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., 2019Carroll P, Kellogg Parsons J, Andriole G, Bahnson RR, Carlsson S and Castle EP (2019) NCCN Clinical Practice Guidelines - Prostate Cancer Early Detection, Version 2.2019, 2019, https://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf (accessed 22 august 2023) https://www.nccn.org/professionals/physi...
; Hugosson et al., 2019Hugosson J, Roobol MJ, Månsson M, Tammela TLJ, Zappa M, Nelen V, Kwiatkowski M, Lujan M, Carlsson SV, Talala KM et al. (2019) A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol 76:43-51.; Kovac et al., 2020Kovac E, Carlsson SV, Lilja H, Hugosson J, Kattan MW, Holmberg E and Stephenson AJ (2020) Association of baseline prostate-specific antigen level with long-term diagnosis of clinically significant prostate cancer among patients aged 55 to 60 years: A secondary analysis of a cohort in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. JAMA Netw Open 3:e1919284.. |
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., 2013Perdona S, Bruzzese D, Ferro M, Autorino R, Marino A, Mazzarella C and Terracciano D (2013) Prostate health index (phi) and prostate cancer antigen 3 (PCA3) significantly improve diagnostic accuracy in patients undergoing prostate biopsy. Prostate 73:227-235.; Barisiene et al., 2020Barisiene M, Bakavicius A, Stanciute D, Jurkeviciene J, Zelvys A, Ulys A, Vitkus D and Jankevicius F (2020) Prostate Health Index and Prostate Health Index Density as diagnostic tools for improved prostate cancer detection. Biomed Res Int 21:9872146.; Fan et al., 2021Fan YH, Pan PH, Cheng WM, Wang HK, Shen SH, Liu HT, Cheng HM, Chen WR, Huang TH, Wei TC et al. (2021) The Prostate Health Index aids multi-parametric MRI in diagnosing significant prostate cancer. Sci Rep 11:1286.. |
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., 2015Parekh DJ, Punnen S, Sjoberg DD, Asroff SW, Bailen JL, Cochran JS and Zappala SM (2015) A multi-institutional prospective trial in the USA confirms that the 4Kscore accurately identifies men with high-grade prostate cancer. Eur Urol 68:464-470.; Rannikko et al., 2022Rannikko A, Leht M, Mirtti T, Kenttämies A, Tolonen T, Rinta-Kiikka I, Kilpeläinen TP, Natunen K, Lilja H, Lehtimäki T et al. (2022) Population-based randomized trial of screening for clinically significant prostate cancer ProScreen: A pilot study. BJU Int 130:193-199.; Assel et al., 2019Assel M, Sjöblom L, Murtola TJ, Talala K, Kujala P, Stenman UH, Taari K, Auvinen A, Vickers A, Visakorpi T et al. (2019) A four-kallikrein panel and β-microseminoprotein in predicting high-grade prostate cancer on biopsy: an independent replication from the finnish section of the European Randomized Study of Screening for Prostate Cancer. Eur Urol Focus 5:561-567.. |
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., 2017Ravipaty S, Wu W, Dalvi A, Tanna N, Andreazi J, Friss T, Klotz A, Liao C, Garren J, Schofield S, et al. (2017) Clinical validation of a serum protein panel (FLNA, FLNB and KRT19) for diagnosis of prostate cancer. J Mol Biomark Diagn 8:323. |
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., 2019Steuber T, Tennstedt P, Macagno A, Athanasiou A, Wittig A, Huber R, Golding B, Schiess R and Gillessen S (2019) Thrombospondin 1 and cathepsin D improve prostate cancer diagnosis by avoiding potentially unnecessary prostate biopsies. BJU Int 123:826-833. . |
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., 2014Wei JT, Feng Z, Partin AW, Brown E, Thompson I, Sokoll L, Chan DW, Lotan Y, Kibel AS, Busby JE et al. (2014) Can urinary PCA3 supplement PSA in the early detection of prostate cancer? J Clin Oncol 32:4066-4072.; Fradet et al., 2018Fradet V, Toren P, Nguile-Makao M, Lodde M, Lévesque J, Léger C, Caron A, Bergeron A, Ben-Zvi T, Lacombe L et al. (2018) Prognostic value of urinary prostate cancer antigen 3 (PCA3) during active surveillance of patients with low-risk prostate cancer receiving 5α-reductase inhibitors. BJU Int 121:399-404.; Rubio-Briones et al., 2021Rubio-Briones J, Casanova J, Dumont R, Rubio L, Fernandez-Serra A, Casanova-Salas I, Domínguez-Escrig J, Ramírez-Backhaus M, Collado A, Gómez-Ferrer A et al. (2021) Liquid biopsy-based exo-oncomiRNAs can predict prostate cancer aggressiveness. Cancers (Basel) 13:250. . |
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., 2018McKiernan J, Donovan MJ, Margolis E, Partin A, Carter B, Brown G, Torkler P, Noerholm M, Skog J, Shore N et al. (2018) A prospective adaptive utility trial to validate performance of a novel urine exosome gene expression assay to predict high-grade prostate cancer in patients with prostate-specific antigen 2-10ng/ml at initial biopsy. Eur Urol 74:731-738. ; Tutrone et al., 2020Tutrone R, Donovan MJ, Torkler P, Tadigotla V, McLain T, Noerholm M, Skog J and McKiernan J (2020) Clinical utility of the exosome based ExoDx Prostate (IntelliScore) EPI test in men presenting for initial Biopsy with a PSA 2-10 ng/mL. Prostate Cancer Prostatic Dis 23:607-614.. |
