The role of chemotherapy in localized and locally advanced rectal cancer: A systematic revision

•This review confirms the role of ChT in combination with neoadjuvant long-course RT.•Adjuvant ChT could be of value in MRI defined high-risk patients.•Further investigation is warranted on more intensified neoadjuvant regimens. Curative treatment of rectal cancer depends on an optimal surgical resection, with the addition of neoadjuvant radiotherapy (RT) with or without concomitant chemotherapy (ChT) in more advanced tumors. The role of adjuvant ChT is controversial and a more intensified neoadjuvant approach with the addition of ChT before or after RT, or even as single modality, is currently being explored in trials. A systematic review selecting randomised phase II and III trials on the role of ChT in localized rectal cancer was performed. Data show that neoadjuvant ChRT improves locoregional control in resected rectal cancer. Short-course RT (SCRT) could give similar outcomes to ChRT. The addition of oxaliplatin to neoadjuvant ChRT marginally increases the pathological complete remission rate without improving survival and increasing toxicity. A more intensified approach remains investigational as trials to date have not shown significant advantages. Adjuvant ChT trials after preoperative ChRT are contentious, although the addition of oxaliplatin in high risk patients may benefit outcomes. Despite a wide heterogeneity in the target population, different staging procedures and diverse treatment approaches among different trials, this systematic review confirms the role of ChT in combination with neoadjuvant long-course RT. Adjuvant ChT could be of value in selected patients with high-risk features, mainly if they do not respond to neoadjuvant RT. Further investigation is warranted on more intensified neoadjuvant regimens including ChT for MRI-defined high-risk patients.