Esophageal cancer: Clinical sciences

Esophageal cancer is a malignant tumor of the esophagus or esophagogastric junction. Two main pathologic types of esophageal cancer include squamous cell carcinoma and adenocarcinoma. Esophageal cancer is associated with high morbidity and mortality as more than 50% of patients present with advanced disease. However, even with early diagnosis and treatment, esophageal cancers have very poor long-term outcomes.

When a patient presents with chief concern suggestive of esophageal cancer, the first step is to obtain a focused history and physical, and labs including CBC and CMP. Although most patients are asymptomatic, some might report dysphagia, odynophagia, epigastric or retrosternal pain, regurgitation of food or saliva, cough, and hoarseness. They might also have associated anemia or weight loss.

Additionally, history might reveal risk factors, such as tobacco or alcohol use, high BMI, gastroesophageal reflux disease or Barrett's esophagus, as well as a family history of esophageal cancer, or genetic conditions like Fanconi Anemia or Bloom Syndrome.

The physical exam is typically unremarkable, but might reveal cachexia, and sometimes lymphadenopathy and hepatomegaly if the disease has metastasized. Finally, labs typically show anemia, electrolyte abnormalities, or elevated liver enzymes. So, if you see these findings, suspect esophageal cancer.

Your next step is to obtain imaging. The first choice is an upper endoscopy with biopsy and an endoscopic ultrasound with fine-needle aspiration if there are any suspicious lymph nodes. However, bronchoscopy can be performed if you suspect a tumor above the carina.

Endoscopy allows us to see macroscopic features, such as strictures, ulcerations, or an exophytic, fungating, or circumferential mass. Biopsy of these suspicious features will likely show invasive adenocarcinoma or squamous cell carcinoma, also known as SCC.

Here’s a clinical pearl! Imaging can be done, where upper GI fluoroscopy can show a classic apple core lesion, or CT imaging can be done, which would show circumferential thickening of the esophagus. In addition, you can expect the ultrasound to show the invasion of the mucosa, submucosa, or even beyond such as full-thickness invasion of the esophageal wall. The ultrasound can also show any locoregional lymphadenopathy that might be present. The combination of these findings confirms the diagnosis of esophageal cancer.

Okay, back to our biopsy, if it shows squamous cell carcinoma, that’s your diagnosis! The next step in your workup is to stage the cancer using the TNM staging system by evaluating the size of the lesion, lymph node involvement, and the presence of metastatic disease. Since you were able to determine the size of the tumor and locoregional lymph node involvement using endoscopy and ultrasound, you’ll need to evaluate for involvement of distant lymph nodes or metastatic disease by ordering a CT of the chest and abdomen. Sometimes, you might need additional imaging like a CT of the pelvis or a PET scan.

If endoscopy reveals a tumor that’s less than 2 cm, and ultrasound and biopsy show no invasion of deep submucosa in addition to no signs of lymphadenopathy or distant metastasis on CT, you have stage 1A esophageal cancer.

This is a favorable diagnosis, and the treatment of choice is endoscopic resection. A complete resection confirmed through pathological assessment is regarded as curative, and can be followed only by surveillance. Surveillance includes a history and physical every 3 to 6 months for years 1 and 2, then every 6 to 12 months for years 3 to 5, and annually thereafter. Esophagogastroduodenoscopy or EGD is performed every 6 months during year 1, and then annually up to year 5. On the other hand, if you have an incomplete resection, your next step is to obtain a surgical consultation for an esophagectomy to achieve complete resection of the tumor.

Now let’s go back and talk about a more advanced disease. On endoscopy, these lesions are typically greater than 2 cm, and ultrasound shows invasion of the submucosa. If no distant metastasis is present, staging is based on specific tumor characteristics. Stage 1B to 2 disease means that the tumor has low-risk features. This means a size less than 3 cm and well-differentiated with no lymphovascular invasion on histopathology. The treatment for these patients mainly involves surgical consultation for esophagectomy. Once complete resection of the tumor has been achieved, the patient can go into surveillance.

On the other hand, tumors with high-risk features, including deep level of tissue invasion, or lymph node involvement are considered to be Stage 2, 3, or 4A. Stage 2 with high-risk features means that the tumor is greater than 3 cm, poorly differentiated, and invades through the muscularis propria with lymphovascular invasion. Stages 3 and 4A imply full-thickness invasion with nodal involvement.