Response evaluation of neoadjuvant therapy in MIBC: clinical trial-derived evidence to guide practice
Roberto Contieri1, Bas W G van Rhijn2,3,4, Richard Cathomas5
1Department of Urology, Istituto Nazionale Tumori di Napoli, IRCCS 'G. Pascale', Naples, Italy.
Objectives:
To review how response to neoadjuvant therapy (NAT) is assessed in clinical trials of muscle-invasive bladder cancer (MIBC), and to determine whether trial-derived evidence can inform response evaluation in contemporary practice.
Subjects/Patients And Methods:
We searched PubMed, Embase and ClinicalTrials.gov through August 2025 for randomised controlled trials (RCTs) of neoadjuvant chemotherapy, chemo-immunotherapy or immunotherapy in non-metastatic MIBC (cT2-T4a N0-1 M0), and for prospective single-arm chemo-immunotherapy or immunotherapy trials. We extracted data on imaging modality and coverage, endoscopic and biomarker-based assessment, timing, correlation with final pathology and diagnostic accuracy. Given heterogeneity in definitions and reporting, no meta-analysis was performed.
Results:
We identified 22 studies, including 14 RCTs. Most incorporated response evaluation, yet methods differed widely. Computed tomography (CT) was the most frequent modality in RCTs, whereas bladder magnetic resonance imaging (MRI) predominated in recent single-arm immunotherapy trials. Timing was inconsistent and usually post-treatment; only two trials performed interim assessment. Endoscopic evaluation was concentrated in bladder-preservation trials, and circulating tumour DNA (ctDNA) was used selectively. Only five studies correlated restaging with final pathology; multiparametric MRI scored with nacVI-RADS predicted pathological complete response with 72%-83% accuracy. No trial reported imaging accuracy for distant metastases after NAT.
Conclusion:
Response assessment after NAT in MIBC remains insufficiently standardised. Trial-derived evidence supports cross-sectional imaging before radical local treatment, with CT the most established modality, largely reflecting trial-design conventions and availability rather than demonstrated diagnostic superiority; bladder MRI is more accurate for local restaging. Emerging biomarkers such as ctDNA require validation. Harmonising timing, modalities and response definitions is needed to enable evidence-based treatment adaptation.
Insights
Response assessment in muscle-invasive bladder cancer (MIBC) clinical trials lacks standardization. Evidence suggests cross-sectional imaging, particularly MRI, aids evaluation, but consistent methods are needed for treatment adaptation.
Area of Science:
- Oncology
- Diagnostic Imaging
- Clinical Trials
Background:
- Neoadjuvant therapy (NAT) is crucial for muscle-invasive bladder cancer (MIBC).
- Standardized assessment of NAT response is vital for treatment decisions and clinical trial design.
- Current practices for evaluating NAT response in MIBC are inconsistent.
Purpose of the Study:
- To review response assessment methods in clinical trials for muscle-invasive bladder cancer (MIBC) receiving neoadjuvant therapy (NAT).
- To evaluate if clinical trial evidence can inform current practices for NAT response assessment in MIBC.
- To identify inconsistencies in imaging, biomarkers, and timing for response evaluation.
Main Methods:
- Systematic literature search of PubMed, Embase, and ClinicalTrials.gov for randomized controlled trials (RCTs) and prospective single-arm trials of NAT in non-metastatic MIBC.
- Data extraction focused on imaging modalities, endoscopic and biomarker assessments, timing, correlation with pathology, and diagnostic accuracy.
- No meta-analysis was performed due to heterogeneity in definitions and reporting.
Main Results:
- 22 studies (14 RCTs) were identified, showing wide variation in response evaluation methods.
- Computed tomography (CT) was common in RCTs; bladder magnetic resonance imaging (MRI) predominated in recent immunotherapy trials.
- Multiparametric MRI with nacVI-RADS showed 72%-83% accuracy for pathological complete response; ctDNA requires validation. No data on distant metastases accuracy.
Conclusions:
- Response assessment after NAT in MIBC is not sufficiently standardized.
- Trial evidence supports cross-sectional imaging (CT established, MRI more accurate locally) before radical treatment.
- Harmonization of timing, modalities, and response definitions is essential for evidence-based treatment adaptation.