كتاب
Esophageal and Esophagogastric Junction Cancer
- Recommendations
1.Primary preventions
The following intervention 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
2.Secondary prevention (Screening)
• Screening of esophageal and GEJ tumors in the general population is not cost effective and should not be done.
Strong recommendation, high grade evidence (1).
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 recommendation, moderate grade evidence (2).
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 recommendation, moderate grade evidence (3)
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 recommendation, moderate grade evidence (4)
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 recommendation, high grade evidence (5)
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.
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 recommendation, moderate grade evidence (6).
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 recommendation, high grade evidence (7).
5C. Consider 18F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)
in patients who are candidates for esophagectomy.
Conditional recommendation, moderate grade evidence (8).
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 recommendation, high grade evidence (9).
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 recommendation, moderate grade evidence (10).
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 recommendation, high grade evidence (11).
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 recommendation, moderate grade evidence (12)
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 recommendation, high grade evidence (13-14).
6D. In patients at nutritional risk, we recommend feeding jejunostomy in operable patients and
percutaneous gastrostomy tubes for inoperable patients..
Strong recommendation, moderate grade evidence (15-16).
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 recommendation, high grade evidence (17-18).
6F. Parentral 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 recommendation, moderate grade evidence (19-20).
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 recommendation, high Grade evidence (21).
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 recommendation, low grade evidence (22,23).
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 recommendation, Low quality evidence (22-25).
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 recommendation low grade evidence (25).
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 (see 10D) followed by surgery, or definitive CRT with close surveillance and salvage surgery for local tumor persistence or progression.
Strong recommendation, high grade evidence (26,27).
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 recommendation, high grade evidence (28)
8C. Definitive CRT is recommended for cervically localized tumors where surgery would entail a laryngectomy
Adenocarcinoma
8D. We recommend the use of perioperative chemotherapy or neoadjuvant CRT (see 10D).
Strong recommendation, high grade evidence (29)
9. Surgery
9A. Esophageal surgery should be carried out in experienced centers only.
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 recommendation, low grade evidence (30).
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 recommendation, low grade evidence (30).
9D. We recommend transhiatal esophagectomy without transthoracic access with a similar reconstruction to the cervical esophagus in frail patients with distal tumors.
Strong recommendation, low grade evidence (30).
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 cisplatin5-FU (or capecitabine) combined with RT to a dose of 50.4 Gy in 28 fractions (or 50 Gy in 25 fractions).
Strong recommendation, high grade evidence (31)
10B. Weekly carboplatin - paclitaxel, as used in the CROSS regimen, combined with RT as definitive treatment is also recommended
Strong recommendation, high grade evidence (32)
10C. RT should be delivered using 3D conformal RT, but intensity modulated RT or volumetric arc therapy are preferred if available.
Strong recommendation, moderate grade evidence (33)
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 recommendation, high grade evidence (34,35).
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 recommendation, high grade evidence (36).
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 recommendation, high grade evidence (37,38)
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 recommendation, high grade evidence (39).
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 recommendation, high grade evidence (40).
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 recommendation, high grade evidence (41).
13B. The preferred regimens for HER2-negative disease also include a fluoropyrimidine
(Fluorouracil or capecitabine) combined with either oxaliplatin or cisplatin
Strong recommendation, high grade evidence (42).
13C.We recommend FOLFOX for elderly or frail patients due to lower toxicity.
Strong recommendation, high grade evidence (42,43).
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 recommendation, high grade evidence (43,44).
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 recommendation, moderate grade evidence (45).
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 recommendation, moderate grade evidence (46).
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 recommendation, high grade evidence (47).
16. Second line and subsequent systemic therapy for unresectable, metastatic and
recurrent SCC
Taxanes (paclitaxel or docetaxel) or irinotecan monotherapies are recommended as
further-line treatment options
Strong recommendation, moderate grade evidence (48,49).
