MC is a rare malignancy that has only been increasingly recognized and studied in the last 20 years. To our knowledge, no study has reported on the MC nomogram. Therefore, we constructed a nomogram to predict the prognosis of MC patients. Five variables (age, N stage, M stage, tumor size, and chemotherapy) were identified using a random forest method based on cox regression and incorporated into the nomogram. The validation of the nomogram showed that it had good discriminatory and calibration ability.
Some authors suggested that MSI was necessary to diagnose MC[21, 22]. In addition, MC patients with MSI had a better prognosis than other poorly differentiated adenocarcinomas[4]. Since there was no record of immunohistochemistry for MC patients in the SEER database, which prevented us from further investigating the effect of MSI on OS. Therefore, we did not include MSI in our nomogram. Of all the literature we reviewed on MC, there were few reports on the prognosis of MC patients, and the influence of clinicopathological features other than MSI on MC’s prognosis was unclear. MC is a subtype of colon cancer, and there is minimal report on its prognostic factors. The variables included in the current study were selected based on the predictive factors of colon cancer that had been identified in previous studies.
In our study, MC occurred mainly in patients > 60 years old, which may be related to hMLH1 hypermethylation with an accompanying lack of protein expression[23]. Multivariate COX regression analysis showed that > 60 years was a risk factor for MC prognosis, consistent with previous studies reporting the effect of age on colon cancer prognosis[24]. Previous studies have demonstrated that lymph node metastasis was also an important prognostic factor for patients with colon cancer[24]. Previous studies had demonstrated that lymph node metastasis was also an important prognostic factor for patients with colon cancer[25, 26]. Our findings showed that a more positive number of lymph nodes was associated with a worse prognosis of MC, and survival curves suggested significant survival differences between patients with different numbers of lymph node metastases. According to the 7th edition AJCC criteria, M0 represented no distant organ metastasis, and M1 represented a single distant organ metastasis. The prognosis of patients with M1 was significantly worse than that of patients with M0. The predictive results of the N-stage and M-stage variables in our nomogram were the same as those of the N-stage and M-stage in the TNM staging system. Other studies revealed that tumor size was also an independent prognostic factor for colon cancer and was negatively associated with patient survival[27, 28]. We used the X-Tile software to determine the optimal cut-off values for tumor size (3–37 mm, 38–97 mm, and 98–162 mm, respectively), and the survival curves for the three groups of tumor sizes were significantly different. The results of COX regression analysis showed that the larger the tumor (98–162 mm), the poorer the prognosis of patients, which was consistent with the results of previous studies on the association between tumor size and the prediction of colon cancer.
NCCN guidelines recommend surgery and postoperative adjuvant chemotherapy as the standard treatment principles for non-metastatic colon cancer[29]. However, because MC is a rare disease, most previous studies were about pathomorphological features, and few were about therapeutic methods. Until now, there are no treatment guidelines and consensus on MC. A total of 276 patients treated with surgery were included in this study; only 6 received radiotherapy, and 83 received chemotherapy. The results of our COX regression analysis suggested that chemotherapy was a protective factor for the prognosis of MC patients. We could not find any reports on chemotherapy and the prognosis of patients with MC. However, many reports confirmed that chemotherapy could significantly improve the survival of patients with colon cancer[30, 31]. Similarly, our findings suggested that chemotherapy improves OS in MC patients. Based on the above reports and the results of our analysis, we incorporated age, N stage, M stage, tumor size, and chemotherapy to construct a nomogram for predicting OS in patients with MC.
A nomogram is a tool commonly used to estimate the survival rate of individual cancer patients, and it can calculate the cumulative effect by integrating all prognostic factors. There have been many reports on constructing prognostic nomograms for colon cancer. However, no prognostic nomograms have been developed for patients with MC. The SEER database covers approximately 30% of the U.S. population and can provide sufficient patient data for rare tumors. In this study, we created prognostic nomograms of MC from the SEER database to predict the incidence of 1-year, 3-year, and 5-year OS. Internal validation showed good efficacy of the nomogram, and DCA showed that our nomogram had more significant advantages than the TNM staging system.
There are several limitations to our study. First, as a retrospective study, selection bias is inevitable. Second, immunohistochemical information (e.g., MSI) is unavailable in the SEER database, and MSI is generally associated with prognosis in patients with MC. Finally, because MC is a rare disease, it was tough for us to collect enough clinical data for external validation. The nomogram we developed still requires further verification and improvement in future clinical practice to make it more convincing.