The Use of Single-Agent Versus Multiple-Agent Concurrent Chemoradiotherapy in the Treatment of Locally Advanced Rectal Cancer

Purpose: The use of concurrent chemoradiotherapy is frequently recommended in the treatment of locally advanced rectal cancer; however, the ideal chemotherapy regimen remains unknown, and there is variability in chemotherapy agents used among different institutions. We sought to examine differences in overall survival between patients receiving single versus multiple-agent concurrent chemoradiotherapy.

Methods: The National Cancer Database was used to identify 31,025 patients with rectal cancer who received concurrent chemoradiotherapy between 01/2006 and 12/2016. We compared patients who received single-agent chemotherapy with those who received multiple-agent concurrent chemoradiotherapy. The primary outcome of interest was overall survival. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors.

Results: 18,544 patients received single-agent and 12,481 patients received multiple-agent chemotherapy. The former were older with more comorbidities as evidenced by their higher Charlson-Deyo Scores. Those receiving multiple-agent chemotherapy were more likely to have clinical stage III disease (52.9% vs 43.3%, p < 0.001) and less likely to have well-differentiated cancer (6.9% vs 7.7%, p < 0.001). The rates of negative resection margin were identical (p = 0.225) between the two groups. On multivariable analysis after adjusting for comorbidities, radiation dose, and resection margins, single-agent chemotherapy was associated with worse overall survival (HR 1.09, 95% CI 1.057-1.124, p < 0.001).

Conclusion: Multiple-agent chemoradiotherapy is associated with improved overall survival in locally advanced rectal cancer; however, chemotherapy regimen does not affect resection margins. The modest overall survival benefit with multiple-agent chemotherapy must be balanced with the potential associated toxicity.