PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer
Abstract
:1. Introduction
2. Classic PCa Diagnosis Pathways
2.1. DRE (Digital Rectal Examination)
2.2. PSA (Prostate-Specific Antigen) and fPSA (freePSA)
2.3. PSA Density (PSAD)
2.4. MpMRI (Multiparametric Magnetic Resonance imaging)
3. Non-Invasive Biomarkers in PCa Diagnosis
3.1. Prostate Health Index (PHI) and Prostate Health Index Density (PHID)
3.2. 4 Kscore (4 Kallikreins Score)
3.3. The Stockholm-3 Model for Prostate Cancer Detection (STHLM3)
4. Imagistic Techniques
4.1. Mp-MRI (Multiparametric Magnetic Resonance Imaging)
4.2. Mp-US (Multiparametric Ultrasound)
5. Combined Tests
6. Other Perspectives
7. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
4K | 4 kalikrein score |
68 Ga-PET-CT | Gallium 68 positron emission tomography- computer tomography |
ACS | American Cancer Society |
ADC | apparent diffusion coefficient |
AS | active surveillance |
AUA | American Urology Association |
AUC | area under the curve |
BMI | body mass index |
BpMRI | bi parametric magnetic resonance imaging |
BPH | benign prostatic hyperplasia |
BRCA | breast cancer gene |
CAP | The Cluster Randomized Trial of PSA Testing for Prostate Cancer |
CDUS | color Doppler ultrasound |
CEUS | contrast-enhanced ultrasound |
csPCa | clinically significant PCa |
DCE | dynamic contrast enhancement |
DRE | digital rectal examination |
DWI | diffusion-weighted imaging |
EAU | European Association of Urology |
ERSPC | European Randomized Study of Screening for Prostate Cancer trial |
ESMO | European Society of Medical Oncology |
FDA | Food and Drug Administration |
fPSA | freePSA |
GG | Gleason Grade |
HG | high grade |
ISUP | International Society of Urological Pathology |
MIC1 | macrophage inhibitory cytokine-1 |
MicroRNAs | MiRNA |
Mp MRI | multiparametric magnetic resonance imaging |
Mp US | multiparametric ultrasound |
MRGB | magnetic resonance guided biopsy |
MSMB | microseminoprotein beta |
NPV | negative predictive value |
PCa | prostate cancer |
PCA3 | prostate cancer antigen 3 |
PCPT | Prostate Cancer Prevention Trial |
PET-CT | positron emission tomography- computer tomography |
PHID | prostate health index density |
PHI | prostate health index |
PI-RADS | Prostate Imaging–Reporting and Data System |
PLCO | The Prostate, Lung, Colorectal and Ovarian |
PPV | positive predictive value |
PRI-MUS | Prostate risk identification-micro ultrasound |
PSA | prostatic specific antigen |
PSAD | PSA density |
ROC | receiver operating characteristics |
RPCRC | Rotterdam Prostate Cancer Risk Calculator |
SB | systematic biopsy |
SE | strain elastography |
SMI | spectacular micro-vascular imaging |
STHLM3 (S3M) | Stockholm 3 test |
SWE | shear wave elastography |
T2W | T2 weighted image |
TB | targeted biopsy |
TP | transperineal |
TPM | template prostate mapping |
tPSA | Total PSA |
TR | transrectal |
TRES | transrectal elastography |
TRUS | TransRectal UltraSound |
TRUSGB | transrectal ultrasound-guided biopsy |
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Screening Recommendation Associations | Recommendations |
---|---|
AUA (American Association of Urology) [30] | PSA screening for men 55–70 years old Urinary, serum biomarkers, imaging, Risk Calculators can be used for men with a suspicious PSA level Screening at 2 years or more can be applied to reduce the harm of screening No screening if life expectancy is <15 years old, or men >70 years old |
EAU (European Association of Urology) [8] | PSA screening for men over 50-year-old or over 45 if they had a family history of PCa, African descent or over 40 if carrying BRCA2 mutations Men with PSA level >1 ng/mL at 40-year-old or >2 ng/mL at 60-year-old are at risk Men with PSA 2–10ng/mL and normal DRE, prior to biopsy, use additional tests (PCA3, PHI, 4Kscore, Kallikreins, TMPRSS2-ERG or Risk Calculators, Imaging (mpMRI) PSA screening every 2 years for those at risk |
