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Open Access Highly Accessed Study protocol

Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

Robert Siegel1, Susen Burock1, Klaus-Dieter Wernecke2, Albrecht Kretzschmar3, Manfred Dietel4, Volker Loy5, Stephan Koswig6, Volker Budach6 and Peter M Schlag7*

Author Affiliations

1 Department of Surgery and Surgical Oncology, Charité – Universitätsmedizin Berlin, Berlin, Germany

2 Institute of Medical Informatics and Biometry, Charité – Universitätsmedizin Berlin, Berlin, Germany

3 Department of Haematology and Oncology, Helios Kliniken, Berlin, Germany

4 Institute of Pathology, Charité – Universitätsmedizin Berlin, Berlin, Germany

5 Institute of Pathology, Vivantes Hospital, Berlin, Germany

6 Department of Radiotherapy, Helios Kliniken, Bad Saarow, Germany

7 Department of Surgery and Surgical Oncology, Charité Comprehensive Cancer Center, Charité – Universitätsmedizin Berlin, Berlin, Germany

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BMC Cancer 2009, 9:50  doi:10.1186/1471-2407-9-50

Published: 6 February 2009

Abstract

Background

The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control.

Methods and design

Patients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4–6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function).

Discussion

Similar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.