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Patients with stage 0 and early stage I (T1a) tumors are often amenable to endoscopic resection. Endoscopic resection avoids the high potential morbidity of esophageal resection. Tumors that are T1b are amenable to surgical resection alone without adjuvant therapies (chemotherapy or radiation). However, most esophageal cancers (T2 or higher, or any nodal involvement) are treated with combination chemotherapy and radiation (chemoradiation) before surgical resection (see table Staging Esophageal Adenocarcinoma). One study shows chemoradiation before surgery has a clear benefit to survival compared to surgery alone (1).

Another study showed that after surgery, immunotherapy (with nivolumab) added to neoadjuvant chemoradiation improved survival more than placebo (2).

Shallow (superficial) adenocarcinomas sometimes are cured by radiofrequency ablation.

Patients who are unable or unwilling to undergo surgery may receive some benefit from chemoradiation. Radiation or chemotherapy alone is of little benefit. Patients with stage IV disease require palliation and should not undergo surgery.

After treatment, patients typically are screened for recurrence by endoscopy and CT of the neck, chest, and abdomen at 6-month intervals for 2 to 3 years. Endoscopy is used after treatment with chemoradiation alone or endoscopic resection alone.

Patients with Barrett esophagus require intense long-term treatment for gastroesophageal reflux disease and endoscopic surveillance for malignant transformation at 3- to 12-month intervals depending on the degree of metaplasia.

Superficial, early, noninvasive cancers (Tis, T1a, N0) may be treated with endoscopic mucosal resection or endoscopic submucosal dissection (usually by gastroenterologists at tertiary care centers) if the superficial nature of the lesion has been confirmed by endoscopic ultrasound. However, in the large majority of cases, en bloc resection for cure requires removal of the entire tumor, proximal and distal margins of normal tissue, all potentially malignant lymph nodes, and a portion of the proximal stomach sufficient to contain the distal draining lymphatics. The procedure requires gastric pull-up with esophagogastric anastomosis, small-bowel interposition, or colonic interposition. Pyloroplasty (surgical widening of the pylorus) is required to ensure proper gastric drainage because esophagectomy necessarily results in bilateral vagotomy. This extensive surgery may be poorly tolerated by patients > 75 years, particularly those with underlying cardiac or pulmonary disease (ejection fraction < 40%, or forced expiratory volume in 1 second [FEV1] < 1.5 L/minute). Overall, operative mortality is about 5%.

Complications of surgery include anastomotic leaks, fistulas, and strictures; bilious gastroesophageal reflux; and dumping syndrome. The burning chest pain of bile reflux after distal esophagectomy can be more annoying than the original symptom of dysphagia and may require subsequent Roux-en-Y jejunostomy for bile diversion. An interposed segment of small bowel or colon in the chest has a tenuous blood supply, and torsion, ischemia, or gangrene of the interposed bowel may result.

Radiation is usually used in combination with chemotherapy for patients who are poor candidates for curative surgery, including those with advanced disease. Radiation is contraindicated in patients with tracheoesophageal fistula because tumor shrinkage enlarges the fistula. Similarly, patients with vascular encasement by tumor may experience massive hemorrhage with tumor shrinkage.

During the early stages of radiation therapy, edema may worsen esophageal obstruction, dysphagia, and odynophagia. This problem may require preradiation dilation and/or placement of a stent. Some patients may require a temporary percutaneous gastrostomy feeding tube. Other adverse effects of radiation therapy include nausea, vomiting, anorexia, fatigue, esophagitis, excess esophageal mucus production, xerostomia, stricture, radiation pneumonitis, radiation pericarditis, myocarditis, and myelitis (spinal cord inflammation).

Tumors are poorly responsive to chemotherapy alone. Response rates (defined as ≥ 50% reduction in all measurable areas of tumor) vary from 10 to 40%, but responses generally are incomplete (minor shrinkage of tumor) and temporary. No drug is notably more effective than another.

Most commonly, cisplatin and 5-fluorouracil are used in combination. However, several other drugs, including mitomycin, doxorubicin, vindesine, bleomycin, and methotrexate, also are active against squamous cell carcinoma.

Immunotherapy plus chemotherapy is now recommended as first-line therapy for advanced esophageal squamous cell cancer and can be given regardless of programmed cell death ligand 1 (PD-L1) status. This treatment modality also is offered as first-line therapy for advanced esophageal adenocarcinoma, but patients with overexpression of PD-L1 had greater responses in randomized trials (combined positive score > 5) (3).

Palliation is directed at reducing esophageal obstruction sufficiently to allow oral intake. Suffering caused by esophageal obstruction can be significant, with salivation and recurrent aspiration. Options include manual dilation procedures (bougienage), orally inserted stents, radiation therapy, laser photocoagulation, and photodynamic therapy. In some cases, cervical esophagostomy with feeding jejunostomy is required.

Relief provided by esophageal dilation rarely lasts more than a few days. Flexible metal mesh stents are more effective at maintaining esophageal patency. Some plastic-coated models can also be used to occlude malignant tracheoesophageal fistulas, and some are available with a valve that prevents reflux when the stent must be placed near the lower esophageal sphincter.

Endoscopic laser therapy can palliate dysphagia by burning a central channel through the tumor and can be repeated if needed. Photodynamic therapy uses an injection of porfimer sodium, a hematoporphyrin derivative that is taken up by tissues and acts as a photosensitizer. When activated by a laser beam directed on the tumor, this substance releases cytotoxic oxygen singlets that destroy tumor cells. Patients receiving this treatment must avoid sun exposure for 6 weeks after treatment because the skin is also sensitized to sunlight.

1. 1. Shapiro J, van Lanschot JJB, Hulshof MCCM, et al: Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): Long-term results of a randomised controlled trial. Lancet Oncol 16(9):1090–1098, 2015. doi: 10.1016/S1470-2045(15)00040-6

2. 2. Kelly RJ, Ajani JA, Kuzdzal J, et al: Adjuvant nivolumab in resected esophageal or gastroesophageal junction cancer. N Engl J Med 384(13):1191-1203, 2021. doi: 10.1056/NEJMoa2032125. Clarification and additional information. N Engl J Med 388(7):672, 2023.

3. 3. Wang H, Xuan T, Chen Y, et al: Investigative therapy for advanced esophageal cancer using the option for combined immunotherapy and chemotherapy. Immunotherapy 12(10):697–703, 2020. doi: 10.2217/imt-2020-0063