The Association of Radiotherapy and Chemotherapy: Esophageal Cancer

Over the past 30 years, significant advances have been made in the integration of radiation therapy and chemotherapy in the treatment of patients with esophageal malignancies. The therapeutic goal of chemoradiotherapy is to enhance local control resulting in improved loco-regional control and survival of these patients. To define the optimal sequence, the need of combination with surgery, and the efficacy of these modalities, several trials have been conducted, mainly as phase II studies and often underpowered or flawed phase III studies. The clinical evidence strongly suggests that preoperative chemoradiotherapy improves outcome. Therefore, this strategy has replaced single-modality approaches (surgery, radiotherapy) becoming a standard treatment option in patients with operable advanced disease. Moreover, recent published studies indicate that patients treated with 'definitive' chemoradiotherapy have similar survival to patients undergoing neoadjuvant chemoradiotherapy followed by surgery. Attempts to improve outcome by intensifying conventional cytotoxic drugs or increasing radiation dose have not been successful. The use of other novel agents (camptothecin, taxane …) combined with radiation has altered the toxicity profile, but substantial prognostic improvement has yet to be demonstrated. Future improvements will likely require the incorporation of targeted agents and the use of molecular predictors of response as a strategy to select the treatment. Early identification of responders will also be required in order to guide and select the therapy. This overview highlights current results, controversies and potential future directions in the chemoradiotherapeutic treatment of selected esophageal cancer.