Esophageal and Esophagogastric Junction

Disclaimer

This manual is not a substitute for consultation with an appropriate specialist.
The contents of this manual have been developed through consensus of a Provincial Tumour Group. Please note the various update dates for each section as some of the content of the manual may not be up to date.

1. Screening

There are no recommended screening guidelines for esophageal cancer.

Barrett’s esophagus:

- Characterized by replacement of stratified squamous epithelium of the distal esophagus by columnar epithelium with intestinal metaplasia (on review by expert gastrointestinal pathologists)

- Risk of progression to adenocarcinoma of the esophagus depends on factors including length of Barrett’s (short vs long segment), and grade of dysplasia (low vs high-grade dysplasia).

- American Gastroenterological Association (AGA) recommends screening for Barrett's esophagus in patients with multiple risk factors associated with esophageal adenocarcinoma (age 50 years or older, male sex, white race, chronic gastro-esophageal reflux disease (GERD), hiatal hernia, elevated body mass index, or intra-abdominal distribution of body fat), but not for the general population with GERD.

- Acid-reducing agents, specifically proton-pump inhibitors, can reduce symptoms and heal endoscopic findings of erosive esophagitis, but its effect on progression to dysplasia or cancer has not been well established

- Endoscopic ablative treatment (eg. radiofrequency ablation)/mucosal resection (EMR) and surveillance recommendations depend on the presence and grade of dysplasia within the Barrett’s segment:

No dysplasia: Endoscopic treatment not recommended, and surveillance endoscopy every 3 - 5 years
Low grade dysplasia: Endoscopic treatment can be considered, and in its absence, surveillance endoscopy every 6 - 12 months
High grade dysplasia: Endoscopic ablation/esophagectomy generally recommended, and in its absence, surveillance endoscopy every 3 months

2. Diagnostic and Staging Work-Up

Added 06 March 2013

- Esophagogastroduodenoscopy can identify, localize (from the incisors) and biopsy suspicious intraluminal masses. CT scan of the chest and abdomen is recommended to assess the extent of local involvement and to exclude distant metastases.

- Locoregional staging can be performed by endoscopic ultrasound (EUS).

- PET should be considered in cases with no evidence of distant metastases on CT imaging. If no metastases are seen on baseline imaging, a PET scan may exclude occult metastases.

- In patients who are being considered for surgery or radical external beam radiotherapy, pulmonary function tests are required

- Recommended baseline tumour markers at diagnosis: CEA, CA19-9

3. Primary Surgical Therapy

Added 06 March 2013

Phase III evidence supports the initiation of chemotherapy, radiation or both pre-operatively which is preferable to post-operative therapy.

Early referral to a thoracic surgeon, medical and radiation oncologist is strongly recommended to plan optimal therapy.
Esophagectomy: transhiatal or transthoracic
For those with cancer of the esophagogastric junction where a “gastric pull-up” procedure is anticipated, referral to the BCCA at the time of diagnosis is recommended for consideration of preoperative treatment.

4. Pathology

Added 06 March 2013

per College of American Pathologists (CAP) 2012 guidelines

Specimen: specify

Type
Procedure

Tumour: specify

Primary tumour site- cervical esophagus, mid-esophagus, distal esophagus, esophago-gastric junction (EGJ). [Adenocarcinoma arising at the EGJ or within the proximal 5cm of the stomach and involving the EGJ are staged as an esophageal tumour ]
Histologic type
Histologic grade (well, moderately, poorly differentiated or undifferentiated)
Size (Longitudinal tumour dimension, semi-circumferential/ circumferential lesion)
Microscopic tumour extension/invasion
Lymph-Vascular invasion (present/absent)
Surgical margins: proximal, distal, omental (radial), deep (for endoscopic resections); state if involved by dysplasia or invasive carcinoma; state closest approach of invasive carcinoma to margin in mm.)
Treatment effect(post neo-adjuvant therapy, if applicable) (present/absent)
Status of background mucosa (i.e. Barrett’s esophagus, dysplasia, etc.)
Lymph node status (x of y lymph nodes positive)
HER2-neu testing in gastroesophageal adenocarcinoma:

by immunohistochemistry (IHC)
fluorescence in-situ hybridization if IHC is 2+

pTNM tumour stage (AJCC 7th edition)

Primary Tumour (pT) (Note: this is optional)

pTX: Cannot be assessed

pT0: No evidence of primary tumour

pTis: High-grade dysplasia

pT1: Tumour invades lamina propria, muscularis mucosae, or submucosa

pT1a: Tumour invades lamina propria or muscularis mucosae

pT1b: Tumour invades submucosa

pT2: Tumour invades muscularis propria

pT3: Tumour invades adventitia

pT4: Tumour invades adjacent structures (specify): ______________________

pT4a: Resectable tumour invading pleura, pericardium, or diaphragm

pT4b: Unresectable tumour invading other adjacent structures, such as aorta, vertebral body, trachea, etc

