Development and validation of prognostic nomograms for early-onset colon cancer in different tumor locations: a population-based study
Authors: Zhu Sirui , Tu Jiawei , Pei Wei , Zheng Zhaoxu , Bi Jianjun , Feng Qiang 
Published: October 2023

Abstract
Objective
The prevalence of early-onset colon cancer (EOCC) among individuals below the age of 50 has shown a marked upward trend in recent years. The embryology, clinical symptoms, incidence, molecular pathways, and oncologic outcomes differ between right-sided and left-sided colon cancers. However, the differences have not been fully researched in EOCC. Our study aims to develop and validate prognostic nomograms predicting overall survival (OS) and cancer-specific survival (CSS) for EOCC in different tumor locations based on the Surveillance, Epidemiology, and End Results (SEER) database.

Methods
Using the SEER database, a total of 5,588 patients with EOCC were extracted and divided into development and validation cohorts in a random allocation ratio of 7:3 across three groups. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors influencing OS and CSS outcomes. These factors were then utilized to construct nomogram models. The prognostic capabilities of the three models were assessed through various evaluation metrics, including the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and validation cohorts respectively. Additionally, survival curves of the low- and high-risk groups were calculated using the Kaplan–Meier method together with the log-rank test.

Results
Significant differences in clinical features were observed between right-sided and left-sided EOCCs, particularly in terms of OS (52 months vs 54 months) as demonstrated by Kaplan–Meier curves. Transverse-sided EOCCs exhibited clinical characteristics similar to right-sided EOCCs, suggesting a potential shared tumor microenvironment and therapeutic considerations. Advanced stage, liver metastasis, poor grade, elevated pretreatment carcinoembryonic antigen (CEA) level, chemotherapy, and perineural invasion were identified as independent prognostic factors across all three tumor locations and were incorporated into the nomogram model. Nomograms were constructed to predict the probability of 3- and 5-year OS and CSS. The C-index and calibration plots showed that the established nomograms had good consistency between actual clinical observations and predicted outcomes. ROC curves with calculated area under the curve (AUC) values exceeded 0.8 for all three groups in both the development and validation cohorts, indicating robust predictive performance for OS and CSS. Furthermore, decision curve analysis (DCA) plots revealed a threshold probability range of 0.1 to 0.9, within which the nomogram model exhibited maximum benefit. Kaplan–Meier curves exhibited significant differences between the low- and high-risk groups in EOCC for all three tumor locations in OS and CSS, further validating the prognostic value of the nomogram models.

Conclusions
We successfully developed three precise nomogram models for EOCCs in different tumor locations, providing valuable support for clinicians in guiding clinical treatments and facilitating further prospective follow-up studies.