；② 有既往恶性肿瘤病史；③ 多原发性CRC。本研究通过复旦大学附属肿瘤医院医学伦理委员会批准（伦理编号：050432-4-2108*）。使用R软件的survminer包（surv_cutpoint算法）计算LNR相对于无病生存期（disease-free survival，DFS）的最佳临界值并依此将患者分为低LNR组和高LNR组，比较两组的临床病理学特征和DFS。采用COX比例风险回归模型筛选不良病理学特征并使用survival包和rms包绘制DFS列线图预测模型。

结果：

共纳入489例患者，男性289例，女性200例，中位年龄为56岁（23~80岁），中位随访时间为1 062 d。随访期间，164例（33.5%）患者死亡。整个队列中，204例（41.7%）患者检出淋巴结数不足12枚。LNR的最佳临界值为0.29，317例患者划为低LNR组（LNR≤0.29），172例患者划为高LNR组（LNR

0.29）。高LNR组相比低LNR组DFS更短[风险比（hazard ratio，HR）=2.103，95% CI：1.582~2.796，

0.000 1

]

。多变量COX回归分析显示，LNR是DFS的独立预后危险因素（HR=1.825，95% CI：1.391~2.394，

0.001）。根据纳入LNR的多分类DFS列线图预测模型可以有效地评估接受新辅助治疗的Ⅲ期CRC患者的DFS。

结论：

LNR是ypⅢ期CRC患者的独立预后因素，与其他不良临床病理学特征联合使用具有良好的DFS预测效力。因此，将LNR作为TNM分期的补充可以提高CRC的预后评估准确率。

Abstract

Background and purpose:

Currently

for patients with mid-to-low locally advanced rectal cancer and potentially resectable T4bM0 colon cancer

guidelines recommend neoadjuvant therapy strategies to enhance the response rate and increase the likelihood of conversion surgery. Among these patients

ypⅢ stage colorectal cancer (CRC) is assessed using the Union for International Cancer Control (UICC)/American Joint Committee on Cancer

(AJCC) TNM staging system for postoperative pathological features. However

neoadjuvant therapy can lead to lymph node regression in the surgical area

resulting in an insufficient number of detected lymph nodes (less than 12)

preventing classification according to conventional TNM staging. Thus

TNM staging often fails to predict the prognosis of ypⅢ patients who have undergone neoadjuvant therapy. This study aimed to evaluate the prognostic value of the positive lymph node ratio (LNR) in ypⅢ stage CRC patients treated with neoadjuvant therapy.

Methods:

Retrospective data was collected from ypⅢ stage CRC patients who received neoadjuvant therapy and underwent radical surgery at Fudan University Shanghai Cancer Center between 2008 and 2018. Collect clinical pathological characteristics such as age

gender

primary tumor location

tumor differentiation grade

pathological staging

and whether the patient has relapsed or died during follow-up at the time of surgery. Inclusion criteria: CRC patients who have received neoadjuvant therapy and surgery and have been confirmed to be stage Ⅲ by postoperative pathological examination. Exclusion criteria: ① Preoperative imaging examination or intraoperative exploration reveals distant organ metastasis; ② History of malignant tumors in the past; ③ Multiple primary CRC. This study was approved by the medical ethics committee of Fudan University Shanghai Cancer Center (ethics number: 050432-4-2108*). The R software survminer package (surv_cutpoint algorithm) was used to calculate the optimal cutoff value for LNR relative to disease-free survival (DFS)

and patients were divided into low and high LNR groups accordingly. Clinical pathological characteristics and DFS were compared between the two groups. COX proportional hazards regression models were employed to identify adverse pathological features

and survival plots along with prediction models for DFS were generated using the survival and rms packages.

Results:

A total of 489 patients were inc

luded

comprising 289 males and 200 females

with a median age of 56 years (23-80 years) and a median follow-up time of 1 062 d. During the follow-up period

164 patients (33.5%) died. In the entire cohort

204 (41.7%) patients had fewer than 12 lymph nodes detected. The optimal cutoff value for LNR was 0.29

classifying 317 patients into the low LNR group (LNR≤0.29) and 172 patients into the high LNR group (LNR

0.29). The high LNR group exhibited shorter DFS compared to the low LNR group [hazard ratio (HR)=2.103

95% CI: 1.582-2.796

0.000 1

]

. Multivariate COX regression indicated that LNR was an independent prognostic factor for DFS (HR=1.825

95% CI: 1.391-2.394

0.001). The inclusion of LNR in a multicategory DFS nomogram prediction model effectively assessed DFS in stage Ⅲ CRC patients who had undergone neoadjuvant therapy.

Conclusion:

LNR is an independent prognostic factor for ypⅢ stage CRC patients

showing good predictive power for DFS when combined with other adverse pathological features. Therefore

incorporating LNR as a supplement to TNM staging can improve the accuracy of CRC prognosis assessment.

关键词

Keywords

references

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