International Journal of Radiation Oncology*Biology*Physics
Clinical investigation: esophagusCombined modality radiotherapy and chemotherapy in nonsurgical management of localized carcinoma of the esophagus: A practice guideline☆
Introduction
Carcinoma of the esophagus has a poor overall prognosis. The extent of disease at presentation and a patient’s performance status are the most powerful predictors of the potential for cure 1, 2. The opportunity exists to eradicate disease localized at presentation through therapy given with curative intent. The current TNM staging system (6th edition, 2002; 3) incorporated major prognostic factors, including the extent of esophageal wall involvement (T1–T4) and whether locoregional nodes are involved (N1). The extent of disease that oncologists consider amenable to curative intent is evolving. The changes in the precision and accuracy of diagnostic modalities, including the use of tools such as minimally invasive staging techniques, are improving the accuracy of clinical staging. Within this context, most would consider patients with T4 disease and extensive nodal involvement incurable. Evidence is increasing that patients with fewer than five nodes involved may have a better outcome than those with more extensive disease (4). Furthermore, the definition of nodal stations that are considered regional and still amenable to potentially curative therapies is also evolving. For the purpose of this guideline, patients with T1–T3, small volume N1, M0 were considered potential candidates for curative therapy.
Both primary surgery and radiotherapy (RT) are offered as treatment options to suitable candidates. In cervical tumors, the desire to avoid laryngoesophagectomy, together with the retrospective data supporting a better prognosis with cervical esophageal tumors, has resulted in the general acceptance of an organ-preserving approach for these patients. For patients with thoracic esophageal tumors, the recommendation for a primary surgical approach vs. a primary RT approach had predominantly been based on the patient’s medical operability, the patient’s preference, and the treating physician’s estimation of the relative morbidity of the outcomes. A well-known attempt in the United Kingdom to compare surgery and RT through a randomized study failed through the inability to accrue patients (5). Two randomized studies compared surgery alone vs. RT alone 6, 7. In 1994, Fok et al. (6) reported a four-arm study comparing surgery alone, preoperative RT and surgery, postoperative RT and surgery, and RT alone. The study was conducted in Hong Kong and included 156 patients. The median survival for surgery vs. RT was 21.6 vs. 8.2 months (p <0.001). Similarly, in 1999, Badwe et al. (7) reported a randomized study comparing surgery alone vs. RT alone. A total of 99 patients participated in this study. The overall survival was significantly superior in the surgery arm vs. the RT arm (p = 0.002). The ability to generalize these results to contemporary surgical and RT techniques and practices and the selection factors that need to be considered when choosing between these two treatment modalities are discussed in a separate guideline for the overall management of esophageal cancer that will be produced in due course.
Studies of the patterns of care of esophageal cancer in North America have shown an increase in the use of combined chemoradiotherapy (RTCT). Daly et al. (8) analyzed patterns of care using the U.S. National Cancer Database and found that the treatment modality most commonly used for esophageal cancer is combined RTCT (30.2%), followed by surgery alone (18%). The most common chemotherapy regimen used in combination with RT is 5-fluorouracil (5-FU) and cisplatin. In the Patterns of Care Study (9), the chemotherapy agents most frequently used were 5-FU (84%), cisplatin (64%), and mitomycin (9%). Youssef et al. (10) compared the management and outcome of carcinoma of the esophagus in Ontario and the United States. Controlling for age, gender, histologic type, and subsite, the rate of esophagectomy was similar, but the rate of primary RT was lower in Ontario. Practice patterns for the use of RT vs. combined RTCT and the types of chemotherapy used have not been described for Ontario or Canada.
This practice guideline report addresses the question of whether the addition of chemotherapy to a primary RT approach improves patient outcomes. A separate guideline is being prepared on the use of neoadjuvant or adjuvant therapy for resectable esophageal cancer when surgery is the primary modality (Practice Guidline 2–11: Neoadjuvant or adjuvant therapy for resectable esophageal cancer). Eventually, the Gastrointestinal Cancer Disease Site Group will consolidate both guidelines to produce a comprehensive recommendation for patients with localized carcinoma of the esophagus who are treated with curative intent.
Section snippets
Guideline development
This practice guideline report was developed by the Cancer Care Ontario Practice Guidelines Initiative (CCOPGI), using the method of the Practice Guidelines Development Cycle (11). Evidence was selected and reviewed by two members of the CCOPGI’s Gastrointestinal Cancer Disease Site Group (Gastrointestinal Cancer DSG) and methodologists. Members of the Gastrointestinal Cancer DSG disclosed potential conflict-of-interest information.
The practice guideline report is a convenient and up-to-date
Literature search results
No fully published reports of meta-analyses were identified, although the pooling of data presented in this guideline report was published in abstract form in 1999 (23). This abstract is not discussed further, because the meta-analysis was updated for this guideline report. A related study by Smith et al. (24) was excluded because surgery was a planned option within the study design.
