Prostate tumor markers: diagnosis, prognosis and management

Lawisch, Gabriela Kniphoff da Silva; Dexheimer, Geórgia Muccillo; Biolchi, Vanderlei; Seewald, Rafael Armando; Chies, José Artur Bogo

doi:10.1590/1678-4685-GMB-2023-0136

person Gabriela Kniphoff da Silva Lawisch

conceived this study · performed the main review of the study · analyzed the data · wrote the initial version of the manuscript · read and approved the final version

schoolUniversidade do Vale do Taquari (Univates), Lajeado, RS, Brasil.schoolUniversidade Federal do Rio Grande do Sul, Departamento de Genética, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil.

person Geórgia Muccillo Dexheimer

review and data analyses · read and approved the final version

schoolUniversidade do Vale do Taquari (Univates), Lajeado, RS, Brasil.

person Vanderlei Biolchi

review and data analyses · read and approved the final version

schoolUniversidade do Vale do Taquari (Univates), Lajeado, RS, Brasil.

person Rafael Armando Seewald

clinical review of the article · read and approved the final version

schoolUniversidade do Vale do Taquari (Univates), Lajeado, RS, Brasil.schoolHospital Bruno Born, Centro de Oncologia, Lajeado, RS, Brasil.

person José Artur Bogo Chies

conceived this study · supervised · read and approved the final version

schoolUniversidade Federal do Rio Grande do Sul, Departamento de Genética, Programa de Pós-Graduação em Genética e Biologia Molecular, Porto Alegre, RS, Brasil.

0000-0001-7025-0660

personSend correspondence to José Artur Bogo Chies. Universidade Federal do Rio Grande do Sul, Departamento de Genética, Av. Bento Gonçalves, 9500, 91501-970, Campus do Vale, Porto Alegre, RS, Brazil. E-mail:
jabchies@terra.com.br.

Conflict of Interests

The authors declare that there is no conflict of interest that could be perceived as prejudicial to the impartiality of the reported research.

Associate Editor:

Lavínia Schüler-Faccini

Assay	Sample	Biomarker	Advantages	Disadvantages	Reference
PCA screening - tests that help in diagnosis and biopsy decision
Prostatic Specific Antigen	Serum	Total PSA.	Screening of man without symptoms.	Low specificity and does not indicate aggressiveness.	Carroll et al., 2019; Hugosson et al., 2019; Kovac et al., 2020.
Prostate Health Index (PHI)	Serum	Total PSA, free PSA (fPSA) and p2PSA.	Helps in clinical decisions (avoid unnecessary biopsies).	Different cutoffs described (mainly in different ethnic groups).	Perdona et al., 2013; Barisiene et al., 2020; Fan et al., 2021.
4KScore	Serum	Total PSA, fPSA, intact PSA and hK2.	Indicated for patients with altered PSA or DRE. Identify high risk cases, and help in biopsy decisions.	Values can be altered due to different individual clinical conditions.	Paerkh et al., 2015; Rannikko et al., 2022; Assel et al., 2019.
Filamin A, Filamin B, Keratin-19	Serum	FLNA, FLNB and KRT19.	Improved predictive power in detecting PCA (combined with PSA analysis).	The markers can be dysregulated in a variety of cancers, and need to be part of a panel.	Ravipaty et al., 2017.
Thrombospondin and D Cathepsin	Serum	Thrombospondin and D cathepsin.	Combined with free PSA, can improve PCA diagnosis and may reduce the number of unnecessary prostate biopsies.	Needs to be evaluated in different cohorts to establish a cutoff value.	Steuber et al., 2019.
PCA3	Urine	PCA3	Biopsy result prediction when combined with PSA and others.	The cutoff is not well established, there are cases with a high PCA3 value without PCA. Can’t be analyzed alone.	Wei et al., 2014; Fradet et al., 2018; Rubio-Briones et al., 2021.
ExoDXProstate	Urine	Exosomal mRNA for PCA3, ERG and SPDEF.	The test can discriminate high-grade from low-grade cancer and benign disease. And guides the biopsy-decision.	Should be used in combination with the PSA and other personal health factors.	McKiernan et al., 2018; Tutrone et al., 2020.
PCA staging- tests that help establish the aggressiveness of the disease
MiPS	Urine	mRNA PCA3 and TMPRSS2:ERG.	Diagnosis and prognosis with prediction of aggressiveness.	There are still no cutoff values determined.	Salami et al., 2013; Grupp et al., 2015; Tomlins et al., 2016; Alinezhad et al., 2016.
SelectMDX	Urine	mRNA HOXC6, TDRD1 and DLX1.	Early diagnosis and predictor of aggressiveness (Gleason 7 or more).	No determined cutoff values, due to different values in distinct ethnic groups. Recommended before the biopsy decision.	Leyten et al., 2015; Hendriks et al., 2021.
ConfirmMDx	Tissue	DNA hypermethylation (GSTP1, APC, RASSF1)	Screens for prostate cancer at a molecular level, useful for patients who have a negative or inconclusive biopsy but there’s a high suspicion of PCA.	Accuracy and sensibility varies among studies, not FDA approved.	Wojno et al., 2014; Partin et al., 2014.
PCA prognosis - tests that help to guide the treatment strategy
Prolaris	Tissue	Gene expression (31 genes).	Analyzes cell cycle progression score (predicts cancer aggressiveness, metastasis).	Needs an invasive sample, so can be done only after biopsy or prostatectomy.	Freedland et al., 2013; Cuzick et al., 2012.
OncotypeDx GPS	Tissue	Gene expression: AZGP1, FAM13C, KLK2, SRD5A2, FLNC, GSN, GSTM2, TPM2, BGN, COL1A1, SFRP4, TPX2, ARF1, ATP5E, CLTC, GPS1, PGK1.	Guides treatment (analyzes risk stratification) and aggressiveness (metastasis).	Only for organ confined PCA, and can be done after biopsy confirmation (invasive sample).	Van Den Eeden et al., 2018; Klein et al., 2014; Cullen et al., 2015.
Decipher	Tissue	Gene expression: NFIB, NUSAP1, ZWILCH, ANO7, PCAT-32, UBE2C, CAMK2N1, MYBPC1, PBX1, THBS2, EPPK1, IQGAP3, LASP1, PCDH7, RABGAP1, GLYATL1P4, S1PR4, TNFRSF19, TSBP.	Analyzes tumor aggressiveness, mortality and metastasis risk.	Only for organ confined PCA, and can be done after biopsy confirmation (invasive sample).	Gore et al., 2017; Cooperberg et al., 2015; Feng et al., 2021.
Promark	Tissue	Proteomics: DERL1, CUL2, SMAD4, PDSS2, HSPA9, FUS, pS6, YBOX1.	The test result is expressed as a score (from 0 to 100), with higher scores indicating a greater risk of aggressive disease.	The test is only meant to be performed on patients with biopsy Gleason specific scores, and needs a biopsy sample.	Shipitsin et al., 2014.
DNA-ploidy	Tissue	Assessment of DNA’s aberrant amount.	Prognostic marker in several cancer types. Patients with nondiploid tumors have an increased risk of poor prognosis compared to patients with diploid tumors.	General test, needs to be analyzed in combination with other biomarkers, and need a invasive sample.	Lennartz et al., 2016.
IMPROD bpMRI	Tissue	mRNA expression of ACSM1, AMACR, CACNA1D, DLX1, PCA3, PLA2G7, RHOU, SPINK1, SPON2, TMPRSS2-ERG, and TDRD1.	Diagnosis and analysis of aggressiveness.	The test is still being validated in different population groups.	Perez et al., 2020.