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Life sciences · Journal article
Frontiers in Cardiovascular Medicine · October 16, 2026
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Background Non-muscle-invasive bladder cancer (NMIBC) is commonly managed with intravesical BCG, whereas pembrolizumab is reserved for selected BCG-unresponsive high-risk disease. Cardiovascular adverse events (CVAEs) may occur during cancer therapy, but BCG-related systemic inflammatory effects and immune checkpoint inhibitor (ICI)-mediated cardiovascular immune-related adverse events have distinct pathophysiology and clinical kinetics. We evaluated serial urinary NGAL and CK20 as non-invasive candidate biomarkers for dynamic CVAE risk stratification. Methods A retrospective single-center cohort of 215 NMIBC patients (2021–2023) underwent serial urinary NGAL (ELISA) and CK20 mRNA (qRT-PCR) assessment at baseline and 1, 3, 6, and 12 months after TURBT. Biomarker cutoffs were derived in a 70% training split and evaluated in the remaining 30% internal validation split. Cardiovascular surveillance included echocardiography, ECG, BNP, and high-sensitivity troponin I. The primary endpoint was CTCAE-graded CVAE; Cox regression evaluated associations with cardiovascular event-free survival (CVEFS). Results CVAEs occurred in 74/215 patients (34.4%). The BCG cohort comprised 112 patients; the pembrolizumab subgroup comprised only 25 patients and is therefore interpreted exploratorily. Four ICI-associated myocarditis cases occurred in the pembrolizumab subgroup (16.0%; exact 95% CI 4.5–36.1%). Baseline urinary NGAL was higher in patients with subsequent CVAEs (128.7 ± 38.9 vs. 69.3 ± 33.7 ng/mL, p < 0.001). Combined NGAL + CK20 yielded an internally validated 6-month AUC of 0.913 (95% CI 0.866–0.960), and dual positivity was associated with CVAE risk (aHR=4.12, 95% CI 2.71–6.26). The reported lead-time analysis suggested earlier NGAL change before echocardiographic LVEF decline; this finding requires prospective confirmation. Conclusions Serial urinary NGAL and CK20 are promising candidate markers for CVAE risk stratification in this retrospective NMIBC cohort. The findings are driven principally by the overall cohort and the larger BCG-treated group; ICI-specific observations are hypothesis-generating because only 25 patients received pembrolizumab. The proposed biomarker thresholds and surveillance framework require prospective, multicenter external validation before clinical implementation.