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., 2013Salami SS, Schmidt F, Laxman B, Regan MM, Rickman DS, Scherr D, Bueti G, Siddiqui J, Tomlins SA, Wei JT et al. (2013) Combining urinary detection of TMPRSS2:ERG and PCA3 with serum PSA to predict diagnosis of prostate cancer. Urol Oncol 31:566-571.; Grupp et al., 2015Grupp K, Roettger L, Kluth M, Hube-Magg C, Simon R, Lebok P, Minner S, Tsourlakis MC, Koop C, Graefen M et al. (2015) Expression of DNA ligase IV is linked to poor prognosis and characterizes a subset of prostate cancers harboring TMPRSS2:ERG fusion and PTEN deletion. Oncol Rep 34:1211-1220. ; Tomlins et al., 2016Tomlins SA, Day JR, Lonigro RJ, Hovelson DH, Siddiqui J, Kunju LP, Dunn RL, Meyer S, Hodge P, Groskopf J et al. (2016) Urine TMPRSS2: ERG plus PCA3 for individualized prostate cancer risk assessment. Eur Urol 70:45-53.; Alinezhad et al., 2016Alinezhad S, Väänänen RM, Tallgrén T, Perez IM, Jambor I, Aronen H, Kähkönen E, Ettala O, Syvänen K, Nees M et al. (2016) Stratification of aggressive prostate cancer from indolent disease-Prospective controlled trial utilizing expression of 11 genes in apparently benign tissue. Urol Oncol 34:255. e15-22.. |
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., 2015Leyten GH, Hessels D, Smit FP, Jannink SA, de Jong H, Melchers WJ, Cornel EB, de Reijke TM, Vergunst H, Kil P et al. (2015) Identification of a candidate gene panel for the early diagnosis of prostate cancer. Clin Cancer Res 21:3061-3070. ; Hendriks et al., 2021Hendriks RJ, van der Leest MMG, Israël B, Hannink G, YantiSetiasti A, Cornel EB, Hulsbergen-van de Kaa CA, Klaver OS, Sedelaar JPM, Van Criekinge W et al. (2021) Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis: A prospective, multicenter study in biopsy-naïve men. Prostate Cancer Prostatic Dis 24:1110-1119. . |
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., 2014Wojno KJ, Costa FJ, Cornell RJ, Small JD, Pasin E, Van Criekinge W, Bigley JW and Van Neste L (2014) Reduced rate of repeated prostate biopsies observed in ConfirmMDx clinical utility field study. Am Health Drug Benefits 7:129-134.; Partin et al., 2014Partin AW, Van Neste L, Klein EA, Marks LS, Gee JR, Troyer DA, Rieger-Christ K, Jones JS, Magi-Galluzzi C, Mangold LA et al. (2014) Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies. J Urol 192:1081-1087.. |
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., 2013Freedland SJ, Gerber L, Reid J, Welbourn W, Tikishvili E, Park J, Younus A, Gutin A, Sangale Z, Lanchbury JS et al. (2013) Prognostic utility of cell cycle progression score in men with prostate cancer after primary external beam radiation therapy. Int J Radiat Oncol Biol Phys 86:848-853.; Cuzick et al., 2012Cuzick J, Berney DM, Fisher G, Mesher D, Møller H, Reid JE, Perry M, Park J, Younus A, Gutin A et al. (2012) Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 106:1095-1099.. |
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., 2018Van Den Eeden SK, Lu R, Zhang N, Quesenberry CP Jr, Shan J, Han JS, Tsiatis AC, Leimpeter AD, Lawrence HJ, Febbo PG et al. (2018) A biopsy-based 17-gene genomic prostate score as a predictor of metastases and prostate cancer death in surgically treated men with clinically localized disease. Eur Urol 73:129-138; Klein et al., 2014Klein EA, Cooperberg MR, Magi-Galluzzi C, Simko JP, Falzarano SM, Maddala T, Chan JM, Li J, Cowan JE, Tsiatis AC et al. (2014) A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 66:550-560.; Cullen et al., 2015Cullen J, Rosner IL, Brand TC, Zhang N, Tsiatis AC, Moncur J, Ali A, Chen Y, Knezevic D, Maddala T et al. (2015) A biopsy-based 17-gene genomic prostate score predicts recurrence after radical prostatectomy and adverse surgical pathology in a racially diverse population of men with clinically low- and intermediate-risk prostate cancer. Eur Urol 68:123-131.. |
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., 2017Gore JL, du Plessis M, Santiago-Jiménez M, Yousefi K, Thompson DJS, Karsh L, Lane BR, Franks M, Chen DYT, Bandyk M et al. (2017) Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: interim results from the multicenter prospective PRO-IMPACT study. Cancer 123:2850-2859.; Cooperberg et al., 2015Cooperberg MR, Davicioni E, Crisan A, Jenkins RB, Ghadessi M and Karnes RJ (2015) Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort. Eur Urol 67:326-333.; Feng et al., 2021Feng FY, Huang HC, Spratt DE, Zhao SG, Sandler HM, Simko JP, Davicioni E, Nguyen PL, Pollack A, Efstathiou JA et al. (2021) Validation of a 22-gene genomic classifier in patients with recurrent prostate cancer: an ancillary study of the NRG/RTOG 9601 randomized clinical trial. JAMA Oncol 7:544-552.. |
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., 2014Shipitsin M, Small C, Choudhury S, Giladi E, Friedlander S, Nardone J, Hussain S, Hurley AD, Ernst C, Huang YE et al. (2014) Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error. Br J Cancer 111:1201-1212.. |
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., 2016Lennartz M, Minner S, Brasch S, Wittmann H, Paterna L, Angermeier K, Öztürk E, Shihada R, Ruge M, Kluth M et al. (2016) The combination of DNA ploidy status and PTEN/6q15 deletions provides strong and independent prognostic information in prostate cancer. Clin Cancer Res 22:2802-2811.. |
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. |