Radiation, chemotherapy and biological therapy in the curative treatment of locally advanced rectal cancer

Objective To review the published evidence relating to the use of radiotherapy (RT), chemotherapy and biological therapy as adjuncts to surgery in the curative treatment of rectal cancer. Methods Searches were carried out of the MEDLINE and CANCERLIT databases together with conference abstracts from key meetings including the American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancers Symposium and the ECCO/ESMO Multidisciplinary Congress. Results RT reduces local pelvic recurrence when used as an adjunct to surgery, even when this is performed optimally by total mesorectal excision (TME). RT is usually given as short-course preoperative radiotherapy (SCPRT) followed by immediate surgery which produces no or very little downstaging or long-course concurrent chemoradiation (CRT) followed by a 6-8 week gap prior to surgery which produces significant downstaging. The prognostic importance of achieving a clear histological circumferential resection margin is now well recognised and pathological assessment of the quality of surgery can predict long-term outcomes. Internationally there is considerable heterogeneity in the staging modalities and criteria used in deciding which approach might be used, in the reporting of histological results and in RT parameters (time/dose/fractionation/volume). Attempts to increase the potency of CRT have included the addition of concurrent chemotherapeutic and biological agents to the standard fluoropyrimidine although there is little randomised data and none with regard to long-term survival outcomes. Neither SCPRT nor downstaging CRT have been shown to reduce the rate of subsequent distant metastatic relapse which remains a significant clinical problem. The potential additional benefit of neoadjuvant or adjuvant chemotherapy in addition to SCPRT or long-course CRT remains ill-defined. Late morbidity can include bowel and sexual dysfunction, pelvic fractures and second malignancies with considerably more being known in relation to SCPRT than long-course CRT. Conclusions Improvements in imaging, pathology and surgical technique combined with multimodality treatment using RT and chemotherapy are leading to continuing improvements in the long term outcome for patients with rectal cancer although much remains to be learnt regarding the optimum strategy for use of these in different clinical contexts and their relationship to long-term morbidity.