Comparison of Diagnostic Accuracy of Luminal Index and MP MRI for Accelerated deTEction of Significant Prostate Cancer

Prostate Cancer Clinical Trial

— CLIMATE  

Official title:

A Comparison of the Diagnostic Accuracy of Luminal Index Magnetic Resonance Imaging and Multi-parametric Magnetic Resonance Imaging for the Accelerated Detection of Significant Prostate Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05020522
• Other study ID #: 281621
• Status: Recruiting
• Phase: N/A
• Start date: May 1, 2022
• Est. completion date: March 1, 2025

Study information

• Verified date: October 2023
• Source: University College, London
• Contact: Trial Manager
• Phone: 02076795279
• Email: ncita.climate[@]ucl.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multi-parametric (mp) MRI has now internationally been incorporated as standard of care in the work-up of participants with suspected prostate cancer. The standard mpMRI protocol requires 30-45 minutes to be performed and has a sensitivity and specificity of approximately 90% and 50% for the detection of clinically significant prostate cancer. Compared to the non-targeted systematic transrectal ultrasound (TRUS) biopsy approach in men with clinically suspected prostate cancer (e.g.: elevated PSA), performing mpMRI as a triage test allows to detect clinically significant cancer in more men (38% vs 26%) and clinically insignificant cancer in less men (9% vs 22%), while avoiding biopsy in roughly one third of men. However, there is need for improvement in the prostate diagnostic pathway even after incorporation of mp-MRI, specifically mpMRI can miss significant cancer in around 10% of cases and only 50% of positive scans turn out to harbor significant cancer at biopsy. Moreover, the key functional imaging sequence of mp-MRI (i.e.: DWI) often suffers from image artifacts causing difficulty in scan interpretation. To address these issues the investigators aim to investigate Luminal Index MRI (LI-MRI), a novel method of MR imaging that requires only up to 10 minutes to be performed and doesn't require the use of contrast media. LI-MRI has shown promising results for the characterization of prostate cancer. In this study the diagnostic performance of LI-MRI and mpMRI for the detection of prostate cancer will be directly compared.

Description:

Luminal Index MRI (LI-MRI). LI-MRI is a novel technique that allows the assessment of luminal water fraction (LWF). The normal prostate consists of a glandular lumen and cellular areas; cancer alters the balance of glandular to cellular spaces, reducing the fraction of glandular lumen. This fraction decreases further as the grade of tumor increases. Using a multiecho T2-weighted sequence, investigators can differentiate between long T2 values of the luminal space and the short T2 values of the stromal/epithelial space. The luminal index of an image pixel can be calculated as a fraction of the area of the luminal space to the sum of cellular-stromal and luminal space. Studies have shown a good correlation between LWF and its histological measurement, with potential to detect prostate cancer and predict tumor grade. From the results of preliminary studies, the optimized LI-MRI sequence has been very good at differentiating clinically significant and non-significant tumors. PURPOSE. The purpose of the study is to compare the diagnostic performance of LI-MRI (up to 10 minutes scan, no contrast required) and mp-MRI (35-40 min scan, intravenous contrast injection required) for the detection of clinically significant prostate cancer. DESIGN. This is a prospective, multi-centre, paired, non-randomised, comparative study. Patients with clinically suspected prostate cancer that are scheduled for mpMRI as part of their routine diagnostic workup will be asked to participate to the study. All participants will undergo an additional LI-MRI sequence during the clinical scan session. Mp-MRI and LI-MRI images will be interpreted independently by different radiologists, blinded to the results of the other test. Targeted biopsies will be performed for any suspicious lesion (i.e. MRI score 3-4-5) detected with mpMRI and/or LI-MRI, blinded to the source of the lesion. The diagnostic performance of the two techniques will then be assessed using the results of the targeted biopsy. An optional translational study will also be performed to investigate the ability of DNA methylation signatures in the plasma to identify men at high risk of metastases from high risk prostate cancer.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 702
• Est. completion date: March 1, 2025
• Est. primary completion date: March 1, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men with clinically suspected prostate cancer and referred for prostate MRI
• Willing and able to provide a written informed consent

Exclusion Criteria:

• Prostate specific antigen (PSA) level > 20ng/ml within 6 months
• Previous diagnosis of prostate cancer
• Ongoing hormone treatment within 3 months prior to MRI, excluding antiandrogens or 5-alpha reductase inhibitors
• Contraindication to MRI scan
• Contraindication to administration of gadolinium-based contrast agents

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Diagnostic Test:
• Luminal Index MRI (LI-MRI)
Multiecho T2 sequence; eventual biopsy of lesion(s) detected with LI-MRI only.
• LI-MRI targeted prostate biopsy
Biopsy targeted to suspicious lesions detected with LI-MRI only
• Plasma methylation signature (ctMethSig)
Blood sample.

Locations

Country	Name	City	State
United Kingdom	University College London Hospitals NHS Foundation Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
University College, London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	ctMethSig and risk of metastases	Correlation of ctMethSig with other clinical factors known to be associated with risk of metastasis (e.g. Gleason grade)	3 years
Primary	Diagnostic accuracy of mp-MRI and LI-MRI	Comparison of per-participant diagnostic accuracy of mp-MRI and LI-MRI for the detection of clinically significant prostate cancer (i.e. Gleason 3+4 or higher). Two endpoints are included in the primary outcome: difference in sensitivity and difference in specificity.	3 years
Secondary	Diagnostic accuracy of LI-MRI as an add-on test	Per-participant diagnostic accuracy of LI-MRI as an add-on test in combination with mp-MRI for the detection of clinically significant cancer.	3 years
Secondary	Proportion of correct clinical recommendation	Comparison of the proportion of men who would receive a correct clinical recommendation that biopsy could be avoided using mp-MRI and LI-MRI by retrospective analysis.	3 years
Secondary	Per-lesion diagnostic accuracy of mp-MRI and LI-MRI	Comparison of per-lesion diagnostic accuracy of LI-MRI and mp-MRI for clinically significant cancer (difference in sensitivity and specificity).	3 years
Secondary	Proportion of non-significant cancer detection	Comparison of the proportion of men diagnosed with non-significant cancer (Gleason 3+3) based on LI-MRI and mp-MRI targeted biopsies.	3 years
Secondary	Value of MRI in diagnostic models	Evaluation of the added value of MRI when included in a diagnostic model of clinically significant cancer based on the clinical features of age and PSA density.	3 years
Secondary	Luminal Index quantitative analysis	Correlation between Luminal Index quantitative metric and tumor Gleason grade	3 years
Secondary	Interobserver agreement on LI-MRI scores	Interobserver agreement among radiologists on LI-MRI scores.	3 years
Secondary	Interobserver agreement on Gleason scores	Interobserver agreement among histopathologists on Gleason scores at biopsy.	3 years
Secondary	ctMethSig true positive rate	Proportion of men with clinically significant cancer who are positive with ctMethSig.	3 years
Secondary	ctMethSig false positive rate	Proportion of men without clinically significant cancer who are positive with ctMethSig.	3 years