The Treatment Strategy Of Neoadjuvant Short-course Radiotherapy For The Primary Advanced Mid-lower Rectal Cancer:Mate-analysis And Efficiency And Security Evaluation For The Future Clinical Trial

Objective:There’re two different pre-operative radiotherapy regimens for the advanced mid-lower rectal cancer, including short course radiotherapy (5Gy×5F) and conventionally fractionated regimen (so-called long-course radiotherapy, fractionated in1.8-2.0Gy×25-28F), often combined with chemotherapy. Aimed at the argument between them, this article is designed to declare the advantages and disadvantages in pCR, R0resection, sphincter preservation, local recurrence, distant metastasis, overall survival and adverse event by Meta-analysis. Meanwhile, a part of the ongoing clinical trial data will be published here to state the efficiency and security of the new strategy for rectal cancer, including pCR, sphincter preservation, down-staging effect, complications and mortality.Material and Methods:Electronic searches were performed by using domestic and international biomedical information databases to collect studies of randomized control trial of short-course radiotherapy vs TME surgery-alone or short-course radiotherapy vs long-course radiotherapy to perform systematic review of meta-analysis study. Details of information on pCR, RO resection, sphincter preservation, down-staging effect, local recurrence, distant metastasis, disease-free survival, overall survival and adverse event, were listed and calculated to further investigate the distribution. At the same time, the primary results of the new regimes, short-course radiotherapy with subsequently neo-chemotherapy followed by TME surgery, will be depicted.Results:Seven domestic and worldwide prospective RCTs has been included, with total4489patients:SC+Surgery vs Surgery-alone subgroup contains2studies, consisting of1544into SC+Surgery arm and1584into Surgery-alone arm; SC+Surgery vs LC+Surgery subgroup contains5studies, consisting of885in SC arm and474in LC arm. According to the data analysis, the SCRT arm and Surgery-alone arm didn’t present statistic difference in RO resection (RR=1,95%CI=0.97-1.04, P=0.91) and sphincter preservation (RR=0.97,95%CI=0.92-1.03, P=0.33). However, compared with surgery alone, SCRT actually reduce the risk of local recurrence (2years:RR=0.34,95%CI=0.25-0.48, P<0.00001;5years:RR=0.45,95%CI=0.25-0.48, P<0.00001) and distant metastasis (2years:RR=0.94,95%CI=0.80-1.09, P=0.39; RR=0.89,95%CI=0.76-1.05, P=0.17), and improves3-year disease-free survival (RR=1.08,95%CI=1.02-1.15, P=0.01) and5-year overall survival (RR=1.04,95%CI=0.98-1.09, P=0.17). When comes to the subgroup of SCRT vs LCRT, the risk ratio for pCR (RR=0.0895%CI=0.03-0.20, P<0.00001), down staging of ypT (RR=0.66,95%CI=0.55-0.80, P<0.00001), RO resection (RR=0.95,95%CI=0.91-0.99, P=0.02) and sphincter preservation (RR=0.92,95%CI=0.84-1.00,P=0.06) are all below one, but there’s no statistic difference in sphincter preservation. Meanwhile, in this subgroup, there is also no statistic difference in local recurrence (2-year RR=0.77; 5-year RR=0.84), distant metastasis (2-year RR=0.83;5-year RR=0.86),3-year disease-free survival (RR=0.93) and5-year overall survival (RR=1.05). As to the adverse events, SCRT leads a better outcome with acute adverse events RR=0.11(P<0.00001) and late adverse events RR=0.95(P=0.80). According to the data collected from our clinical trial,2of5patients preserved anal sphincter,4of5patients reached down stage in ypT,2of5patients reached down stage in ypN,1of5patients reached pathological complete response and the NAR score ranged from1to30.Conclusion:The current evidence suggests that compared with surgery alone, short course radiotherapy decrease the local recurrence and distant metastasis and improves3-year disease-free survival, but have no differences in R0resection, sphincter preservation and overall survival. As to the long course radiotherapy, SCRT, no longer sharing any advantages, is inferior to LCRT in pCR, down staging effect (ypT) and R0resection and have no statistic difference in sphincter preservation, local recurrence, distant metastasis,3-year disease-free survival and5-year overall survival. The regimen tried in our department shows a significant effect on pCR, down-staging and sphincter reservation, while the adverse events can be tolerated.