Table 3.
Studies reporting on imaging modalities for metastases staging in newly diagnosed prostate cancer
| Author (year) | Study design | Imaging type | Tracer/sequences | No. Patients |
Patient cohort | Endpoint/event rate | Standard reference | Reader, Blinding | Sensitivity | Specificity | NPV | PPV | Accuracy/AUC (%) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hirmas (2019) | R, SC | 1) PET/CT 2) BS |
68Ga PSMA | 21 | HR GS ≥8 67% PSA median 38 ng/ml |
Bone mets (per lesion) NR |
Clinical, imaging (20CT, 16BS, 15MRI) baseline data + FU | 2, NR | 1) 100% 2) 63% |
92% 88% |
100% 70% |
90% 83% |
95 75 |
|
Hofman (2020)
proPSMA |
RCT, MC ACTRN12617000005358 |
1) PET/CT 2) cCT/BS with SPECT/CT |
68Ga PSMA | 302 | HR ISUP ≥3 98% PSA ≥20ng/ml 22% |
LN + Dist. mets. Overall: 87/295 mets: 48/295 |
Histology, clinical, biochemical and imaging FU at 6mo | Diff, NB | Overall: 1) 85% 2) 38% Metastases: 1) 92% 2) 54% |
98% 91% 99% 93% |
94% 76% 98% 91% |
94% 67% 96% 59% |
92 65 95 74 |
| Janssen (2018) | R, SC | 1) PET/CT 2) SPECT/CT |
68Ga PSMA | 54 | NR |
Bone mets 29/54 |
Clinical and imaging baseline data + FU | 2, NR | 1) 100% 2) 83% |
100% 84% |
NR | NR | 100 83 |
| Lengana (2018) | P, SC | 1) PET/CT 2) BS |
68Ga PSMA | 113 | Newly diagnosed, GS >7 54% PSA >20 75.2% |
Bone mets 26/113 |
Histology, imaging (CT, MRI, skeletal) correlation + clinical FU | 2, B | 1) 96% 2) 73% |
100% 87% |
99% 92% |
100% 63% |
99 84 |
| Pyka (2016) | R, SC | 1) PET/CT 2) BS |
68Ga PSMA | Subgroup 37 | Mean PSA 45ng/ml | Bone mets NR |
Clinical and imaging baseline + FU | 2, NR | 1) 100% 2) 57% |
91-100%* 65-96 |
NR | NR | 100 77 |
| Dyrberg (2019) | P, SC | 1) PET/CT 2) PET/CT 3) WB-MRI |
1) 68Ga PSMA 2) 18F-NaF 3T, DWI |
55 | 10 staging 3 under AS/WW 37 ADT |
Bone mets 20/55 |
Concordance between 3 index tests, clinical, biochemical and imaging FU of at least 0.5-1.5 years in case of disconcordance | 2 each, B | 1) 100% 2) 95% 3) 80% |
100% 97% 83% |
100% 97% 88% |
100% 95% 73% |
100 96 82 |
| Fonager (2017) | P, MC | 1) PET/CT 2) SPECT/CT 3) BS |
18F-NaF | 37 | HR PSA ≥50ng/ml |
Bone mets 27/37 |
Clinical, biochemical and imaging baseline +FU | 2, B | 1) 89% 2) 89% 3) 78% |
90% 100% 90% |
75% 77% 60% |
96% 100% 96% |
89 92 81 |
| Mosavi (2012) | P, SC | 1) PET/CT 2) WB-MRI |
18F-NaF 1.5T, DWI |
49 | HR | Bone mets 5/49 |
Consensus imaging and clinical FU | 2 each, B | 1) 100% 2) 100% |
91% 98% |
56% 83% |
100% 100% |
NR |
| Wondergem (2018) | R, SC | 1) PET/CT 2) BS |
18F-NaF | 104 NaF 122 BS |
PSA median 1) 89ng/ml 2) 29ng/ml |
Bone mets NR |
Baseline imaging + clinical, biochemical, imaging FU at ≥6mo | 2, B | 1) 97-100%* 2) 84-95%* |
98-100%* 72-100%* |
95-100%* 93-96%* |
98-100%* 61-100%* |
98-99 79-95 |
| Zacho (2020) | R, SC | PET/CT | 18F-NaF | 211 | 129 staging 67 BCR 23 mCRPC |
Bone mets 64/211 |
Clinical, biochemical and imaging baseline +FU | 2, B | 88-91%* | 90-97%* | 94-97%* | 70-93%* | NR |
| Poulsen (2014) | P, SC, NCT00956163 |
PET/CT 3) BS |
1) 18F-NaF
2) 18F-FCH |
50 | Bone mets in primary BS, PSA median 84ng/ml |
Spine mets NR |
Spine MRI | 4, B | 1) 93% 2) 85% 3) 51% |
54% 91% 82% |
78% 75% 43% |
82% 95% 86% |
81 87 61 |
| Metser (2018) | P, SC | 1) PET/MRI 2) PET/CT 3) WB-MRI 4) CT/BS |
18F-FCH 3T, DWI |
58, 10 PET/MRI, 48 PET/CT + WB-MRI |
HR | Metastases 77 met sites |
Histology, imaging and clinical FU Analyses per site |
PET: 1 MRI: 2, NR |
1) 100% 2) 94% 3) 74% 4) 64% |
NR | NR | NR | NR |
