Saudi Oncology Society clinical management guideline series. Esophageal cancer 2014.

A total of 123 case of esophageal cancer have been diagnosed in Saudi Arabia in 2010 accounting for 1.25% of all cancers for that year.1 The age standardized rate was 1.4/100,000 for males and 1/100,000 for females.1

A committee of experts in the medical and surgical treatment of esophageal cancer was established under the supervision of the SOS.

The evidence adopted in these guidelines is rated at 3 levels: 1) Evidence level-1 (EL-1) (highest level) evidence from phase III randomized trials or meta-analyses, 2) EL-2 (intermediate-level) evidence from good phase II trials or phase III trials with limitations, and 3) EL-3 (low-level) from retrospective or observational data and/or expert opinion. This easy-to-follow grading system is convenient for the reader and allows accurate assessment of the applicability of the guidelines in individual patients.2

All esophageal cancer cases are preferably seen or discussed in a multidisciplinary form.

Pre-treatment evaluation:

Clinical examination

Blood count

Barium swallow

Upper gastrointestinal (GI) endoscopy and biopsy. Multiple biopsies are preferred.

Computed tomography (CT) scan of the chest, abdomen, and pelvis

Endoscopic ultrasound (EUS) ± biopsy

Positron emission tomography (PET)/PET-CT in patients who lack evidence of distant metastasis on CT scan

Bronchoscopy: preoperative bronchoscopy with biopsy and brush cytology for patients with locally advanced non-metastatic tumors that are located at or above the level of the carina

Laparoscopy (optional): if no evidence of metastatic (M1) disease by radiological examination and tumor is at the gastroesophageal (GE) junction. Biopsy confirmation is mandatory

Her-2 testing if metastatic adenocarcinoma is documented

Nutritional assessment (in preoperative setting): consider naso-gastric tube (percutaneous endoscopic gastrostomy is not recommended)

Surgical pathology report requirement. The following parameters should be mentioned in all surgical pathology reports of esophageal cancer;

Specimen

Tumor site (location)

Relationship of tumor to esophagogastric junction

Distance of tumor center from esophagogastric junction (specify, if applicable)

Tumor size

Histologic type

Histologic grade

Microscopic tumor extension

Margins: proximal, distal, and circumferential or deep

If all margins uninvolved by invasive carcinoma: distance of invasive carcinoma from closest margin in cm

Treatment effect (applicable to carcinomas treated with neoadjuvant therapy)

Lymphovascular invasion

Perineural invasion

Pathological tumor-node-metastasis: this should include number of lymph nodes examined, number of lymph nodes involved, and distant metastasis (pM)

Additional pathologic findings

Clinical history

Staging:

TNM - 2007 pathological staging system will be used6

Treatment:

Clinically localized resectable disease: Treatment will depend on the clinical status of the patient and resectability of the tumor

Medically fit and resectable disease

Stage Tis (in-situ), N0: Endoscopic mucosal resection (EMR) or ablation7 (EL-3)

Stage T1a, N0: Endoscopic mucosal resection8 (EL-2) or esophagectomy9 (EL-2)

Stage T1b, N0: Esophagectomy (for non-cervical esophagus) (EL-1) and chemoradiation10,11 (for cervical esophagus)

For stage T2 or higher (except T4b): Any N or stage T1-4aN+: options are:

Preoperative chemoradiotherapy with 41.4-50.4 Gy of external beam radiotherapy + concurrent chemotherapy (EL-1) (options of the regimen include 2 courses of cisplatin and 5-fluorouracil (5-FU) + 50.4 Gy of radiotherapy,12 or low-dose weekly carboplatin plus paclitaxel regimen + 41.4 Gy)13

Preoperative/perioperative chemotherapy for adenocarcinoma of distal esophagus or gastro-esophageal junction (GEJ, EL-1) (options include epirubicin, cisplatin, plus fluorouracil [ECF] chemotherapy or equivalent used in The Medical Research Council Adjuvant Gastric Infusional Chemotherapy trial,14 or infusional 5-FU plus cisplatin or equivalent as was used in the Federation Nationale des Centres de Lutte contre le Cancer/Federation Francophone de Cancerologie Digestive trial)15

