Introduction

Esophageal cancer is one of the leading causes of cancer-related deaths globally, primarily due to late-stage detection and resistance to current treatments. Current treatment guidelines recommend surgery combined with neoadjuvant chemoradiation therapy, however, only about 20% of patients will have a complete response to treatment. Our study aims to investigate if pretreatment with statins improves response to neoadjuvant chemoradiotherapy by decreasing TNM staging at time of surgery among patients undergoing neoadjuvant chemoradiotherapy prior to surgical resection.

Methods

We performed a retrospective review of patients who received neoadjuvant chemotherapy before surgical resection of their esophageal adenocarcinoma at a single center between 2014-2024. Patients were grouped by statin use throughout neoadjuvant chemotherapy. The primary outcome was a significant reduction in TNM staging post neoadjuvant chemotherapy. The secondary outcome was overall mortality. Chi-square analysis was performed to determine significance. Logistic regression was performed to control for age, gender, and race. For the secondary outcome of overall mortality, logistic regression was performed to evaluate the association between statin use and mortality while adjusting for other covariates.

Results

There were 602 patients identified (84% male, average age 64 years), 17 were excluded from further analysis for not receiving preoperative radiation. Baseline characteristics were similar between the two groups however, patients who received preoperative statins were significantly older (Table 1). Pre-operative statin use demonstrated a significant decrease in tumor and nodal down-staging. There was no significant difference for overall downstaging. Logistic regression models for overall downstaging and nodal downstaging were not significant however, tumor downstaging remained significant. Receiving a preoperative statin was an independent predictor of tumor downstaging (p=0.016; OR 1.53). Pre-operative statin use was not significantly associated with overall mortality (p-value > 0.05).

Conclusions

Preoperative statin use is associated with improved response to neoadjuvant chemoradiation therapy for patients undergoing surgical resection for esophageal cancer. In particular, significant decreases in tumor size and number of diseased lymph nodes at the time of surgery were seen. Future work should be focused on determining which esophageal cancer patients may benefit from statin use prior to initiation of neoadjuvant therapy.

Tables and Figures

Table 1. Baseline Characteristics

References

1. American Cancer Society. Cancer Facts & Figures 2024. Atlanta: American Cancer Society; 2024.

2. Mukkamalla SKR, Wang Y, Lyons S, et al. Esophageal Cancer. [Updated 2023 Mar 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459267/

3. Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and Esophagogastric Junction Cancers, Version 2.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(4):393-422. doi:10.6004/jnccn.2023.0019

4. Lv J, Chen P, Wu J, Wen Z, Zhao C. The association between statin use and prognosis in esophageal cancer patients: A meta-analysis. Medicine (Baltimore). 2023;102(12):e33359. doi:10.1097/MD.0000000000033359

5. Zhou C, Zhong X, Gao P, Wu Z, Shi J, Guo Z, Wang Z, Song Y. Statin use and its potential therapeutic role in esophageal cancer: a systematic review and meta-analysis. Cancer Manag Res. 2019 Jun 19;11:5655-5663. doi: 10.2147/CMAR.S193945. PMID: 31417309; PMCID: PMC6592054.

6. Chen WM, Yu YH, Chen M, Shia BC, Wu SY. Statin Use During Concurrent Chemoradiotherapy With Improved Survival Outcomes in Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Nationwide Cohort Study. J Thorac Oncol. 2023 Aug;18(8):1082-1093. doi: 10.1016/j.jtho.2023.04.005. Epub 2023 Apr 20. PMID: 37085031.

7. Holmberg D, Gottlieb-Vedi E, Hedberg J, Lindblad M, Mattsson F, Lagergren J. Aspirin or statin use in relation to survival after surgery for esophageal cancer: a population-based cohort study. BMC Cancer. 2023;23(1):375. Published 2023 Apr 25. doi:10.1186/s12885-023-10819-0

8. Lindner K, Borchardt C, Schöpp M, et al. Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer. J Exp Clin Cancer Res. 2014;33(1):73. Published 2014 Sep 1. doi:10.1186/s13046-014-0073-x

9. Lindner K, Borchardt C, Schöpp M, Bürgers A, Stock C, Hussey DJ, Haier J, Hummel R. Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer. J Exp Clin Cancer Res. 2014 Sep 1;33(1):73. doi: 10.1186/s13046-014-0073-x. PMID: 25175076; PMCID: PMC4431491.