Abstract
Background Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. Methods We performed a meta-analysis of data from the PubMed and Embase databases. We included patients with LARC who received neoadjuvant (chemo) radiotherapy and curative surgery. Overall survival (OS), disease-free survival (DFS), toxicity, and compliance were analyzed in the oxaliplatin/fluorouracil- (OX/FU-) based group compared with the FU-based group, and in the chemotherapy group compared with the observation group. Results Twenty studies were included in the analysis. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio [HR] = 0.78, 95%CI = 0.67–0.91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. Subgroup analysis showed the same results in both the ypStage II and ypStage III groups. Compared with those in the observation group, patients in the chemotherapy group also showed an increase in DFS (HR = 0.75, 95%CI = 0.60–0.93). No significant increase was observed in OS (HR = 1.04, 95%CI = 0.87–1.24) or DFS (HR = 0.98, 95%CI = 0.76–1.27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis also indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. Conclusions For patients with LARC who have already received neoadjuvant (chemo) radiotherapy and curative surgery, adjuvant chemotherapy improves OS over that in the observation group. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy.
Highlights
Colorectal cancer is the second most frequent cancer in women and the third most frequent cancer in men [1]
4.34 (d) stage, the clinical tumor stage is an important factor used to define the guidelines for recommendation of administration of adjuvant chemotherapy; we conducted further subgroup analysis based on the clinical tumor stage, and the results showed that disease-free survival (DFS) was not significantly different between the OX/FU-based group and FU-based group in both clinical stage II and III subpopulation (clinical stage II: hazard ratio (HR) = 0:95, 95%confidence interval (CI) = 0:59 – 1:52, p = 0:831, Figure 4(c); clinical stage III: HR = 1:09, 95%CI = 0:84 – 1:41, p = 0:533, Figure 4(d))
In an randomized controlled trials (RCTs) of 473 rectal cancer patients, 86% of the patients who received preoperative short-course radiotherapy and 14% of patients who received preoperative long-course chemoradiation were randomly assigned to a chemotherapy group and observation group, and the results showed a similar 5-year DFS in the chemotherapy group versus the observation group (62.7% versus 55.4%) [35]
Summary
Colorectal cancer is the second most frequent cancer in women and the third most frequent cancer in men [1]. Neoadjuvant (chemo) radiotherapy is used as a standard treatment for locally advanced rectal cancer (LARC), but there is no general consensus on either the efficacy of postoperative adjuvant chemotherapy in patients with LARC after neoadjuvant treatment and surgery, or whether the addition of oxaliplatin to adjuvant chemotherapy provides survival benefits. Our results indicated that adjuvant chemotherapy prolonged OS (hazard ratio 1⁄2HR = 0:78, 95%CI = 0:67 – 0:91) in patients with LARC treated with neoadjuvant (chemo) radiotherapy and surgery compared with those in the observation group. No significant increase was observed in OS (HR = 1:04, 95%CI = 0:87 – 1:24) or DFS (HR = 0:98, 95%CI = 0:76 – 1:27) when oxaliplatin was added to FU-based adjuvant chemotherapy, as compared with the FU-based treatment, and subgroup analysis indicated no survival benefits in the clinical stage II, clinical stage III, ypStage II, and ypStage III groups. Adding oxaliplatin to FU-based adjuvant chemotherapy does not confer survival benefits beyond those from FU-based adjuvant chemotherapy
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