According to the inclusion and exclusion criteria, a total of 3026 young RC patients were finally included in the analysis, of which 2120 patients were randomly assigned to the training cohort and the other 906 patients to the validation cohort. There was no significant difference between the training cohort and the validation cohort. In the training cohort, a majority of patients were in the age of 40 to 49 years (77.5%), male (54.8%), and white (79.2%). The most common histological type was adenocarcinoma (94.6%), followed by mucinous adenocarcinoma (4.7%), and signet ring cell carcinoma (0.7%). The most common tumor grade was grade II (79.6%), followed by grade III (11.4%), grade I (6.7%), and grade IV (2.3%). Most patients were diagnosed with T3 (61.4%), N0 (49.2%), and normal CEA level (42.5%). For the tumor size, more than half of patients were < 5cm (60.8%). Most patients received number of LN examined ≥12 (82.1%), chemotherapy (74.6%), and radiotherapy (58.2%). The demographic and clinical characteristics of all the patients are exhibited in Table 1.
Factors associated with OS
For the training cohort, sex, race, histological type, tumor grade, T stage, N stage, tumor size, CEA level, number of LN examined, radiotherapy, and chemotherapy were correlated with OS in the univariate analysis and subjected to the multivariate analysis. As shown in table 2, race, histological type, tumor grade, T stage, N stage, CEA level, and number of LN examined were confirmed to be the independent prognostic factors for the OS of young non-metastatic RC patients after curative resection (p < 0.05). The associations between the independent prognostic factors ( race, pathological type, tumor grade, T stage, N stage, CEA level, and number of LN examined ) and OS was presented in Fig 2.
Nomogram construction for young RC patients
All the above independent prognostic factors were used to create a OS prognostic nomogram. The nomogram for 3- , 5-, and 8- year OS is shown in Fig 3. By adding up the scores to the bottom scales, we can predict 3- , 5-, and 8-year OS of individual young non-metastatic RC patients after curative resection.
Validation of the nomogram
In the present study, C-index, ROC curves, calibration plots and DCA curves were used to identify the superiority of the nomogram in predicting the prognosis of young non-metastatic RC patients after curative resection. The C-indexes of the nomogram were 0.723 (95% confidence interval (95%CI): 0.709-0.737) in the training cohort and 0.739 (95%CI: 0.719-0.759) in the validation cohort. In the ROC curves, high area under the ROC (AUC) was observed both in the training cohort and validation cohort (Fig 4). AUC values for 3- , 5-, and 8-year OS of the training cohort were 0.769, 0.735 and 0.715 (Fig 4a) , as for the values of the validation cohort were 0.774, 0.753 and 0.737 (Fig 4b). Meanwhile, calibration plots presented a good agreement between the actual observation and the nomograms prediction for 3- , 5-, and 8- year OS rates in the training cohort as well as the validation cohort (Fig 5). Furthermore, DCA results demonstrated that the nomogram model was clinical useful, which can play a practical role in decision-making (Fig 6).
Performance of the nomogram in stratification
All patients were categorized into three subgroups according to the cut-off values of the nomogram for OS: low risk (score ≤ 203), intermediate risk (203 < score ≤ 245) , and high risk (245 < score). Kaplan-Meier survival curves analysis indicated that, both in the training cohort and the validation cohort, patients in the high risk group suffered a significant poorer prognosis than those in the intermediate risk group and low risk group (Fig 7).