Diffusion-weighted MRI to determine response and long-term clinical outcomes in muscle-invasive bladder cancer following neoadjuvant chemotherapy

Abstract

Objective: This study aims to determine local treatment response and long-term survival outcomes in patients with localised muscle-invasive bladder cancer (MIBC) patients receiving neoadjuvant chemotherapy (NAC) using diffusion-weighted MRI (DWI) and apparent diffusion coefficient (ADC) analysis.

Methods: Patients with T2-T4aN0-3M0 bladder cancer suitable for NAC were recruited prospectively. DWI was performed prior to NAC and was repeated following NAC completion. Conventional response assessment was performed with cystoscopy and tumour site biopsy. Response was dichotomised into response (<T2) or poor response (≥T2). Patients proceeded to either radical cystectomy or chemo-radiotherapy as standard of care. Tumour ADC values were calculated for all b-values (ADC_all) and high b-values (ADC_b100). Mean ADC, percentiles, skew, kurtosis, and their change (ΔADC and %ΔADC) were determined. Threshold predictive of response with highest specificity was ascertained using receiver operating characteristic (ROC) analysis. Median overall survival (OS), bladder-cancer-specific survival (bCSS), progression-free survival (PFS), and time to cystectomy were estimated using Kaplan-Meier method. Significant area under the curve (AUC) cut points were used to determine relationship with long-term endpoints and were compared using log-rank test.

Results: Forty-eight patients (96 DWI) were evaluated. NAC response was associated with significant increase in mean ΔADC and %ΔADC compared to poor response (ΔADC_all 0.32×10^-3 versus 0.11×10^-3 mm²/s; p=0.009, and %ΔADC_all 21.70% versus 8.23%; p=0.013). Highest specificity predicting response was seen at 75th percentile ADC (AUC, 0.8; p=0.01). Sensitivity, specificity, positive predictive power, and negative predictive power of %ΔADC_b100 75th percentile was 73.7%, 90.0%, 96.6%, and 52.9%, respectively. %ΔADC_b100 75th percentile >15.5% was associated with significant improvement in OS (HR, 0.40; 95% CI, 0.19-0.86; p=0.0179), bCSS (HR, 0.26; 95% CI, 0.08-0.82; p=0.0214), PFS (HR, 0.16; 95% CI, 0.05-0.48; p=0.0012), and time to cystectomy (HR, 0.19; 95% CI, 0.07-0.47; p=0.0004).

Conclusions: Quantitative ADC analysis can successfully identify NAC response and improved long-term clinical outcomes. Multi-centre validation to assess reproducibility and repeatability is required before testing within clinical trials to inform MIBC treatment decision making.

Advances in knowledge: We successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes.

Keywords: MRI; diffusion weighted magnetic resonance imaging (DWI); imaging biomakers; muscle invasive bladder cancer (MIBC); neoadjuavant chemotherapy.