Computed tomography-derived extracellular volume fraction is associated with high-grade recurrence in non-muscle-invasive bladder cancer treated with intravesical gemcitabine and docetaxel.

Abstract

To evaluate whether extracellular volume (ECV) fraction derived from contrast-enhanced computed tomography (CT) is associated with recurrence risk in patients with treatment-naïve high-risk non-muscle-invasive bladder cancer (HR-NMIBC) receiving intravesical gemcitabine/docetaxel (Gem/Doce) therapy. This retrospective cohort study, conducted at a tertiary referral centre, included 103 patients with HR-NMIBC treated with intravesical Gem/Doce between 2012 and 2024. All patients underwent pre-resection contrast-enhanced CT with an equilibrium phase (~3 min post-injection). Tumour ECV fraction (%) was calculated using the formula: ECV = (ΔHUtumour/ΔHUaorta) × (1 - haematocrit) × 100, where Δ Hounsfield units (HU) represents the change in attenuation between non-contrast and equilibrium phases. Regions of interest were manually placed in the tumour and abdominal aorta, and haematocrit values obtained within ±10 days were used. Associations between clinical variables, ECV, and recurrence were evaluated using Cox proportional hazards models, with discrimination assessed by Uno's C-statistic. The median (interquartile range) follow-up was 17 (10-25) months. High-grade recurrence-free survival (HG-RFS) was 76% at 12 months and 69% at 24 months. CT-derived ECV was the only variable significantly associated with HG-RFS (hazard ratio 1.05, 95% confidence interval 1.03-1.08), demonstrating strong discrimination (C-statistic, 0.81; P < 0.01). A 15% threshold offered the best sensitivity-specificity trade-off (~70% each) for predicting HG-RFS at 12 and 24 months. Patients with ECV ≤15% had markedly better HG-RFS than those with ECV >15% at 24 months (88% vs 41%). The CT-derived ECV is a practical, first-of-its-kind imaging biomarker associated with recurrence risk and useful for risk stratification in patients with HR-NMIBC treated with intravesical Gem/Doce, a regimen increasingly used in the setting of global Bacillus Calmette-Guérin shortages and intolerance. ECV can be rapidly quantified from routine contrast-enhanced CT using standard picture archiving and communication system (PACS) tools, without additional imaging or proprietary software, making it a feasible metric for integration into risk-adapted management pending large-scale validation with extended follow-up.