Neoadjuvant chemotherapy in MRI-staged high-risk rectal cancer in addition to or as an alternative to preoperative chemoradiation?

For patients with resectable rectal cancer chemoradiation (CRT) or short-course preoperative radiotherapy (SCPRT) reduces locoregional failure, without extending disease-free survival (DFS) or overall survival (OS). Compliance to postoperative adjuvant chemotherapy is poor. Neoadjuvant chemotherapy (NACT) offers an alternative strategy. A systematic computerised database search identified studies exploring NACT alone or NACT preceding/succeeding radiation. The primary outcome measure was pathological complete response (pCR). Secondary outcome measures included acute toxicity, surgical morbidity, circumferential resection margin, locoregional failure, DFS and OS. Four case reports, 12 phase I/II studies, 4 randomised phase II and one randomised phase III study evaluated chemotherapy before CRT. Four prospective studies reviewed chemotherapy after CRT. Three phase II studies investigated chemotherapy using FOLFOX plus bevacizumab without radiotherapy. In 24 studies of 1271 patients, pCR varied from 7% to 36%, but with no impact on metastatic disease. NACT before CRT delivers does not compromise CRT but has not increased pCR rates, R0 resection rate, improved DFS or reduced metastases. NACT following CRT is an interesting strategy, and the utility of NACT alone could be explored compared with SCPRT or CRT in selected patients with rectal cancer where the impact of radiotherapy on DFS and OS is marginal.