Academic Background

Muscle-invasive bladder cancer (MIBC) is a highly aggressive malignancy. The standard treatment typically involves cisplatin-based neoadjuvant chemotherapy (NAC) or immunotherapy, followed by radical cystectomy (RC) and bilateral pelvic lymph node dissection. However, radical cystectomy significantly impacts patients’ quality of life. Therefore, for patients who achieve a pathologic complete response (pCR) after neoadjuvant therapy, avoiding cystectomy and adopting bladder-sparing strategies has become a potential alternative. Nevertheless, accurately assessing patients’ response to neoadjuvant therapy to select suitable candidates for bladder-sparing strategies remains a critical clinical issue.

Multiparametric magnetic resonance imaging (mpMRI) has shown significant promise in evaluating the response of other solid tumors to neoadjuvant therapy. In recent years, the Vesical Imaging Reporting and Data System (VI-RADS) has been introduced to standardize the acquisition and evaluation of bladder mpMRI. However, VI-RADS was initially designed for patients who had not received treatment or had only undergone diagnostic transurethral resection of bladder tumor (TURBT), and its value in assessing residual disease after neoadjuvant therapy remains unclear. To address this, researchers have proposed a modified scoring system—the Neoadjuvant Chemotherapy VI-RADS (NACVI-RADS)—to evaluate tumor response after neoadjuvant therapy.

Source of the Paper

This paper was co-authored by Giorgio Brembilla, Giuseppe Basile, Michele Cosenza, and others from IRCCS Ospedale San Raffaele in Milan, Italy, University College London, and other institutions. It was published in the journal Radiology in 2024. The primary aim of the paper was to evaluate the diagnostic accuracy and reproducibility of NACVI-RADS in assessing MIBC response to neoadjuvant immunotherapy.

Research Process and Results

Research Process

This study was a retrospective analysis of patients enrolled in the PURE-01 study (NCT02736266) between February 2017 and December 2019. These patients received three cycles of pembrolizumab immunotherapy before undergoing radical cystectomy and had mpMRI scans before and after treatment. A total of 110 patients were included, with each patient undergoing two MRI scans, resulting in 220 scans. Five radiologists independently evaluated the scans using VI-RADS and NACVI-RADS criteria, with the final histopathologic diagnosis from radical cystectomy serving as the reference standard.

MRI Protocol

All MRI scans were performed at IRCCS Istituto Nazionale dei Tumori in Milan, Italy, using a 1.5T scanner (Philips Healthcare). The scanning protocol included multiplanar (axial, sagittal, and coronal) T2-weighted sequences, diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) maps, dynamic contrast-enhanced (DCE) sequences, and delayed axial T1-weighted imaging.

Image Evaluation

Five radiologists independently evaluated the pre- and post-treatment MRI scans using an open-source medical image viewer (Horos, version 4.0.0) in a blinded manner. The NACVI-RADS scoring system consists of five levels: scores 1–2 indicate a complete radiologic response, score 3 indicates downstaging to non-muscle-invasive disease, score 4 indicates a partial response with persistent MIBC, and score 5 indicates no response or disease progression.

Statistical Analysis

Diagnostic accuracy was assessed using sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy. Additionally, interreader agreement for NACVI-RADS and VI-RADS scores was evaluated using the Gwet agreement coefficient AC1, Conger κ coefficient, and percentage of agreement.

Key Results

Patient Characteristics

The study included 110 patients with a median age of 67 years, of whom 96 were male and 14 were female. 73% of the patients had pure urothelial carcinoma, while 27% had mixed variant histology. Based on the final histopathologic diagnosis after radical cystectomy, 42% of patients achieved complete pathologic response (ypT0), 19% were downstaged to ypT1, Tis, or Ta, and 39% had persistent MIBC (ypT≥2).

Diagnostic Accuracy of NACVI-RADS

For residual disease (>ypT0), NACVI-RADS scores of 3 or higher had a sensitivity of 67%–84%, specificity of 63%–96%, negative predictive value of 63%–75%, and overall accuracy of 72%–81%. For residual muscle-invasive disease (>ypT1), NACVI-RADS scores of 3 or higher had a sensitivity of 91%–98%, specificity of 55%–94%, negative predictive value of 93%–98%, and overall accuracy of 71%–95%.

Diagnostic Accuracy of VI-RADS

Post-treatment VI-RADS scores of 3 or higher for residual muscle-invasive disease had a sensitivity of 84%–93%, specificity of 75%–99%, negative predictive value of 89%–95%, and overall accuracy of 80%–95%.

Interreader Agreement

The percentage of agreement for NACVI-RADS scores was 82%, with a Conger κ coefficient of 0.62–0.65, indicating high interreader agreement.

Conclusions and Significance

This study demonstrates that NACVI-RADS scores have good diagnostic accuracy and reproducibility in assessing MIBC response to neoadjuvant immunotherapy. NACVI-RADS effectively distinguishes complete response from residual disease, particularly showing high negative predictive value for detecting residual muscle-invasive disease. These results provide a robust tool for noninvasively selecting candidates for bladder-sparing strategies.

Research Highlights

1. Innovative Scoring System: NACVI-RADS is a novel scoring system specifically designed to evaluate tumor response after neoadjuvant therapy, addressing a gap in the existing VI-RADS framework.
2. High Diagnostic Accuracy: NACVI-RADS performs exceptionally well in detecting residual muscle-invasive disease, with a negative predictive value as high as 98%, significantly outperforming traditional clinical restaging methods.
3. High Interreader Agreement: NACVI-RADS scores show high interreader agreement, indicating the reliability of this scoring system in practical applications.

Other Valuable Information

Despite the strong performance of NACVI-RADS in assessing neoadjuvant therapy response, the study has some limitations. First, all MRI scans were performed at a single institution, and the generalizability of the results needs further validation. Second, the study only included patients who received neoadjuvant immunotherapy, and future research is needed to explore its application in other treatment regimens. Additionally, all patients underwent TURBT before MRI, and future studies should evaluate the performance of NACVI-RADS in patients who have not undergone TURBT.

NACVI-RADS provides a new tool for the noninvasive assessment of MIBC patients after neoadjuvant therapy, and future research will further validate its value in different therapeutic contexts.