# Long-Term Outcomes of Concurrent Chemoradiotherapy With S-1 in Older Patients With Esophageal Cancer: A Secondary Analysis of a Randomized Clinical Trial

## TL;DR

This study shows that combining chemotherapy with S-1 and radiation improves long-term survival in older patients with esophageal cancer without increasing non-cancer deaths.

## Contribution

The study provides the first long-term data supporting the use of CCRT with S-1 in older esophageal cancer patients.

## Key findings

- CCRT with S-1 significantly improved overall survival compared to radiation alone.
- Long-term follow-up showed no increase in noncancer-related mortality with CCRT.
- Eight-year survival rates were 26.2% for CCRT and 16.1% for RT alone.

## Abstract

This secondary analysis of a randomized clinical trial reports the long-term survival rates and cancer- and noncancer-related causes of death associated with concurrent chemoradiotherapy with S-1 in older patients in China.

Is concurrent chemoradiotherapy (CCRT) with S-1 associated with differences in survival compared with radiotherapy alone in older patients with esophageal cancer (EC)?

In this secondary analysis of a randomized clinical trial involving 298 patients with EC, the first prospective long-term data (median follow-up of 87 months) on treatment outcomes were reported. Patients in the CCRT with S-1 group showed significantly better overall survival than those in the RT-alone group, and long-term follow-up revealed no increase in noncancer-related mortality among patients receiving CCRT with S-1.

These results support CCRT with S-1 as an effective and tolerable treatment option for older patients with EC, addressing the critical evidence gap for this underrepresented population.

Most older patients with esophageal cancer (EC) are unable to complete standard platinum-based concurrent chemoradiotherapy (CCRT) due to reduced organ reserve, comorbidities, and malnutrition. A new treatment option—CCRT with S-1—has been found to have high efficacy and fewer toxic effects for this population, yet long-term data supporting its use remain limited.

To evaluate the long-term outcomes of CCRT with S-1 vs radiotherapy (RT) alone in older patients with EC.

This secondary analysis of a phase 3 randomized clinical trial conducted at 23 centers in China was not prespecified in the trial protocol. Patients aged 70 to 85 years with histologically confirmed EC were enrolled between June 1, 2016, and August 31, 2018. Data cutoff date was February 1, 2025, with an additional follow-up of 54 months beyond the primary analysis. Data were analyzed from February 1 to April 1, 2025.

Patients were randomly assigned 1:1 to receive CCRT with S-1 consisting of 54 Gy in 30 fractions with S-1, 70 mg/m2 per day on days 1 to 14 and 29 to 42, or RT alone consisting of 60 Gy in 30 fractions, 2.0 Gy per day 5 days per week.

The primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), cause-specific mortality, cumulative incidence of death from EC or other reasons, and cumulative incidences of locoregional or distant metastasis during treatment or relapse after treatment.

A total of 298 patients (median [IQR] age, 77 [74-79] years; 180 males [60.4%]) were enrolled. There were 151 patients (50.7%) clinically diagnosed with stage III to IV disease. With a median (IQR) follow-up of 87 (85-92) months, the median OS was 24.7 (95% CI, 21.2-37.6) months in the CCRT group and 15.1 (95% CI, 12.4-18.6) months in the RT group (hazard ratio [HR], 0.69; 95% CI, 0.53-0.90; P = .005). The 5-year OS rates were 33.5% (95% CI, 26.7%-42.1%) and 24.4% (95% CI, 18.3%-32.4%) for the CCRT and RT groups, respectively; the 8-year OS rates were 26.2% and 16.1%, respectively. The median PFS was 18.7 (95% CI, 13.1-25.8) months in the CCRT group and 9.2 (95% CI, 7.9-12.7) months in the RT group (HR, 0.69; 95% CI, 0.54-0.90; P = .005). Cause-specific analyses showed reduced EC-related mortality with CCRT (HR, 0.67; 95% CI, 0.50-0.89; P = .005), with 8-year absolute risks of 58.5% vs 72.9%, respectively, and no excess noncancer-related mortality.

In this secondary analysis of a randomized clinical trial, long-term results showed that CCRT with S-1 was associated with a sustained survival benefit compared with RT alone, without increased noncancer-related mortality. This finding supports CCRT with S-1 as the preferred regimen for patients aged 70 to 85 years with EC.

ClinicalTrials.gov Identifier: NCT02813967