2. Diagnosis and treatment process for esophageal cancer

3. Principles of diagnosis and treatment

3.1 Clinical diagnosis

3.1.1 Risk factors and high-risk group

3.1.2 Clinical manifestations

3.2 Examinations

3.2.1 Lab tests

3.2.2 Tumor marker

3.2.3 Images

3.2.4 Endoscopy

3.2.5 Other tests

3.3 Diagnosis

3.3.1 Clinical diagnosis

3.3.2 Pathological diagnosis

3.4 Differential diagnosis

3.4.1 Other malignancies of esophagus

3.4.2 Benign tumors or tumor-like lesions of esophagus

3.4.3 Benign esophageal diseases

3.5 Pathological classification and staging

3.5.1 Segment of esophagus

3.5.2 Macroscopic type of esophageal carcinoma (Appendix A)

3.5.3 Pathological subtype and classification

3.5.4 Types of specimen and principle of specimen fixation

3.5.5 Principle of tissue dissection and description

3.5.6 Content and principle of pathological report

4. Standard treatment of esophageal carcinoma

4.1 Principle of treatment

4.2 Surgery

4.2.1 Principle of surgery

4.2.2 Indication of surgery

4.2.3 Contraindication of surgery

4.2.4 Follow-up

4.3 Radiotherapy

4.3.1 Indications for radiotherapy

4.3.2 Assessment of radiotherapy

4.3.3 Principle of radiotherapy

4.3.4 Dose

4.3.5 Normal tissue tolerance dose-limits

4.3.6 Concurrent chemotherapy regimens and dosing

4.3.7 Radiotherapy associated complications

4.3.8 Follow-up after radiotherapy

4.4 Medical management

4.4.1 Indications of chemotherapy for esophageal cancer

4.4.2 Assessment before chemotherapy

4.4.3 Regimens and dosing

4.4.4 Assessment of therapeutic effect

4.4.5 Prophylaxis and treatment of chemotherapy associated complications

4.4.6 Follow-up after chemotherapy

4.4.7 Progress in molecular targeted therapy and immunotherapy

4.4.8 Supportive and palliative treatment

4.5 Principle of early-stage cancer/precancerous disease of esophagus and endoscopic treatment

4.5.1 High-risk group of esophageal cancer

4.5.2 Methods of screening

4.5.3 Preoperative assessment of endoscopic treatment on early stage esophageal cancer

4.5.4 Endoscopic therapy for early-stage esophageal carcinoma

4.5.5 Follow-up for high-risk group and patients underwent endoscopic therapy

4.6 Treatment model for esophageal cancer

4.6.1 Stage I (T1N0M0)

4.6.2 Stage Ib, stage II and part of stage IIIa (T1b3N0M0, T12N1M0)

4.6.3 Stage III (T3N1M0, T4N01M0)

4.6.4 Stage IV (any T, any N, M1, N3 or T4b)

4.7 Traditional Chinese Medicine

Despite its wide variations in China, the case fatality rate of esophageal cancer is still high. In 2012, an estimation of 455,800 people would be diagnosed with esophageal cancer and 400,200 people would eventually die of their disease worldwide. Esophageal cancer is the 4th most common cause of cancer deaths in China, although its incidence somehow decreased during the recent years. According to Chen et al.’s report in 2017, the new cases of esophageal cancer in China reached 277,000 and 206,000 people died of this disease. The crude incidence rate of esophageal cancer in China is 20.35/100,000, including 15.03/100.000 in urban population and 30.73/100,000 in rural population while the crude death rate is 15.17/100,000 nationwide, including 14.41/100,000 in urban population and 21.05/100,000 in rural population. The incidence of esophageal cancer in China is more common in males and in rural population. High-prevalence areas mainly locate around the Taihang Mountain (e.g. provinces such as Henan, Hebei, Shanxi, Anhui, some areas of Shandong province such as: Taian, Jining, Heze, and the north of Jiangsu province). In the highest prevalence areas like Yangcheng of Shanxi province, Yangzhong of Jiangsu province and Cixian of Shanxi province, the crude incidence rate even reaches 109.5/100,000, 109.3/100,000 and 103.5/100,000, respectively (2003). Other high-prevalence areas are associated with the migration of people from the middle regions of China, including Nanchong and Yanting of Sichuan province, Shantou of Guangdong province and Fuzhou of Fujian province, etc. The incidence rate and death rate of esophageal cancer rank the 6th and the 4th in all malignancies, respectively. Therefore, esophageal cancer has long been one of the most threatening malignant tumors. Screening for the high-risk groups and for people living in the high-prevalence areas, early diagnosis and treatment are important to the improvement of the prognosis and living quality of patients with esophageal cancer. It effectively helps alleviate the medical cost of the people and government. Moreover, standardized diagnosis and treatment are also effective methods to improve the prognosis to benefit patients with mid-late esophageal cancer. Screening, early detection and standardized diagnosis and treatment should be important tasks for the hospitals and physicians nationwide.

Esophageal cancers are histologically classified as squamous cell carcinoma (SCC) and adenocarcinoma. SCC is the most common histological type in China (more than 90%), and adenocarcinoma is more common in North America and most European countries (about 70%). Smoking and alcohol abuse are major risk factors for SCC. Risk of SCC increases 3−8 times among the smokers and 7−50 times among the heavy drinkers. In the high-prevalence areas in China, nitrosamine and certain mold/fungi are the major risk factors. For adenocarcinoma, gastroesophageal reflux disease (GERD) and Barrett’s esophagus are the two major risk factors.

High-risk group for esophageal cancer refers to people over 40 years old living in the high-prevalence areas with family history of esophageal cancer, malignancies of digestive system or other malignancies, or with precancerous diseases or lesions. The methods to decrease the incidence rate of esophageal cancer include restraining from high-risk factors (smoking, alcohol abuse, etc.), adopting mold resisting measures, avoiding intaking nitrosamine, life style modification, and nutrition/hygiene improvement. Screening for individuals with high-risk factors is essential to the prevention and treatment of esophageal cancer that helps early detection, diagnosis and treatment.

The treatment of esophageal cancer is based on the stage of the disease. For early esophageal cancer which is limited in mucosa, endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) is the option for treatment. For early-mid esophageal cancers that invade into the submucosal layer, surgery is the main treatment. Postoperative adjuvant chemotherapy or radiotherapy may be offered if necessary. For mid-late esophageal cancer, the surgery-based comprehensive treatment is the choice. Either preoperative chemoradiotherapy, chemotherapy, or radiotherapy followed by surgery is usually utilized for the patients with lesions difficult to dissect or with more than 2 lymph nodes metastases. Postoperative chemotherapy or radiotherapy should be considered for these patients if necessary.