Preoperative and adjuvant therapies for upper gastrointestinal cancers.

Survival of esophageal, gastrointestinal junction and gastric cancers is poor given that they frequently present with locally advanced or metastatic disease. The incidence of gastrointestinal junction adenocarcinoma is increasing whereas that of squamous cell carcinoma of the esophagus is decreasing. The accuracy of staging has improved with newer diagnostic techniques, including positron emission tomography, endoscopic ultrasound and laparoscopy, and this should be integrated in prospective Phase III clinical trials evaluating neoadjuvant and adjuvant therapies for some esophageal and all gastric carcinomas. For esophageal cancer (except for one trial by Walsh and colleagues), four randomized Phase III trials comparing preoperative chemoradiation followed by surgery versus surgery alone have not shown a survival benefit. Neither have the trials, where preoperative chemoradiation followed by surgery, is compared with definitive chemoradiation. Nevertheless, it is commonly practiced in the USA and has become a preferred combined modality approach. Postoperative chemoradiation is favored in the USA for good performance status patients with resected, high-risk gastric or gastroesophageal junction carcinoma (more than Stage IA). The UK-MAGIC trial results, showing survival benefit with perioperative chemotherapy in operable gastric and lower esophageal cancers, probably has an impact on the treatment practice of these cancers in Europe and Asia. Promising results from trials involving preoperative chemoradiation followed by surgery in gastric cancer (pathologic complete response of 20-30%) need to be further evaluated in a Phase III setting and compared with postoperative chemoradiation. Active ongoing research will help us clarify the role of preoperative and adjuvant therapies in esophageal and gastric cancers. The role of molecular profiling is evolving and will help us differentiate the responders from the nonresponders.