Treatment of Locally Advanced Esophageal Carcinoma

Publication Date: June 22, 2020
Last Updated: March 14, 2022



Multimodality therapy should be offered to patients with locally advanced esophageal carcinoma. (B)

Note: Although outside the scope of recommendations for locally advanced esophageal cancer, the Expert Panel recommends that for patients with clinical earlier stage esophageal cancer (T2, N0), surgery alone may be considered after discussion with a multidisciplinary team. Within this group, surgery alone may be more appropriate for patients with low risk cT2NO lesions (i.e. well-differentiated, less than 2 cm), and where there is a sufficient degree of confidence in the results of pretreatment staging.

Preoperative chemoradiotherapy (CRT) or perioperative chemotherapy (CT) should be offered to patients with locally advanced esophageal adenocarcinoma.

Subgroup considerations:
  • For the subgroup of patients for whom surgery is not feasible, CRT without surgery is recommended.
  • Preoperative CT should be considered for patients who are not candidates for radiation or postoperative chemotherapy.
  • Postoperative complications may be more severe with CRT as compared to CT. Consider the potential for patient tolerance of the addition of RT based on tumor location and other factors.
  • The addition of radiotherapy is expected to be more beneficial in the setting of less extensive surgery. Adequate quality and extent of surgery includes clear surgical margins and adequate nodal dissection within appropriate nodal fields, e.g. abdominal and thoracic, with a goal of obtaining at least 16 to 18, and preferably greater than 20 lymph nodes. Lymphadenectomy fields and extent of surgery will be affected by tumor location. Detailed recommendations for surgical approach are beyond the scope of this guideline.
Note: While outside the scope of the systematic review, the Expert Panel recognizes FLOT as the standard of care for perioperative chemotherapy in esophageal adenocarcinoma. The FLOT regimen includes four preoperative and four postoperative 2-week cycles of 50 mg/m² docetaxel, 85 mg/m² oxaliplatin, 200 mg/m² leucovorin and 2600 mg/m² fluorouracil as 24-hr infusion on day 1. Where the FLOT regimen is not available or feasible, the Expert Panel suggests cisplatin-fluorouracil (two 3-weekly cycles of cisplatin [80 mg/m² intravenously on day 1] and fluorouracil [1 g/m² per day intravenously on days 1–4]), or a similar platinum-based regimen.
Preoperative CRT or CRT without surgery (definitive CRT) should be offered to patients with locally advanced esophageal squamous cell carcinoma.

Subgroup considerations:

  • Historical studies suggest that in patients who respond completely to CRT, the addition of surgery may offer minimal benefit. In patients with squamous cell carcinoma who appear to have a complete response to CRT, the option of surveillance and salvage surgery upon progression may be considered, where salvage esophagectomy is practiced. At this time, randomized controlled trials are exploring the question of surveillance and salvage surgery after CRT compared to planned surgery after CRT.
  • In patients for whom radiation is not an option, preoperative CT (without radiation) may be considered.
  • Definitive CRT is recommended for patients with tumors located in the cervical esophagus; surgery should be considered in the event of persistent or recurrent disease.
  • While CRT and surgery are preferred, definitive CRT is an option for patients who cannot tolerate or choose not to undergo surgery.

Practice Statement 

For patients with esophageal squamous cell carcinoma, the decision to undertake surgery should be considered in the context of shared decision making, considering age, comorbidities, patient preference, caregiver support, and other factors. (H)

Recommendation Grading




Treatment of Locally Advanced Esophageal Carcinoma

Authoring Organization

Publication Month/Year

June 22, 2020

Last Updated Month/Year

June 9, 2022

Document Type


External Publication Status


Country of Publication


Document Objectives

To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer.

Inclusion Criteria

Female, Male, Adolescent, Adult, Older adult

Health Care Settings

Hospital, Outpatient, Radiology services

Intended Users

Nurse, nurse practitioner, physician, physician assistant


Management, Treatment

Diseases/Conditions (MeSH)

D000230 - Adenocarcinoma, D004938 - Esophageal Neoplasms, D000077277 - Esophageal Squamous Cell Carcinoma


