Esophageal and Esophagogastric Junction Cancers

Esophageal cancer is a major health hazard in many parts of the world. Several advances have been made in staging procedures and therapeutic approaches. Unfortunately, esophageal cancer is often diagnosed late; therefore, most therapeutic approaches are palliative. Multidisciplinary team management is essential for treating patients with esophageal cancer. Adenocarcinoma and SCC are the 2 major types of esophageal cancer. SCC is most common in the endemic regions of the world, whereas adenocarcinoma is most common in nonendemic regions. Tobacco and alcohol abuse are major risk factors for SCC, whereas the use of tobacco is a moderate established risk factor for adenocarcinoma. Barrett's esophagus, obesity, and GERD seem to be the major risk factors for development of adenocarcinoma of the esophagus or EGJ. EMR or ablation is the primary treatment option for medically fit patients with Tis tumors, whereas those with T1a tumors should be treated with EMR and ablation or esophagectomy. Esophagectomy is the preferred primary treatment option for medically fit patients with resectable noncervical cancer (T1b, any N), whereas chemoradiation is the preferred modality for those with cervical cancer. In medically fit patients with locally advanced resectable disease (T2 or higher, any N tumors), primary treatment options include preoperative chemoradiation (preferred for adenocarcinoma of the distal esophagus or EGJ), definitive chemoradiation (preferred for cervical cancer), rarely preoperative chemotherapy (for adenocarcinoma of the distal esophagus or EGJ), or esophagectomy. Postoperative treatment is based on histology, surgical margins, and nodal status. Among patients with SCC (irrespective of their nodal status), node-negative adenocarcinoma (T2-3, N0 tumors), and node-positive adenocarcinoma of proximal or mid esophagus, no further treatment is necessary if they have no residual disease at the surgical margins (R0 resection). Fluoropyrimidine-based chemoradiation is recommended for patients with node-negative adenocarcinoma (T2-3, N0 tumors), node-positive adenocarcinoma of proximal or mid esophagus, and adenocarcinoma of the distal esophagus and EGJ. Postoperative chemotherapy is recommended (only if preoperative chemotherapy was given) for patients with completely resected node-negative adenocarcinoma (T2-T3, N0) and node-positive adenocarcinoma of the lower esophagus and EGJ. All patients with residual disease at surgical margins (R1 and R2 resections) may be treated with fluoropyrimidine-based chemoradiation. Fluoropyrimidine- or taxane-based concurrent chemoradiation is recommended for unresectable disease, for patients with technically resectable disease who choose not to undergo surgery, and for those medically unfit for surgery and able to tolerate chemotherapy. Targeted therapies have produced encouraging results in the treatment of patients with advanced esophageal and gastroesophageal junction cancers. Based on the results of the ToGA trial, the NCCN panel has included trastuzumab plus chemotherapy as a new treatment option for patients with HER2-neu-positive advanced EGJ adenocarcinoma. HER2-neu testing is recommended if metastatic disease is documented or suspected. The efficacy of VEGFR and EGFR inhibitors in combination with chemotherapy for patients with advanced EGJ cancers is being evaluated in ongoing randomized phase III trials. Best supportive care is an integral part of treatment, especially in patients with locally advanced disease. Assessing disease severity and related symptoms is essential to initiate appropriate palliative interventions that will prevent and relieve suffering and improve quality of life for patients and their caregivers. Metastatic disease in patients with good performance status can be treated with chemotherapy plus best supportive care, whereas best supportive care is recommended for those with poor performance status. Endoscopic palliation of esophageal cancer has improved substantially because of improving technology. These guidelines emphasize that considerable advances have been made in the treatment of locoregional esophageal cancer. Novel therapeutic modalities, such as targeted therapies, vaccines, gene therapy, and antiangiogenic agents, are being studied in clinical trials for patients with esophageal cancer. The panel encourages patients with esophageal cancer to participate in well-designed clinical trials to enable further advances. © JNCCN-Journal of the National Comprehensive Cancer Network.