Incidental use of angiotensin system inhibitors during neoadjuvant therapy for esophageal adenocarcinoma: An analysis of survival

Objective

Renin-angiotensin-aldosterone system signaling affects tumorigenesis and treatment susceptibility of various cancers. We investigate the impact of angiotensin system inhibitors on survival in patients treated for locally advanced esophageal adenocarcinoma.

Methods

Patients with esophageal adenocarcinoma receiving trimodal therapy from 2002 to 2017 at a single institution were abstracted. Primary outcomes were overall survival and disease-free survival, analyzed with the Kaplan–Meier method, Cox regression, and propensity score–matched analysis. Secondary outcomes included pathologic complete response and tumor regression grade.

Results

A total of 375 patients with esophageal adenocarcinoma were included; 92 patients (25%) were angiotensin system inhibitor users, and 283 patients (75%) were angiotensin system inhibitor nonusers. Median follow-up was 32.4 months. Compared with angiotensin system inhibitor nonusers, angiotensin system inhibitor users were older (mean age, 62 vs 64 years) and had higher rates of comorbidities (P < .05 for all). Distribution of tumor stages was similar between groups (P = .3). Compared with angiotensin system inhibitor nonusers, angiotensin system inhibitor users showed improved median overall survival (30 vs 59 months, P = .025) and disease-free survival (18 vs 26 months, P = .032). After controlling for age and comorbidities, angiotensin system inhibitor users showed improved overall survival (hazard ratio, 0.633, P = .031) and disease-free survival (hazard ratio, 0.661, P = .036) compared with angiotensin system inhibitor nonusers. Among 182 propensity score–matched patients, angiotensin system inhibitor users showed greater median overall survival (59 vs 26 months, P = .025) and disease-free survival (25 vs 13 months, P = .030) than angiotensin system inhibitor nonusers. The hazard ratio was 0.623 for overall survival (95% CI, 0.410-0.946, P = .027) and 0.651 for disease-free survival (95% CI, 0.440-0.961, P = .031), both favoring angiotensin system inhibitor users. No differences between groups were identified with respect to secondary outcomes (P > .05).

Conclusions

Angiotensin aldosterone system inhibition during esophageal cancer treatment is associated with improved outcomes. Our study suggests that angiotensin system inhibitors may provide additional survival benefits in the multi-modality treatment of esophageal adenocarcinoma.