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Impact of Angiotensin Converting Enzyme Inhibitors on Pathologic Complete Response With Neoadjuvant Chemotherapy for
William Paul Skelton1, Jack Masur2, Jonathan Thomas3
1University of Virginia Comprehensive Cancer Center, Department of Oncology, Charlottesville, VA; H. Lee Moffitt Cancer Center and Research Institute, Department of Oncology, Tampa, FL.
Introduction:
The renin-angiotensin system (RAS) has been demonstrated to modulate cell proliferation, desmoplasia, angiogenesis and immunosuppression. We examined the association of RAS inhibitors (RASi)-namely angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB)-with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) preceding radical cystectomy (RC).
Patients And Methods:
We retrospectively investigated concurrent RASi use with NAC prior to RC in 302 patients with MIBC from 3 academic institutions. Outcomes included pathologic complete response (pCR) and overall survival (OS). Pathologic features, performance status (PS), clinical stage, type/number of cycles of NAC, and toxicities were collected.
Results:
Overall pCR rate was 26.2% and 5-year OS was 62%. Concurrent ACEi intake with NAC approached significance for association with pCR (odds ratio [OR] = 1.71; 95% CI, 0.94-3.11; P = .077). Patients with cT3/4N0-N1 disease receiving ACEi had higher pCR rates (30.8% vs. 17.7%, P = .056) than those not on ACEi. Female sex had a statistically significant favorable interaction for pCR with ACEi intake (P = .044). ACEi intake was not associated with OS, while pCR, PS and lower clinical stage were significantly associated with improved OS.
Conclusion:
ACEi intake is potentially associated with increased pCR in patients with MIBC receiving NAC prior to RC, and this association is more pronounced in patients with higher clinical stage of disease at the initiation of therapy and female sex. Our data suggest the potential relevance of the RAS as a therapeutic target in aggressive MIBC.
Insights
Angiotensin converting enzyme inhibitors (ACEi) may improve pathologic complete response (pCR) in muscle-invasive bladder cancer (MIBC) patients undergoing neoadjuvant chemotherapy (NAC). This effect is more significant in females and those with advanced-stage disease.
Area of Science:
- Oncology
- Pharmacology
- Urology
Background:
- The renin-angiotensin system (RAS) influences tumor growth and immune response.
- RAS inhibitors (RASi), including ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs), are commonly used medications.
- Their role in muscle-invasive bladder cancer (MIBC) treated with neoadjuvant chemotherapy (NAC) is not well understood.
Purpose of the Study:
- To investigate the association between RAS inhibitor use and outcomes in patients with MIBC receiving NAC before radical cystectomy (RC).
- To explore potential predictive factors for treatment response.
Main Methods:
- Retrospective analysis of 302 MIBC patients undergoing NAC and RC.
- Concurrent use of RAS inhibitors (ACEi/ARBs) with NAC was assessed.
- Outcomes included pathologic complete response (pCR) and overall survival (OS).
Main Results:
- The overall pCR rate was 26.2%, with a 5-year OS of 62%.
- ACEi use approached significance for improved pCR (OR=1.71, P=0.077), particularly in advanced stages (cT3/4N0-N1).
- Female sex showed a significant favorable interaction with ACEi for pCR (P=0.044).
Conclusions:
- ACE inhibitor intake may be associated with increased pCR in MIBC patients receiving NAC.
- The association is more pronounced in female patients and those with higher clinical stage disease.
- These findings suggest the RAS as a potential therapeutic target in aggressive MIBC.
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