1000/1000
Hot
Most Recent
Prostate cancer (PCa) is a heterogeneous disease, with a large percentage of prostate tumors being indolent, and with a relatively slow metastatic potential. However, due to the high case numbers, the absolute number of PCa-related deaths is still high. In fact, it causes the second highest number of cancer deaths in American men. As a first step for the diagnosis of PCa, the PSA test has been widely used. However, it has low specificity, which results in a high number of false positives leading to overdiagnosis and overtreatment. Newer derivatives of the original PSA test, including the Food and Drug Administration (FDA)-approved 4K (four kallikreins) and the PHI (Prostate Health Index) blood tests, have higher specificities. Tissue-based PCa tests are problematic as biopsies are invasive and have limited accuracy due to prostate tumor heterogeneity. Liquid biopsies offer a minimally or non-invasive choice for the patients, while providing a more representative reflection of the spatial heterogeneity in the prostate. In addition to the abovementioned blood-based tests, urine is a promising source of PCa biomarkers, offering a supplementary avenue for early detection and improved tumor classification. Four urine-based PCa tests are either FDA- or CLIA-approved: PCA3 (PROGENSA), ExoDX Prostate Intelliscore, MiPS, and SelectMDx.
Biomarker Test |
Molecular Markers |
Approval |
---|---|---|
Serum-based |
||
Prostate Serum Antigen |
PSA |
FDA |
Prostate Health Index, PHI, Beckman Coulter Inc., Brea, CA, USA |
Total PSA, fPSA, p2PSA |
FDA |
4Kscore, OPKO Health company, BioReference Laboratories Inc., Township, NJ, USA |
Total PSA, fPSA, intact PSA, hK2 |
CLIA |
Urine-based |
||
Progensa PSA3 Assay, Hologic, MA, USA |
PCA3 |
FDA |
ExoDX Prostate (Intelliscore), Exosome Diagnostics Inc., Waltham, MA, USA |
Exosomal RNA (PCA3, ERG) |
CLIA |
MiPS, MyProstateScore, MCTP, Arbor, MI, USA |
PCA3, TMPRSS2-ERG |
CLIA |
SelectMDX, MDx Health, Irvine, CA, USA |
HOXC6, DLX1 |
CLIA |
Biomarker Test |
Urine Sample |
Advantages |
Limitations |
---|---|---|---|
Progensa PSA3 Assay, Hologic, Marlborough, MA, USA |
Post-DRE |
Assay score correlates with the likelihood of repeat biopsy |
Sample collection requirements, clinical data and risk factors should be considered before decision, certain conditions, procedures and medications may influence assay score |
ExoDX (Prostate Intelliscore), Exosome Diagnostics Inc., Waltham, MA, USA |
Non-DRE |
Non-invasive test, at-home collection kit, assay score correlates with risk for advanced PCa |
All clinical data should be considered before decision |
MiPS, MyProstateScore, MCTP, Arbor, MI, USA |
Post-DRE |
Assay score correlates with a need for biopsy |
All clinical data required to generate final score and should be considered before decision |
SelectMDX, MDx Health, Irvine, CA, USA |
Post-DRE |
Assay score predicts advanced PCa in biopsy |
Sample collection requirements, all clinical risk factors should be considered before decision |
Table 3 summarizes examples of promising methylation and RNA-based urinary biomarkers in development.
Table 3. Examples of promising methylation and RNA-based urinary biomarkers in development.
Molecular Target |
Patient Cohort, N |
Sensitivity % |
Specificity% |
AUC |
Reference |
---|---|---|---|---|---|
24 gene methylation panel |
104 |
100 |
97 |
0.88–0.99 |
[31] |
miR-34b/c, mir193b methylation |
161 |
97 |
80 |
0.98 |
[32] |
RARβ2 methylation, meta study |
1181 |
- |
- |
- |
[33] |
APC, CRIP3, GSTP1, HOXD8 methylation |
153 |
- |
- |
- |
[34] |
HOXD3, GSTP1 methylation |
408 |
57 |
97 |
0.8 |
[35] |
miR-148a, miR-375 |
277 |
83 |
79 |
0.79–0.84 |
[36] |
miR-21, miR-375, 5 miRNA panel |
70–215 |
- |
- |
0.87 |
|
miR-222-3p/miR-24-3p/miR-30c-5p |
249–1047 |
- |
- |
0.71–0.95 |
|
PSGR |
146–215 |
- |
- |
0.68–0.90 |
|
PCGEM1, PCA3 |
271 |
- |
- |
0.88 |
[43] |
PSMA, PSGR, PCA3 |
154 |
- |
- |
0.82 |
[44] |