Chemotherapy before surgery for patients with surgically removable cancer of the esophagus

Question

In patients who have cancer of the esophagus that is potentiallly removable by surgery, does the use of chemotherapy before surgery result in improved survival?

Background

Cancer of the esophagus often is not discovered until it is at quite an advanced stage. This means that even removing the tumor through surgery is not very successful, and many people die within five years. Chemotherapy (cancer-fighting drugs such as cisplatin) has been used before surgery to try to shrink the tumor, making it easier to operate on and stopping it from spreading. Therefore, chemotherapy may help people to live longer.

Study characteristics

This review included information from 13 randomized studies and combined results from 2122 patients to answer our question regarding survival.

Key results

This review of 13 trials, including patients with esophageal cancer of any cell type, found some evidence that cisplatin-based chemotherapy may help them to live longer. However, chemotherapy may introduce side effects.

Quality of the evidence

This review used information from randomized studies that is considered to represent the highest quality of evidence.

Authors' conclusions: 

In summary, preoperative chemotherapy plus surgery offers a survival advantage compared with surgery alone for patients with resectable thoracic esophageal cancer, but the evidence is of moderate quality. Some evidence of toxicity and preoperative mortality have been associated with chemotherapy.

Read the full abstract...
Background: 

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

Objectives: 

The objective of this review is to determine the role of preoperative chemotherapy in the treatment of patients with resectable thoracic esophageal carcinoma.

Search strategy: 

We identified trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (1966 to 2013), EMBASE (1988 to 2013), and CANCERLIT (1993 to 2013). We did not confine our search to English language publications. We updated searches in CENTRAL, MEDLINE, and EMBASE in October 2013.

Selection criteria: 

All trials of patients with potentially resectable carcinoma of the esophagus (of any histologic type) who were randomly assigned to chemotherapy or no chemotherapy before surgery.

Data collection and analysis: 

The primary outcome was survival, which was assessed with the use of hazard ratios. This is an amendment to the original review, which used risk ratios to assess survival at yearly intervals. Hazard ratios (HRs) have now been introduced to summarize the complete survival experience in a single analysis. Risk ratios (RRs) were used to compare rates of resection, tumor recurrences, and treatment morbidity and mortality.

Main results: 

We identified a total of 13 randomized trials involving 2362 participants. Ten trials (2122 participants) reported sufficient detail on survival to be included in a meta-analysis for the primary outcome. Preoperative chemotherapy improves overall survival (HR 0.88, 95% confidence interval (CI) 0.80 to 0.96) and is associated with a significantly higher rate of complete (R0) resection (RR 1.11, 95% CI 1.03 to 1.19).

No evidence suggests that the overall rate of resection (RR 0.96, 95% CI 0.92 to 1.01), tumor recurrence (RR 0.81, 95% CI 0.54 to 1.22) or nonfatal complications (RR 0.90; 95% CI 0.76 to 1.06) was different for preoperative chemotherapy compared with surgery alone. Trials reported risks of toxicity with chemotherapy that ranged from 11% to 90%.

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