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BACKGROUND

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The majority of esophageal carcinomas are represented by two histologies: squamous cell carcinoma and adenocarcinoma. Esophageal squamous cell carcinoma (ESCC) is the predominant histological type in Asia. Although treatment strategies differ slightly between Western and Asian countries, surgery traditionally remains the standard therapy for esophageal cancer. However, survival after surgery alone remains poor because of the high rates of local and systemic failure. Thus, multimodality therapies using various combinations of all modalities including surgery, radiotherapy, chemotherapy, and chemoradiotherapy (CRT) have been investigated. In this chapter, we described recent issues regarding multimodality therapy for esophageal cancer in Eastern countries.

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ADJUVANT THERAPY

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Adjuvant Chemotherapy

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A randomized controlled trial of patients with squamous cell carcinoma (SCC) was conducted by the Japan Clinical Oncology Group (JCOG)/Esophageal Oncology Group and compared surgery followed by adjuvant cisplatin/vindesine and surgery alone in 205 patients with SCC.1 No significant difference was observed in 5-year overall survival rates between the two arms; therefore, it was concluded that postoperative chemotherapy added no survival benefit. In another randomized trial performed in Japan, 242 patients with resected SCC of the esophagus were randomized to receive two cycles of postoperative 5-fluorouracil (5-FU)/cisplatin or surgery alone.2 No significant difference was again observed in the 5-year overall survival rates between the two arms. However, the 5-year disease-free survival rate was longer in the adjuvant therapy arm (55% vs. 45%, p = 0.037). Adjuvant therapy, in particular, improved the 5-year overall survival rate in patients with positive lymph nodes. These findings suggested a recurrence-preventive effect in patients with positive lymph nodes, whereas no such effect was noted in those with negative lymph nodes. Although these findings suggested that adjuvant chemotherapy may be beneficial for select patients with esophageal SCC, a meta-analysis including these randomized controlled trials showed no beneficial effect of adjuvant chemotherapy on survival rates.3

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Adjuvant Radiotherapy

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A randomized controlled trial of patients with squamous cell carcinoma was conducted by Fok et al,4 in which 130 patients with resected esophageal carcinoma were randomized to receive adjuvant radiotherapy at a dose of 49.5 Gy in 3.5 Gy fractions or observation only. The overall survival of patients after adjuvant radiotherapy was 8.7 months, which was shorter than that of 15.2 months for the observation group (p = 0.02). In a prospective randomized study performed by Xiao et al,5 495 patients with resected ESCC were randomized to receive adjuvant radiotherapy at a dose of 50 to 60 Gy in 2 Gy fractions or surgery alone. The results obtained showed no significant difference in the overall 5-year survival rates between the two groups (31.7% with surgery alone vs. 41.3% with adjuvant radiotherapy; p = 0.447). However, the addition of adjuvant radiotherapy improved the overall 5-year survival rate of stage III patients (from 13.1 to 35.1%; p = 0.0027). A meta-analysis including these controlled trials showed no significant improvement in survival rates after ...

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