Sex Differences in Cancer-specific Survival for Locally Advanced Esophageal Cancer After Neoadjuvant Chemoradiotherapy: A Population-based Analysis

Objective: Neoadjuvant chemoradiotherapy (nCRT) is the recommended standard treatment for locally advanced esophageal cancer (LA-EC). This study aimed to determine whether sex makes a difference in cancer-specific survival (CSS) and construct a novel nomogram model to predict CSS for LA-EC after nCRT based on the SEER database.

Methods: Patients coded by 04-15 were identified from the SEER database. Patients with systemic treatment and radiotherapy before surgery were defined as nCRT. We further divided this population into a training group and a verification group at a ratio of 7:3. Univariate and multivariate cox analyses were applied to determine the prognostic risk factors based on the training cohort, and then the Nomogram model was established. The area under the curve (AUC) was used to evaluate the predictive ability of the model. We used the calibration curve to evaluate the consistency between the predicted status and actual status and decision curve analysis (DCA) to evaluate the clinical value. We used X-tile software to determine the best cut-off value of nomogram scores and divided the population into low-risk, medium-risk, and high-risk groups, and Kaplan-Meier analysis was applied to compare the CSS.

Results: A total of 2096 LA-EC patients were included for further analysis, with 1,540 in the training cohort and 656 in the validation group. Male (HR: 1.29, 95% CI, 1.04 -1.58), T stage, N stage, and M stage were identified as independent risk factors of CSS based on the training cohort. A Nomogram model was constructed to predict the 3-, 5- and 7-years CSS. ROC curve and AUC confirmed that this nomogram has median discrimination ability. The calibration curve showed good agreement between predicted status and actual status. The DCA curves confirmed the clinical value. Kaplan-Meier analysis indicated that patients in the high-risk subgroup had poorer CSS in both the training cohort and validation cohort ( < 0.001).

Conclusion: Male patients had poorer CSS in LA-EC patients after nCRT. A nomogram model composed of sex, T stage, N stage, and M stage was constructed to identify the high-risk population and provide a personalized follow-up plan.