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Gastric and esophageal cancers are one of the most aggressive malignancies worldwide. Complete surgical resection offers the only chance of cure but many cases are presented at advanced stages or recur even after R0 resections. In gastric cancer (GC), 5-year survival rates (SRs) of stages II and III after curative resection range respectively from 30%-49% and 10-20% in Western countries, and respectively 70-80% and 40-50% in Japan and Korea (Fujii et al., 1999; Hundahl et al., 2000; J.P.Kim et al., 1998; Shimada et al., 1999). With regard to esophageal cancer (EC), the 5-year SRs in older series were 14-20% in the United States (Daly et al., 1996; Ries et al., 2007) and ranging from 3 to 11% in European countries, with an average of 10% (Faivre et al., 1998) while they improved to 42% in a recent series (Rice et al., 2009; Ruol A et al., 2009), which is comparable to those (36-46%) after an esophagectomy in Japan (The Japan Esophageal Society). Even in Japan, however, T3 or stage III EC, the most frequently encountered tumor depth or tumor stage, has exhibited respectively lower 5-year SRs of 27-29% and 17-20% after esophagectomy (Ando et al., 2000; The Japan Esophageal Society). Although stage-specific survival rates differ between reports from Western and Asian institutions, the survival decline according to the stage progression suggests that recurrence does occur even for those who undergo curative resection. Furthermore, a more extended (>D2) lymph node dissection (LND) in GC unfortunately fails to improve survival outcomes (Sasako et al., 2008). Such disappointing treatment results in GC and EC even in Japan -where aggressive LND has been performedhave reminded researchers a plateau effectiveness of, and little likelihood of further improvement by, surgical therapy only. These facts have encouraged physicians to establish more effective multimodal strategies to improve survival, including newly developed regimens incorporating molecular targeting agents as well as to determine candidate molecules or genes that could help establish individualized therapies. These multimodal therapies have mainly consisted of chemotherapy (CTx), radiotherapy (RTx), and chemoradiotherapy (CRTx) administered after curative resection (adjuvant settings), or for recurrent or inoperable diseases (advanced settings), or before surgical resection (neoadjuvant settings). Recently, CRTx has become a focus of research, because of the radiosensitizing properties of some chemotherapeutic agents that could potentiate the anticancer activities of both CTx and RTx (Kleinberg et al., 2007). Table lists the theoretical advantages and disadvantages of adjuvant and neoadjuvant treatments (Rice et al., 2003). Adjuvant and neoadjuvant treatments require balancing advantages and disadvantages to maximize treatment effects. This chapter focuses on past, current, and potential future directions in the field of multimodal therapies in GC and EC.

Multimodal Therapies for Upper Gastrointestinal Cancers – Past, Now, and Future