OPTIMIZING PROSTATE CANCER DIAGNOSTICS: CAN BIOMARKERS DECREASE THE BURDEN OF OVER-INVESTIGATION?

Mikolaj Kurczynski; Aleksandra  Suszczyńska; Angelika Wiatr; Ksenia  Jakubiak; Julia  Witkowska; Ewa  Wojtanowska; Aleksandra  Pietrucień; Monika  Krasoń

doi:10.31435/ijitss.3(51).2026.6322

Authors

Mikolaj Kurczynski Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0005-6484-6229
Aleksandra Suszczyńska “UNIDENT” Dental Clinic, Dąbrowa Tarnowska, Poland https://orcid.org/0009-0009-0923-8529
Angelika Wiatr Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0002-0202-4535
Ksenia Jakubiak Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0003-0291-9942
Julia Witkowska Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0008-6106-9665
Ewa Wojtanowska Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0007-4813-9473
Aleksandra Pietrucień Medical Center of Pabianice, ul. Jana Pawła II 68, 95-200 Pabianice, Poland https://orcid.org/0009-0000-5777-3301
Monika Krasoń Central Teaching Hospital of the Medical University of Lodz, ul. Pomorska 251, 92-213 Łódź, Poland https://orcid.org/0009-0000-5571-9440

DOI:

https://doi.org/10.31435/ijitss.3(51).2026.6322

Keywords:

Prostate Cancer, Biomarkers, Biopsy, Multiparametric MRI (mpMRI), Prostate Health Index (PHI), 4Kscore, Stockholm3, ExoDx, SelectMDx

Abstract

The foundation of current prostate cancer diagnostics still remains the interpretation of total PSA (tPSA) results, but it is an imperfect test due to its low specificity and diagnostic ambiguities in patients within the "gray zone," meaning patients with a result of (2.0/4.0–10.0 ng/mL). This fact leads to many cases of "overdiagnosis" and an excess of unnecessarily performed biopsies. This article summarizes the diagnostic value of blood-based biomarkers and tests (PHI, 4Kscore, Stockholm3) as well as urine-based ones (SelectMDx and ExoDx). These tests achieve high AUC values (0.76–0.88) and a high negative predictive value (up to 98%) in detecting clinically significant prostate cancer (csPCa, GG ≥ 2), underscoring their advantage over traditional methods. Combining them with multiparametric MRI allows for a 30–65% reduction in unnecessary biopsies while maintaining high oncological safety for the patient. Despite promising results, the high costs of individual tests, lack of reimbursement, and absence of full standardization in international urological guidelines remain a continuous challenge and a hurdle to their introduction into daily practice.

References

Zhong, X., Xiong, Y., Yang, F., Yang, Y., Gong, X., Wang, S., & Xia, Q. (2026). Prostate health index enhances prostate cancer management in Chinese populations: Evidence from the nation’s large cohort and transnational multicohort harmonization. BMC Cancer, 26, 254. https://doi.org/10.1186/s12885-026-15577-3

Hatakeyama, S., Yoneyama, T., & Ohyama, C. (2026). Beyond total PSA: Clinical significance of S2,3PSA% in reducing unnecessary prostate biopsies. International Journal of Urology, 33(2), e70371. https://doi.org/10.1111/iju.70371

Jeon, S. S., Song, W., Kang, M., Sung, H. H., Jeon, H. G., Jeong, B. C., Seo, S. I., & Chung, J. H. (2025). Diagnostic value of prostate health index in patients with no index lesion on mpMRI or negative previous combined biopsy. Investigative and Clinical Urology, 66(2), 124–129. https://doi.org/10.4111/icu.20250007

Josefsson, A., Månsson, M., Kohestani, K., Spyratou, V., Wallström, J., Hellström, M., Lilja, H., Vickers, A., Carlsson, S. V., Godtman, R., & Hugosson, J. (2024). Performance of 4Kscore as a reflex test to prostate-specific antigen in the GÖTEBORG-2 prostate cancer screening trial. European Urology, 86(3), 223–229. https://doi.org/10.1016/j.eururo.2024.04.037

de Almeida S, R., Jr., Thomas, J., Mason, M. M., Becerra, M. F., Merhe, A., Reis, I. M., Kwon, D., Soodana-Prakash, N., Tewari, A., Patel, V., Wagaskar, V., Konety, B., Kasraeian, A., Czarniecki, S., Thoreson, G. R., Kim, E. H., Swain, S., Parekh, D. J., & Punnen, S. (2023). Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging. BJUI Compass, 4(5), 591–596. https://doi.org/10.1002/bco2.235

