PSMA-PET and MRI for Detection of Recurrent Prostate Cancer After Radical Treatment

PSMA-PET and MRI for Detection of Recurrent Prostate Cancer After Radical Treatment - a Multicenter Study

Approximately one third of prostate cancer patients experience biochemical relapse following initial radical prostatectomy or curative radiotherapy. To determine further treatment, it is of utmost importance to accurately differentiate local and regional recurrence from distant metastatic disease. Unfortunately, the currently used medical imaging methods (MRI and bone scan) lack sensitivity for detection of nodal and skeletal metastases, which can lead to over-treatment of patients with occult metastatic disease. PET imaging with prostate specific membrane antigen (PSMA)-ligands has shown a promising potential for improving the detection accuracy in recurrent prostate cancer, especially when combined with the excellent soft-tissue contrast of MRI. However, evidence is mostly based on retrospective single center studies so far, including patients with a wide variety of PSA levels.

Improving the sensitivity for detection of metastatic disease is a crucial step in reducing over-treatment of prostate cancer patients with biochemical relapse following radical treatment. The purpose of this prospective multi-center study is to standardize PSMA PET/CT and PET/MRI imaging across three university hospitals in Norway, and investigate its merit for detection of recurrent prostate cancer. The long-term overall goal is offering prostate cancer patients a more personalized treatment plan aiming to improve the chances of survival and quality of life.

Study Overview

• Status: Completed
• Conditions: Prostatic Neoplasms
• Intervention / Treatment: Diagnostic test: PSMA PET/CT; Diagnostic test: PSMA PET/MR

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway
  • Trondheim, Norway
    • St Olavs hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Prostate cancer patients with biochemical relapse after radical treatment, or patients with persistently elevated PSA levels after radical prostatectomy, who have been (or will be) referred to standardized PSMA PET/CT and PSMA PET/MRI at one of the participating Norwegian hospitals.

Based on the local patient populations, 120 patients are expected to be included in Trondheim, 120 in Bergen, and 60 in Tromsø.

Description

Inclusion Criteria (surgery cohort):

• Prostate cancer patients with biochemical relapse in accordance with the European Association of Urology (EAU) guidelines on prostate cancer; two consecutive measurements with PSA ≥ 0.2 ng/ml following radical prostatectomy or PSA > 2.0 ng/ml above the nadir following definitive radiotherapy
• Potential candidates for loco-regional pelvic salvage treatment based on age and co-morbidity

Exclusion Criteria:

• Previous salvage therapy for recurrent prostate cancer
• General contra-indications for an MRI exam (pacemaker, aneurysm clips, any form of metal in the body, or severe claustrophobia)
• Serious concomitant systemic disorders or reduced cognitive functioning that in the opinion of the investigator would compromise the patient's ability to complete the study or interfere with the evaluation of the efficacy and safety of the study objectives
• Impaired renal function defined as estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2
• Hormonal treatment during the last three months

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
relapse after radical treatment for prostate cancer; prostate cancer patients with biochemical relapse following radical treatment, or patients with persistently elevated PSA levels after radical prostatectomy, that have been (or will be) referred to PSMA PET/CT and PSMA PET/MRI at one of the participating hospitals.	Diagnostic test: PSMA PET/CT; Whole-body PET/CT (contrast enhanced CT or low-dose CT); from vertex to thighs.; Diagnostic test: PSMA PET/MR; Pelvic PET/MR in addition to targeted PET/MR according to other findings from the PET/CT (e.g. columna)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Detection rates of prostate cancer recurrence after radical treatment using a standardized imaging protocol consisting of PSMA PET/CT and PET/MR	Consensus scoring and decision by nuclear medicine physician and radiologist on presence of local recurrent or metastatic lesions	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in detection rates between 68Ga- and 18F-PSMA tracers	Comparison of detection rates between the two radioisotopes based on consensus scoring	baseline
Differences in detection rates after radical treatment between whole-body PET/CT with and without PET/MR	Comparison of number of present local recurrent or metastatic lesions	baseline
Number of equivocal findings with and without addition of PET/MR to the whole-body PET/CT	Comparison of the number of local recurrent and metastatic lesions scored as equivocal	baseline
Detection rates of the combined PET/MR and PET/CT protocol compared with MRI-only.	Comparison of detection rates using MRI only compared to the detection rates based on consensus decision using the combined PET/MR and PET/CT protocol	baseline
Detection rate dependency on prostate specific antigen (PSA) level and kinetics at time of imaging in addition to Gleason score and stage of primary cancer	Detection rates stratified according to PSA levels, kinetics and Gleason score	baseline
Inter-reader variability for interpretation of the PSMA PET/CT and PET/MR	Retrospective re-evaluation of images at minimum three sites	baseline
Detection of differences in image quality between participating centra	Image quality will be scored on a 5-point Likert Scale by a nuclear medicine physician and radiologist and compared between the centra	baseline
Sensitivity and specificity of the standardized whole-body PET/CT and targeted PET/MR protocol for detection of recurrence based on long-term clinical follow-up	A reference standard based on evidence from histopathology, clinical follow-up and follow-up imaging will be established using criteria defining presence and absence of local recurrent and metastatic disease	baseline images and long term follow-up
Head to head comparison of uptake patterns of 68Ga- and 18F-PSMA	A selected subset of patients will be invited for a second imaging session.	baseline
Evaluation of locoregional PET-uptake according to primary radical treatment	Comparison of locoregional PET-uptake in patients treated with primary radiotherapy versus primary prostatectomy	baseline

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: University Hospital of North Norway; Haukeland University Hospital; St Olavs Hospital University Hospital in Trondheim
• Investigators: Study Director: Øystein Risa, phd, NTNU, Fac of Med and Health Sci, Dept of Circulation and Medical Imaging; Study Director: Edmund Søvik, md phd, St Olavs Hospital, Dept of Radiology and Nuclear Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2020
• Primary Completion (Actual): May 1, 2023
• Study Completion (Actual): May 1, 2023

Study Registration Dates

• First Submitted: March 4, 2020
• First Submitted That Met QC Criteria: March 4, 2020
• First Posted (Actual): March 6, 2020

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Positron-Emission Tomography; Prostate-Specific Antigen; Diagnostic Imaging; Neoplasm Recurrence, Local
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms
• Other Study ID Numbers: 83009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We will consider to openly share a completely anonymized dataset of the cohort at the end of the project

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No