ESMO (European Society of Medical Oncology) [31] | Subclinical PCa is common in men >50-year-old PSA screening for men 55–70 years old PSA level >1 ng/mL for men at 40 years old and >2 ng/mL for men at 60-year-old represents a risk Early PSA screening for men >50 years old, >45 with a family history of PCa, African-American, and BRCA 1/2 carriers Do not test if life expectancy is <10 years Use Risk Calculators or mpMRI before biopsy |
ACS (American Cancer Society) [32] | Informed PSA screening for men >50 years old, >45 if African-American or men with first-degree relative diagnosed with PCa (under the age 65), >40 years old if they have more than one first degree relative with PCa Early screening for men with PSA level 2.5 ng/mL If the biopsy is negative, additional tests can help (PHI, 4Kscore, PCa3, ConfirmMDx) |
Marker/Technique | Number of Patients | Study Design | Cancer Detection | Other Details |
---|---|---|---|---|
PHI [41] | 545 | Prospective, multicentric study | PHI AUC 0.82 PSAD AUC 0.79 PSA AUC 0.70 | If MRI is negative, PHI AUC for positive PCa 0.78 If PHI ≥ 30, 35% of MRIs could be avoided Spared 40% of biopsies Missed 8% PCas |
4Kscore [46] | 2 224 PCa 2 230 controls | Prospective, multicentric, case-control, multiethnic | 4K AUC 0.782 PSA+fPSA AUC 0.739 PSA AUC 0.685 | The AUCs represent the identification of aggressive PCas 4kscore can accurately differentiate between benign and malign cases, indolent and aggressive tumors |
S3M [50] | 59 149 | Prospective, population baased, diagnostic trial | S3M AUC 0.75 PSA AUC 0.58 | 34% of biopsies spared |
MRI [76] | 576 | Prospective, multicenter, paired-cohort | sensitivity 93%, specificity 41% | Could avoid 27% of biopsies TRUS directed by MRI, could diagnose 18% more csPCas |
mpUS [68] | 1040 | Prospective, multicenter | mpUS sensitivity 94%, specificity 22% | Results were similar with mpMRI sensitivity 93%, specificity 23% |
4Kscore, MRI, PSAD [72] | 266 | Retrospective, unicentric | 4Kscore and MRI if 4K > 7.5 | 4kscore followed by MRI if 4K > 7.5 and biopsy if MRI is positive or biopsy if MRI negative and 4K > 18 |
Country | Test | Costs |
---|---|---|
Germany [34] | PHID | 100 EUR |
China, Hong Kong [82] | PHI | 370 USD |
US [15] | PHI | 80 USD |
4Kscore | 500 USD | |
PCA 3 | 300 USD | |
MiPS | 700 USD | |
SelectMDx | 300 USD | |
ERSPC RPCRC Risk Calculator | 0 | |
PCPT Risk Calculator | 0 | |
MRI | 1000 USD | |
Europe [15] | MRI | 300–500 EUR |
UK [71] | US Scanner | 35,000–150,000 USD |
MRI machine | Approx. 3 million USD | |
MRI + biopsy | 965 GBP |
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Share and Cite
Munteanu, V.C.; Munteanu, R.A.; Gulei, D.; Schitcu, V.H.; Petrut, B.; Berindan Neagoe, I.; Achimas Cadariu, P.; Coman, I. PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer. Diagnostics 2020, 10, 806. https://doi.org/10.3390/diagnostics10100806
Munteanu VC, Munteanu RA, Gulei D, Schitcu VH, Petrut B, Berindan Neagoe I, Achimas Cadariu P, Coman I. PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer. Diagnostics. 2020; 10(10):806. https://doi.org/10.3390/diagnostics10100806
Chicago/Turabian StyleMunteanu, Vlad Cristian, Raluca Andrada Munteanu, Diana Gulei, Vlad Horia Schitcu, Bogdan Petrut, Ioana Berindan Neagoe, Patriciu Achimas Cadariu, and Ioan Coman. 2020. "PSA Based Biomarkers, Imagistic Techniques and Combined Tests for a Better Diagnostic of Localized Prostate Cancer" Diagnostics 10, no. 10: 806. https://doi.org/10.3390/diagnostics10100806