Review
A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer

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Abstract

Background

Esophagectomy is a standard treatment for resectable esophageal cancer but relatively few patients are cured. Combining neoadjuvant chemoradiation with surgery may improve survival but treatment morbidity is a concern. We performed a meta-analysis of randomized controlled trials (RCTs) that compared the use of neoadjuvant chemoradiation and surgery with the use of surgery alone for esophageal cancer.

Methods

Medline and manual searches were done to identify all published RCTs that compared neoadjuvant chemoradiation and surgery with surgery alone for esophageal cancer. A random-effects model was used and the odds ratio (OR) was the principal measure of effect. Systematic quantitative review was done for outcomes unique to the neoadjuvant chemoradiation treatment group, such as pathological complete response.

Results

Nine RCTs that included 1,116 patients were selected with quality scores ranging from 1 to 3 (5-point Jadad scale). Odds ratio (95% confidence interval [CI]; P value), expressed as chemoradiation and surgery versus surgery alone (treatment versus control; values <1 favor chemoradiation-surgery arm), was 0.79 (0.59, 1.06; P = 0.12) for 1-year survival, 0.77 (0.56, 1.05; P = 0.10) for 2-year survival, 0.66 (0.47, 0.92; P = 0.016) for 3-year survival, 2.50 (1.05, 5.96; P = 0.038) for rate of resection, 0.53 (0.33, 0.84; P = 0.007) for rate of complete resection, 1.72 (0.96, 3.07; P = 0.07) for operative mortality, 1.63 (0.99, 2.68; P = 0.053) for all treatment mortality, 0.38 (0.23, 0.63; P = 0.0002) for local-regional cancer recurrence, 0.88 (0.55, 1.41; P = 0.60) for distant cancer recurrence, and 0.47 (0.16, 1.45; P = 0.19) for all cancer recurrence. A complete pathological response to chemoradiation occurred in 21% of patients. The 3-year survival benefit was most pronounced when chemotherapy and radiotherapy were given concurrently (OR 0.45, 95% CI 0.26 to 0.79, P = 0.005) instead of sequentially (OR 0.82, 95% CI 0.54 to 1.25, P = 0.36).

Conclusions

Compared with surgery alone, neoadjuvant chemoradiation and surgery improved 3-year survival and reduced local-regional cancer recurrence. It was associated with a lower rate of esophageal resection, but a higher rate of complete (R0) resection. There was a nonsignificant trend toward increased treatment mortality with neoadjuvant chemoradiation. Concurrent administration of neoadjuvant chemotherapy and radiotherapy was superior to sequential chemoradiation treatment scheduling.

Section snippets

Methods

Medline and manual searches were done (completed independently and in duplicate) to identify all published (manuscripts and abstracts) randomized controlled trials (RCTs) that compared neoadjuvant chemoradiation and surgery with surgery alone for resectable esophageal cancer. Trials were not excluded because of cancer histology (squamous or adenocarcinoma) or language of publication. The Medline search was done on PubMed (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi). A set was

Results

The two trial assessors agreed on the selection of nine RCTs [9], [10], [11], [12], [13], [14], [15], [16], [17]. Combining these trials yielded data on 1,116 patients. The RCT quality scores ranged from 1 to 3 (5-point scale), with a mean of 2.1. The quality scores were artificially low because of the importance placed on blinding in the scoring system, and the inherent difficulty in blinding a treatment such as chemoradiation [18], [20].

Survival of the two patient groups was similar at one

Comments

Surgeons and oncologists remain disappointed with surgery as a solitary treatment modality for esophageal cancer. Not surprisingly, various combinations of chemotherapy, radiotherapy, and surgery (multimodality treatment) have been investigated [6], [7], [8]. Both neoadjuvant radiotherapy and surgery, and surgery and adjuvant radiotherapy, have been studied. Randomized controlled trials and meta-analyses of trials have not shown a significant survival advantage for these combinations of surgery

References (37)

  • B.P Whooley et al.

    Analysis of reduced death and complication rates after esophageal resection

    Ann Surg

    (2001)
  • M.B Orringer et al.

    Transhiatal esophagectomyclinical experience and refinements

    Ann Surg

    (1999)
  • P Sutton et al.

    Neo-adjuvant treatment for oesophageal cancer

    GI Cancer

    (2000)
  • T Lehnert

    Multimodal therapy for squamous carcinoma of the esophagus

    Br J Surg

    (1999)
  • J.I Geh et al.

    Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer

    Br J Surg

    (2001)
  • K Nygaard et al.

    Pre-operative radiotherapy prolongs survival in operable esophageal carcinomaa randomized, multicenter study of pre-operative radiotherapy and chemotherapy. The second Scandinavian trial in esophageal cancer

    World J Surg

    (1992)
  • C Apinop et al.

    A prospective study of combined therapy in esophageal cancer

    Hepatogastroenterology

    (1994)
  • E Le Prise et al.

    A randomized study of chemotherapy, radiation therapy, and surgery versus surgery for localized squamous cell carcinoma of the esophagus

    Cancer

    (1994)

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