Quantifying statistical cure in unresectable locally advanced esophageal squamous cell carcinoma treated with radiotherapy-based regimens: a cure model analysis with SEER validation

Purpose 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. Methods and Materials 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. Results 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). Conclusions 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.