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Development and Validation of a Simplified Negative and Positive Nodal Score (sNPNS) for Precise Nodal Staging in Colorectal Cancer: An International, Multi-Cohort Study
35 Pages Posted: 11 Jan 2024
More...Abstract
Background: The American Joint Committee on Cancer nodal staging (AJCC N staging) of colorectal cancer (CRC) is only defined by the number of positive lymph node (pLN), and few nodal staging give attention to the prognostic value of negative lymph node (nLN). We aimed to derive a novel nodal score by combining the number of pLN and nLN for precising the staging diagnosis of CRC.
Methods: We derived the Negative and Positive Nodal Score (NPNS) from the SEER database, and externally validated it through a large-scale Chinese retrospective cohort, a Japanese retrospective cohort and a Chinese prospective cohort. Data on stage III CRC patients who under initial surgical resection were recorded by experienced specialists from each center. Contoured multivariable regression Cox models produced overall survival (OS) estimates based on the number of nLN and pLN as continuous variables. Furthermore, we established a simplified NPNS (sNPNS) for clinical application. The predictive performance and discrimination of NPNS and sNPNS was compared with the AJCC N staging.
Findings: We included 70335 stage III CRC patients: 60721 in the SEER cohort, 6673 in the Chinese cohort, 1390 in the Japanese cohort, and 1551 in the Prospective cohort. Increasing number of pLN and decreasing number of nLN were independent risk factors for CRC patients. The NPNS and sNPNS systems consistently achieved improved prognostic prediction capability exceeding the current AJCC N staging in four cohorts. Patients were divided into the positive nodal score (PNS, sNPNS≥ 0) and negative nodal score (NNS, sNPNS< 0), respectively. Patients in the PNS group had significantly worse 5-year OS than those in the NNS group (SEER cohort, 41.9% vs. 62.3%, p<0.05; Chinese cohort, 54.6% vs. 77.3%, p<0.05; Japanese cohort, 51.8% vs. 80.6%, p<0.05; Prospective cohort, 52.7% vs. 77.2%, p<0.05). Furthermore, the re-stratification according to sNPNS was effective in identifying individuals misclassified by the current AJCC N staging.
Interpretation: The sNPNS promisingly elevated the significance of nLN in nodal staging and provides a clinically user-friendly nodal staging to precisely distinguish the stage III CRC patients.
Funding: This paper was supported by the National Key R&D Program for Young Scientists (Grant Number: 2022YFC2505700), Sanming Project of Medicine in Shenzhen (Grant Number: SZSM201911012), National Natural Science Foundation of China (Grant Number: 82100598, 82072750) and Shanghai Sailing Program (Grant Number: 21YF1459300).
Declaration of Interest: All the authors declared that they have no conflicts of interest to this work.
Ethical Approval: The data collection for this study was conducted according to the principles contained in the Declaration of Helsinki. The study protocol and data sharing were evaluated and approved by the review boards of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College and Saitama Medical University International Medical Center.
Keywords: AJCC TNM stage, colorectal cancer, lymph nodes, nodal staging, stage III
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