A. Devi1, A. Olowofela2, T. Lodhi1,3, P. Hoskin1,3, L. K. Ballas4, A. Choudhury1,3, and S. L. Kerns2; 1Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom, 2Medical College of Wisconsin, Milwaukee, WI, 3Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom, 4Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, CA
Purpose/Objective(s): Bladder preservation with transurethral resection of bladder tumor, neoadjuvant cisplatin-based chemotherapy followed by radiotherapy with a radiosensitizer is an established alternative to radical cystectomy for muscle-invasive bladder cancer (MIBC). Despite its efficacy, a subset of patients develop genitourinary (GU) and gastrointestinal (GI) toxicity, which can significantly impact the patients quality of life. Recent studies involving men undergoing radiotherapy for prostate cancer have indicated that those taking angiotensin-converting enzyme inhibitors (ACEi) experience reduced GU toxicity. While ACEi demonstrated radioprotective effects in preclinical animal models, there is a lack of research focusing on patients treated for bladder cancer. We hypothesize that concurrent administration of ACEi diminishes the risk of GU toxicity in patients undergoing curative radiotherapy for bladder cancer. Materials/Methods: A comprehensive dataset of patients who underwent bladder preservation at a single large-volume cancer center was collected, recording baseline demographics, drug history, treatment details, acute and late toxicity. Acute and late clinician-reported toxicity was assessed using CTCAE V5 grading weekly during treatment, as well as at 6 weeks and 12 months post-treatment. The statistical analysis was performed using Stata 18.0 SE with student t-tests for continuous variables and Chi-Square test for categorical variables to compare the outcomes. Multivariable logistic regression analysis was conducted to explore the association between ACEi use and GU toxicity outcomes while adjusting for potential confounding factors.
Results: All patients who underwent bladder preservation following the diagnosis of MIBC were identified between 2017 and 2022. A total of 387 patients were analyzed, with 103 receiving ACEi treatment and 284 not receiving ACEi treatment. Patient demographics reported no statistically significant differences in baseline characteristics, including age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), tumor stage, and smoking status, between the two groups. On evaluation of acute GU toxicity of Grade =2 during treatment and at 6 weeks, there was no statistically significant difference between the ACEi and no ACEi groups, 40.5% vs 44.1%, p =0.81 and 57.3% vs 55.6% p = 0.92. The late Grade =2 GU toxicity at 12 months post-radiation was also similar between the groups (ACEi vs no ACEi group, 18.6% vs 21.9%, p = 0.56), resulting in an odds ratio of 0.81 (CI 0.40 to 1.64, p= 0.56).
Conclusion: The study found no significant impact of ACEi administration on either acute or long-term GU toxicity. There were inherent limitations, including its retrospective nature and a relatively small sample size. Large, prospective studies are needed to investigate this hypothesis further.
