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Preoperative chemotherapy for resectable thoracic esophageal cancer

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Abstract

Background

Surgery has been the treatment of choice for localized esophageal cancer. A number of studies have investigated whether preoperative chemotherapy followed by surgery leads to an improvement in cure rates, but the individual reports have been conflicting. An explicit systematic update of the role of preoperative chemotherapy in the treatment of resectable thoracic esophageal cancer is therefore warranted.

Objectives

The objective of this review is to determine the role of preoperative chemotherapy on patients with resectable thoracic esophageal carcinomas.

Search methods

Trials were identified by searching the Cochrane Controlled Trials Register, MEDLINE (1966 ‐ 2003), EMBASE (1988 ‐ 2003) and CancerLit (1993 ‐ 2003). There were no language restrictions.

Selection criteria

Types of studies

Studies that randomised patients with potentially resectable carcinomas of the esophagus (of any histologic type) to chemotherapy or no chemotherapy before surgeries were included in this review.

Types of participants

The participants consisted of patients with localized potentially resectable thoracic esophageal carcinomas. Trials involving patients with carcinomas of the cervical esophagus were excluded.

Types of interventions

Trials that compared chemotherapy before surgery (esophagectomy) with surgical resections alone (esophagectomy) were included.
Types of outcome measures

The primary outcome was overall survival at yearly intervals after randomisation. Secondary outcomes of interest included rates of resections, response to chemotherapy, rates of local and distant recurrences, quality‐of‐life, and treatment morbidity and mortality.

Data collection and analysis

All analyses were carried out on intention‐to‐treat. Survival at 1, 2, 3, 4 and five years were used as endpoints of clinical relevance along with the median survival. The risk ratio (relative risk; RR) was the primary measure of effect for survival, rates of resections, and tumour recurrences. The risk difference (RD) was used to describe differences in response to chemotherapy, treatment morbidity and mortality.

Main results

There were 11 randomised trials involving 2051 patients. At 1‐ year and 2‐year the risk ratios showed no difference in survival between preoperative chemotherapy and surgery alone. The 3‐year risk ratios found a 21% increase in survival (RR = 1.21; 95% CI 0.88 to 1.68; p = 0.25) and a 24% increase in survival with preoperative chemotherapy at 4 years (RR = 1.24; 95% CI 0.92 to 1.68; p = 0.15) but they did not reach statistical significance. Only at 5 years did the results become significant (RR = 1.44; 95% CI 1.05 to 1.97; p = 0.02).

The overall rate of resections and the rate of complete resections (R0) did not differ between the preoperative chemotherapy arm and surgery alone. The pooled clinical response to chemotherapy was about 36% (RD = 0.36; 95% CI 0.26 to 0.47) but the complete pathologic response was a disappointing 3% (RD = 0.03; 95% CI 0.01 to 0.04). No single agent or combination of chemotherapeutic agents was found to be superior to the others. There was a 19% reduction in local recurrence with preoperative chemotherapy, but this was not significant (RR = 0.81; 95% CI 0.54 to 1.22; p = 0.3). Preoperative chemotherapy was somewhat more harmful to patients than surgery alone.

Authors' conclusions

In summary, preoperative chemotherapy plus surgery appears to offer a survival advantage at 3, 4, and 5 years, which reached significance only at 5 years compared to surgery alone for resectable thoracic esophageal cancer of any histologic type. The number needed to treat for one extra survivor at five years is eleven patients. The results are tempered by the increased toxicity and mortality associated with chemotherapy. The most beneficial chemotherapy combination appears to be cisplatin and 5‐flurouracil based, however, the dosing is unclear.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

Chemotherapy before surgery may improve the survival of patients with surgically removable esophageal cancer.

Cancer of the esophagus (gullet) is relatively uncommon but over 90% of people with this cancer die within five years. The tumour is often surgically removed, but this is not generally successful because of the advanced state of the cancer before symptoms occur. Chemotherapy (cancer fighting drugs such as cisplatin) has been used before surgery to try to decrease the activity of the tumour and hopefully increase quality‐of‐life and life expectancy. Studies using chemotherapy before surgery have tried to improve survival. This review of eleven trials of patients with esophageal cancer on any histologic type found some evidence that cisplatin‐based chemotherapy, when given before surgery, improved a patient's chances of survival at five years. Chemotherapy did, however, increase the rate of some side effects.