Esophageal Cancer

Epidemiology and Etiology

Esophageal cancer is estimated to account for approximately 18,440 deaths in the US in 2020.¹ Esophageal cancer is 3-4 times more common in men.

Pathology

Adenocarcinomas are most common in the lower third of the esophagus and at the gastroesophageal junction, with incidence rising sharply over the last few decades in the US. Squamous cell carcinomas are more common in the upper and mid-esophagus.

Clinical Presentation

A small percentage of patients have asymptomatic tumors detected during endoscopy for unrelated causes or surveillance for Barrett esophagus. However, most patients present with dysphagia, initially to solids when the esophageal lumen is 13 mm or less, but progressing to liquids as the tumor grows and the lumen narrows. The diagnosis may be delayed because patients adjust the dietary intake to avoid foods that cause dysphagia. Other less common presentations include cough, hoarseness due to recurrent laryngeal nerve involvement, palpable cervical lymph nodes, and iron deficiency anemia from chronic gastrointestinal blood loss.

Diagnostic Testing

• The diagnosis is usually established through upper endoscopy with biopsy. Staging workup includes CT of the chest and abdomen, with or without the addition of PET scan, to determine the presence of distant metastases. For patients without distant metastases, endoscopic ultrasonography (EUS) is required to define tumor depth and lymph node status for staging and treatment planning.

• Tumors located above the carina increase the risk of tracheoesophageal (TE) fistula formation and should be evaluated with bronchoscopy.

Staging

The TNM classification is similar between squamous and adenocarcinoma histologies, including Tis (carcinoma in situ), T1 (invades lamina propria, muscularis mucosa or submucosa), T2 (invades muscularis propria), T3 (invades adventitia), T4 (invades adjacent structures), N0 (no lymph node involvement), N1 (1-2 regional lymph nodes), N2 (3-6 regional lymph nodes), N3 (7 or more lymph nodes), M0 (no metastases), M1 (distant metastases). Stage: staging varies slightly by histology, but in general: I (T1N0), II-III (T2-3 and/or N1), IVA (T4 or N2-3), IVB (M1).

TREATMENT

• Stage I (local): Endomucosal or surgical resection.

• Stage II-III (locally advanced, resectable): The standard therapy typically includes concurrent neoadjuvant chemoradiation with a platinum-based regimen followed by surgical resection. Patients who have residual disease on postoperative pathology may benefit from adjuvant nivolumab.¹⁰

• Stage IVA (locally advanced, unresectable): Standard therapy typically includes definitive concurrent chemoradiation with a platinum-based regimen.¹¹

• Stage IVB (metastatic): Patients with metastatic disease may be treated with combination chemotherapy regimens including fluoropyrimidines (5-FU or capecitabine), platinum agents (cisplatin or oxaliplatin), taxanes (docetaxel or paclitaxel), and irinotecan. Commonly used regimens include leucovorin, 5-FU and oxaliplatin (FOLFOX), capecitabine and oxaliplatin (CAPEOX or XELOX), and cisplatin and 5-FU. Patients with adenocarcinoma and HER2+ tumors should receive trastuzumab in combination with first-line chemotherapy. Patients with PD-L1 CPS #8805;5 may benefit from the addition of pembrolizumab to initial chemotherapy. Options for previously treated patients with recurrent disease include use of a regimen not used previously, including taxanes, irinotecan, ramucirumab, and pembrolizumab (if PD-L1 CPS #8805;1, deficient mismatch repair (dMMR), or micro-satellite instability (MSI-high) is present).