Chemoradiotherapy for rectal cancer - is there an optimal combination?

Purpose: Chemoradiotherapy is increasingly used in the primary management of rectal cancer. A critical review of present knowledge of whether an optimal combination exists was made for each of the major clinical situations. Results: As preoperative therapy to reduce local recurrence rates in primarily resectable rectal cancers, radiotherapy has almost exclusively been used as single modality, and combined chemoradiotherapy should remain experimental until further evidence is available. This can only be achieved in randomised trials. Postoperatively, a combination of chemotherapy and radiotherapy appears to be more efficient in reducing local failure rates and improving survival than either modality alone, but the literature-based evidence is partly conflicting. As a reference treatment, a combination of continuous infusion 5-fluorouracil (5-FU) and radiotherapy can be advocated based upon one trial. In primarily irresectable cancer, there is some support that chemoradiotherapy may be more efficient than radiotherapy alone in causing tumour regression allowing radical surgery, but the literature is again conflicting. A great number of phase II studies have been performed in these cancers and in those considered to be locally advanced, revealing promising activity and claims of superiority to radiotherapy alone or other schedules. The studies are, however, inconclusive with respect to antitumour activity, and patient selection may be of greater relevance for the results. Chemoradiation has also increasingly been used to facilitate a sphincter-preserving procedure in low-lying cancers. Again, literature is inconclusive as to whether an optimal combination exists, whether it is superior to radiotherapy alone, or if it actually facilitates sphincter preservation at all. Long-term functional outcome is poorly known. Again, 5-FU has been most extensively used, but many other drugs are presently being tested in various combinations. Conclusions: An optimal combination of chemoradiotherapy for rectal cancer does not exist. Actually, a critical review of the literature shows that the support for superiority of chemoradiation over radiation alone is weak, or lacking. There is a great need of both more conclusive study designs and a more rational exploration of drug-radiation interactions prior to clinical testing.