The Vesical Imaging Reporting and Data System (VI-RADS) criteria are expanding, providing fine differentiation of bladder wall layers involvement. Up to now, VI-RADS has proved to be able to address this critical yet unsolved topic, including standardized criteria for reporting the imaging outcomes reflecting differences across cT stages, high inter-readers agreement, and high diagnostic accuracy for MIBC. However, it has been validated solely in the pre-TURBT setting. Instead, the body of evidence for the widespread use in the of MRI clinical practice for response to therapy assessment and prediction is growing, nonetheless it needs to be reinforced; our research is born from these necessities.
We aimed at exploring the feasibility of a novel categorical scoring, born from VI-RADS: the Neoadjuvant chemotherapy VI-RADS (nacVI-RADS) for radiologic assessment of response (RaR), to define the spectrum of treatment response among patients with muscle invasive bladder cancer (MIBC). Patients diagnosed with non-metastatic MIBC will be addressed to NAC and mpMRI before staging resection and after the chemotherapy cycles. The follow-up MRI assessment will be performed using the nacVI-RADS algorithm for evaluation of response to therapy. NacVI-RADS categorically define complete RaR, based on prior VI-RADS score, presence of residual disease, tumor size and infiltration of the muscularis propria. We foresee that NacVI-RADS categories will be able to match the final radical cystectomy pathology both for complete pT0 responders and for the patients defined as partial or minimal responders, who only showed some RaR inter-scoring class downstaging. The findings might lead to possible paradigmatic shifts for cancer-specific survival risk assessment and to possibly drive the therapeutic decision through active surveillance programs, bladder sparing modalities or to the standard of care.
MRI can be considered as a safe tool to monitor local bladder treatment response given its higher anatomical tissue layers resolution and non-invasiveness. Recently, the mpMRI VI-RADS standardization imaging protocols and reporting criteria have been retrospectively, prospectively and multicentric validated for fine discrimination of NMI vs. MIBC in the pre-TURBT setting among several groups (1-3). In this project, we aim at exploring nacVI-RADS feasibility and performance to provide reliable information on NAC response among patients' candidate to curative RC.
Complete response following induction NAC with achievement of pT0 at RC is indeed critical to improve survival among MIBCs. At the same time patients who show partial, or absence of response are exposed to morbidity and a delay in their effective treatment (4). Consequently, in such delicate decision-making algorithm, the identification of reliable predictors within clinical staging or post-NAC restaging phase evaluation is a crossway in the prognosis assessment of these patients. Recently, clinical restaging based on re-TUR sampling and tumor sequencing were found to be inaccurate indicators of response to NAC (5). On the contrary, the applicability of mpMRI to assess therapeutic response to NAC was originally demonstrated by and several other groups, as previously described.
To date, Necchi et al. (6,7) were the first reporting the outcomes on the use of MRI for tumor response to neoadjuvant pembrolizumab assessment form the PURE-01 trial. In this experience, three readers assessed response to therapy relying on a dichotomized answer to predefined per-sequence question whether the mpMRI was suggestive for residual disease. While the diagnostic accuracy of the internally and externally assessed complete radiologic response (RaR) for pT0 outcome was comparable, the outcomes from the combined complete/partial responders' assessment were less promising. Additionally, the spectrum for optimal partial responders¿ classification was not reached with for RaR judgment, suffering from granular distribution and thus not consistent with clinical applicability. As consequence, this articulated proposal resulted only in acceptable inter-agreement among raters which may negatively influence the applicability of the proposal.
Up to now, VI-RADS has proved to be able to address this critical yet unsolved topic, including standardized criteria for reporting the imaging outcomes reflecting differences across cT stages, high inter-readers agreement (8), and high diagnostic accuracy for MIBC.
This project will provide the preliminary evidence of the feasibility of nacVI-RADS criteria for response to therapy assessment. These findings might lead to future possible paradigmatic shifts for both cancer-specific survival risk assessment and even more ambitiously for modeling the contribution of the predicted NAC response to personalized therapeutic pathways. On this regard, we also aim to present a hypothetic future algorithm where not only post-NAC, but also inter-NAC cycles nacVI-RADS score determination may drive the therapeutic decision through active surveillance programs, bladder sparing modalities or conversely to the standard of care.
References
1. Barchetti G, et al. Multiparametric MRI of the bladder: inter-observer agreement and accuracy with the Vesical Imaging-Reporting and Data System (VI-RADS) at a single reference center. Eur Radiol. 2019
2. Del Giudice F, et al. Prospective Assessment of Vesical Imaging Reporting and Data System (VI-RADS) and Its Clinical Impact on the Management of High-risk Non¿muscle-invasive Bladder Cancer Patients Candidate for Repeated Transurethral Resection. European Urology. 2020
3. Metwally MI, et al. The validity, reliability, and reviewer acceptance of VI-RADS in assessing muscle invasion by bladder cancer: a multicenter prospective study. Eur Radiol. 2021
4. Rosenblatt R, et al. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol. 2012
5. Becker REN, et al. Clinical Restaging and Tumor Sequencing are Inaccurate Indicators of Response to Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer. Eur Urol. 2021
6. Necchi A, et al. Multiparametric Magnetic Resonance Imaging as a Noninvasive Assessment of Tumor Response to Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer: Preliminary Findings from the PURE-01 Study. Eur Urol. 2020
7. Bandini M, et al. The Value of Multiparametric Magnetic Resonance Imaging Sequences to Assist in the Decision Making of Muscle-invasive Bladder Cancer. Eur Urol Oncol. 2020
8. Del Giudice F, Pecoraro M, et al. Systematic Review and Meta-Analysis of Vesical Imaging-Reporting and Data System (VI-RADS) Inter-Observer Reliability: An Added Value for Muscle Invasive Bladder Cancer Detection. Cancers (Basel). 2020