Comparative Study on Treatment Strategies for Esophageal Cancer

Academic Background

Esophageal cancer is one of the digestive system tumors with high incidence and mortality rates worldwide, particularly in Asia, where the incidence of esophageal squamous cell carcinoma (SCC) is notably prominent. Although significant progress has been made in the diagnosis and treatment of esophageal cancer in recent years, there is still controversy regarding the treatment strategies for early-stage esophageal cancer (T1b-2N0-1). Currently, the main treatment modalities include surgery alone (SA), surgery plus adjuvant therapy (ST), and neoadjuvant therapy plus surgery (NS). However, the effects of these treatment modalities on cancer-specific survival (CSS) and overall survival (OS) remain inconclusive.

To further clarify the long-term survival impact of different treatment strategies on early-stage esophageal cancer patients, a research team from Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University conducted a retrospective study based on the SEER database and a Chinese cohort. The study aimed to compare the effects of NS, SA, and ST on CSS and OS in patients with T1b-2N0-1 esophageal cancer and to develop a nomogram for predicting OS to assist clinicians in formulating personalized treatment plans.

Source of the Paper

The study was conducted by Lingling Xia, Wei Shi, Yuxin Cai, Zhengkai Liao, Zhen Huang, Hu Qiu, Jing Wang, and Yongshun Chen from the Cancer Center of Renmin Hospital of Wuhan University. The paper was published online on June 26, 2024, in the International Journal of Surgery, titled “Comparison of Long-Term Survival of Neoadjuvant Therapy Plus Surgery Versus Upfront Surgery and the Role of Adjuvant Therapy for T1b-2N0-1 Esophageal Cancer: A Population Study of the SEER Database and Chinese Cohort.”

Research Process and Results

1. Study Subjects and Data Sources

The study data were obtained from the SEER database of the National Cancer Institute and a Chinese cohort from Renmin Hospital of Wuhan University and Zhongnan Hospital of Wuhan University. The SEER database included patients diagnosed with T1b-2N0-1 esophageal cancer between 2004 and 2019, while the Chinese cohort included patients who underwent surgery between January 2014 and March 2022, with follow-up until October 2023. The study enrolled 584 patients from the SEER database and 323 patients from the Chinese cohort.

2. Research Methods

The study employed propensity score matching (PSM) to reduce intergroup differences. Survival curves were plotted using the Kaplan-Meier method and compared using the log-rank test. Cox proportional hazards regression models were used to analyze prognostic factors. Additionally, a nomogram for predicting OS was developed, and its performance was evaluated using the Harrell concordance index (C-index), area under the curve (AUC) of the receiver operating characteristic curve, calibration plots, and decision curve analysis (DCA).

3. Main Results

a) Comparison of Neoadjuvant Therapy Plus Surgery (NS) and Surgery Alone (SA)

In the SEER database, after PSM analysis, the 3-year CSS and OS rates in the NS group were 80.3% and 75.8%, respectively, significantly higher than the 62.1% and 55.5% in the SA group (p=0.016 and p=0.006). This indicates that NS significantly improved long-term survival in patients with T1b-2N0-1 esophageal cancer.

b) Comparison of Neoadjuvant Therapy Plus Surgery (NS) and Surgery Plus Adjuvant Therapy (ST)

After PSM analysis, there was no significant difference in 3-year CSS and OS rates between the NS and ST groups, with rates of 71.3% vs. 68.3% (p=0.560) and 69.8% vs. 62.9% (p=0.330), respectively. This suggests that NS and ST have similar effects in improving patient survival.

c) Comparison of Surgery Alone (SA) and Surgery Plus Adjuvant Therapy (ST)

After PSM analysis, there was no significant difference in 3-year CSS and OS rates between the SA and ST groups, with rates of 54.6% vs. 66.7% (p=0.220) and 50.2% vs. 57.9% (p=0.290), respectively. However, subgroup analysis showed that for patients with positive lymph nodes (N1 stage), CSS was significantly better in the ST group than in the SA group (HR=0.56, 95% CI: 0.32-0.98, p=0.044).

4. Development and Validation of the Nomogram

The study developed a nomogram for predicting OS in patients with T1b-2N0-1 esophageal cancer, incorporating five clinicopathological variables: T stage, N stage, age, number of examined lymph nodes, and treatment modality. The C-index of the nomogram was 0.648, 0.663, and 0.666 in the training group, external validation group 1, and external validation group 2, respectively, demonstrating good predictive performance. The 1-year, 3-year, and 5-year AUC values were 0.659, 0.639, and 0.612 in the training group; 0.786, 0.758, and 0.692 in validation group 1; and 0.805, 0.760, and 0.693 in validation group 2.

Conclusions and Significance

The main conclusion of the study is that for patients with T1b-2N0-1 esophageal cancer, neoadjuvant therapy plus surgery (NS) significantly improves long-term survival compared to surgery alone (SA), but it does not show a significant advantage over surgery plus adjuvant therapy (ST). Additionally, for patients with positive lymph nodes, postoperative adjuvant therapy (ST) can provide survival benefits.

The significance of this study lies in providing new evidence to support treatment strategies for early-stage esophageal cancer, particularly the value of adjuvant therapy for patients with positive lymph nodes. Furthermore, the developed nomogram offers a practical tool for clinicians to assist in personalized treatment decision-making.

Research Highlights

1. Significant Advantage of Neoadjuvant Therapy: NS significantly improved CSS and OS in patients with T1b-2N0-1 esophageal cancer, especially in those with T2 and N1 stages.
2. Value of Adjuvant Therapy: Postoperative adjuvant therapy (ST) significantly improved CSS in patients with positive lymph nodes.
3. Clinical Application of the Nomogram: The developed nomogram demonstrated good predictive performance, helping clinicians assess OS risk and formulate personalized treatment plans.

Other Valuable Information

The study also found through subgroup analysis that factors such as tumor size, grade, and vascular infiltration have a cross-sectional relationship with patient survival. These findings provide new directions for further research on prognostic factors in esophageal cancer.

This study provides important clinical evidence for the treatment strategies of early-stage esophageal cancer and lays the foundation for future prospective randomized clinical trials.