Ignite Creation Date:
2024-05-06 @ 11:29 AM
Last Modification Date:
2024-10-26 @ 12:46 PM
Study NCT ID:
NCT03537391
Status:
COMPLETED
Last Update Posted:
2022-05-04
First Post:
2018-04-26
Brief Title:
Novel Imaging in Staging of Primary Prostate Cancer
Sponsor:
Turku University Hospital
Organization:
Turku University Hospital
Study Overview
Official Title:
Imaging for Prostate Cancer Metastasis Detection - Traditional Imaging Bone Scan and CT Versus PSMA-PET-CT SPECT-CT and Whole-Body MRI
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PROSTAGE
Brief Summary:
Prostate cancer PC is the most common cancer among men and one quarter of diagnosed PC are metastatic at the time of diagnosis Accurate staging is paramount as the stage is the most important factor when treatment decisions are made The stage is also the single most important prognostic factor Currently traditional imaging methods for detection of PC metastasis including bone scan BS and contrast enhanced whole-body computer tomography CT are rather inaccurate Respectively novel imaging techniques are evolving and novel imaging modalities are emerging in PC diagnostics and staging but their clinical relevance is unclear and lacking prospective studies comparing traditional imaging with novel imaging
This prospective single-institutional study compares the diagnostic accuracy of novel imaging modalities to traditional imaging modalities aiming to find the most appropriate staging modality in high-risk PC at the time of initial staging
This prospective single-institutional study compares the diagnostic accuracy of novel imaging modalities to traditional imaging modalities aiming to find the most appropriate staging modality in high-risk PC at the time of initial staging
Detailed Description:
Prostate cancer PC is the most common cancer among men The incidence of PC has increased dramatically in Finland since 1980s and lately approximately 4500 new PC cases have been diagnosed annually in Finland
About one quarter of diagnosed PC are metastatic at the time of diagnosis Accurate staging is extremely important as the stage is single most important factor when treatment decisions are made and stage is the single most important prognostic factor Localized PC is treated with active surveillance low risk cases or with treatment modalities with curative intent radical prostatectomy or radiotherapyAlthough recently radical treatments have been suggested to play a role in low volume metastatic disease the standard treatment of metastatic disease is castration therapy
In PC staging the most important anatomic locations to be imaged are i bone ii lymph nodes especially pelvic lymph nodes and iii extranodal soft tissues
Detection of tumor bone metastases is commonly performed by BS However the results of recent studies have raised many doubts whether BS is as effective for confirming or excluding metastatic bone disease Moreover the sensitivity for 99mTc-methylene diphosphonate bone scintigraphy 99mTc-MDP BS is only 50-70 The detection of bone metastases in patients with high-risk PC is significantly improved by SPECT compared to planar BS Other imaging modalities with potentially improved accuracy to detect bone metastases in PC include PET-scan and whole body MRI
The value of positron emission tomography PET imaging depends on the suitability of used isotope tracer to identify lesions of the imaged tumor type When bone is imaged with PET 18F-fluoride has been the most commonly used tracer Other commonly used PET tracers in PC include 18F-FDG and 18F11C-choline but both have been late more or less replaced by PSMA-PET Prostate-specific membrane antigen PSMA is a trans-membrane protein with an increased expression on cell membranes of PC cells 68Ga-PSMA HBED-CC Glu-NH-CO-NH-Lys- Ahx-68GaHBED-CC was designed as an extracellular PSMA inhibitor for PET imaging and has been shown to demonstrate high specificity for PSMA-expressing tumor cell PSMA-PET results have been reported in several studies but only in three prospective one including 20-30 patients Of those studies only study by Fendler and coworkers investigated overall staging the other two studies by van Leeuwen focused on intraprostatic tumor detection or nodal metastases Nevertheless PSMA-PETCT is a promising imaging modality both for soft tissues and bone Recently 68Ga-PSMA was reported to outperform 99mTc-DPD-SPECT in detection of bone metastases in PC
