OESOPHAGEAL CANCER OVERVIEW

OESOPHAGEAL CANCER OVERVIEW

  • Esophageal cancer is subdivided into the following four groups: epithelial tumors, metastatic tumors, lymphomas, and sarcomas.
  • Cancers of epithelial origin, predominantly squamous cell and adenocarcinomas, are the most common, and other histologic types are rare.
  • The appropriate categorization of gastroesophageal junction tumors has been controversial, and patients have been included in clinical trials directed both at esophageal and gastric cancers.
  • Within the United States, the incidence of esophageal cancer in persons younger than 80 years is 3.2 per 100,000 persons.
  • Historically and internationally, squamous cell tumors are the most common histologic type; however, a dramatic increase in the incidence of adenocarcinoma has been documented in the United States, United Kingdom, and Western Europe.
  • Exact etiology is unknown.
  • The data support the hypothesis that epithelial tumors arise as a result of chronic irritation from a wide variety of sources, including gastric contents in chronic reflux and known carcinogens.
  • A strong association of Barrett esophagus and adenocarcinoma is seen, but a benefit to screening endoscopy for those at risk for or with known Barrett esophagus is unknown as the overall risk of cancer-related mortality is low. Studies with longer-term follow-up are needed to clarify this issue. Other identified risk factors are gastroesophageal reflux disease (GERD), obesity, and smoking.
  • Squamous cell carcinoma is associated with smoking as well as alcohol use, and the declining incidence has paralleled the decline in smoking.
  • Point mutations, increased copy number, and promotor region hypermethylation all appear important in the progression to malignancy.
  • Symptoms and demographics will strongly suggest the diagnosis.
  • Endoscopy is the best screening examination but esophagram may also be used.
  • Diagnosis is made by endoscopy with cytology and biopsy of tumor.
  • Transoesophageal ultrasound should be used to assess T and N stage to guide optimal definitive therapy.
  • Computed tomography (CT) of chest and abdomen is useful in screening for metastatic disease.
  • Positron emission tomographic (PET) scan is useful to detect additional cases of metastatic disease before costly and toxic definitive therapy. It may be superior to endoscopic ultrasound (EUS) in detecting intraabdominal lymph nodes, but not periesophageal nodes adjacent to the primary tumor.
  • Additional studies include laparoscopy, thoracoscopy, bone scan, and CT of the brain when indicated by clinical circumstances.
  • The new AJCC/UICC 7 staging system contains important changes: adenocarcinoma and squamous cell carcinoma are separate; grade of histology is incorporated; the gastroesophageal junction is defined; nodal staging is based on number of involved nodes, similar to gastric cancer; Tis includes high graded dysplasia; and T4 is subcategorized by features suggestive of resectability.
  • Staging is based on pathological findings at the time of resection, but therapy is often guided by staging estimated by clinical testing.
  • Treatment of premalignant dysplasia is guided by grade of histology. Low-grade dysplasia should be closely followed by endoscopy. High-grade dysplasia is treated with endoscopic therapy or esophagectomy, although close follow-up may be appropriate for selected patients.
  • Selection of appropriate treatment for carcinoma depends on tumor stage and patient performance status.
  • Surgery is an accepted single-modality therapy for patients with early localized disease (T1-2N0M0) or for patients who may not tolerate combined-modality therapy. The selection of surgical approach depends upon location and experience, but no approach has been demonstrated to lead to superior cure rates.
  • Combined chemoradiation leads to prolonged median survival and long-term survival compared with radiation alone used as a definitive nonoperative approach, at the price of increased toxicity. This represents a potentially curative alternative to surgery for squamous cell cancers and is appropriate for most unresectable T4N and M0 lesions of either histology. Because most patients treated on prospective chemoradiation trials had squamous cell carcinomas, the benefits of nonoperative management for adenocarcinoma are not known.
  • Randomized trials have not confirmed a survival benefit with surgery added to potentially curative chemoradiation in squamous cell carcinoma, but there was a significant local control benefit. This question has not been well studied for adenocarcinoma, for which definitive chemoradiation is of uncertain curative potential.
  • Accumulating evidence convincingly demonstrates that combination therapy with preoperative chemoradiation followed by surgery survival compared with surgery alone for both locally advanced (clinically staged T2-T4 or node positive) adenocarcinoma and squamous cell carcinoma. There is less certainty about the value of preoperative chemotherapy alone.
  • Postoperative adjuvant chemotherapy or chemoradiation is less well studied in locally advanced esophageal cancer, but trials in gastric cancer including gastroesophageal junction adenocarcinoma have demonstrated a benefit.
  • Combined-modality chemotherapy regimens frequently include 5-fluorouracil (5-FU) or paclitaxel and platinum agents; other commonly used regimens include docetaxel and irinotecan.
  • Endoscopic palliative therapy includes laser or electrical fulguration, mucosal resection, photodynamic therapy (PDT), or stenting. Excepting very superficial lesions, these therapies are not alternatives to surgery as they do not address deeper disease or lymphatic spread.
  • Radiation therapy, with or without chemotherapy, may be used to palliate local symptoms.
  • Chemotherapy may be used for metastatic disease, but response rates and duration of response are modest for most patients. Clinical trials are recommended.

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Genomic Medicine UK is the home of comprehensive genomic testing in London. Our consultant medical doctors work tirelessly to provide the highest standards of medical laboratory testing for personalised medical treatments, genomic risk assessments for common diseases and genomic risk assessment for cancers at an affordable cost for everybody. We use state-of-the-art modern technologies of next-generation sequencing and DNA chip microarray to provide all of our patients and partner doctors with a reliable, evidence-based, thorough and valuable medical service.

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