Ten randomized trials of concomitant RTCT met the inclusion criteria 25, 26, 27, 28, 29, 30, 31, 32, 33, 34.
Discussion
On the basis of the pooled analyses, concomitant RTCT compared with RT alone was associated with an absolute reduction of 1-year mortality from 67% to 56%, with an NNT of 9. The recurrence rate was reduced from 69% with RT alone to 55% with concomitant RTCT, with an NNT of 7. These benefits, although relatively modest, are not trivial considering the generally poor survival rates and morbidity associated with an uncontrolled primary tumor. However, these advantages are associated with a
Practice guideline
This practice guideline reflects the integration of the draft recommendations with feedback obtained from the external review process. It has been approved by the Gastrointestinal Cancer DSG and the Practice Guidelines Coordinating Committee.
References (48)
- et al.
Prognostic factors in esophageal cancerSurgical factors in esophageal cancer
Surg Oncol Clin North Am
(1997) - et al.
Oesophageal cancer treatmentStudies, strategies and facts
Ann Oncol
(1998) - et al.
Meta-analysis in clinical trials
Controlled Clin Trials
(1986) - et al.
Chemotherapy added to locoregional treatment for head and neck squamous-cell carcinomaThree meta-analyses of updated individual data
Lancet
(2000) - et al.
Assessing the quality of reports of randomized clinical trialsIs blinding necessary?
Controlled Clin Trials
(1996) Is combination radiotherapy chemotherapy (RTCT) superior to radiotherapy (RT) alone in the non-surgical management of localized esophageal carcinoma? A meta analysis [Abstract]
Int J Radiat Oncol Biol Phys
(1999)- et al.
Combined chemoradiotherapy vs radiotherapy alone for early stage squamous cell carcinoma of the esophagusA study of the Eastern Cooperative Oncology Group
Int J Radiat Oncol Biol Phys
(1998) - et al.
A controlled evaluation of combined radiation and bleomycin therapy for squamous cell carcinoma of the esophagus
Int J Radiat Oncol Biol Phys
(1980) - et al.
Irradiation, chemotherapy and surgery in esophageal cancerA randomized clinical study. The first Scandinavian trial in esophageal cancer
Radiother Oncol
(1984) - et al.
Palliative therapy of inoperable oesophageal carcinoma with radiotherapy and methotrexateFinal results of a controlled clinical trial
Int J Radiat Oncol Biol Phys
(1989)
Bleomycin/cis-platin as neoadjuvant chemotherapy before radical radiotherapy in localized, inoperable carcinoma of the esophagusA prospective randomized multicentre study—The second Scandinavian trial in esophageal cancer
Radiother Oncol
Prognostic factors for patients with esophageal cancer treated with radiation therapy in PCSA preliminary study
Radiat Med
An MRC prospective randomised trial of radiotherapy versus surgery for operable squamous cell carcinoma of the esophagus
Ann R Coll Surg Engl
Prospective randomised study in the treatment of oesophageal carcinoma
Asian J Surg
The quality of swallowing for patients with operable esophageal carcinoma
Cancer
National Cancer Data Base report on esophageal carcinoma
Cancer
The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagusResults of the 1992–1994 Patterns of Care Study
Cancer
Comparison of the management and outcome of carcinoma of the esophagus in Ontario and the United StatesThe Royal College of Physicians and Surgeons of Canada Annual Meeting (CARO), Vancouver, September 1997
Clin Invest Med
The practice guidelines development cycleA conceptual tool for practice guidelines development and implementation
J Clin Oncol
Standard chemotherapy in squamous cell head and neck cancerWhat have we learned from randomized trials?
Semin Oncol
Radiotherapy-chemotherapy combinations in head and neck squamous cell carcinomaOverview of randomized trials
Anticancer Res
Improved treatment for cervical cancerConcurrent chemotherapy and radiotherapy
N Engl J Med
Cited by (0)
- ☆
Supported by Cancer Care Ontario and Ontario’s Ministry of Health and Long-Term Care.
- 1
The Cancer Care Ontario Practice Guidelines Initiative Gastrointestinal Cancer Disease Site Group includes J. Maroun, M.D. (Chair); O. Agboola, M.D.; M. Citron; B. Cummings, M.D.; F. G. DeNardi, M.D.; C. Earle, M.D.; A. Figueredo, M.D.; S. Fine, M.D.; B. Fisher, M.D.; C. Germond, M.D.; D. Jonker, M.D.; K. Khoo, M.D.; W. Kocha, M.D.; M. Lethbridge; W. Lofters, M.D.; R. McLeod, M.D.; M. Moore, M.D.; and V. Tandan, M.D. Please see the Cancer Care Ontario Practice Guidelines Initiative (CCOGPI) web site (http://www.ccopebc.ca/) for a complete list of current Gastrointestinal Cancer Disease Site Group members. Ottawa, ON, Canada.