Role of Renin-Angiotensin System Blockers on BCG Response in Nonmuscle Invasive, High Risk Bladder Cancer

Clin Genitourin Cancer. 2022 Aug;20(4):e303-e309. doi: 10.1016/j.clgc.2022.02.007. Epub 2022 Feb 24.

Abstract

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.

Keywords: ACE-inhibitors; Angiotensin receptor blockers; Cancer recurrence; Immunomodulatory; Instillations.

MeSH terms

  • Administration, Intravesical
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • BCG Vaccine / therapeutic use
  • Disease-Free Survival
  • Humans
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / pathology
  • Renin-Angiotensin System
  • Retrospective Studies
  • Urinary Bladder Neoplasms* / pathology

Substances

  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • BCG Vaccine