Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT03149861 |
| Other study ID # |
CAPCR ID:17-5295 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
June 8, 2017 |
| Est. completion date |
May 9, 2025 |
Study information
| Verified date |
June 2024 |
| Source |
University Health Network, Toronto |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background:
Currently, patients suspected of having prostate cancer undergo ultrasound-guided systematic
biopsies of the prostate. However, up to a quarter of clinically significant tumors, which
may pose a risk to patient's well-being, may be missed on random biopsies. MRI enables
detection of further tumors in this patient population, but also has limited accuracy.
Study hypothesis:
We hypothesize that hybrid PET-MRI, a novel scanner which incorporates MRI with molecular
imaging will improve the detection rate of clinically significant tumors.
Study design:
In this prospective trial, we will recruit 57 men who are suspected of having prostate cancer
but have had negative systematic biopsies, who have been diagnosed with low-risk disease but
have clinically signs of more aggressive tumor or who have a focal tumor detected and are
candidates for minimally-invasive tumor ablation (=tumor destruction with laser or ultrasound
waves), in whom it is crucial to exclude other tumor sites.
All patients will undergo PET/MRI after injection of a radiopharmaceutical called
"18F-DCFPyL". This is a radioactive probe which has been shown in preliminary studies to be
sensitive and specific for detection of prostate cancer.
All lesions detected on PET/MRI will undergo biopsy under ultrasound using fused PET/MRI and
ultrasound images for guidance, and compared to histopathology. The primary outcome measure
in this study is the proportion of clinically significant prostate cancers that are detected
with PET/MRI compared to MRI alone. Improved detection of clinically significant prostate
cancer may enable a tailored, personalized therapeutic approach, decreasing morbidity and
potentially improving overall patient outcome.
Description:
Prostate cancer overview:
Prostate cancer (PCa) is the 3rd leading cause of death from cancer in men and constitutes
almost 1/4 of all new cancer cancers in men. Although PCa is prevalent, the risk of clinical
or fatal PCa in a 50 year old man is estimated at only 10% and 3%, respectively Currently,
over 2/3 of men diagnosed with PCa are diagnosed with organ confined, low risk disease (PSA <
10 ng/ml, Gleason score (=GS) 3+3, cT1c). Management is depending on tumor grade, size and
stage and clinical parameters (e.g. life expectancy) and may range from active surveillance
to radical therapy including definitive whole gland treatment (radical prostatectomy (RP), or
radiotherapy). Although radical whole gland therapy is effective from an oncological
standpoint, it may be associated with significant side effects. A more conservative approach
in select patients may be enrollment in an active surveillance program. The concept behind
this approach is that small volume, low grade PCa may have an indolent course and may not
progress to biological significance in the absence of treatment in the patient's lifetime.
Conventional workup of patients with clinical suspicion of PCa:
Transrectal Ultrasound (TRUS)-guided biopsies: Current workup of patients with clinical
suspicion of PCa includes TRUS-guided systematic biopsies. These are associated with a
relatively high false negative rate, especially for areas difficult to access for biopsy,
with csPCa missed in approximately 1 of 4 patients. Furthermore, there is only ˜50%
correlation between biopsy obtained GS and final pathology at RP, with upgrading in more than
1 in 3 cases. This may lead to inaccurate risk stratification and inappropriate selection of
therapy.
Role of multiparametric-MR & MR-Ultrasound Fusion Biopsy:
In recent years, multiparametric MR (mpMR) has been incorporated in the workup of patients
with suspected PCa. T2- weighted imaging (T2WI) in combination with diffusion-weighted
imaging (DWI) and dynamic contrast enhanced (DCE)-MR have shown promise in the detection,
local staging and risk stratification of PCa, with a reported sensitivity and specificity of
0.74 & 0.88, respectively. Prostate MR is interpreted using a 5-point scoring scale (PI-RADS
- Prostate Imaging and Reporting Archiving Data System), with an overall sensitivity &
specificity of 77.0% & 71.4%, respectively, for detection of csPCa using PI-RADS-v2. Using
MR-US fusion targeted biopsy for mpMR detected lesions improves detection of csPCa compared
to standard biopsy (median: 9.1%) and improves correlation of biopsy-derived and surgical
tumor grade.
Focal ablation therapy:
In recent years, trials have evaluated various focal ablative therapies (FT) as alternative
management for select patients with low/ intermediate risk, organ-confined disease. FT for
PCa involves varying degrees of predefined subtotal glandular ablation using a myriad of
ablative energy sources e.g high intensity focused ultrasound (HIFU), or laser ablation. The
common aim of all of these methods is curative-intent tumor ablation while minimizing
morbidity, thereby potentially providing the best balance between oncologic control and side
effects of radical therapy. FT relies on the notion that the index lesion can be identified
by mpMRI, and localized for intervention. Although no long term data exists on the safety and
oncologic outcome of FT, FT appears well-tolerated and associated with significantly less
morbidity than whole-gland treatment. At our institution, in-bore focal laser ablation
program (MRgFLT) allows patients with a single site of csPCa to be treated while the in-bore
HIFU program allows inclusion of patients with up to 2 sites of csPCa confirmed on MR-TRUS
fusion biopsy.
One of the main risks with a strategy of FT in PCa is selection failure. Although data is
scarce, residual or unrecognized cancer was detected on follow-up biopsy in 22-50% of
patients from two separate small series, including cancers in portions of the prostate not
appreciated prior to intervention. Although it is uncertain how many of these are csPCa, this
highlights the potential limitations of current workup algorithms for patients considered for
FT. As only recognized index tumor site is targeted, detection of any further site of csPCa
is paramount for appropriate patient selection and therapy success.
Molecular imaging in PCa:
There are shortcomings of current workup of patients with clinical suspicion of PCa,
including significant false negative rate of TRUS-biopsies and mpMR. At least 1 in 5 patients
in active surveillance program thought to have low-risk disease based on biopsies, turns out
to have unfavorable features on surgical pathology. As specific patient management is based
on accurate risk stratification, there is a clinical need for further tools to improve
identification and characterization of csPCa. There has been increasing interest in molecular
imaging in PCa in recent years. The most common radiopharmaceuticals used include choline
(11C-Choline/ 18F-Fluorocholine) and 68Ga-PSMA.
PSMA, a type II transmembrane protein, is expressed in normal prostate epithelium and highly
expressed in ~90% primary PCa and metastases. 68Ga-PSMA-HBED-CC, the most common PSMA PET
radiopharmaceutical assessed to date, has shown high sensitivity in detecting recurrent
disease. Recently developed 18F-labelled PSMA compounds (e.g. 18F-DCFPyL) offer several
technical advantages over 68Ga including high imaging statistic and higher image resolution.
Initial preclinical studies have shown favorable tissue binding and the first clinical
investigation in 9 patients has shown very high levels of uptake in primary tumors and
metastases with further pilot data suggesting additional metastases identified in >20% of
patients compared to 68Ga-PSMA.
Recently introduced hybrid PET/MR scanners allow simultaneous acquisition of MR & PET data,
incorporation the advantages of MR and molecular imaging. Emerging data is showing PET/MR to
be potentially robust for assessment of oncology indications, particularly those that are
better addressed with MR such as PCa. A recently published trial on 68Ga-PSMA PET/MR in
intermediate-high risk patients has shown that mpMR, PET and PET/MR had a sensitivity of 66%,
92% and 98%, respectively in localizing Pca. PSMA-PET may also help characterize equivocal
lesions on mpMR (PI-RAD v.2 score 3) and may facilitate targeted fusion biopsies of lesions
not seen on MR.