Regional Lymph Nodes (pN)

pNX: Cannot be assessed

pN0: No regional lymph node metastasis

pN1: Regional lymph node metastasis involving 1 to 2 nodes

pN2: 3 to 6 nodes involved

pN3: 7 or more nodes involved

Distant Metastasis (pM)

Not applicable

pM1: Distant metastasis (specify site(s))

5. Staging

EsophagusCardiaStagingDiagramRevised13Aug2012.pdf

6. Treatment Options by Stage

Added 06 March 2013

Treatment options are based on current evidence

Tis-T1, N0, M0

Esophagectomy is preferred

Endoscopic mucosal resection for superficial disease

Photodynamic therapy or other ablative therapy for superficial disease

Primary chemoradiation (GIEFUPRT) in those who are not candidates for esophagectomy (including squamous cell carcinomas of the proximal esophagus)

Radiotherapy alone in those who are not candidates for esophagectomy or chemotherapy

Nutrition consultation and placement of a feeding tube should be considered in patients undergoing multimodality treatment

T2, N0, M0

Consider pre-operative chemoradiation.

Esophagectomy

Primary chemoradiation (GIEFUPRT) in those who are not candidates for esophagectomy

Nutrition consultation and placement of a feeding tube should be considered in patients undergoing multimodality treatment

T3-4a or N+, M0

Preoperative multidisciplinary evaluation by surgery, medical oncology and radiation oncology is recommended for these patients with high-risk resectable disease for consideration of:

Neoadjuvant chemoradiotherapy (UGIENACTRT) followed by esophagectomy or
Perioperative chemotherapy for adenocarcinoma of the distal esophagus or esophagogastric junction (GIGECC, GIGECF) with esophagectomy
Following preoperative therapy, restaging with CT and, preferably, with PET imaging is recommended prior to resection to assess clinical response

Primary chemoradiation (GIEFUPRT) in those who are not candidates for esophagectomy

Nutrition consultation and placement of a feeding tube should be considered in patients undergoing multimodality treatment

Unresectable, recurrent, or metastatic disease

Palliative radiation, endoscopic dilation or stenting can improve symptoms, such as dysphagia and bleeding, and quality of life. Palliative chemotherapy may be given to help improve symptoms and quality of life, and extend survival in appropriately selected patients.

Adenocarcinoma is more responsive to chemotherapy than squamous cell carcinoma.

Currently approved chemotherapeutic agents for advanced esophageal carcinoma include: 5-fluorouracil (5-FU), capecitabine, cisplatin, epirubicin, and irinotecan.

The most commonly used regimens are:
- For squamous cell carcinoma: 5-FU and cisplatin (GIFUC)
- For adenocarcinoma:
  - 5-FU and cisplatin (GIFUC)
  - Epirubicin, cisplatin and 5-FU (ECF) or capecitabine (ECC)
  - 5-FU and irinotecan (FOLFIRI)
The choice and sequence of chemotherapy is determined by disease-related factors, patient factors and patient preferences as assessed by the medical oncologist.

In 20-25% of patients with gastroesophageal junction adenocarcinoma, there is tumour over-expression of the HER2 protein. Patients with HER2 2+/FISH+ or 3+ disease may benefit from the addition of the targeted agent trastuzumab.

The most commonly used regimen combines trastuzumab with cisplatin, and 5-FU (UGIGAVCFT) or capecitabine (UGIGAVCCT)
Patients who are responding after 6 cycles of chemotherapy with trastuzumab may continue with maintenance single agent trastuzumab (UGIGAVTR) until disease progression.

Please refer to current treatment protocols for indications, dosing and eligibility criteria.

Consider treatment on a clinical trial, if available.

Symptom management, best supportive care, and involvement of palliative care services as indicated by patient’s clinical status.

7. Follow-up

Added 06 March 2013

Patients who have undergone treatment for superficial disease should have endoscopic surveillance.
Patients who had radiation or surgery are at risk of developing esophageal strictures resulting in dysphagia which can be treated with dilation or stenting. There is no evidence that routine imaging or laboratory investigations are useful in detecting recurrences or metastases at a stage where interventions are curative. Early detection of asymptomatic metastases does not enhance survival.
Investigations should be performed based the clinical presentation of a patient who is suspected of having recurrent or metastatic disease.