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Esophageal and gastric cancer
Esophageal cancer
Key Points About Esophageal cancer
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Relatively uncommon cancer (annual incidence 4.3/100,000)
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The median age at diagnosis is 68 years.
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The incidence of squamous cell cancer of the esophagus has declined substantially, whereas the incidence of adenocarcinoma of the distal esophagus and especially the gastroesophageal junction has increased in recent decades.
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The most common risk factors for squamous cell esophageal cancer are alcohol use and tobacco smoking and for esophageal adenocarcinoma obesity and chronic gastroesophageal reflux disease (GERD).
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5-year survival prognosis is approximately 20% overall; survival beyond 2 years is uncommon in metastatic disease.
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Esophageal cancer limited to the mucosa can often be endoscopically resected.
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Patients with more advanced, but localized tumors, T3, T4, or node-positive, are usually treated with multimodality therapy, most commonly, neoadjuvant chemoradiotherapy followed by resection.
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Systemic therapy is the primary treatment for metastatic disease, historically, with fluoropyrimidines and platinum drugs, and more recently, with the addition of immune checkpoint inhibitors.
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Both systemic therapy and radiotherapy for esophageal cancer have the potential to result in cardiotoxicity in patients undergoing treatment, but cardiotoxicity for localized disease is rare.
Incidence
According to the Surveillance, Epidemiology, and End Results (SEERs) registry, the estimated number of new cases of esophageal cancer in the United States in 2019 was 17,650. The annual incidence is 4.3/100,000. Esophageal cancer is more common in males than females, and the difference is more prominent in cases of adenocarcinoma. Worldwide, esophageal cancer is estimated to affect almost 600,000 patients, with the majority of them dying as a result of the cancer.
Risk factors
Established risk factors for squamous cell carcinoma of the esophagus include tobacco smoking and alcohol use, especially when used in combination. Less-common causes include achalasia, prior thoracic radiation therapy, and ingestion of caustic chemicals resulting in tissue injury. Intake of fruits and vegetables appears protective and some studies have suggested an increased risk related to red meat consumption and drinking of very hot beverages. Although the incidence of squamous cell carcinoma has decreased markedly in the United States and Europe, squamous cell cancer remains the most common esophageal cancer histology worldwide. The decrease in the incidence of esophageal squamous cell cancer is likely in large part explained by a decrease in tobacco smoking. On the other hand, the incidence of esophageal adenocarcinoma has increased substantially in the United States and Europe, largely owing to increased rates of obesity and chronic gastrointestinal reflux disease (GERD). The development of adenocarcinoma in patients with GERD is thought to be secondary metaplasia of the squamous epithelium or Barrett’s esophagus. Consequently, patients with chronic GERD are at an increased risk of developing esophageal adnocarcinoma. Other risk factors associated with esophageal adenocarcinoma include smoking and obesity.
Prognosis
Overall, the prognosis of esophageal cancer remains poor, and survival highly depends on stage. Among all patients diagnosed with esophageal cancer, approximately 20% are expected to be alive 5 years from diagnosis. Survival beyond 2 years is uncommon in metastatic disease. With the exception of the earliest stages (T1N0) esophageal tumors, almost half of patients with locoregional esophageal cancer will experience recurrence of the malignancy and eventually die of metastatic disease. Overall, the prognosis for patients with esophageal cancer has improved over the last few decades, and the improvement in survival is seen across all stages of the disease.
Treatment overview
Very early stage disease (T1a)
In cases of early-stage esophageal cancer, endoscopic therapy can be very effective and even curative, but such therapy is generally limited to the earliest stages of the cancer (T1a), where there is minimal invasion limited to the mucosa or for cancer in situ . Endoscopic mucosal resection, endoscopic submucosal dissection, and radiofrequency ablation are among the endoscopic techniques used.
Localized disease
The management of more advanced, but localized, esophageal cancer is best done in a multidisciplinary setting. Patients with node-negative T1b and T2 tumors are typically treated with esophagectomy alone. In cases of nodal involvement and/or more advanced primary tumors (T3 and T4), multimodality therapy is required for optimal outcomes. The role of neoadjuvant chemoradiation therapy for resectable T2N0 esophageal cancer is unclear. For patients with squamous cell carcinoma, neoadjuvant chemoradiotherapy, typically combining external beam radiotherapy with weekly carboplatin and paclitaxel, is preferred, and results in outcomes better than observed with surgery alone. , In patients where radiotherapy is contraindicated, neoadjuvant chemotherapy followed by resection yields better outcomes than surgery alone. The additional benefit of resection following chemoradiotherapy has been questioned in patients with squamous cell carcinoma because of the exceptional responses seen with chemoradiotherapy, with pathologic complete response rates approaching 50%. However, given the lack of definitive data for chemoradiotherapy alone, surgery is recommended following neoadjuvant therapy (trimodality therapy) with definitive chemoradiotherapy alone (bimodality therapy) reserved for patients either unfit for surgery or unwilling to undergo surgery. A similar treatment paradigm is used for patients with adenocarcinoma of the esophagus, although resection is considered an essential component of the treatment unless contraindicated owing to comorbidities. Data do support neoadjuvant and adjuvant chemotherapy (with omission of chemoradiotherapy), particularly for Siewert type III disease, and chemotherapy with FLOT (5- f luorouracil, l eucovorin, o xaliplatin and docetaxel [ T axotere]).
Patients with nonmetastatic, but inoperable esophageal cancer, including cervical esophageal cancer, but fit for combined modality therapy, should be considered for definitive chemoradiotherapy. Patients with squamous cell carcinoma can be considered for cisplatin and 5-fluorouracil (5-FU) given concurrently with radiation therapy. Carboplatin and paclitaxel is also a reasonable combination with radiation therapy, especially for adenocarcinoma.
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