Preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer: Meta-analysis with trial sequential analysis of long-term survival data

<div><p>Background and purpose</p><p>The role of preoperative short-course radiotherapy (SCRT) in rectal cancer treatment, when compared to long-course radiochemotherapy (LCRT), is still controversial. Thus the meta-analysis with trial sequential analysis (TSA) was performed to evaluate the long-term survival of SCRT and LCRT as therapeutic regimens for locally advanced rectal cancer.</p><p>Material and methods</p><p>PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to August 2017 for eligible studies. Hazard ratios (HRs) or odds ratios (ORs) of overall survival (OS), disease free survival (DFS) and local recurrence (LR) with the corresponding 95% confidence intervals (CIs) were calculated and TSA was applied.</p><p>Results</p><p>11 studies with 1984 patients were included. There was no significant difference in OS (HR = 0.92, 95% CI: 0.75–1.13, <i>p</i> = 0.44), DFS (HR = 0.94, 95% CI: 0.79–1.12, <i>p</i> = 0.50) and LR (OR = 0.73, 95% CI: 0.49–1.08, <i>p</i> = 0.11) between SCRT and LCRT groups. TSA suggested firm evidence for lacking on average a -10% relative risk reduction (RRR) in 4-year OS but no statistical significance in 4-year DFS.</p><p>Conclusions</p><p>Preoperative SCRT is as effective as LCRT for locally advanced colorectal cancer in long-term survival. SCRT could be preferential while facing long waiting lists or lacking medical resource.</p></div

Meta-analysis of cumulative disease free survival.

<p>No significant difference was found (HR = 0.94, 95% CI: 0.79–1.12, <i>p</i> = 0.50) in disease free survival. Subgroup analysis showed that the difference remained insignificant when RCTs and non-RCTs were analyzed separately.</p

Characteristics and Jadad scores of included studies.

<p>Characteristics and Jadad scores of included studies.</p

Trial sequential analysis of 4-year overall survival.

<p>5a, Trial sequential analysis of 4-year overall survival. The required heterogeneity-adjusted information size using 5% risk of type I error and 20% risk of type II error. The cumulative z curve crossed the futility boundary, suggesting firm evidence for lack of on average a -10% relative risk reduction in 4-year OS. <b>5b,</b> Trial sequential analysis of 4-year disease free survival. When compared with LCRT treatment in 4-year DFS, neither the traditional boundary nor the trial sequential monitoring boundary was crossed for a -10% relative risk reduction with SCRT. In addition, the futility boundary was not crossed.</p

Flowchart of eligible studies identification.

<p>11 studies (4 RCTs and 7 non-RCTs) with a total of 1984 patients were included in this meta-analysis.</p

Meta-analysis of cumulative overall survival.

<p>There was no significant difference in OS between SCRT and LCRT groups (HR = 0.92, 95% CI: 0.75–1.13, <i>p</i> = 0.44). The subgroup analysis of RCTs or non-RCTs found similar results.</p