Neoadjuvant therapy before surgical treatment

Neoadjuvant treatment in terms of preoperative radiotherapy reduces local recurrence in rectal cancer, but this improvement has little if any impact on overall survival. Currently performed optimal quality-controlled total mesorectal excision (TME) surgery for patients in the trial setting can be associated with very low local recurrence rates of less than 10% whether the patients receive radiotherapy or not. Hence metastatic disease is now the predominant issue. The concept of neoadjuvant chemotherapy (NACT) is a potentially attractive additional or alternative strategy to radiotherapy to deal with metastases. However, randomised phase III trials, evaluating the addition of oxaliplatin at low doses plus preoperative fluoropyrimidine-based chemoradiotherapy (CRT), have in the main failed to show a significant improvement on early pathological response, with the exception of the German CAO/ARO/AIO-04 study. The integration of biologically targeted agents into preoperative CRT has also not fulfilled expectations. The addition of cetuximab appears to achieve relatively low rates of pathological complete responses, and the addition of bevacizumab has raised concerns for excess surgical morbidity. As an alternative to concurrent chemoradiation (which delivers only 5–6 weeks of chemotherapy), potential options include an induction component of 6–12 weeks of NACT prior to radiotherapy or chemoradiation, or the addition of chemotherapy after short-course preoperative radiotherapy (SCPRT) or chemoradiation (defined as consolidation chemotherapy) which utilises the “dead space” of the interval between the end of chemoradiation and surgery, or delivering chemotherapy alone without any radiotherapy.