Early Prediction of Neoadjuvant Chemotherapy Response in Bladder Cancer Using Quantitative Multiparametric MRI

Overview

Bladder cancer is a prevalent malignancy globally, with muscle-invasive disease having a five-year survival rate below 50%. Neoadjuvant chemotherapy (NAC) before radical cystectomy has shown efficacy for resectable muscle-invasive bladder cancer (MIBC). However, non-response to NAC can lead to delayed surgery and unnecessary toxicity. Magnetic resonance imaging (MRI), particularly multiparametric MRI (mpMRI) with dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI), offers functional and quantitative biomarkers that may predict NAC response early in treatment.

Bladder cancer is a major global health concern, ranking as the sixth most common malignancy in males and the 17th most common in females, with an estimated annual incidence of approximately 550,000 new cases worldwide. Among these, muscle-invasive bladder cancer (MIBC) accounts for around 20% of diagnoses and is associated with a poor prognosis, with five-year survival rates remaining below 50%. Muscle invasion is a key negative prognostic factor, likely due to early dissemination of micro-metastatic disease at the time of diagnosis. Despite radical cystectomy (RC) being the standard of care for localized MIBC, nearly 50% of patients with ≥T2 stage disease develop distant metastases within two years following surgery, contributing to high disease-specific mortality. Multiple randomized Phase III trials have demonstrated a survival benefit for neoadjuvant cisplatin-based combination chemotherapy prior to RC in patients with resectable MIBC (clinical stage cT2-T4aN0M0). However, the benefit is largely restricted to responders, as non-responders may experience delays in definitive surgical management and unnecessary chemotherapy-related toxicity without added survival gain. Given the variability in treatment response, there is a critical need for early and accurate tools to assess therapeutic efficacy and guide personalized treatment strategies. Early identification of non-responders to neoadjuvant chemotherapy (NAC) could allow for timely modification of the treatment plan, avoiding ineffective therapy and associated morbidity. Magnetic resonance imaging (MRI), particularly multiparametric MRI (mpMRI), has emerged as a valuable imaging modality for bladder cancer due to its superior soft tissue contrast and ability to characterize tissue microarchitecture. mpMRI protocols that include dynamic contrast-enhanced (DCE) imaging and diffusion-weighted imaging (DWI) have shown promise in assessing tumor vascularity, cellularity, and extracellular space - features that are altered during treatment response. Recent studies suggest that quantitative mpMRI-derived parameters, including the volume transfer constant (K\^trans\^), the extracellular extravascular volume fraction (Ve), and the apparent diffusion coefficient (ADC), may serve as early biomarkers for predicting response to NAC. Changes in these parameters after the first chemotherapy cycle could provide early indications of therapeutic efficacy, enabling clinicians to adapt treatment pathways accordingly. This study aims to prospectively evaluate the predictive value of early mpMRI biomarkers - specifically K\^trans\^, Ve, and ADC - in assessing treatment response following the first cycle of NAC in patients with muscle-invasive bladder cancer. The overarching goal is to determine whether early changes in these imaging parameters correlate with pathological response at cystectomy. This could lead to a more individualized approach to MIBC management and improve clinical outcomes by minimizing ineffective treatment exposure and optimizing timing of surgery.