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).
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.
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.
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.
Clinical genitourinary cancer. 2024 Jun 24 [Epub ahead of print]
William Paul Skelton, Jack Masur, Jonathan Thomas, Parvaneh Fallah, Rohit K Jain, Praful Ravi, Charlene Mantia, Bradley Alexander McGregor, Pier Vitale Nuzzo, Elio Adib, Talal El Zarif, Mark A Preston, Timothy Nguyen Clinton, Roger Li, Graeme S Steele, Wassim Kassouf, Dory Freeman, Gregory Russell Pond, Rakesh K Jain, Guru P Sonpavde
University of Virginia Comprehensive Cancer Center, Department of Oncology, Charlottesville, VA; H. Lee Moffitt Cancer Center and Research Institute, Department of Oncology, Tampa, FL., University of Virginia Comprehensive Cancer Center, Department of Oncology, Charlottesville, VA., Dana-Farber Cancer Institute, Department of Oncology, Boston, MA., McGill University, Department of Oncology, Montreal, Quebec, Canada., H. Lee Moffitt Cancer Center and Research Institute, Department of Oncology, Tampa, FL., Brigham and Women's Hospital, Department of Oncology, Boston, MA., McMaster University, Department of Oncology, Hamilton, ON, Canada., Massachusetts General Hospital, Department of Oncology, Boston, MA., Dana-Farber Cancer Institute, Department of Oncology, Boston, MA; AdventHealth Cancer Institute and the University of Central Florida, Department of Oncology, Orlando, FL. Electronic address: .