Effectiveness of radiotherapy for local control in T3N0 rectal cancer managed with total mesorectal excision: a meta-analysis

Abstract

Introduction: The total mesorectal excision (TME) significantly improved rectal cancer outcomes. Radiotherapy's benefit in T3N0 rectal cancer patients managed with TME has not been clearly demonstrated. A systematic review and meta-analysis were undertaken to determine whether radiotherapy altered the risk of locoregional recurrence (LR) in T3N0 rectal cancer patients managed with a TME.

Materials and methods: Studies indexed on PubMed or Embase were systematically searched from inception to October 18, 2020. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were observed for the literature search, study screening, and data extraction; the Newcastle Ottawa Scale evaluated bias; Grades of Recommendation, Assessment, Development, and Evaluation Working Group system evaluated certainty; and all were performed independently by at least two investigators. Studies that reported LR data specific to T3N0 rectal cancer patients managed with TME, treated with and without radiotherapy, were included. Data was pooled using a random-effects model. Meta-analyses of the relative risk of local recurrence were conducted.

Results: Five retrospective cohort studies involving 932 unique patients reported LR outcomes; no prospective studies met eligibility criteria. Median follow-up ranged from 38.4-78 months. Adjuvant radiotherapy was provided in 3 studies. Chemotherapy was delivered and reported in 4 studies, providing both concurrent and adjuvant chemotherapy. A non-significant LR reduction with radiotherapy alongside TME was estimated, mean relative risk (RR) 0.63 (95% Confidence Interval 0.31-1.29; I² = 41.8%).

Conclusions: A non-significant LR benefit with radiotherapy's addition was estimated. Meta-analysis of exclusively retrospective cohort studies was concerning for biased results. Adequately powered randomized trials are warranted.

Keywords: meta-analysis; radiotherapy; rectal cancer; systematic review; total mesorectal excision.

Figure 1. PRISMA flow chart for study selection and reporting.

Figure 2. Forest plot of the relative risk of local recurrence in the included retrospective cohort studies.

For each study, the black diamond indicates the point estimate, the black line the 95% confidence interval (CI), and the grey box the relative weight of the study. The hatched redline marks the point estimate of the pooled relative risk, the blue diamond portrays its 95% CI, and the blue line indicates the entire estimated predictive interval.