Esophageal Cancer: An Updated Review

Michael DiSiena, MD; Alexander Perelman, DO; John Birk, MD; Houman Rezaizadeh, MD


South Med J. 2021;114(3):161-168. 

In This Article


The treatment for AC and SCC is a complex individualized process that is beyond the scope of this review, but we discuss some general treatment options at each stage of EC. For low-grade noninvasive lesions such as high-grade dysplasia, one may treat with photodynamic therapy, cryotherapy, argon plasma coagulation, or radiofrequency ablation.[71–74]

T1a (limited to mucosa) lesions are candidates for endoscopy mucosal resection (EMR) if they are <2 cm and involve less than one-third circumference of the lumen. Success rates of EMR for such lesions is >90%. Complications include bleeding (approximately 10%), perforation (<5%), and stricture formation (approximately 4% but can be up to approximately 40% when there is resection of at least 50% of the esophageal mucosal circumference).[75–78] For T1b Sm1 lesions (superficial submucosa), endoscopic submucosal dissection can be used with comparable complication rates to EMR, and for lesions that are >2 cm and/or are T1b Sm2 (involving deep submucosa), a multidisciplinary and multimodality approach is best.[79–81]

For T2 and T3 esophageal malignancies, patients generally undergo neoadjuvant chemoradiation and then surgery. Common chemotherapy regimens are cisplatin and 5-fluorouracil and carboplatin and paclitaxel. Unresectable disease is generally managed with palliative chemoradiation. In addition, new immunologic systemic therapies are showing promise.[82]

Ramucirumab is a recombinant monoclonal antibody that binds and blocks tyrosine kinase receptor activation of the vascular endothelial growth factor (VEGF) receptor-2, and in turn, inhibits the effects of VEGF, which is associated with poor prognosis because it regulates angiogenesis and vascular permeability.[83] Trials using ramucirumab for gastric or AC have shown statistically significant improvement of progression-free survival (PFS) and median overall survival. Although the results were modest, with a PFS of 2.1 versus 1.3 months and a median overall survival of 5.2 versus 3.8 months (hazard ratio 0.78, 95% CI 0.60–0.99) when used with supportive care versus placebo, another trial using ramucirumab in conjunction with the chemotherapy paclitaxel noted a PFS of 4.4 versus 2.9 months and median overall survival improved to 9.6 versus 7.4 months (hazard ratio 0.807, 95% CI 0.678–0.962).[84,85]Ramucirumab alone or in combination with paclitaxel are now Food and Drug Administration-approved treatments of advanced gastric or AC junctional cancer.

Another immunomodulator, pembrolizumab, has been approved as a third-line treatment after a patient has failed chemotherapy and expresses programmed cell death (PD) ligand 1 in SCC or AC of the esophagus. Trials have showed superiority with the addition of pembrolizumab over standard systemic chemotherapy in patients with SCC or AC of the esophagus.[86–88]Pembrolizumab is an anti-PD receptor 1 (PD-1) monoclonal antibody. PD-1 is a critical immune checkpoint receptor that is expressed by activated T cells, and cancer uses the PD-1 pathway to evade immune surveillance by expressing ligands that bind PD-1 and cause immunosuppression, which in turn, prevents the immune system from rejecting the tumor.[89,90]