Review suggests chemotherapy may improve overall survival in esophageal cancer
An analysis compared FLOT chemotherapy with CROSS chemoradiotherapy given before surgery for esophageal and junctional adenocarcinomas.
Moderate evidenceReviewSome caution advised
Medical disclaimer: This article summarizes research findings and is for informational purposes only. It is not medical advice.
Editorial illustration — not from the study.
Researchers combined results from four directly comparative studies involving 824 patients. One study was randomized, while three used statistical matching rather than random assignment, so differences between treatment groups may still have affected the results.
The analysis found a pooled overall-survival hazard ratio of 0.79 for FLOT compared with CROSS, with the estimate favoring FLOT. However, three-year survival was not significantly different, and the studies found no significant differences in complete tumor response, removal with cancer-free margins, deaths around surgery, leaks at the surgical connection, or other major complications.
What the review covered
The researchers conducted a systematic review and meta-analysis of studies published or indexed from January 2010 through December 2025. They included randomized controlled trials and propensity-score-matched studies that directly compared FLOT chemotherapy with CROSS chemoradiotherapy before surgery in people with esophageal or esophagogastric junction adenocarcinoma. Four studies met the criteria, comprising 824 patients. The researchers assessed overall survival, three-year survival, R0 resection, pathological complete response, and perioperative complications. This was a review of human clinical studies; no animal or laboratory findings were reported.
What the evidence shows
The pooled hazard ratio for overall survival was 0.79, with a 95% confidence interval of 0.68 to 0.93, favoring FLOT in the analysis. This is an association in a combined evidence set and does not by itself establish that FLOT caused longer survival. Three-year survival was similar between groups, with an odds ratio of 1.19 and a 95% confidence interval of 0.89 to 1.60.
There were no statistically significant differences in R0 resection, meaning removal with no cancer seen at the surgical margins, or pathological complete response, meaning no cancer detected in the removed tissue after treatment. There were also no significant differences in perioperative mortality, anastomotic dehiscence, which is a leak where surgical sections are joined, or other major complications. The reported odds ratios were 0.77 for R0 resection, 0.87 for pathological complete response, 0.54 for perioperative mortality, 0.80 for anastomotic dehiscence, and 1.04 for other major complications; each confidence interval included the possibility of no difference.
Who this may apply to
The findings may be relevant to people with locally advanced esophageal or esophagogastric junction adenocarcinoma who are similar to the patients in the included studies and are being considered for treatment before surgery. They may not apply to other cancer types, earlier or more advanced disease, people unable to undergo surgery, or patients with substantially different health characteristics. The results are a summary of limited comparative evidence and should not be read as establishing that one regimen is appropriate for every patient.
Why it matters
The analysis addresses an important treatment comparison for people with locally advanced esophageal adenocarcinoma who are being evaluated for treatment before surgery. It suggests that FLOT may be associated with better overall-survival results in the combined studies, but the lack of a clear difference in three-year survival and other outcomes means the findings do not provide a complete or definitive comparison of the two regimens.
Limitations & evidence assessment
Only four studies and 824 patients were included. Three studies were not randomized, so matching may not have removed all important differences between the groups; the analysis therefore cannot establish that the treatment itself caused the observed overall-survival association. The abstract provides limited information about differences among the studies, length of follow-up, treatment details, and the individual risk-of-bias results. The evidence also combines one randomized study with three observational, propensity-matched studies, which can make the pooled estimate less certain.
Why this evidence level: This meta-analysis combined four studies involving 824 people, including one randomized trial and three propensity-score-matched studies. The relatively small evidence base and inclusion of non-randomized studies limit confidence compared with a large body of consistent randomized-trial evidence.
Evidence levels are editorial estimates derived from study metadata — they are not clinical appraisals.
// Source
Diseases of the Esophagus · 2026 · DOI: 10.1093/dote/doag077.204
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