Abstract
Background Evaluation of lymph node status is critical in colorectal carcinoma (CRC) treatment. However, as patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The aims of this study were to assess the impact of the ELN on the survival of patients with stage II colorectal cancer and to determine the optimal number. Methods Data from the US Surveillance, Epidemiology, and End Results (SEER) database on stage II resected CRC (1988-2013) were extracted for mathematical modeling as ELN was available since 1988. Relationship between ELN count and stage migration and disease-specific survival was analyzed by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS (Locally Weighted Scatterplot Smoothing) smoother, and the structural break points were determined by the Chow test. An independent cohort of cases from 2014 was retrieved for validation in 5-year disease-specific survival (DSS). Results An increased ELN count was associated with a higher possibility of metastasis LN detection (OR 1.010, CI 1.009-1.011, p < 0.001) and better DSS in LN negative patients (OR 0.976, CI 0.975-0.977, p < 0.001). The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p < 0.001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p < 0.001). The cut-off value of the ELN count in site-specific surgeries was analyzed as 20 nodes in the right hemicolectomy (HR 0.674, CI 0.638-0.713, p < 0.001), 19 nodes in left hemicolectomy (HR 0.691, CI 0.639-0.749, p < 0.001), and 20 nodes in rectal resection patients (HR 0.671, CI 0.604-0.746, p < 0.001), respectively. Conclusions A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least 21 lymph nodes be examined for accurate diagnosis of stage II colorectal cancer.
Highlights
Evaluation of lymph node (LN) status is critical for predicting the prognosis of patients who have undergone radical surgery for colorectal carcinoma (CRC), plays a vital role in precise nodal staging, and affects postoperative adjuvant therapies
Patient Characteristics and Distribution of the Examined Lymph Node Number. 173,355 patients from the SEER cohort with stage II CRC met the criteria and included into the main data analysis
Data for 135,130 patients who suffered from stage III with T3 or T4 was extracted in order to analyze the correlation between examined lymph node (ELN) count and LN positive incidence
Summary
Evaluation of lymph node (LN) status is critical for predicting the prognosis of patients who have undergone radical surgery for colorectal carcinoma (CRC), plays a vital role in precise nodal staging, and affects postoperative adjuvant therapies. Patients with LN involvement (stage III CRC) may be incorrectly classified into stages I or II if the number of ELNs is too small These patients may escape subsequent adjuvant therapy and suffer the worsen prognosis. As patients with node involvement may be incorrectly classified into earlier stages if the examined lymph node (ELN) number is too small and escape adjuvant therapy, especially for stage II CRC. The cut-off point analysis showed a threshold ELN count of 21 nodes (HR 0.692, CI 0.667-0.719, p < 0:001) and was validated with significantly better DSS in the SEER 2009 cohort CRC (OR 0.657, CI 0.522-0.827, p < 0:001). A higher number of ELNs are associated with more-accurate node staging and better prognosis in stage II CRCs. We recommend that at least lymph nodes be examined for accurate diagnosis of stage II colorectal cancer
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