Short-course radiotherapy followed by neo-adjuvant chemotherapy in locally advanced rectal cancer – the RAPIDO trial
1 Department of Molecular Medicine and Surgery, Karolinska Institutet and Center for Surgical Gastroenterology, Karolinska University Hospital, Solna P9:03, SE 171 76 Stockholm, Sweden
2 Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands
3 Department of Medical Oncology, University Medical Center Groningen, Groningen, The Netherlands
4 Department of Surgical Science, Uppsala University, Uppsala, Sweden
5 Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
6 Department of Radiology, Maastricht University Medical Center, Maastricht, The Netherlands
7 Department of Diagnostic Radiology, Karolinska University Hospital Solna, Stockholm, Sweden
8 Department of Radiation Oncology, University Medical Center Groningen, Groningen, The Netherlands
9 Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands
10 Department of Clinical Oncology, Leiden University Medical Center, Leiden, The Netherlands
11 Department of Pathology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands
12 Department of Radiology, Oncology and Radiation Science, Uppsala University, Uppsala, Sweden
13 Department of Oncology and Pathology, Karolinska Institutet, Solna, Sweden
BMC Cancer 2013, 13:279 doi:10.1186/1471-2407-13-279Published: 7 June 2013
Current standard for most of the locally advanced rectal cancers is preoperative chemoradiotherapy, and, variably per institution, postoperative adjuvant chemotherapy. Short-course preoperative radiation with delayed surgery has been shown to induce tumour down-staging in both randomized and observational studies. The concept of neo-adjuvant chemotherapy has been proven successful in gastric cancer, hepatic metastases from colorectal cancer and is currently tested in primary colon cancer.
Methods and design
Patients with rectal cancer with high risk features for local or systemic failure on magnetic resonance imaging are randomized to either a standard arm or an experimental arm. The standard arm consists of chemoradiation (1.8 Gy x 25 or 2 Gy x 25 with capecitabine) preoperatively, followed by selective postoperative adjuvant chemotherapy. Postoperative chemotherapy is optional and may be omitted by participating institutions. The experimental arm includes short-course radiotherapy (5 Gy x 5) followed by full-dose chemotherapy (capecitabine and oxaliplatin) in 6 cycles before surgery. In the experimental arm, no postoperative chemotherapy is prescribed. Surgery is performed according to TME principles in both study arms. The hypothesis is that short-course radiotherapy with neo-adjuvant chemotherapy increases disease-free and overall survival without compromising local control. Primary end-point is disease-free survival at 3 years. Secondary endpoints include overall survival, local control, toxicity profile, and treatment completion rate, rate of pathological complete response and microscopically radical resection, and quality of life.
Following the advances in rectal cancer management, increased focus on survival rather than only on local control is now justified. In an experimental arm, short-course radiotherapy is combined with full-dose chemotherapy preoperatively, an alternative that offers advantages compared to concomitant chemoradiotherapy with or without postoperative chemotherapy. In a multi-centre setting this regimen is compared to current standard with the aim of improving survival for patients with locally advanced rectal cancer.