Chemotherapy in addition to preoperative radiotherapy in locally advanced rectal cancer - a systematic overview

The value of chemotherapy with radiotherapy has been explored in recent randomised clinical trials in locally advanced rectal cancer (LARC). An overview of these trials was made together with a discussion of what constitutes LARC. Although imaging is required for adequate staging of primary rectal cancer, the term 'locally' advanced has no consistent definition and has been used differently in the trials. Three large randomised trials, however, in different subsets, show that radiochemotherapy (RTCT) with 5-FU-based treatment compared to the same radiotherapy (RT) improves local control and has some influence on systemic relapses and possibly overall survival, without being too toxic. Whether the chemotherapy acts as a radiosensitizer is not known. Preoperative short-course RT alone (5 x 5 Gy) had in one trial similar activity as preoperative RTCT and less toxicity and was, in another trial, superior to selectively given postoperative RTCT. In conclusion, preoperative RTCT, using 5-FU is a new evidence-based treatment in the most locally advanced rectal cancers (T4 tumours growing into neighbouring organs), whereas its use in the slightly less advanced cancers could be discussed. Several phase I - II trials have indicated that combinations of drugs with RT can be even more efficient, but this must be proven in randomised trials since patient selection is of great importance.