Massachusetts Chapter of the American College of Surgeons

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The use of single-agent versus multiple-agent neoadjuvant chemotherapy in the treatment of locally advanced rectal cancer
Thomas Peponis, Caitlin Stafford, James Cusack, Christy Cauley, Robert Goldstone, David Berger, Liliana Bordeianou, Hiroko Kunitake, Todd Francone, Rocco Ricciardi
Massachusetts General Hospital, Boston, MA

Background: The use of neoadjuvant chemotherapy is considered the standard of care in the treatment of locally advanced rectal cancer however the ideal chemotherapy regimen remains unknown. We sought to examine differences in overall survival between patients receiving single-agent versus multiple-agent neoadjuvant chemotherapy.
Methods: The National Cancer Database was used to identify 31,025 patients with rectal cancer who received neoadjuvant treatment between 01/2006 through 12/2016. We compared patients who received single-agent chemotherapy with those who received multiple-agent chemotherapy. We excluded patients with clinical Stage IV disease. 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 (p<0.05). 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 several variables including 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 neoadjuvant chemotherapy is associated with improved overall survival in locally advanced rectal cancer, however chemotherapy regimen does not affect resection margins. The tradeoff between overall survival benefit must be balanced with the toxicity impact on quality of life.


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