Series 2-11 Version 4 REQUIRES UPDATING. It is still appropriate for this document to be available while this updating process unfolds. The PEBC has a formal and standardized process to ensure the currency of each document (PEBC Assessment & Review Protocol). EBS 2-11v4 is comprised of 4 sections.# Guideline Report History

# TARGET POPULATION
These recommendations apply to adult patients with resectable, operable, and potentially curable thoracic (lower two thirds of esophagus) esophageal cancer for whom surgery is considered appropriate.
- Preoperative cisplatin-based chemotherapy plus radiotherapy is recommended as the preferred modality for the management of surgically resectable patients with esophageal cancer.
- Preoperative cisplatin-based chemotherapy alone is an alternative choice for the management of surgically resectable patients with esophageal cancer.

# QUALIFYING STATEMENTS
- Based upon results from the "CROSS" trial, the Gastrointestinal Cancer Disease Site Group (GI DSG) acknowledges that recommendations indicating use of "preoperative cisplatin These guideline recommendations have been ENDORSED, which means that the recommendations are current and relevant for decision making. Please see Section 4: Document Review Summary and Review Tool for a summary of the updated evidence published between 2012 and 2016, and for details on how the Clinical Practice Guideline was ENDORSED based" chemotherapy should be revised to include the use of "preoperative platinum based" chemotherapy.
The GI DSG acknowledges there is evidence indicating survival benefits with either preoperative chemotherapy or chemoradiotherapy compared with surgery alone. Based on the majority of the evidence available at this time, the GI DSG believes that preoperative chemoradiotherapy for resectable carcinoma of the esophagus is the preferred approach.
- Clinicians should recognize that the survival advantage of preoperative therapy may be minimal and a discussion with patients regarding potential adverse effects is required.
Decisions to administer preoperative therapy should be based on patient preferences, comorbidities, and suitability for trimodality therapy.

# KEY EVIDENCE
- A literature meta-analysis of 10 randomized trials comparing preoperative chemoradiotherapy followed by surgery to surgery alone showed a 13% absolute benefit in survival at two years for preoperative chemoradiotherapy (hazard ratio 0.81; 95% confidence interval 0.70-0.93; p=0.002) (1).
- A published abstract of an individual patient data (IPD)-based meta-analysis of nine randomized trials (2,102 patients) comparing preoperative chemotherapy followed by surgery (CT+S) to surgery alone demonstrated a 4% (from 16 to 20%) absolute overall survival advantage for chemotherapy at five years (HR, 0.87; 95% CI, 0.79-0.95; p=0.003).
Based on seven trials (1,849 patients), the HR for disease-free survival (DFS) was 0.82 (95% CI, 0.74-0.91; p=0.001) in favour of chemotherapy plus surgery, representing a fiveyear absolute DFS benefit of 4% (from 6 to 10%). No difference was seen in postoperative death (6.7%) (2).
- Randomized trials demonstrated no survival benefit for radiotherapy given alone, either preoperatively or postoperatively, compared with surgery alone.
- Randomized trials demonstrated no survival benefit for postoperative chemotherapy given alone compared with surgery alone.

# RELATED GUIDELINES
- PEBC Practice Guideline Report #2-12: Combined Modality Radiotherapy and Chemotherapy in the Non-surgical Management of Localized Carcinoma of the Esophagus. Copyright This report is copyrighted by Cancer Care Ontario; the report and the illustrations herein may not be reproduced without the express written permission of Cancer Care Ontario. Cancer Care Ontario reserves the right at any time, and at its sole discretion, to change or revoke this authorization.