AUTHOR=Hafeez Shaista , Koh Mu , Jones Kelly , Ghzal Amir El , D’Arcy James , Kumar Pardeep , Khoo Vincent , Lalondrelle Susan , McDonald Fiona , Thompson Alan , Scurr Erica , Sohaib Aslam , Huddart Robert Anthony 

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

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.961393

DOI=10.3389/fonc.2022.961393

ISSN=2234-943X

ABSTRACT=Abstract 
Objective 
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).  Patients proceeded to either radical cystectomy or chemo-radiotherapy as standard of care. 

Tumour ADC values was calculated for all b values (ADCall) and high b values (ADCb100).  Mean ADC, percentiles, skew, kurtosis, and their change (ΔADC and %ΔADC) was determined.  Threshold predictive of response with highest specificity was ascertained using 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 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 ADC and %ADC compared to poor response (ADCall 0.32x10-3mm2/s versus 0.11x10-3mm2/s; p=0.009, and %ADCall 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 %ADCb100 75th percentile was 73.7%, 90.0%, 96.6%, and 52.9% respectively.  %ΔADCb100 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.