| Mortensen (2019) | P, SC, NCT02232685 |
1) PET/CT 2) BS |
18F-FCH | 143 | GS median 7 PSA median 18ng/ml |
Bone mets 8/143 |
Consensus of BS+PET+MRI | 2, NR | 1) 100% 2) 38% |
96% 85% |
NR | NR | NR |
| Evangelista (2015) | R, SC | 1) PET/CT 2) BS |
18F-FCH | 48 | 40% IR 60% HR |
Bone mets 11/48 |
Clinical, biochemical and imaging FU | 2, NR | 1) 100% 2) 90% |
92% 77% |
100% 94% |
79% 64% |
94 81 |
| Gauvin (2019) | R, SC | PET/CT | 18F-FCH | 76 | HR | Metastases NR |
Histology, clinical and imaging FU at least 6Mo | 1, NR | 86% | 100% | 98% | 100% | NR |
| Johnston (2019) | P, SC | 1) PET/CT 2) WB-MRI 3) BS |
18F-FCH 3T, DWI |
Subgroup 18 | 11% IR 89% HR |
Bone mets 5/18 |
Clinical and imaging baseline +FU | 2, B | 1) 80% 2) 90% 3) 60% |
92% 88% 100% |
92 97% 87% |
80% 81% 100% |
NR |
| Strandberg (2016) | R, SC | 1) PET/CT 2) BS |
11C-acetate | 66 | HR | Bone mets | Concordance of index tests, clinical, biochemical and imaging FU in case of disconcordance | 2, NR | 1) 100% 2) 69% |
98% 94% |
100% 93% |
93% 75% |
NR |
| Shen (2018) | R, SC | 1) PET/CT 2) BS |
18F-FDG | 46 | HR | Bone mets | Clinical and imaging FU at least 12mo | 2, B | 1) 90% 2) 90% |
92% 80% |
92% 91% |
91% 79% |
NR |
| Yi (2016) | R, SC | PET/CT |
1) 13N-ammonia
2) 18F-FDG |
26 | GS ≥8 or PSA >20ng/ml or ≥T2c | Bone mets | Histology, clinical and imaging baseline + FU 4mo | 2, B | 1) 100% 2) 100% |
100% 83% |
NR | NR | NR |
| Pasoglou (2014) | P, SC |
1) WB-MRI 2) BS + TXR |
3T, DWI, DCE | 30 | HR | Bone mets 9/30 |
Clinical, biochemical and imaging baseline +FU at 6mo | 2, NR | 1) 100% 2) 89% |
100% 90% |
100% 95% |
100% 80% |
100 90 |
| Pasoglou (2015) | P, SC | WB-MRI | 3T, DWI 1) 2D 2) 3D |
30 | HR | Bone mets NR |
Clinical, biochemical and imaging baseline +FU at 6mo | 1, B | 1) 90% 2) 100% |
100% 100% |
95% 100% |
100% 100% |
95 100 |
| Eyrich (2020) | R, MC |
1) mpMRI (pelvis to aortic bifurcation) 2) BS |
1.5-3T, NR | 646 | Mostly HR PSA median 9ng/ml |
Bone mets 38/646 |
Imaging and clinical FU | Diff, B | 1) 42-71%* 2) 68% |
95-98%* 98% |
96-98%* 98% |
47-67%* 63% |
NR |
| Vargas (2017) | R, SC | MRI (prostate) | 1.5-3T, +/−ERC | 228 | 33% LR 35% IR 32% HR |
Bone mets 53/228 |
Histology, clinical and imaging baseline + FU at least 12mo | 2, B | 89/67%# | 98/99%# | NR | NR | 97/90# |
| Woo (2016) | R, SC | mpMRI (prostate) | 3T, DWI, DCE | 308 | 119 HR | Bone mets 21/308 |
Histology, clinical and imaging baseline + FU | 2, NR | 95%* | 99-100%* | 100%* | 87-100%* | NR |
Abbreviations:
NPV negative predictive value
PPV positive predictive value
AUC Area under the ROC curve
R retrospective
P prospective
RCT randomized controlled trial
SC single center
MC multicenter
PET/CT positron emission tomography/computed tomography
SPECT single photon emission computed tomography
PSMA prostate specific membrane antigen
18F-NaF 18F-Sodiumfluoride
18F-FCH 18F-Fluorocholine
18F-FDG 18F-Fluorodeoxyglucose
18F FACBC 18F-Fluciclovine
cCT contrast enhanced computed tomography
BS bone scintigraphy
TXR target X-ray
mp/WB-MRI multiparametric/whole body magnetic resonance imaging
DWI diffusion weighted imaging
DCE dynamic contrast enhanced
ERC endorectal coil
LR, IR, HR low-, intermediate-, high-risk patients
GS Gleason score
PSA prostate specific antigen
BCR biochemical recurrence
mCRPC metastatic castration resistant prostate cancer
LN lymph nodes
FU follow-up
B blinded
NB not blinded
NR not reported
*
optimistic/pessimistic approach (equivocal results)
#
among different readers