squamous cell carcinoma, esophageal adenocarcinoma, esophageal carcinoma

Supplemental Methodology Resources

Data Supplement


Number of Source Documents
Literature Search Start Date
January 1, 1999
Literature Search End Date
December 31, 2019
Description of External Review Process
ASCO has a rigorous review process for guidelines. After the draft has been approved by the Expert Panel, the guideline is independently reviewed and approved by the Clinical Practice Guideline Oversight Committee (CPGC). Select members of the CPGC are asked to critically review the guideline prior to the next scheduled CPGC meeting. The CPGC members then present the results of their reviews to the full committee, discuss the review with the full committee, and the CPGC votes on whether to approve the guideline (with recusals from members who have relationships with affected companies). Approved ASCO Guidelines are then submitted to the Society’s journal for consideration of publication.
Description of Public Comment Process
ASCO Guidelines are available for open comment for a 2 to 3‐week period. Guideline recommendations available for open comment are posted on‐comment‐guidelines. Prospective reviewers must contact ASCO to request to review the draft guideline recommendations and are required to sign a non‐disclosure and confidentiality agreement before receiving the draft guideline recommendations. Reviewers must identify themselves by name and affiliation; anonymous comments will not be accepted. Guidelines staff review and summarize comments and bring relevant comments to the Expert Panel Co‐ chairs, and to the entire panel if necessary. Any changes made from the open comment process will be reviewed by the entire panel prior to CPGC approval. Comments are advisory only and ASCO is not bound to make any changes based on feedback from open comment. ASCO does not respond to reviewers or post responses to comments; however, major edits to the draft will be reflected in the open comment discussion.
Specialties Involved
Gastroenterology, Oncology, Medical Oncology, Surgical Oncology, Radiation Oncology, Oncology, Oncology, Oncology
Description of Systematic Review
The Protocol specifies the purpose of the guideline product, target patient population, clinical outcomes of interest, key features of the systematic literature review, and a proposed timeline for completion. ASCO staff, the Expert Panel Co‐Chairs, and possibly other panel members selected by the Co‐Chairs (the Expert Panel Steering Committee), will typically draft the protocol for full panel review. A standard protocol worksheet is used for consistency. Once the Co‐Chairs have approved a first draft of the Protocol, the Protocol will be shared with the full Expert Panel. At the discretion of the Guidelines Director, the CPGC leadership and/or the CPGC Methodology Subcommittee may review the Protocol to make suggestions for revision intended to clarify aspects of the plan for developing the guideline. These suggestions are sent to the Expert Panel Co‐Chairs. Work on the systematic literature review can proceed upon the sign‐off of the Protocol by the Expert Panel.
List of Questions
Refer to full text
Description of Study Criteria
Refer to full text
Description of Search Strategy
Upon approval of the Protocol, a systematic review of the medical literature is conducted. ASCO staff use the information entered into the Protocol, including the clinical questions, inclusion/exclusion criteria for qualified studies, search terms/phrases, and range of study dates, to perform the systematic review. Literature searches of selected databases, including The Cochrane Library and Medline (via PubMed) are performed. Working with the Expert Panel, ASCO staff complete screening of the abstracts and full text articles to determine eligibility for inclusion in the systematic review of the evidence. Unpublished data from meeting abstracts are not generally used as part of normal ASCO guideline development (“Meeting Data”). However, abstract data from reputable scientific meetings and congresses may be included on a case‐by‐case basis after review by the CPGC leadership. Expert Panels should present a rationale to support integration of abstract data into a guideline. The CPGC leadership will consider the following inclusion criteria for the unpublished scientific meeting data: 1) whether the data were independently peer reviewed in connection with a reputable scientific meeting or congress; 2) the potential clinical impact of the unpublished data; 3) the methodological quality and validity of the associated study; 3) the potential harms of not including the data; and 4) the availability of other published data to inform the guideline recommendations.
Description of Study Selection
Literature search results were reviewed and deemed appropriate for full text review by two ASCO staff reviewers in consultation with the Expert Panel Co-Chairs. Data were extracted by two staff reviewers and subsequently checked for accuracy through an audit of the data by another ASCO staff member. Disagreements were resolved through discussion and consultation with the Co-Chairs if necessary. Evidence tables are provided in the manuscript and/or in Data Supplement.
Description of Evidence Analysis Methods
ASCO guideline recommendations are crafted, in part, using the GuideLines Into DEcision Support (GLIDES) methodology. ASCO adopted a five‐step approach to carry out quality appraisal, strength of evidence ratings and strength of recommendations ratings. The ASCO approach was primarily adapted from those developed by the AHRQ,, USPSTF, and GRADE, however with the validation of the GRADE methodology, the sole use of GRADE is being evaluated by the Clinical Practice Guidelines Committee.
Description of Evidence Grading
High: High confidence that the available evidence reflects the true magnitude and direction of the net effect (i.e., balance of benefits v harms) and that further research is very unlikely to change either the magnitude or direction of this net effect. Intermediate: Moderate confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research is unlikely to alter the direction of the net effect; however, it might alter the magnitude of the net effect. Low: Low confidence that the available evidence reflects the true magnitude and direction of the net effect. Further research may change either the magnitude and/or direction this net effect. Insufficient: Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. The use of the consensus opinion of experts is reasonable to inform outcomes related to the topic.
Description of Recommendation Grading
ASCO uses a formal consensus methodology based on the modified Delphi technique in clinically important areas where there is limited evidence or a lack of high‐quality evidence to inform clinical guidance recommendations. Evidence Based: There was sufficient evidence from published studies to inform a recommendation to guide clinical practice. Formal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. Therefore, the Expert Panel used a formal consensus process to reach this recommendation, which is considered the best current guidance for practice. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). The results of the formal consensus process are summarized in the guideline and reported in the Data Supplement (see the Supporting Documents" field). Informal Consensus: The available evidence was deemed insufficient to inform a recommendation to guide clinical practice. The recommendation is considered the best current guidance for practice, based on informal consensus of the Expert Panel. The Panel agreed that a formal consensus process was not necessary for reasons described in the literature review and discussion. The Panel may choose to provide a rating for the strength of the recommendation (i.e., "strong," "moderate," or "weak"). No recommendation: There is insufficient evidence, confidence, or agreement to provide a recommendation to guide clinical practice at this time. The Panel deemed the available evidence as insufficient and concluded it was unlikely that a formal consensus process would achieve the level of agreement needed for a recommendation.
Description of Funding Source
ASCO provides funding for Guideline Development.
Company/Author Disclosures
ASCO Conflict of Interest Policy complies with the CMSS Code for Interactions with Companies. ASCO requires disclosure by individuals involved in drafting, reviewing, and approving guideline recommendations.
Percentage of Authors Reporting COI