A systematic review and meta-analysis of adjuvant chemotherapy after neoadjuvant treatment and surgery for rectal cancer

Current guidelines support the use of adjuvant chemotherapy (CT) following neoadjuvant chemoradiotherapy (CTRT) and surgery to treat rectal cancer, although clinical trials have provided little evidence that it is effective. We performed a systematic review of published studies to assess whether adjuvant CT improves outcome after neoadjuvant therapy and radical surgery in cases of rectal cancer. We conducted an electronic database search for randomized and nonrandomized studies in PubMed, EMBASE, Web of Science, Scopus and the Cochrane Register of Controlled Trials. We then carried out a meta-analysis by using the fixed- or random-effects models. The primary endpoint was 5-year overall survival (OS) reported as odds ratios (ORs) and 95 % confidence intervals (CIs). Two randomized controlled trials (RCTs), one pooled analysis of five RCTs and 10 retrospective studies that included a total of 5,457 patients matched our selection criteria. Meta-analysis showed that for rectal cancer patients treated with surgery and neoadjuvant CTRT, adjuvant CT improves 5-year OS (OR, 0.64; 95 % CI, 0.46-0.88; p = 0.006) and 5-year disease-free survival (DFS) (OR, 0.71; 95 % CI, 0.6-0.83; p < 0.0001). The 5-year OS benefit was significantly larger in downstaged patients and in retrospective series. A better DFS was instead noted in all studies due to a reduced risk of local relapse. Amongst rectal cancer patients treated with neoadjuvant therapy and surgery, adjuvant CT seems to improve the 5-year DFS and OS rates and may be discussed with patients. However, the benefit derives mainly from retrospective evidence.