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Primary Combined-Modality Therapy for Esophageal Cancer

Primary Combined-Modality Therapy for Esophageal Cancer

In this issue of ONCOLOGY, Dr. Minsky provides a compelling argument for combined-modality therapy (ie, chemotherapy and radiation therapy) for esophageal carcinoma. The need for sustained improvements in both local and systemic control is painfully real to our patients and to physicians treating this disease. In the United States, approximately 14,450 new cases of esophageal carcinoma will be diagnosed in 2006, and 13,770 patients—more than 75% male—will die of the disease.[1] According to the Surveillance, Epidemiology, and End Results (SEER) statistics, the 5-year survival rate for esophageal carcinoma based on stage at diagnosis (1995-2001) is 14.9% overall: 31.4% for local disease; 13.8 for regional disease, and 2.7 % for distant disease.[1] Combined-modality therapy for systemic control has become a well-accepted standard for unresectable or medically inoperable patients.[2]

Challenges of Combined-Modality Therapy

Combined-modality therapy has been used successfully to treat carcinoma of the esophagus.[3] In North America, most patients with this disease have distal adenocarcinoma of the esophagus, which may involve the gastro-esophageal junction. A meta-analysis of induction combined-modality therapy followed by resection noted that this treatment sequence improved 3-year survival and reduced local recurrence compared to resection alone.[4]

Although complete pathologic response is associated with improved survival following combined-modality therapy, we cannot consistently define which patients will have a complete response and which will have residual microscopic disease,[5] to select patients who would optimally benefit from resection. Esophagectomy after combined-modality therapy decreases locoregional recurrence compared to no resection[6] but may increase morbidity.

The recent MRC Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial[7] noted that perioperative chemotherapy significantly improved resectability, progression-free survival, and overall survival in operable gastric and lower esophageal cancer patients. National Comprehensive Cancer Network (NCCN) guidelines recommend combined-modality therapy alone, or induction combined-modality therapy with resection.[2]

The use of combined-modality therapy in lieu of resection poses specific challenges, including:

  • Inconsistent clinical staging prior to any therapeutic intervention.

  • Variable systemic and local control without resection.

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