Preoperative Statin Use May Improve Response to Neoadjuvant Chemoradiation in Patients With Esophageal Cancer

Background Esophageal cancer is often detected late and resistant to current treatment. Only 20% of patients will have a complete response to neoadjuvant chemoradiation which is associated with improved long-term outcomes. Statin use has shown ability to increase sensitivity to chemotherapy and radiation. Our study aims to investigate if statin usage prior to neoadjuvant chemoradiotherapy improves response by increasing pathologic downstaging at time of surgical resection for esophageal cancer. Methods A retrospective review of esophageal cancer patients who received neoadjuvant chemotherapy prior to surgical resection at a single, high-volume center between 2014–2024 was performed. Patients were stratified by statin use prior to neoadjuvant chemoradiation. Primary and secondary outcomes were reduction in T/N/M staging post neoadjuvant chemotherapy and overall mortality, respectively. Chi-square analysis was performed to determine tumor, nodal, and overall downstaging for the two groups. Multivariable logistic regression controlling for age, gender, and race was performed to evaluate the association between statin use and mortality. Results 585 patients met inclusion criteria (84% male, average age 64 years); 231 received a preoperative statin. Baseline characteristics were similar however, preoperative statin users were significantly older (Table 1). 48.5% of statin users prior to therapy had T downstaging compared to 37.8% without a statin (p = 0.011). 39.9% of statin users prior to therapy had N downstaging compared to 31.1% not on a statin (p = 0.030). There was no significant difference for overall downstaging (p = 0.054). Receiving a preoperative statin was an independent predictor of tumor downstaging (p = 0.016; OR 1.53) on multivariable regression. Pre-operative statin use was not associated with overall mortality (p > 0.05). Conclusion Preoperative statin use is associated with improved response to neoadjuvant chemoradiation therapy for patients undergoing surgical resection of their esophageal cancer. In particular, significant decreases in tumor size and nodal staging at the time of surgery were seen. Future work is needed to determine tumor and patient related characteristics resulting from statin benefit.