Colorectal neuroendocrine neoplasms (NENs) are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum. Previous studies have pointed out that the status of lymph node may be used to predict the prognosis.

To investigate the predictive values of lymph node ratio (LNR), positive lymph node (PLN), and log odds of PLNs (LODDS) staging systems on the prognosis of colorectal NENs treated surgically, and compare their predictive values.

This cohort study included 895 patients with colorectal NENs treated surgically from the Surveillance, Epidemiology, and End Results database. The endpoint was mortality of patients with colorectal NENs treated surgically. X-tile software was utilized to identify most suitable thresholds for categorizing the LNR, PLN, and LODDS. Participants were selected in a random manner to form training and testing sets. The prognosis of surgically treating colorectal NENs was examined using multivariate cox analysis to assess the associations of LNR, PLN, and LODDS with the prognosis of colorectal NENs. C-index was used for assessing the predictive effectiveness. We conducted a subgroup analysis to explore the different lymph node staging systems’ predictive values.

After adjusting all confounding factors, PLN, LNR and LODDS staging systems were linked with mortality in patients with colorectal NENs treated surgically (P < 0.05). We found that LODDS staging had a higher prognostic value for patients with colorectal NENs treated surgically than PLN and LNR staging systems. Similar results were obtained in the different G staging subgroup analyses. Furthermore, the area under the receiver operating characteristic curve values for LODDS staging system remained consistently higher than those of PLN or LNR, even at the 1-, 2-, 3-, 4-, 5- and 6-year follow-up periods.

LNR, PLN, and LODDS were found to significantly predict the prognosis of patients with colorectal NENs treated surgically.

Colorectal neuroendocrine neoplasms (NENs) are a rare malignancy that primarily arises from the diffuse distribution of neuroendocrine cells in the colon and rectum[1]. Recently, its prevalence has increased due to the widespread adoption of colonoscopy and the introduction of colorectal cancer screening measures[2]. Typically, colorectal NENs exhibit a poor prognosis when lymph node metastasis occurs, which greatly reduces the survival rates of patients[3].

Previous studies have pointed out that the status of lymph node may be used to predict the prognosis[3,4]. According to the World Health Organization classification, colorectal NENs was subdivided into well-differentiated colorectal neuroendocrine tumors [colorectal NETs; grade (G)1 and G2], and poorly differentiated colorectal neuroendocrine carcinomas (colorectal NECs; G3)[5]. However, when it comes to colorectal NETs and colorectal NECs, lymph node (N) staging protocols were adopted by the American Joint Committee on Cancer (AJCC): The staging system for colorectal NETs was relied on the identification of positive lymph nodes (PLNs), whereas for colorectal NECs it was determined by the quantity of PLNs[6]. The lymph node ratio (LNR) indicating PLNs to the total number of lymph nodes examined, serves as a significant prognostic factor for patients with colorectal cancer[7]. In the study of Zhang et al[8], a higher LNR was found to be significantly associated with a shorter overall survival of colorectal cancer patients. The log odds of PLNs (LODDS), reported as a novel prognostic factor for colonic cancers, exhibited higher predictive accuracy in comparison to LNR stages[9,10]. LODDS is calculated by the following formula: Log [(PLNs + 0.5)/(negative lymph nodes + 0.5)]. A study was conducted by Gao et al[11] utilizing retrospective data to compare the predictive accuracy of LNR, PLN, and LODDS staging systems in forecasting cause-specific survival rates among pancreatic NENs, and their findings revealed that PLN staging system outperformed both LNR and LODDS staging methods. However, to our knowledge, there are few studies to explore the predictive significance of LNR and LODDS staging systems for colorectal NENs.

Thus, we intended to investigate the predictive values of various lymph node staging systems on the prognosis of colorectal NENs treated surgically, and compare their predictive values, which might provide a reference for the improvement of lymph node staging of colorectal NENs.

The prognosis of NENs could be influenced by the presence of lymph node metastasis[3,14]. Different staging systems for lymph nodes have been suggested, and are extensively employed in predicting the prognosis of NENs[15]. In this study, we examined the associations of PLN, LNR, and LODDS with the prognosis of patients with colorectal NENs treated surgically, and compared the predictive values of three staging systems. It was found that PLN, LNR, and LODDS staging systems were correlated with the death risk of colorectal NENs patients. After comparison, we concluded that the LODDS staging system had a higher prognostic value for colorectal NEN patients compared to the other two staging systems.

