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

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.