Quantifying statistical cure in unresectable locally advanced esophageal squamous cell carcinoma treated with...

This study aimed to quantify the statistical cure in patients with unresectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) treated with definitive radiotherapy (RT)-based strategies and to explore the independent prognostic factors of cure.

This retrospective study analyzed 801 patients with unresectable LA-ESCC at Affiliated Cancer Hospital of Zhengzhou University from 2014 to 2023. All patients received definitive RT and were stratified into chemoradiotherapy (CRT, n=689) or CRT combined with immunity checkpoint inhibitors (CRT+ICIs, n=112) based on treatment received. A relative survival (RS)-based mixture cure modeling methodology was used to estimate the cure fraction and cure point. The model was externally validated using a dataset of 5,000 matched patients from the SEER database.

Our model estimated a cure fraction of 10.4% and a cure point of 6.7 years. Subset analysis indicated that patients treated with CRT+ICIs had a higher cure fraction than those treated with CRT (30.6% vs 10.9%), with a shorter time to cure (3.9 vs 7.1 years). Validation with the SEER dataset showed a comparable cure fraction (10.8%) but a longer cure point (9.3 years). Multivariable analysis suggested that the favorable independent prognostic factors of statistical cure included a higher BMI (β, 0.10; 95% CI, 0.01 to 0.19; p=0.039) and the CRT+ICIs regimen (β, 2.18; 95% CI, 0.91 to 3.44; p<0.001). Factors associated with a lower probability of cure were age ≥65 years (β -0.04; 95% CI, -0.09 to 0.00; p=0.032) and chronic comorbidities (β, -1.10; 95% CI, -2.14 to -0.05; p=0.040).

Statistical cure is achievable in unresectable LA-ESCC patients receiving RT-based regimens. However, the traditional 5-year overall survival (OS) insufficiently reflects long-term survival, indicating that follow-up in the CRT group should be at least 7 years. Incorporation of ICIs facilitated curative potential and shortened cure point, supporting a 4-year OS surrogate endpoint for CRT+ICIs. These findings emphasize the value of integrating cure models into clinical practice to optimize individualized treatment and surveillance strategies.