Clinical Investigations
Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (oesophageal cancer collaborative group)

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Abstract

Purpose: The existing randomized evidence has failed to conclusively demonstrate the benefit or otherwise of preoperative radiotherapy in treating patients with potentially resectable esophageal carcinoma. This meta-analysis aimed to assess whether there is benefit from adding radiotherapy prior to surgery.

Methods and Materials: This quantitative meta-analysis included updated individual patient data from all properly randomized trials (published or unpublished) comprising 1147 patients (971 deaths) from five randomized trials.

Results: With a median follow-up of 9 years, the hazard ratio (HR) of 0.89 (95% CI 0.78–1.01) suggests an overall reduction in the risk of death of 11% and an absolute survival benefit of 3% at 2 years and 4% at 5 years. This result is not conventionally statistically significant (p = 0.062). No clear differences in the size of the effect by sex, age, or tumor location were apparent.

Conclusion: Based on existing trials, there was no clear evidence that preoperative radiotherapy improves the survival of patients with potentially resectable esophageal cancer. These results indicate that if such preoperative radiotherapy regimens do improve survival, then the effect is likely to be modest with an absolute improvement in survival of around 3 to 4%. Trials or a meta-analysis of around 2000 patients would be needed to reliably detect such an improvement (15→20%).

Introduction

Surgical resection is standard therapy for patients with carcinoma of the esophagus (5), but the prognosis for these patients remains poor, with 5-year survival of approximately 10% (4). Local recurrences are frequent even after intended curative resection. Following the results of numerous uncontrolled historical studies [reviewed (8)] there has been interest in the use of preoperative radiotherapy as a possible means of reducing local spread, thereby, improving survival. By downstaging the tumor, it may also increase resectability and perhaps alleviate symptoms.

Five prospective randomized controlled trials have investigated the effects of preoperative radiotherapy. Although pathological responses were reported in four of these trials 3, 8, 10, 15, resectability appeared to be unaffected in all trials and a conventionally significant survival benefit was detected in only the most recent (11). All but one of these trials involved fewer than 250 patients, and they were, therefore, too small to detect moderate treatment effects. However, combining the results of these trials quantitatively in a meta-analysis of updated individual patient data, increases the statistical power to detect such differences and is the most reliable and unbiased way to evaluate the evidence (12) from these trials.

Such a meta-analysis was therefore suggested by the Medical Research Council (MRC) Oesophageal Cancer Working Party, initiated by the MRC Cancer Trials Office, Cambridge and carried out on behalf of the Oesophageal Cancer Collaborative Group.

Section snippets

Methods and materials

The general methods for the meta-analysis were outlined prospectively in a protocol.

Results

The meta-analysis is based on five trials including 1147 patients. This represents 98.5% of patients from all known randomized trials, because data were not available for 17 patients in one (10) of the five trials. All trials included patients with potentially resectable cancer of the thoracic esophagus and with the exception of one (3), restricted entry to patients with squamous carcinoma. Trials included both men and women of most age groups. In general, the majority of patients in the

Discussion

This meta-analysis was based on five trials comparing preoperative radiotherapy with no preoperative radiotherapy. It included 1147 patients representing 98.5% of patients from all confirmed eligible randomized trials. Most of the survival data for these trials were updated for the meta-analysis, many years after the publication of the results and up to 20 years after recruitment had stopped. Therefore, currently, the meta-analysis provides the most comprehensive and reliable assessment of the

Acknowledgements

This meta-analysis and collaborators meeting was supported by the British Medical Research Council (MRC). We would like to thank all those patients who took part in the trials and contributed to this research. The meta-analysis would not have been possible without their help or without the collaborating institutions who kindly supplied their trial data.

References (17)

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