eP239 - Long Interval Between Neoadjuvant Therapy and Surgery in Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

Purpose/Background: Neoadjuvant chemoradiation has become the standard of care for patients with locally advanced rectal cancer (LARC). However, the optimal timing of rectal resection following chemoradiotherapy (CRT) remains unclear. Therefore, we aim to perform a meta-analysis of clinical outcomes comparing timing of surgical resection ( < 12 weeks or ≥12 weeks) after preoperative neoadjuvant therapy.Methods/Interventions: Cochrane Central, Embase and PubMed were systematically searched for studies comparing very long-interval (≥12 weeks) versus long-interval ( < 12 weeks) between neoadjuvant chemoradiation for LARC. Two independent authors conducted study screening and selection, with discordances solved through a third author and consensus between the reviewers. Outcomes assessed were pathologic complete response (pCR), positive circumferential resection margins (CRM), positive distal resection margins (DRM), Clavien-Dindo classification of surgical complications, postoperative complication rates, hospital length of stay (LOS), anastomotic leak occurrence and overall survival (OS). Statistical analysis was performed using Review Manager 5.4.1. Heterogeneity was assessed with I2 statistics and random effects model was used if 𝐼2 > 50%.Results/Outcomes: Out of 1066 screened references, 7 studies that met the inclusion criteria were included (Figure 1), with a total population of 1541 patients on the very long interval group and 8984 on the long interval group. The pCR rate was statistically equivalent on both groups (OR= 0.88; 95% CI 0.59 - 1.31; p= 0.53). Both the positive rates of CRM (OR= 1.54; 95% CI 0.91 - 2.59; p= 0.11) and DRM (OR= 0.53; 95% CI 0.2 - 1.4; p= 0.2) had no statistical differences (Figure 2). The rates of postoperative complications were slightly in favor of less than 12 weeks (OR= 1.14; 95% CI 1.01 - 1.29; p= 0.04), as well as the rates of Clavien-Dindo I or II complications (OR= 1.41; 95% CI 1.04 - 1.89; p= 0.02). Despite this, no differences were seen for the rates of Clavien-Dindo III or IV (OR= 1.24; 95% CI 0.85 -1.82; p= 0.27) or anastomotic leak (OR= 0.96; 95% CI 0.68 - 1.35; p= 0.84). This is reflected on overall similar lengths of hospital stay between groups (MD= 0.31; 95%CI -0.38 - 1.01; p= 0.38). Lastly, the overall survival also showed no difference between groups (HR= 1.12; 95% CI 0.99 - 1.27; p= 0.08) (Figure 3).Conclusion/

Discussion: This meta-analysis found no benefit in prolonging the interval to more than 12 weeks, with a slightly higher risk of both Clavien-Dindo I or II and overall postoperative complications. As this is based mostly on retrospective observational data, there is still some risk of bias. Further randomized studies are needed to better evaluate this interval."Figure 1. PRISMA Flow Diagram

Figure 2. Forest Plots Pathological Outcomes

Figure 3. Forest Plots Clinical Outcomes
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