Population-based analysis on predictors for lymph node metastasis in T1 colon cancer

With great advances in endoscopic techniques, endoscopic resection is advantageous for low-risk submucosal colon cancer, which dramatically decreases postoperative morbidities, increases quality of life, and gives rise to relatively good long-term clinical outcomes comparable to those of radical surgical resection. However, the indications of endoscopic resection in T1 colon cancer should be cautiously managed. In a retrospective study including 428 patients with T1 colorectal cancer [17], the authors indicated that the conventional indications for endoscopic treatment should not be expanded, mainly owing to the risk of LNM. Therefore, accurate identification of the predictors for LNM risk is crucial to distinguishing patients with low risk of LNM who can thus be treated using endoscopic resection, with oncological outcomes comparable to those of radical resection.

In this population-based study, we investigated the predictors for LNM in T1 colon cancer. Mucinous carcinoma, tumor grade, age, and primary tumor location were significant predictors for LNM. Mucinous carcinoma is a relatively rare pathological type of colorectal cancer, accounting for approximately 10–15% of all colorectal cancer cases [18]. As a distinct subtype, mucinous carcinoma has been reported to be associated with higher risks of lymph node involvement in stage I and II colorectal cancer [19, 20]. Our population-based analysis consistently revealed that patients with mucinous carcinoma of the colon had a higher risk of LNM. Not surprisingly, tumor grade was significantly predictive for lymph node involvement. Of note, poorly differentiated carcinoma increased LNM risk by more than 5 times, in comparison with well-differentiated carcinoma, in all three logistic regression models. Consistent with previous findings in T1 rectal cancer [21], in the present study, we identified older age as a significant negative predictor for LNM. Compared with patients age up to 49 years, the risk of LNM in patients age 65–79 years and more than 80 years dropped to approximately 0.65 and 0.44, respectively (both P < 0.001). It has been reported that lymph node yield declines with age in patients with colorectal cancer, with mean lymph node yield reduced by 1 for every 7-year increase in age overall [22].

Primary tumor location has long been reported to have an impact on the risk of LNM in colorectal cancer [4, 23]. The LNM risk in T1 rectal carcinoma has been revealed to be as high as 15% [4, 5, 24], dropping to 8% in the left colon and 3% in the right colon [4]. Here, we report similar observations, which suggests that carcinoma of the ascending colon is a significant negative predictor for the risk of LNM, whereas sigmoid colon cancer significantly increases the LNM risk. The differing LNM risks according to different primary tumor locations might be owing to intrinsic genetic differences [4, 25]. Unlike other studies concerning rectal cancer [21], we found that tumor size was not a predictive factor for the risk of LNM in T1 colon cancer. Consistent with our findings, Okabe et al. also demonstrated an insignificant association between tumor size and LNM risk in T1 adenocarcinoma of the colon and rectum [4]. Therefore, it remains controversial whether primary tumor size is a predictive factor for the risk of LNM in T1 colorectal cancer, a question that deserves further investigation.

During the patient selection process, patients without an adequate number of resected lymph nodes were excluded. The cutoff value for the number of sampled lymph nodes was set to 12, according to the general consensus that at least 12 lymph nodes are required for accurate pathological judgement [26]. In this population-based analysis, LNM was detected in 12.0% (967 out of 8056) of patients with T1 colon cancer, which was slightly higher than the proportion in other studies [4, 27]. It is feasible that the lymph node positive rate increases with an increased number of sampled lymph nodes. In this study, only patients with more than 12 resected lymph nodes were enrolled, which might give rise to a slightly higher LNM rate in our study.

In survival analysis, LNM was a significant prognostic factor for CSS but not for OS. Patients with T1 colon cancer generally have good prognosis. In this study, the cancer-specific death rate and noncancer-specific death rate were 3.26% and 14.02%, respectively, for patients without LNM (Table 2). However, these rates were comparable to those in patients with LNM (9.41% for cancer-specific death and 9.31% for noncancer-specific death). The above observations robustly indicate the importance of lymph node status in determining oncological outcome in T1 colon cancer.

Owing to relatively long survival in patients with T1 colon cancer, long-term patient survival is influenced by other noncancer risks. That is to say, a considerable proportion of patients might die from causes other than cancer-related causes [15, 28, 29]. Therefore, to accurately illustrate the prognostic role of lymph node status in T1 colon cancer, we constructed a competing risks model and estimated the CIF. LNM was revealed as a definite risk factor for prognosis in patients with T1 colon cancer.

In the present population-based analysis, our conclusions are based on real-world outcomes. With a median follow-up of 68 months among 8056 eligible participants, we report these convincing findings with a high degree of statistical power. Nevertheless, certain limitations must be acknowledged. The limited availability of data from the SEER database is the main drawback. Factors including submucosal invasion depth, tumor budding, and lymphovascular invasion might also affect the likelihood of LNM, which were not assessed in our study. In terms of primary tumor location, ascending colon and sigmoid colon carcinomas are significant predictors for lymph node involvement; however, we failed to reveal any association of the hepatic flexure, transverse colon, splenic flexure, and descending colon with the risk of LNM. The relatively small sample of these tumor locations might be the cause.

In conclusion, the overall LNM rate is approximately 12.0% for T1 colon cancer. Mucinous carcinoma, tumor grade, age, and primary tumor location are significant predictors for LNM in patients with T1 colon cancer. Moreover, positive lymph node involvement is a significant prognostic factor for CSS. Thus, careful preoperative assessment of lymph node status is essential in clinical decision making, to achieve better long-term outcomes.