Scuderi, S., Tin, A., Gandaglia, G., Stabile, A., Montorsi, F., Briganti, A., & Vickers, A. J. (2023). Implementation of 4Kscore as a secondary test before prostate biopsy: Impact on US population trends for prostate cancer. European Urology Open Science, 52, 1–3. https://doi.org/10.1016/j.euros.2023.03.011

Brooks, J. D. (2024). Stockholm3 in a multiethnic cohort: Optimizing prostate cancer screening to reduce harm and improve equity. Journal of Clinical Oncology, 42(32), 3768–3772. https://doi.org/10.1200/JCO.24.00941

Björnebo, L., Discacciati, A., Falagario, U., Vigneswaran, H. T., Jäderling, F., Grönberg, H., Eklund, M., Nordström, T., & Lantz, A. (2024). Biomarker vs MRI-enhanced strategies for prostate cancer screening: The STHLM3-MRI randomized clinical trial. JAMA Network Open, 7(4), e247131. https://doi.org/10.1001/jamanetworkopen.2024.7131

Nordström, T., Annerstedt, M., Glaessgen, A., Carlsson, S., Clements, M., Abbadi, A., Grönberg, H., Jäderling, F., Eklund, M., & Discacciati, A. (2024). Repeated prostate cancer screening using prostate-specific antigen testing and magnetic resonance imaging: A secondary analysis of the STHLM3-MRI randomized clinical trial. JAMA Network Open, 7(2), e2354577. https://doi.org/10.1001/jamanetworkopen.2023.54577

Wu, H., Wu, Y., He, P., Liang, J., Xu, X., & Ji, C. (2024). A meta-analysis for the diagnostic accuracy of SelectMDx in prostate cancer. PLOS ONE, 19(2), e0285745. https://doi.org/10.1371/journal.pone.0285745

Calinoiu, P.-C., Badescu, D., Nechita, O.-C., Toma, C.-V., Neculai, D., Rascu, S., Petca, R.-C., Aurelian, J., Sima, C.-S., & Jinga, V. (2025). Refining the management of Prostate Imaging Reporting Category 3 lesions through SelectMDx urinary biomarker evaluation. Maedica, 20(2), 176–181. https://doi.org/10.26574/maedica.2025.20.2.176

Călinoiu, P.-C., Nechita, O.-C., Bădescu, D., Toma, C.-V., Raşcu, Ş., Petca, R.-C., Aurelian, J., Constantin, T., & Jinga, V. (2025). Prostate cancer diagnostics: The independent and combined roles of SelectMDx and mpMRI. Central European Journal of Urology, 78(3), 255–262. https://doi.org/10.5173/ceju.2024.0284

Soeterik, T. F. W., Wu, X., Van den Bergh, R. C. N., Kesch, C., Zattoni, F., Falagario, U., Martini, A., Miszczyk, M., Fasulo, V., Maggi, M., Kasivisvanathan, V., Rajwa, P., Marra, G., Gandaglia, G., Chiu, P. K. F., & EAU-YAU Prostate Cancer Working Party. (2025). Personalised prostate cancer diagnosis: Evaluating biomarker-based approaches to reduce unnecessary magnetic resonance imaging and biopsy procedures. European Urology Open Science, 75, 106–119. https://doi.org/10.1016/j.euros.2025.03.006

Grobholz, R., Burn, F., & Prause, L. (2026). Modern integrative prostate cancer diagnostics. Current Opinion in Urology, 36(2), 171–179. https://doi.org/10.1097/MOU.0000000000001361

Robaczyńska, J., Maj, M., Kiljańczyk, A., Pastuszek, B., Reducha, E., Nurkiewicz, A., & Kiljańczyk, M. (2026). Epigenetic and liquid biopsy biomarkers in prostate cancer: Bridging tumor heterogeneity and clinical implementation. Cancers, 18(3), 389. https://doi.org/10.3390/cancers18030389

Tutrone, R., Lowentritt, B., Neuman, B., Donovan, M. J., Hallmark, E., Cole, T. J., Yao, Y., Biesecker, C., Kumar, S., Verma, V., Sant, G. R., Alter, J., & Skog, J. (2023). ExoDx prostate test as a predictor of outcomes of high-grade prostate cancer—An interim analysis. Prostate Cancer and Prostatic Diseases, 26(3), 596–601. https://doi.org/10.1038/s41391-023-00675-1