Recently the novel PET tracer 18F-PSMA-1007 has been developed as a promising PSMA ligand to even outperform 68Ga-PSMA-PET in overall staging 18F-PSMA-1007 have advantages in comparison to 68Ga-PSMA-PET including primary elimination of 18F-PSMA-1007 via the hepatobiliary excretion route leading to less isotope activity in urinary tract Consequently 18F-PSMA-1007 might lead to better local staging because of its favorable pharmacokinetics and tumor-specific uptake 18F-PSMA-1007-PET combined with CT or even MRI could truly offer a 1-stop solution for both metastatic screening and local staging but more prospective studies are needed to confirm this hypothesis
Whole-body T1-weighted MRI is an effective method for bone imaging and is superior when compared to 99mTc-MDP BS If combined with soft tissue imaging bone and nodal imaging may be performed in single imaging session Diffusion-weighted imaging DWI as a part of routine MRI examination is a promising tool for detection of an early intramedullary malignant lesion before cortical destruction or reactive processes due to bone marrow metastasis DWI performs high contrast resolution between tumor and normal tissue Individual variability of the mean apparent diffusion coefficient ADC values as the result of DWI may decrease the diagnostic accuracy of DWI Diagnostic accuracy of DWI for detection of malignant lesion is better than 18-fluoro-deoxy-glucose FDG and for detection of bone metastasis is comparable to 11C-choline However it is unclear if it is superior compared to the standard T1-weighted imaging or STIR fat suppression technique Currently there is not sufficient data comparing MRI and PSMA-PETCT accuracy on bone imaging in PC
In addition to bone the possible tumor spread to soft tissues especially pelvic lymph node is common in PC staging Traditionally contrast enhanced abdomen and pelvic CT or MRI are used but the sensitivity of these imaging modalities is very limited Diffusion-weighted MRI may improve the diagnostic accuracy when normal sized lymph nodes are evaluated Still different PET-tracers and recently especially 68Ga-PSMA and novel 18F-PSMA have both been considered as the most promising modalities for pelvic lymph node metastasis detection in PC and preliminary results suggest superior diagnostic accuracy of PSMA-PET compared to other modalities
The investigators have previously investigated different imaging modalities for detection of bone metastases in prospective setting Skeleta-trial According to that study 18F-NaF PET-CT and whole-body MRI are superior when compared to 99mTc-MDP SPECT-CT or 99mTc-MDP planar bone scan Nevertheless that study needs validation and further investigations as it was limited by low number n27 of PC patients and PSMA-PET was not included in the study
Clinicians face challenges when choosing optimal imaging modalitymodalities for individual patient Guidelines do not support any imaging in low risk cases For some intermediate risk cases and also for high-risk cases if local treatment is planned accurate staging of pelvic lymph node is important In contrary in very high-risk cases the knowledge of distant metastases is the single most important staging data Optimally for clinicians most appropriate imaging technique would be chosen based on patient related risk factors or a single imaging modality would offer all aspects of needed staging information The rationale for the present study is to find the most appropriate staging modality in high-risk PC at the time of initial staging
About one quarter of diagnosed PC are metastatic at the time of diagnosis Accurate staging is extremely important as the stage is single most important factor when treatment decisions are made and stage is the single most important prognostic factor Localized PC is treated with active surveillance low risk cases or with treatment modalities with curative intent radical prostatectomy or radiotherapyAlthough recently radical treatments have been suggested to play a role in low volume metastatic disease the standard treatment of metastatic disease is castration therapy
In PC staging the most important anatomic locations to be imaged are i bone ii lymph nodes especially pelvic lymph nodes and iii extranodal soft tissues
Detection of tumor bone metastases is commonly performed by BS However the results of recent studies have raised many doubts whether BS is as effective for confirming or excluding metastatic bone disease Moreover the sensitivity for 99mTc-methylene diphosphonate bone scintigraphy 99mTc-MDP BS is only 50-70 The detection of bone metastases in patients with high-risk PC is significantly improved by SPECT compared to planar BS Other imaging modalities with potentially improved accuracy to detect bone metastases in PC include PET-scan and whole body MRI
