Stage I Esophageal Squamous Cell Carcinoma: Surgery vs Chemoradiotherapy

Esophageal squamous cell carcinoma, light micrograph, photo under microscope
Investigators assessed the noninferiority of chemoradiotherapy compared with surgery for patients with T1bN0M0 esophageal squamous cell carcinoma.

For patients with clinical T1bN0M0 esophageal squamous cell carcinoma (ESCC), chemoradiotherapy (CRT) is a noninferior treatment option to surgery, according to study results published in Gastroenterology.

Recent reports have suggested that CRT may be an alternative comparable to surgery for patients with stage IA ESCC, as it is less invasive and may result in better patient quality of life; however, the lack of consensus on the role of CRT in this patient population is apparent. To address this, a team of investigators in Japan conducted a prospective, nonrandomized clinical trial to assess the noninferiority of CRT compared with surgery for patients with T1bN0M0 ESCC.

A total of 368 patients were either assigned to surgery (n=209; 82.8% men) or CRT (n=159; 88.1% men), according to the preference of the patient. Surgery consisted of an esophagectomy with 2- or 3-field lymph node dissections and CRT included 2 courses of 5-fluorouracil (700 mg/m2) on days 1 to 4 and cisplatin (70 mg/m2) on day 1 every 4 weeks, with concurrent radiation (60 Gy). The primary outcome was overall survival, determined via inverse probability weighting with propensity scoring.

The investigators also included a cohort of 11 randomly assigned patients; however, this part of the study was not completed in the present trial.

The median ages in the surgery cohort and CRT cohort were 62 years and 65 years, respectively. Patients were enrolled between December 2006 and February 2013, and by the cutoff date of February 20, 2018, 87.9% of patients in the surgery arm and 98.1% of patients in the CRT arm continued on to receive follow-up care. The median follow-up time for enrolled patients was 7.1 years and 7.7 years for those who continued to receive follow-up care.

The 3-year overall survival rates for patients in the surgery arm and CRT arm were 94.7% and 93.1%, respectively; the 5-year overall survival rates were 86.5% and 85.5%, respectively. Using preplanned weighted propensity scoring, the adjusted hazard ratio (aHR) was 1.052; therefore, CRT met the criteria for noninferiority.

The 3-year progression-free survival rates for the surgery and CRT arms were 84.1% and 76.1%, respectively; 5-year progression-free survival rates were 81.7% and 71.6%, respectively (aHR, 1.478).

Treatment-related serious adverse events were reported in 2 patients in the surgery arm and no cases were reported among those in the CRT arm. The 3- and 5-year cumulative specific death rates were 3.4% and 8.2%, respectively, in the surgery arm and 6.3% and 10.1%, respectively, in the CRT arm (aHR, 0.844).

Limitations of this trial included the lack of completion of the randomized portion of the study. Additionally, patient quality of life was not assessed, nor was a biomarker analysis completed in either treatment arm.  

“Future investigations focused on the use of new treatment combinations (for example, in combination with ICIs) may reveal strategies to increase treatment efficacy. CRT with [elective node irradiation] may diminish local recurrence and improve [progression-free survival]. In this regard, we are conducting a randomized clinical trial (JCOG1904) (NCT04328948) to compare [elective node irradiation] to CRT with involved-field irradiation,” the authors noted.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Kato K, Ito Y, Nozaki I, et al for the Japan Esophageal Oncology Group of the Japan Clinical Oncology Group. Parallel-group controlled trial of surgery versus chemoradiotherapy in patients with stage I esophageal squamous cell carcinoma. Gastroenterol. Published online August 10, 2021. doi:10.1053/j.gastro.2021.08.007