Esophagectomy with postoperative adjuvant chemoradiotherapy for those with adenocarcinoma, node-positive disease or a T2 or higher primary tumor stage16 (EL-3). Can use adjuvant chemotherapy alone if radiotherapy is contraindicated17

Definitive chemoradiation (for cervical cancer).18 If there is still persistent local disease, perform a salvage esophagectomy if possible

Medically unfit for surgery or unresectable T4 (T4b) disease: options include

Definitive concurrent chemoradiotherapy.18 Radiation dose is 45-50.4 Gy, the latter is preferred

Palliative chemotherapy (see metastatic disease)

Palliative radiotherapy if cannot tolerate chemotherapy

Best supportive care if cannot tolerate chemotherapy or radiotherapy

Radiation technique: 3D conformal/intensity-modulated radiation therapy (IMRT)/rapid arc techniques should be used for modern treatment planning to minimize toxicities to adjacent vital organs (namely, heart, lung, spinal cord, or liver)19

Surgical approach

The surgical approach should be based upon anatomic tumor location

Patients with Siewert type I tumors are not appropriate candidates for a purely transabdominal approach to surgical resection. The standard surgical approach is a transthoracic en bloc esophagectomy and partial gastrectomy with 2-field lymphadenectomy20

For the majority of Siewert type II and III tumors, total gastrectomy with a transabdominal/transhiatal resection of the distal esophagus with lymphadenectomy of the lower mediastinum and the abdominal D2 nodal compartment is adequate21

The surgical therapy does not differ in patients who have or have not undergone induction therapy. For most thoracic esophageal cancer resections, it is suggested that a total thoracic esophagectomy with cervical esophagogastrectomy, radical 2-field lymph node dissection, and jejunostomy feeding tube placement22 (EL-2)

Tri-incisional approach is preferred, it consists of initial right posterolateral thoracotomy (or a thoracoscopic approach for mobilization of the intrathoracic portion of the esophagus and node dissection, in centers with expertise in these techniques) followed by laparotomy to obtain complete esophageal dissection and mobilize the gastric conduit, en bloc resection of both mediastinal and upper abdominal lymph nodes, and a left neck incision and cervical anastomosis23

Totally minimally invasive esophagectomy is considered as a second option if expertise is available and the tumor is small and adequate oncological resection is possible24 (EL-2)

Advanced unresectable or metastatic disease: Treatment will consist of palliative chemotherapy, options are as follows:

docetaxel, cisplatin,25 infusional 5-FU (DCF)26 or epirubicin, oxaliplatin and capecitabine (EOX)27 combinations are standard regimens for first-line treatment (EL-1). Alternative regimens are:

Cisplatin/Capecitabine28 or cisplatin / 5FU29

Leucovorin, and oxaliplatin (FOLFOX) regimen and 5-FU30

Trastuzumab, to be added to any of the above regimens (except ECF/EOX) in adenocarcinoma of GEJ with positive Her-2 test (defined by 3+ immunohistochemical staining or florescent in-situ hybridization positivity)31 (EL-1)

For elderly, or patients with performance status 3 (ECOG scale), options include single agent capecitabine, leucovorin modulated fluorouracil or best supportive care32 (EL-3)

Second line chemotherapy: There is no standard approach for second-line therapy after failure of the first-line regimen. For patients who retain an adequate performance status, utilization of other active agents not used in the first-line regimen is reasonable, either in combination or as serial single agents. Quality of life and minimization of side effects are key considerations when choosing the therapeutic approach. Options include single agent irinotecan, or taxanes33

Follow up post esophagectomy or definitive chemoradiotherapy: For asymptomatic patients, follow-up should include a complete history and physical examination every 3-6 months for 1-2 years, then every 6-12 months for 3-5 years, and annually thereafter. Complete blood count, multichannel serum chemistry evaluation, upper GI endoscopy with biopsy and imaging studies should be obtained as clinically indicated (EL-3). Patients with Tis or T1a tumors who undergo EMR should undergo endoscopic surveillance every 3 months for one year, and then annually for 5 years (EL-3)