Evaluation of Concurrent Chemoradiotherapy for Survival Outcomes in Patients With Synchronous Oligometastatic Esophageal Squamous Cell Carcinoma

Importance: The optimal treatment for and potential benefit populations of synchronous oligometastatic esophageal squamous cell carcinoma (SOESCC) remain unclear.

Objectives: To evaluate outcomes of concurrent chemoradiotherapy (CCRT) and to construct decision tree models for predicting the risk of progression and mortality in patients with SOESCC.

Design, Setting, And Participants: This prognostic study included 532 patients with SOESCC who were treated at 2 cancer centers in China from January 2012 to December 2018 and consisted of a development cohort (n = 381) and a validation cohort (n = 151). Data were analyzed from March 2019 to December 2021.

Exposures: All patients received chemotherapy alone or CCRT.

Main Outcomes And Measures: The primary end points of the study were progression-free survival (PFS) and overall survival (OS), and the secondary end points were locoregional control and treatment-related toxic effects. Propensity score matching was performed to control potential confounding factors. Cox regression was used to screen important explanatory variables. Decision trees for optimally partitioning patients were established using recursive partitioning analysis and were then subjected to internal and independent external validation.

Results: Among the 532 patients (median [range] age, 63 [32-82] years; 367 men [69.0%]), 292 patients received chemotherapy alone and 240 patients underwent CCRT. With a median (IQR) follow-up time of 37.0 (21.6-55.8) months, CCRT was associated with improved objective response rate (139 of 240 [57.9%] vs 123 of 292 [42.1%]; P < .001), median (IQR) PFS (9.7 [8.5-10.9] months vs 7.6 [6.6-8.6] months; P < .001), and median (IQR) OS (18.5 [16.1-20.9] months vs 15.2 [13.6-16.8] months; P < .001) compared with chemotherapy alone. Propensity score matching analysis verified the results. Cox multivariate analysis indicated that treatment modality (CCRT vs chemotherapy alone) was an independent prognostic factor related to PFS (hazard ratio, 0.69; 95% CI, 0.57-0.83; P < .001) and OS (hazard ratio, 0.75; 95% CI, 0.61-0.93; P = .008). The final decision trees divided patients with SOESCC into low-, intermediate-, and high-risk groups in both the internal and external validations, and the corresponding cumulative risk function curves had significant differences (all P < .001). Time-dependent maximum areas under receiver operating curves of decision trees for progression risk at 3 years and mortality risk at 5 years were 0.820 (95% CI, 0.693-0.948) and 0.894 (95% CI, 0.822-0.966), respectively. Calibration curves also demonstrated that the decision trees had favorable performance of risk stratification.

Conclusions And Relevance: In this study, CCRT vs chemotherapy alone as a first-line treatment for patients with SOESCC had superior survival. Patients with low risk had promising long-term survival based on the current treatment modality. The predictive information of the decision tree could provide accurate decision-making for the management of patients with SOESCC.