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Endoscopy 2006; 38: 13-17
DOI: 10.1055/s-2006-946644
Invited papers
Esophageal tumors
© Georg Thieme Verlag KG Stuttgart · New York

Reassessment of patients with esophageal cancer after neoadjuvant therapy

A. Das1 , A. Chak2
  • 1Divisions of Gastroenterology, Mayo Clinic Scottsdale, AZ, USA
  • 2Case Western Reserve University School of Medicine, Cleveland, OH, USA
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Publikationsdatum:
26. Juni 2006 (online)

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Introduction

Esophageal cancer is the eighth leading cause of cancer with worldwide estimates of more than 400,000 new cases and over 300,000 cancer related deaths annually [1]. Given the uniformly poor results achieved with surgical intervention alone, treatment at many centers has shifted to a multimodality approach that incorporates pre-operative neoadjuvant chemo-radiotherapy in patients with invasive disease who are potential candidates for subsequent surgical resection [2]. There are several rationales for this treatment strategy. First, down-staging may lead to improved surgical resectability. Second, the use of neoadjuvant therapy up front may prevent the systemic spread of cancer more effectively than post-operative chemo-radiotherapy, which is often deferred for several months to allow for surgical recovery. Third, chemo-radiotherapy (CRT) may be better tolerated preoperatively. Fourth, the tumor tissue may be better oxygenated prior to surgery leading to a higher kill of cancerous cells. Finally, a rather pessimistic argument in favor of neoadjuvant therapy is that sub-clinical metastatic disease may manifest itself in the preoperative period during which the neoadjuvant therapy is being administered and these patients may be spared extensive surgical resection [3]. Although neoadjuvant therapy is supported by sound clinical logic, results from available studies evaluating the role of neoadjuvant therapy in this setting are promising but still equivocal. While two large trials (the United Kingdom MAGIC trial [4] and the UK Medical research Council trial [5]) showed survival advantage with neoadjuvant chemotherapy, another large study from the US (the US Intergroup trial [6]) failed to show any major benefit. A meta-analysis from the Cochrane review group found improved 5-year survival in patients who underwent neoadjuvant chemotherapy. However, the improved survival could not be explained on the basis of proportion of patients undergoing resection or RO resection [7]. Similarly, large randomized trials that evaluated preoperative CRT with surgery against surgery alone and a subsequent meta-analysis failed to show impressive survival benefit with neoadjuvant CRT [8] [9] [10] [11].

With such mixed results, it is clear that only a subgroup of patients with esophageal cancer potentially benefit from neoadjuvant therapy. Therefore, a focus of active research in this field is the identification of the subset of patients who respond to neoadjuvant therapy. From a clinical perspective, one would like to know before or early in the course of neoadjuvant therapy, which cancers are likely to respond. Ideally, if there were biomarkers, histologic characteristics, or morphologic criteria that directly allowed one to predict response to particular chemotherapeutic agents, then appropriate patients could be selected for neoadjuvant therapy. In lieu of such predictive markers, even if there was a method to detect response to neoadjuvant therapy early in the course of treatment, patients unlikely to respond could avoid further toxicity associated with the treatment. In the absence of a method for assessing response early during neoadjuvant treatment, even a method for restaging the tumor after completion of CRT could help guide decisions regarding subsequent curative surgery. Patients with a complete pathological response to induction therapy appear to have the best long term outcome [10] [11] [12]. Thus, a modality that accurately assessed response to treatment could allow stratification of patients according to the likelihood of further surgical benefit and could optimize the management of these patients.

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Amitabh Chak, MD

Division of Gastroenterology

Wearn II

Case Western Reserve University School of Medicine

11100 Euclid Avenue

Cleveland, OH, USA

Telefon: 216 844 5386

Fax: 216 844 8011

eMail: Amitabh.chak@case.edu

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