Neoadjuvant chemotherapy versus Long-course neoadjuvant chemoradiotherapy for locally advanced rectal cancer: A systematic review and meta-analysis of 5168 cases

Wenjie Zhou^1*Xueting Wang²Jie Dan¹Minjie Zhu¹Qian Liao²Ke Liu¹JIANGPENG LI²xianhong Jiang¹Yonghong Wang^1*

• ¹Department of Gastrointestinal Surgery, The People's Hospital of Leshan, Leshan, China
• ²Department of Scientific Research and Teaching, The People's Hospital of Leshan, Leshan, China

[Abstract] Background: Long-course neoadjuvant chemoradiotherapy (Lc-NCRT) is the conventional treatment for locally advanced rectal cancer (LARC). It improves R0 resection rate and reduces local recurrence rate, but it can not improve long-term oncological outcomes. It also causes several radiotherapy-related side effects. In recent years, some studies have shown that neoadjuvant chemotherapy (NCT) may be noninferior to Lc-NCRT. Therefore, we systematically evaluated the efficacy and safety of NCT and Lc-NCRT for LARC. Methods: Cochrane Library, Embase, PubMed, WanFang Data, and CNKI were systematically searched the relevant literature. The Literature was screened independently by two groups, and data were extracted and evaluated for bias. Meta-analysis was performed using Revman5.4 software. The primary outcomes were tumor response to neoadjuvant therapy and long-term oncological outcomes.Results: Seventeen studies with 5168 cases (1957 cases in NCT and 3211 cases in Lc-NCRT) were included in our meta-analysis. Compared with the Lc-NCRT group, although the NCT group had lower pCR rate [RR=0.65, 95% CI (0.56-0.75), P<0.0001], less downstaging[RR=1.11 95%CI 1.03 1.19 P=0.06]and more adverse events of neoadjuvant therapy [RR=1.11, 95% CI (1.03-1.19); P=0.06], it had no difference in Long-term survival outcome [3-year Overall Survival; HR=1.13, 95% CI (0.70-1.83), P=0.62] [3-year Disease-Free Survival: HR=1.16, 95% CI (0.96-1.39), P=0.12] [3-year Local Recurrence Free Survival: HR=1.36,95%CI(0.9-2.08), P=0.15], and serious adverse events [RR=0.84,95%CI(0.45-1.57), P=0.58] with Lc-NCRT group; Moreover, the incidence of anastomotic leakage(RR=0.48,95%CI(0.34 0.45) and permanent stoma rate[RR=0.7,95%CI(0.58-0.84), P<0.0001] after operation was lower in NCT group. Conclusion: NCT is a potential option for the treatment of LARC as it is beneficial for improving the sphincter preservation rate, reducing anastomotic leakage and the long-term oncological outcome is considerable and the safety is controllable. Larger randomized controlled trials RCT with longer follow-up data are needed to clarify the specific regimens of NCT and the risk stratification of rectal cancer.