Early-Onset Endometrial Cancer: Bridging the Gap Between Age and Outcome

In recent years, there has been a notable increase in early-onset endometrial cancer (EOEC) cases, which now account for over 10 percent of diagnoses. While survival rates in this younger population may appear favorable at first glance, recurrence risk and long-term outcomes remain inadequately stratified by conventional staging tools. That’s where a new nomogram developed by Zheng et al. may offer a path forward.

Rethinking Risk Stratification
Existing systems like TNM and SEER staging have long guided management. But when applied to EOEC, they fall short because they fail to incorporate nuances—age brackets, tumor size cutoffs, race, and surgical detail—that disproportionately impact younger patients. Zheng's team approached this gap with a multicenter retrospective analysis, pooling data from 4,345 EOEC patients in the U.S. SEER database and externally validating the model in 230 patients from Chongqing, China.

Using multivariate Cox regression, the team identified six key prognostic factors (age, race, tumor grade, T stage, tumor size, and lymphadenectomy status) to build a survival-predictive nomogram (low-, intermediate-, and high-risk groups)based onindividualized three- and five-year survival probability.

Notable Findings
One of the more surprising findings was that patients aged 47 to 49 were at elevated risk of poorer outcomes, likely due to diagnostic delays tied to perimenopausal bleeding and underappreciated clinical suspicion. While age under 45 years typically conferred a survival advantage, this narrow age subset appeared vulnerable, emphasizing the need for heightened suspicion for diagnosis.

Key predictors included:

• Tumor Grade, which was the strongest predictor. High-grade disease corresponded to the poorest survival.
• Tumor Size over 7.8 centimeters sharply increased mortality risk (HR 2.401, 95 percent CI: 1.450–3.976).
• Lymphadenectomy is still debated in early-stage cases, but conferred protective benefit (HR 0.698, 95 percent CI: 0.526–0.927).
• Race continued to be associated with disparities in endometrial cancer care as Black EOEC patients had significantly worse outcomes compared to White patients.

Clinical Takeaways
With C-index values exceeding 0.89 in external validation, the model outperformed TNM and SEER staging in every cohort tested.

Despite growing interest in fertility-sparing regimens, hysterectomy-based approaches are strongly linked to survival benefits. The mean overall survival (OS) was 87.6 months in the surgical cohort versus 64.0 months in the non-surgical cohort. Surgical patients had one-, three-, and five-year OS rates of 99.8, 92.6, and 90.2percent, respectively. In contrast, non-surgical patients saw 64.2 percent survival at five years.

Despite the model’s strengths, it still has limitations. For example, fertility-sparing strategies need their own nomogram pathways. Current models, like this one, don’t yet capture non-surgical risk dynamics.Additionally,notably absent from the SEER dataset—and thus this model—are critical factors like MMR status, molecular subtypes (e.g., POLE, p53), and treatment specifics (chemo or hormonal agents), limiting its scope.

Reference

1. Zheng Y, Hu R, Yang F, et al. Comparing survival outcomes between surgical and non-surgical treatments in patients with early-onset endometrial cancer and developing a nomogram to predict survival: a study based on Eastern and Western data sets. World J Surg Oncol. 2025;23(1):184. Published 2025 May 11. doi:10.1186/s12957-025-03825-y