Esophageal and Esophagogastric Junction Cancer

Recommendation

Strength of recommendation

1.Primary prevention

The following interventions may help to reduce the risk of esophageal cancer:

·        Treating gastroesophageal reflux disease (GERD) and Barrett's esophagus early

·        Prevention of injury to the esophagus

·        Avoidance of tobacco and alcohol

·        Avoidance of meat, processed food intake, hot beverages.

·        Diet rich in fruits and vegetables

·        Avoid obesity

Good practice statement

      2.Secondary prevention (Screening)

•        Screening of esophageal and GEJ tumors in the general population is not cost effective and should not be done.

Strong

     3.Diagnosis

     3A. All patients with new dysphagia, gastrointestinal bleeding, recurrent aspiration or emesis, weight loss and/or loss of appetite should undergo an upper gastrointestinal endoscopy.

 Strong

    3B. The location of the tumor relative to the lower incisors and GEJ, the length of the tumor, the extent of circumferential involvement, the presence of Barrett esophagus and the degree of

obstruction should be carefully recorded to assist with treatment planning.

Strong

  3C. Multiple biopsies, six to eight, using standard size endoscopy forceps should be performed to provide sufficient material for histologic and molecular interpretation. Larger forceps is                recommended during surveillance endoscopy of Barrett esophagus for the detection of dysplasia.

Strong

3D. Diagnosis should be based on endoscopic biopsies (Chromo-endoscopy if available) with the histological tumor type classified according to the World Health Organization (WHO) criteria.

The differentiation between esophageal SCC and AC is of prognostic and therapeutic relevance.                                 

Strong

3E. Laparoscopy + washings could be done to exclude occult metastatic disease involving peritoneum/diaphragm, especially in locally advanced (T3/T4) adenocarcinoma of the GEJ              infiltrating the anatomical cardia.

Good practice statement

4.Pathology

4A. Histological diagnosis should be reported according to the WHO criteria.

Good practice statement

     4B. Immuno-histochemical staining including HER2 is recommended in poorly differentiated and undifferentiated cancers when differentiation between SCC and AC using morphological             characteristics is not possible.

Good practice statement

5.Staging and risk assessment

5A. Consider Multidisciplinary team meetings (MDTs) for patients with esophageal cancer. MDTs often include surgeons, radiologist, pathologists, medical oncologists, radiation oncologists, gastroenterologists, dietitians, rehabilitation physicians, palliative care specialists and dedicated cancer nurse specialists.

Conditional

   5B. Staging should include a complete clinical examination, Complete blood count (CBC) and comprehensive chemistry profile, endoscopy, chest /abdomen /pelvis CT with oral and IV          contrast.

 Strong

   5C. Consider 18F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) in patients who are candidates for esophagectomy.

Conditional

5D. Endoscopic ultrasound (EUS) is recommended in early lesions in order to assess tumor depth and lymph node status in patients amenable to upfront surgery or candidates for tri-modality      treatment (T3N0, T1-4a and any locoregional N). If not available refer to a specialized center.

Strong

5E. We recommend bronchoscopy for tumors located at or above the carina in the initial staging, which can help in both surgery and radiotherapy treatments.

Strong

5F. Esophageal cancer should be staged according to the American Joint Committee on Cancer AJCC/UICC TNM (tumor/node/metastases) 8th edition staging system

Strong

6.Nutrition

6A. All patients with esophageal cancer should be screened regularly for malnutrition by evaluating nutritional intake, weight change and BMI, beginning with diagnosis and repeated depending on the stability of the clinical situation

Strong

6B. Patients at nutritional risk should be promptly referred for comprehensive nutritional assessment and support clinical nutrition services.

Good practice statement.

6C. We recommend that during radiotherapy an adequate nutritional intake should be ensured primarily by individualized nutritional counseling and/or with use of ONS, to avoid nutritional deterioration, maintain intake and avoid radiotherapy interruptions.

Strong

  6D. In patients at nutritional risk, we recommend feeding jejunostomy in operable patients and percutaneous gastrostomy tubes for inoperable patients.

Strong

 6E. We recommend that vitamins and minerals be supplied in amounts approximately equal to the recommended daily allowance and discourage the use of high-dose micronutrients in the absence   of specific deficiencies.

Strong

 6F. Parenteral nutrition is only recommended if adequate oral/EN is not possible or insufficient e.g. severe mucositis, intractable vomiting, ileus, severe malabsorption, protracted diarrhea or             symptomatic gastrointestinal graft versus host disease.

Strong

 6G. For all cancer patients undergoing either curative or palliative surgery we recommend management within an enhanced recovery after surgery (ERAS) program; within this program every patient should be screened for malnutrition and if deemed at risk, given additional nutritional support.

Strong

7. Early disease (cT1 N0 M0)

7A. Multidisciplinary assessment and planning before any treatment is mandatory.

Good clinical practice

7B. We recommend endoscopic en bloc resection of lesions with intraepithelial high-grade dysplasia and most T1 tumors using either endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD).

Conditional

7C. Examination of the specimen provides accurate staging and endoscopic resection is considered definitive treatment, unless the deep resection margin is involved or there are significant risk factors for lymph node metastases (e.g. depth of invasion, lymph-vascular invasion, low differentiation grade, ulceration and large tumor size).

