3335 - The Impact of ARBs and ACE Inhibitors during Chemoradiotherapy on Outcomes for Muscle Invasive Bladder Cancer
Presenter(s)
Y. Baker1, S. Lakshmi Narayanan Akila1, M. Andreadis2, B. Raizenne3, S. M. Dufault4, M. Semaan2, T. Friedlander2, J. C. Hong5, C. E. Chu3, X. Zhu2, J. Chou2, T. M. M. Ma6, M. H. H. Barcellos-Hoff5, N. Mar7, V. S. Koshkin2, S. P. Porten3, and S. N. Seyedin1; 1University of California, San Francisco, Department of Radiation Oncology, San Francisco, CA, 2University of California, San Francisco, Division of Hematology/Oncology, Department of Medicine, San Francisco, CA, 3University of California, San Francisco, Department of Urology, San Francisco, CA, 4University of California, San Francisco, Department of Epidemiology and Biostatistics, San Francisco, CA, 5University of California San Francisco, Department of Radiation Oncology, San Francisco, CA, 6Department of Radiation Oncology, University of Washington - Fred Hutchinson Cancer Center, Seattle, WA, 7UC Irvine School Of Medicine, Division of Hematology/Oncology, Department of Medicine, Orange, CA
Purpose/Objective(s): Inhibition of the renin-angiotensin system can modulate treatment responses to neoadjuvant chemotherapy and immunotherapy in muscle invasive bladder cancer (MIBC) due to downstream inhibition of transforming growth factor-ß. Its effect on chemoradiotherapy (CRT) efficacy for non-metastatic MIBC remains unknown. We hypothesize that concurrent use of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blockade (ARB) during chemoradiation (CRT) for non-metastatic MIBC would improve treatment outcomes.
Materials/Methods: We retrospectively identified patients with MIBC (cT2-4, cN0-1, M0) who were treated with definitive CRT from 1/2018 to 10/2024 at our institution. Extracted clinical variables include TNM stage, presence of carcinoma in situ (CIS) and hydronephrosis at TURBT, diagnosis age, primary radiotherapy dose, and chemotherapy regimen. Patients lost to follow-up after treatment, insufficient radiation (< 50 Gy), or prior radical cystectomy before radiation were excluded. Patients were divided into two groups based on their usage of an ACEi/ARB at any time during CRT. The primary endpoint of this study was 2-year disease-free survival (DFS) defined from completion of RT. Secondary outcomes include 2-year metastasis-free survival (MFS), rate of local recurrence (LR), and overall survival (OS). Survival for all endpoints was estimated using the Kaplan-Meier method and compared using log-rank test. Predictors of DFS were assessed with univariate Cox proportional hazard models.
Results: Overall, 59 patients were eligible, with a median follow-up 23.7 months. The median age was 71, most had T2 (81%), N0 (90%), pure and predominant urothelial carcinoma (95%), no hydronephrosis (81%) and no CIS at presentation (69%). 21 patients (36%) received either an ACEi or ARB during CRT. Most common chemotherapy was concurrent cisplatin (59%) with starting dose of 35 mg/m2 for most patients (29%) and the median radiation dose of 64.8 Gy. The 2-year DFS was 71% in the group treated with ACEi/ARB, versus 47% in the non-ACEi/ARB group (p = 0.12). The 2-year MFS favored the ACEi/ARB group, (90% vs. 66%, p = 0.035). No significant differences were observed in 2-year LR (86% vs. 82%, p = 0.7) or OS (71% vs. 42%, p = 0.075). No tumor characteristics at TURBT were associated with DFS on univariate analysis.
Conclusion: The use of ACEi/ARBs during CRT prolonged MFS in patients with MIBC and may suggest improvement in other outcomes. These hypothesis-generating results should be assessed in larger datasets and future studies should examine the impact of ACEi/ARB type, dose, and duration, and its impact on TGF-ß in cancer tissues.