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Role of Renin-Angiotensin System Blockers on BCG Response in Nonmuscle Invasive, High Risk Bladder Cancer
Giovanni Motterle1, Alessandro Morlacco2, Giulia Giovannini2
1Department of Surgery- Urology, Piove di Sacco (PD) AULSS 6 Euganea, Padova, Italy.
Introduction:
The gold standard treatment for high-risk NMIBC is BCG immunotherapy. Some studies suggested an immomodulatory effects for commonly used drugs (ie, ACE-I and ARBs). We aimed to determine whether these drugs impact the prognosis of patients with high-risk NMIBC treated with BCG.
Materials And Methods:
Retrospective analysis on 208 patients from a single academic center with primary high-risk NMIBC treated with transurethral resection followed by 6 weekly instillations of BCG and up to 12 monthly maintenance instillations. ARBs or ACE-I use at the time of treatment initiation was recorded. Inverse probability of treatment weighting (IPTW) was used to adjust for clinical and pathological covariates. IPTW-adjusted Kaplan-Meier curves and weighted Cox proportional hazards regression were used to compare 2-yr failure-free (2-yr FFS), failure-free (FFS), overall recurrence-free (RFS) and progression-free survival (PFS).
Results:
A total of 68 patients were on ACE-I, and 38 on ARBs and treatment respectively. At a median follow-up of 26 months, ACE-I treatment had no significant impact on cancer-related outcomes. Conversely, patients treated with ARBs experienced significant improvements in 2-yr FFS (HR 0.3; 0.1-0.9, P = .004), FFS (HR 0.4, 0.1-0.9, P = .005), and PFS (HR 0.001; < 0.001-0.001, P < .001). No significant impact was found for ARB use in RFS (HR 0.6; P = .09). Sensitivity analyses confirmed these results.
Conclusions:
our findings support a potential role of the angiotensin-renin system in bladder cancer development. We identified ARBs as potential beneficial drugs that seems to act in synergy with BCG-immunotherapy.
Insights
Angiotensin II Receptor Blockers (ARBs) show promise in improving outcomes for high-risk bladder cancer patients undergoing BCG immunotherapy. ACE inhibitors did not demonstrate a significant impact on prognosis in this patient group.
Area of Science:
- Urology
- Oncology
- Pharmacology
Background:
- Bacillus Calmette-Guérin (BCG) immunotherapy is the standard treatment for high-risk non-muscle-invasive bladder cancer (NMIBC).
- Some commonly used medications, like Angiotensin-Converting Enzyme Inhibitors (ACE-I) and Angiotensin II Receptor Blockers (ARBs), may possess immunomodulatory effects.
- The impact of these drugs on the prognosis of NMIBC patients treated with BCG is not well-established.
Purpose of the Study:
- To investigate the effect of ACE-I and ARBs on the prognosis of patients with high-risk NMIBC receiving BCG immunotherapy.
- To determine if concomitant use of ACE-I or ARBs influences treatment outcomes in this patient cohort.
Main Methods:
- Retrospective analysis of 208 patients with high-risk NMIBC treated with transurethral resection and BCG immunotherapy.
- Data on ACE-I and ARB use at treatment initiation were collected.
- Inverse Probability of Treatment Weighting (IPTW) was employed to adjust for covariates, followed by Kaplan-Meier and Cox regression analyses to compare survival outcomes.
Main Results:
- Patients on ACE-I (n=68) showed no significant impact on cancer-related outcomes.
- Patients on ARBs (n=38) demonstrated significantly improved 2-year failure-free survival (FFS), FFS, and progression-free survival (PFS).
- No significant impact of ARB use was observed on recurrence-free survival (RFS).
Conclusions:
- The findings suggest a potential role for the renin-angiotensin system in bladder cancer development.
- ARBs may act synergistically with BCG immunotherapy, offering potential benefits for high-risk NMIBC patients.
- Further research into the interaction between ARBs and BCG immunotherapy is warranted.
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