Conditional

7D. Patients with involved deep endoscopic resection margins or significant risk factors for lymph node metastases should be offered further respective surgery with appropriate lymphadenectomy.

Conditional

8. Locally advanced and resectable disease (cT2-T4 or cN1-3 M0)

Squamous cell carcinoma

8A. Locally advanced esophageal SCC should be treated with CRT followed by surgery, or definitive CRT with close surveillance and salvage surgery for local tumor persistence or progression (see 10D).

Strong

8B. For patients not willing to undergo esophageal surgery or who are medically unfit for major surgery, definitive CRT should be preferred as CRT is superior to RT alone.

Strong

8C. Definitive CRT is recommended for cervically localized tumors where surgery would entail a laryngectomy.

Good clinical practice

Adenocarcinoma

8D. We recommend the use of perioperative chemotherapy or neoadjuvant CRT (see 10D).

Strong

9. Surgery

9A. Esophageal surgery should be carried out in experienced centers only.

Good clinical practice

9B. We recommend Ivor Lewis procedure, (abdominal and right chest access is used, and reconstruction is carried out with a gastric tube conduit with esophagi-gastric anastomosis in the upper mediastinum) for esophagi-gastric tumors.

Strong

9C. We recommend McKeown procedure, (abdominal, right chest and cervical access is used with a similar reconstruction to the cervical esophagus) for esophageal tumors.

Strong

9D. We recommend  transhiatal esophagectomy without transthoracic access with a similar reconstruction to the cervical esophagus in frail patients with distal tumors.

Strong

9E. The Siewert tumor type should be assessed in all patients with adenocarcinoma involving the EGJ. The surgical approach for Siewert type 1 and type 2 should be similar to those described in esophageal cancer. Also, Siewert type III tumors should be considered gastric cancer and surgical approach for these tumors should be similar to those described in gastric cancer.

Good clinical practice.

10. Chemoradiotherapy

10A. The recommended traditional standard regimen for definitive CRT is four cycles of cisplatin 5-FU (or capecitabine) combined with RT to a dose of 50.4 Gy in 28 fractions (or 50 Gy in 25 fractions).

Strong

10B. Weekly carboplatin - paclitaxel, as used in the CROSS regimen, combined with RT as definitive treatment is also recommended.

Strong

10C. RT should be delivered using 3D conformal RT, but intensity modulated RT or volumetric arc therapy are preferred if available.

Strong

10D. We recommend against the use of RT dose >50.4 Gy in the definitive treatment of mid and distal esophageal cancer specially if salvage esophagectomy is considered as a therapeutic strategy.

 We recommend the use of dose up to 60 Gy in cervical esophageal cancer.

Strong

11. Preoperative chemotherapy in adenocarcinoma of the esophagus and GEJ

11A. In patients with c T2, N0(with high-risk lesions: LVI≥ 3cm, poorly differentiated) or cT1b-cT2N+ or cT3-cT4a, any N who are scheduled to receive surgery as the primary treatment, pre-operative chemotherapy regimens are recommended.

Strong

11B. FLOT regimen (4 cycles before and after surgery) is the preferred perioperative chemotherapy regimen for patients with good performance status. Cisplatin and 5-fluorouracil (CF) or oxaliplatin-based doublets FOLFOX or CAPOX are also valid options.

Strong

 12. Adjuvant chemotherapy in adenocarcinoma of the esophagus and GEJ (who have not received preoperative chemotherapy)

12A. In patients operated without neoadjuvant treatment, postoperative CT is recommended, particularly in case of R1 resection, N+ lesion, or PT3, T4.

Strong

12B. Postoperative chemotherapy with capecitabine and oxaliplatin is an option in patients with resectable esophageal or GEJ cancers who had not received preoperative therapy. FOLFOX regimen is also a valid option.

Strong

13. First- line systemic therapy for unresectable, metastatic, recurrent adenocarcinoma of the esophagus and GEJ.

13A. Trastuzumab should be added to first-line chemotherapy for patients with advanced HER2 overexpression-positive adenocarcinoma (combination with a fluoropyrimidine and             a platinum   agent is preferred).

Strong

13B. The preferred regimens for HER2-negative disease also include a fluoropyrimidine (fluorouracil or capecitabine) combined with either oxaliplatin or cisplatin.

Strong

13C.We recommend FOLFOX for elderly or frail patients due to lower toxicity.

Strong

14. Second line and subsequent systemic therapy for unresectable, metastatic, recurrent   adenocarcinoma of esophagus and GEJ

14A. Single-agent docetaxel, paclitaxel, and irinotecan are preferred options for second-line subsequent therapy.

Strong

14B.  FOLFIRI is a preferred treatment option that can be safely used in the second-line setting if it was not previously used in first-line therapy.

Strong

15. First line systemic therapy for unresectable, metastatic, recurrent esophageal and GEJ squamous cell carcinoma

15A.  Standard first-line Chemotherapy for advanced untreated   esophageal SCC is a platinum-Fluoropyrimidine doublet chemotherapy.

Strong

15B. For patients with advanced esophageal SCC, who are unfit for full- dose chemotherapy due to advanced age or frailty, dose-reduced oxaliplatin/capecitabine is an alternative option.

Strong

16. Second line and subsequent systemic therapy for unresectable, metastatic and 

      recurrent SCC

16A.Taxanes (paclitaxel or docetaxel) or irinotecan monotherapies are recommended as further-line treatment options.

Strong