The value of positron emission tomography PET imaging depends on the suitability of used isotope tracer to identify lesions of the imaged tumor type When bone is imaged with PET 18F-fluoride has been the most commonly used tracer Other commonly used PET tracers in PC include 18F-FDG and 18F11C-choline but both have been late more or less replaced by PSMA-PET Prostate-specific membrane antigen PSMA is a trans-membrane protein with an increased expression on cell membranes of PC cells 68Ga-PSMA HBED-CC Glu-NH-CO-NH-Lys- Ahx-68GaHBED-CC was designed as an extracellular PSMA inhibitor for PET imaging and has been shown to demonstrate high specificity for PSMA-expressing tumor cell PSMA-PET results have been reported in several studies but only in three prospective one including 20-30 patients Of those studies only study by Fendler and coworkers investigated overall staging the other two studies by van Leeuwen focused on intraprostatic tumor detection or nodal metastases Nevertheless PSMA-PETCT is a promising imaging modality both for soft tissues and bone Recently 68Ga-PSMA was reported to outperform 99mTc-DPD-SPECT in detection of bone metastases in PC
Recently the novel PET tracer 18F-PSMA-1007 has been developed as a promising PSMA ligand to even outperform 68Ga-PSMA-PET in overall staging 18F-PSMA-1007 have advantages in comparison to 68Ga-PSMA-PET including primary elimination of 18F-PSMA-1007 via the hepatobiliary excretion route leading to less isotope activity in urinary tract Consequently 18F-PSMA-1007 might lead to better local staging because of its favorable pharmacokinetics and tumor-specific uptake 18F-PSMA-1007-PET combined with CT or even MRI could truly offer a 1-stop solution for both metastatic screening and local staging but more prospective studies are needed to confirm this hypothesis
Whole-body T1-weighted MRI is an effective method for bone imaging and is superior when compared to 99mTc-MDP BS If combined with soft tissue imaging bone and nodal imaging may be performed in single imaging session Diffusion-weighted imaging DWI as a part of routine MRI examination is a promising tool for detection of an early intramedullary malignant lesion before cortical destruction or reactive processes due to bone marrow metastasis DWI performs high contrast resolution between tumor and normal tissue Individual variability of the mean apparent diffusion coefficient ADC values as the result of DWI may decrease the diagnostic accuracy of DWI Diagnostic accuracy of DWI for detection of malignant lesion is better than 18-fluoro-deoxy-glucose FDG and for detection of bone metastasis is comparable to 11C-choline However it is unclear if it is superior compared to the standard T1-weighted imaging or STIR fat suppression technique Currently there is not sufficient data comparing MRI and PSMA-PETCT accuracy on bone imaging in PC
In addition to bone the possible tumor spread to soft tissues especially pelvic lymph node is common in PC staging Traditionally contrast enhanced abdomen and pelvic CT or MRI are used but the sensitivity of these imaging modalities is very limited Diffusion-weighted MRI may improve the diagnostic accuracy when normal sized lymph nodes are evaluated Still different PET-tracers and recently especially 68Ga-PSMA and novel 18F-PSMA have both been considered as the most promising modalities for pelvic lymph node metastasis detection in PC and preliminary results suggest superior diagnostic accuracy of PSMA-PET compared to other modalities
The investigators have previously investigated different imaging modalities for detection of bone metastases in prospective setting Skeleta-trial According to that study 18F-NaF PET-CT and whole-body MRI are superior when compared to 99mTc-MDP SPECT-CT or 99mTc-MDP planar bone scan Nevertheless that study needs validation and further investigations as it was limited by low number n27 of PC patients and PSMA-PET was not included in the study
Clinicians face challenges when choosing optimal imaging modalitymodalities for individual patient Guidelines do not support any imaging in low risk cases For some intermediate risk cases and also for high-risk cases if local treatment is planned accurate staging of pelvic lymph node is important In contrary in very high-risk cases the knowledge of distant metastases is the single most important staging data Optimally for clinicians most appropriate imaging technique would be chosen based on patient related risk factors or a single imaging modality would offer all aspects of needed staging information The rationale for the present study is to find the most appropriate staging modality in high-risk PC at the time of initial staging
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None