Fast track — ArticlesSurgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial
Introduction
Patients with cancer of the oesophagus have a poor outlook. Resection is the best management in terms of local control, although local recurrence and distant metastases remain an issue after surgery. Postoperative radiotherapy does not improve outcomes,1, 2 and preoperative radiotherapy, chemotherapy, or both, have become the focus of adjuvant strategies. However, toxic effects and compliance with protocols have hindered the development of suitable treatments. In 1989, as part of the multicentre Trans-Tasman Radiation Oncology Group (TROG), several Australian and New Zealand centres began to collaborate in the development of a well-tolerated preoperative chemoradiotherapy regimen that would not only downstage the tumours of most patients having curative resections, but also be suitable for widespread use. Before 1989, a variant of the original Wayne State University regimen3 had been used, consisting of two cycles of chemotherapy with cisplatin and fluorouracil and radiotherapy for 3 weeks. This regimen achieved satisfactory downstaging, but concerns remained about toxic effects.4 Ultimately, TROG developed a well-tolerated and effective regimen of one cycle of chemotherapy with cisplatin and fluorouracil and 35 Gy radiotherapy, which was as effective as the two-cycle regimen with regard to downstaging and postsurgical outcomes, but was associated with fewer toxic effects.5 Moreover, this regimen compared favourably in terms of effectiveness and toxic effects with other contemporary chemoradiotherapy regimens that had been assessed.6
In 1994, we started a randomised controlled trial in which patients with resectable cancer of the oesophagus were randomly assigned to surgery alone or to this preoperative chemoradiotherapy regimen followed by surgery 3–6 weeks later. The trial aimed to assess whether downstaging of the tumour as a result of chemoradiotherapy improved progression-free survival and overall survival after surgery. Here, we report mature data.
Section snippets
Eligibility
Any patient who had histologically confirmed invasive cancer of the thoracic oesophagus was eligible. Endoscopy and CT needed to show that disease was restricted to the oesophagus and regional lymph nodes (ie, clinical T1–3, N0–1 disease), with resectable nodes to be removed as part of the planned surgical procedure. Patients who had involvement of the gastric cardia that was confined to the lower third of the oesophagus were eligible, provided that the tumour was mainly in the oesophagus.
Results
From Nov 7, 1994, to Sept 6, 2000, 257 patients with localised resectable cancer of the oesophagus were randomised (figure 1). Median follow-up was 65·0 months (range 0·4–120·0), and final analysis was done on March 28, 2005.
Of the 257 patients registered on the trial, one patient was deemed ineligible. Although randomised on the basis of having invasive carcinoma, all biopsy samples showed squamous-cell carcinoma in situ, and the patient was excluded from the primary treatment comparison (
Discussion
We have shown that neoadjuvant chemoradiotherapy with cisplatin and fluorouracil did not confer a survival benefit for patients with localised resectable oesophageal cancer. However, preoperative chemoradiotherapy was tolerated well, and patients assigned this treatment had more complete resections with clear margins and fewer positive lymph nodes than did those assigned surgery alone. Univariate exploratory analyses suggested that progression-free survival and overall survival were
References (28)
The current status of combined modality treatment containing chemotherapy in patients with esophageal cancer
Int J Radiat Oncol Biol Phys
(1990)The uniform reporting of treatment-related morbidity
Semin Radiat Oncol
(1994)- et al.
Preoperative radiotherapy in esophageal carcinoma: a meta-analysis using individual patient data (Oesophageal Cancer Collaborative Group)
Int J Radiat Oncol Biol Phys
(1998) - et al.
Preoperative chemotherapy versus surgical therapy alone for squamous cell carcinoma of the esophagus: a prospective randomized trial
J Thorac Cardiovasc Surg
(1997) - et al.
Surgery alone in the curative treatment of localised oesophageal carcinoma
Eur J Surg Oncol
(2004) - et al.
Relapse patterns after chemo-radiation for carcinoma of the oesophagus
Clin Oncol (R Coll Radiol)
(2003) - et al.
Postoperative radiotherapy for carcinoma of the esophagus: a prospective, randomized controlled study
Surgery
(1993) - et al.
Adjuvant postoperative radiation therapy after curative resection of squamous cell carcinoma of the thoracic esophagus: a prospective randomized study
World J Surg
(1995) - et al.
Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery
J Clin Oncol
(1992) - et al.
A combined modality approach to the management of oesophageal cancer
Eur J Surg Oncol
(1997)
Concurrent chemoradiation for oesophageal cancer—factors influencing myelotoxicity
Australas Radiol
Surgical therapy of esophageal carcinoma
Br J Surg
Neoadjuvant chemotherapy in operable esophageal squamous cell cancer: final report of a phase III multicenter randomized trial
Proc Am Soc Oncol
Medical Research Council Oesophageal Cancer Working Party. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial
Lancet
Cited by (876)
The role of surgery or definitive chemoradiotherapy in management of localized squamous cell carcinoma of esophagus – What is the verdict?
2023, Critical Reviews in Oncology/Hematology
- ‡
Members listed at end of report