In this analysis, the mortality rate of patients with colorectal NENs treated surgically was 54.86%. We also found that the mean age of patients was 63.79 years. Regarding treatment options, only a minority of patients with colorectal NENs who underwent surgical intervention (4.92%) opted for radiation therapy[1]. It is widely acknowledged that the staging of PLN solely relies on the quantity of PLN, without taking into account the number of examined lymph nodes[16]. However, patients with an equal number of PLN may exhibit varying prognoses based on their respective counts of examined lymph nodes[17]. The practical application of PLN staging remains controversial. For example, Partelli et al[18] pointed out that the number of PLN could be used to predict the recurrence for pancreatic NENs. Moreover, the number of PLN was considered as an independent prognostic factor in colon NETs[13]. In the study of Huang et al[19], they demonstrated that LNR was a more promising prognostic factor for patients with testicular germ cell tumors than PLN. While considering both the quantity of PLN and the number of examined lymph nodes, LNR staging is taken into account[20]. Although it reduces the likelihood of staging migration caused by an inadequate count of examined lymph nodes, LNR staging does not seem to be applicable to predicting the patient prognosis when there are no PLNs present; and there may be differences in patients’ prognosis when the LNR is the same (e.g., 1/1 vs 10/10)[9,21]. LODDS staging, as a new method to assess the status of lymph nodes, has also been shown to have a better prognostic value than other staging systems[22,23]. The study conducted by Li et al[24] found a significant correlation between the LODDS staging system and postoperative outcomes in patients diagnosed with distal cholangiocarcinoma; the LODDS staging system was demonstrated better performance compared to both PLN staging and LNR staging; and additionally, they also established a prognostic nomogram using the LODDS staging system to predict the overall survival of individuals with distal cholangiocarcinoma[24]. Conversely, PLN staging might offer greater accuracy in predicting the survival of Pancreatic NENs compared to LNR and LODDS staging systems[11]. However, there has been limited researches conducted on evaluating the correlation of LNR and LODDS with the prognosis of colorectal NENs treated surgically. Additionally, there is a lack of comparative analysis regarding the predictive efficacy of these three staging systems on colorectal NENs.

In the present study, we utilized X-tile software for the purpose of categorizing the LNR, PLN, and LODDS. The results of unadjusted and adjusted analyses implied that three staging systems were risk factors for patients with colorectal NENs treated surgically. When the PLN, LNR, and LODDS scores are higher, the prognosis of patients may be worse. These findings might indicate a positive correlation between the three staging systems and patients’ mortality. In addition, we conducted a comparison of the prognostic predictive capabilities among the three scoring systems. The LODDS staging system exhibited a higher C-index compared to the other two staging systems in the testing set, and the consistent findings were observed in the subgroup analyses based on different G stages. The findings also indicated that the LODDS staging system exhibited potential superiority over PLN and LNR staging systems in terms of prognostic prediction for patients with colorectal NEN. Notably, this study observed a little difference in the predicted C-index of LODDS and LNR staging systems. There were 148 patients with PLN of 0 in this study, these patients had a similar prognosis, and all of them belonged to the LODDS tile 1 according to the LODDS staging. This could be the reason for the insignificant advantage of LODDS over LNR. More prospective studies are needed to confirm these findings and gain a deeper understanding of the underlying mechanisms.

This study investigated for the first time the relationship of three lymph node staging systems and the prognosis of colorectal NENs treated surgically; and we assessed and compared their respective prognostic capabilities. However, this study still has some limitations. First, the participants for our research were from the public SEER database that did not record patients’ symptoms[25], surgical margin status[26], and other indicators that might be associated with the prognosis of patients, which may also be confounding factors. Second, we excluded some patients with incomplete clinicopathological characteristic, such as patients with missing information about lymph nodes, PLN, tumor size or staging, which may cause some selection bias. It is critical to further validate these results with more prospective and large-sample studies in the future.

In short, our study revealed a significant association between LNR, PLN, and LODDS staging systems and the mortality risk among the colorectal NENs patients treated surgically. Furthermore, LODDS staging system might be potential to serve as a more effective prognostic indicator for colorectal NENs patients undergoing surgical treatment compared to PLN and LNR staging systems. This could offer valuable insights into the significance of various lymph node staging systems in predicting the prognosis of colorectal NENs patients treated surgically.