All-in-One Prostate Cancer Staging With MRI

Study Overview
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Brief Summary
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Prior to treatment, it is essential to assess not only the extent of prostate cancer within the prostate, but also to determine whether the disease has initiated metastatic spread. Whole-body MRI has become a viable option for the detection of metastatic disease derived from a number of cancers, but is typically performed in a separate scanning session to an initial dedicated prostate MRI in which the local disease is assessed. In patients known to be at high risk for significant prostate cancer prior to this initial MRI, and thus highly likely to proceed to treatment, this delays arriving at a definitive treatment decision. The investigators will evaluate the sensitivity of a protocol that combines bi-parametric prostate MRI, performed according to PI-RADS v2.1 guidelines, with a whole-body MRI based on the METastasis Reporting and Data System for Prostate Cancer (MET-RADS-P) guidelines, for an All-in-One, local and systemic staging of intermediate-favorable or high risk prostate cancer patients. The resulting staging decisions will be compared to the results of systemic staging with those obtained by computed tomography and bone scintigraphy in the standard staging pathway.

Detailed Description
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Accurate tumor staging for unfavorable intermediate- and high-risk prostate cancer patients should underpin both prognostication and management decisions. This void necessitates evaluation of the local, primary disease as well as spread to distant sites including lymph nodes and possible distant metastases. Multi-parametric magnetic resonance imaging (mp-MRI) has become the reference standard practice for local imaging-based assessment in prostate cancer (PCa). Whole-body MRI (WB-MRI) is seeing growing for detection of distant, metastatic disease, and is particularly suited to detection of bone metastases, which are common in PCa. The possibility of a one-stop staging modality has been raised, wherein mp-MRI + whole body MRI (WB-MRI) would be used to further assess nodal and metastatic disease status in a single sitting. Currently however, international guidelines consider bone scintigraphy (BS) and pelvic computed tomography (CT) for distant disease to be the mainstays of imaging-based staging decisions. A further concern with transitioning to All-in-One prostate staging with MRI relates to the duration of scanning required, as an excessive scan duration is likely to lead to patient discomfort, motion and consequently reduce image quality. The prostate imaging reporting and data system (PI-RADS) v2.1 standard published by Turkbey et al. provides guidelines for mp-MRI of the prostate that are widely used as the basis for assessment of local, primary PCa. Recent evidence suggests that some components of the PI-RADS mp-MRI protocol are of little or no benefit to men with a very high risk of aggressive PCa, defined as prostate specific antigen (PSA) ≥10 ng/mL and + digital rectal exam, even before initial biopsy or repeated biopsy. In particular, dynamic contrast enhanced (DCE) imaging and T2-weighted images (T2WI) in a third orthogonal plane does not improve the overall accuracy of mp-MRI. Therefore, biparametric MRI (bp-MRI; i.e. T2WI in two planes, diffusion-weighted imaging (DWI, without contrast agent injection)) has been suggested to reduce examination time and cost, while retaining sufficient diagnostic accuracy to rule out high-grade PCa in biopsy-naïve men. WB-MRI offers greater sensitivity and diagnostic accuracy for bone and nodal disease than BS and conventional CT. Further, a meta-analysis by Woo et al. has shown MRI (DWI + conventional sequences) to have excellent sensitivity and specificity in particular for detection of bone metastases in patients with PCa. The pooled per-patient sensitivity and specificity of MRI in the 10 studies included in the meta-analysis were 0.96 (95% confidence interval (CI) 0.87-0.99) and 0.98 (95% CI 0.93-0.99), respectively. Similar performance for WB-MRI is reported in the meta-analysis of Shen et al. who found the diagnostic performance of WB-MRI to be similar to that of choline PET/CT, with both being superior to BS in the detection of bone metastases. The pooled sensitivities and specificities in this meta-analysis were 0.97/0.95 and 0.79/0.82 for WB-MRI and BS respectively. WB-MRI appears to be more accurate than conventional CT, which not surprising the pooled sensitivities and specificities of CT alone have been reported as 0.42 and 0.82 in a pair of meta-analyses . A recent work by Johnston et al., found that a WB-MRI protocol consisting of unenhanced T1-weighted DIXON and diffusion-weighted scans provides much higher diagnostic accuracy than BS (sensitivity/specificity 0.90/0.88 vs 0.60/1.00) for the primary staging of intermediate- and high-risk PCa. They also found high and very similar sensitivities/specificities for WB-MRI and BS in respect to nodal disease, with values of 1.00/0.96 and 1.00/0.82 for N1 disease and 0.75/ 0.93 and 0.75/0.92 for M1a disease respectively. The investigators are continuing their studies into the role and the added value of WB-MRI in oncologic patients with advanced cancer (prostate, breast, melanoma], lymphoma). The investigators propose to evaluate the sensitivity of a protocol that combines bp-MRI of the prostate, following the PI-RADS v2.1 guideline, with WB-MRI based on MET-RADS-P guidelines, for an All-in-One, local and systemic staging of unfavorable intermediate- and high-risk prostate cancer patients and to compare the results of systemic staging with those obtained with CT and BS in the standard staging pathway. The combination of bp-MRI and WB-MRI is expected to require a scan time of roughly 40 minutes, allowing it to be performed in a conventional mp-MRI scan time allotment.

Official Title
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All-in-One Prostate Cancer Staging With MRI

Conditions
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Prostate Cancer

Intervention / Treatment
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* Diagnostic Test: Prostate Cancer Patients


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: at least one of: International Society of Urological Pathology Grade Group ≥ 3 (Gleason Score ≥ 4+3); cT3 initial diagnosis with any PSA level; PSA ≥ 20 ng/mL with any Gleason score; and all the following: Signed informed consent; Patients eligible to active treatment (either radical prostatectomy or radiotherapy) and/or hormone therapy; Life expectancy ≥ 10 years; Exclusion Criteria: Contraindications to MRI (e.g. severe claustrophobia or MRI unsafe device); Previous or ongoing hormone therapy or radiation therapy for prostate cancer; Significant intercurrent morbidity that, in the judgment of the investigator, would limit compliance with study protocols; Previous mp-MRI performed within six weeks of the outpatient visit and compliant with PI-RADS v2.1 guidelines; Prostate cancer with significant sarcomatoid or spindle cell or neuroendocrine small cell components;

Ages Eligible for Study
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Minimum Age: 35 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prostate Cancer Patients<br>Patients will undergo a combined whole-body MRI + multiparametric prostate MRI examination along with routine staging examinations (PET, CT / bone scintigraphy). Reporting will be performed without and with reference to the whole-body MRI examination. Differences in the resulting staging and in management recommendations based on the two reportings will be recorded. | Diagnostic Test: Prostate Cancer Patients<br>* see arm/group description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Staging Sensitivity | Sensitivity (SE) of the evaluated diagnostic procedures based on the case report forms (CRFs) compiled at the time of reporting | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Staging Specificity | Specificity (SP) and the overall accuracy of the evaluated diagnostic procedures based on the CRFs compiled at the time of reporting | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Prostate Cancer, Staging, Whole-Body Magnetic Resonance Imaging