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

ObjectiveThis 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. MethodsPatients 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 (Delta ADC and %Delta ADC) 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. ResultsForty-eight patients (96 DWI) were evaluated. NAC response was associated with significant increase in mean Delta ADC and %Delta ADC compared to poor response (Delta ADC(all) 0.32x10(-3) versus 0.11x10(-3) mm(2)/s; p=0.009, and %Delta ADC(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 %Delta ADC(b100) 75th percentile was 73.7%, 90.0%, 96.6%, and 52.9%, respectively. %Delta ADC(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). ConclusionsQuantitative 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 knowledgeWe successfully demonstrated that measured change in DWI can successfully identify NAC response and improved long-term survival outcomes.