Treatment Regimens for Esophageal Adenocarcinoma

First-Line Treatment for Localized Disease

The American Society of Clinical Oncology recommends perioperative chemotherapy with FLOT (docetaxel, oxaliplatin, leucovorin, and fluorouracil) as the preferred first-line regimen for locally advanced esophageal adenocarcinoma, with a strength of evidence of high 1
The European Society for Medical Oncology suggests an alternative regimen of cisplatin/5-FU with or without epirubicin for locally advanced disease, with a strength of evidence of moderate 2, 3, 4
Preoperative chemoradiotherapy with carboplatin/paclitaxel plus 41.4-50.4 Gy radiation is an alternative first-line option, with a strength of evidence of high 1, 5

Adequate lymphadenectomy requires harvesting at least 16-18 and preferably 20 lymph nodes, with a strength of evidence of high 1

Perioperative chemotherapy (FLOT) is chosen when the tumor is smaller and located at the gastroesophageal junction, with a high likelihood of achieving complete surgical resection, and the patient cannot tolerate radiation therapy, with a strength of evidence of high 1, 7
Preoperative chemoradiotherapy is chosen when the tumor is bulkier with proximal extension, and there is concern about achieving complete surgical resection, with a strength of evidence of moderate 2, 4, 7

Adjuvant nivolumab should be administered if preoperative chemoradiotherapy was given and residual disease exists in the resection specimen, with a strength of evidence of moderate 7

The European Society for Medical Oncology recommends screening all esophagogastric junction tumors for HER2 overexpression or gene amplification, with a strength of evidence of high 2, 3, 6, 8
For HER2-positive metastatic tumors, trastuzumab plus cisplatin/fluoropyrimidine combination is used as first-line therapy, with a strength of evidence of high 2, 3, 6, 8
Platinum/fluoropyrimidine combinations are standard first-line options for HER2-negative tumors, with a strength of evidence of moderate 2, 6, 8, 9

Definitive chemoradiotherapy with cisplatin/5-FU plus 50.4-60 Gy radiation is the standard treatment for patients unable or unwilling to undergo surgery, with a strength of evidence of high 2, 4, 8

Surgery alone should not be used for locally advanced disease (T3-T4), as complete resection is achieved in only 50-70% and long-term survival rarely exceeds 20%, with a strength of evidence of high 4, 8
HER2 testing should not be skipped in metastatic esophagogastric junction tumors, as trastuzumab significantly improves outcomes in HER2-positive disease, with a strength of evidence of high 2, 3, 6, 8