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Evaluating 4Kscore’s role in predicting progression on active surveillance for prostate cancer independently of clinical information and PIRADS score

Prostate Cancer and Prostatic Diseases volume 28, pages 180–186 (2025)Cite this article

Subjects

Abstract

Background

4Kscore is used to aid the decision for prostate biopsy, however its role in active surveillance (AS) has not been investigated in a magnetic resonance imaging (MRI)-based protocol. Our objective was to assess the association between 4Kscore and progression in men undergoing AS on a prospective MRI-based protocol.

Methods

This was a single-institution, single-arm, non-therapeutic, interventional trial of 166 men with biopsy-confirmed prostate cancer enrolled between 2014–2020. Patients were placed on a trial-mandated AS protocol including yearly multiparametric (mp)MRI, prostate biopsy, and 4Kscore followed for 48 months after diagnosis. We analyzed protocol-defined and grade progression at confirmatory and subsequent surveillance biopsies.

Results

Out of 166 patients, 83 (50%) men progressed per protocol and of them 41 (24.7% of whole cohort) progressed by grade. At confirmatory biopsy, men with a baseline 4Kscore ≥ 20% had a higher risk of grade progression compared to those with 4Kscore < 20% (OR = 4.04, 95% CI: 1.05–15.59, p = 0.043) after adjusting for National Comprehensive Cancer Network (NCCN) risk and baseline PIRADS score. At surveillance biopsies, most recent 4Kscore ≥ 20% significantly predicted per protocol (OR = 2.61, 95% CI: 1.03–6.63, p = 0.044) and grade progression (OR = 5.13, 95% CI: 1.63–16.11, p = 0.005).

Conclusions

For patients on AS, baseline 4Kscore predicted grade progression at confirmatory biopsy, and most recent 4Kscore predicted per-protocol and grade progression at surveillance biopsy.

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Fig. 1
Fig. 2: Scatterplot of 4Kscore of patients over study period.
Fig. 3: Cumulative incidence of progression over the study period.

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Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

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Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA240139 (SCCC); U01CA239141, U01CA27140 and 1R01CA272766 (SP, RS, AP, SMG). SP is also funded in part through Paps Corps Champions for Cancer Research Endowed Chair in Solid Tumor Research.

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Authors and Affiliations

  1. University of Iowa Hospitals and Clinics, Department of Urology, Iowa City, IA, USA

    Helen Y. Hougen

  2. Department of Public Health Sciences, University of Miami Miller School of Medicine, Miami, FL, USA

    Isildinha M. Reis

  3. Biostatistics and Bioinformatics Shared Resources, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, USA

    Isildinha M. Reis & Sunwoo Han

  4. Desai Sethi Urology Institute, University of Miami, Miami, FL, USA

    Nachiketh Soodana Prakash, Jamie Thomas, Oleksandr N. Kryvenko, Chad R. Ritch, Bruno Nahar, Mark L. Gonzalgo, Dipen J. Parekh & Sanoj Punnen

  5. Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA

    Radka Stoyanova, Oleksandr N. Kryvenko, Sandra M. Gaston, Matthew C. Abramowitz, Alan Dal Pra, Brandon A. Mahal & Alan Pollack

  6. Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, USA

    R. Patricia Castillo

  7. Department of Pathology and Laboratory Medicine, University of Miami Miller School of Medicine, Miami, FL, USA

    Oleksandr N. Kryvenko

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  1. Helen Y. Hougen
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Contributions

HYH: writing-original draft, writing-review & editing, methodology, visualization; IMR: methodology, formal analysis, writing-review & editing, visualization; SH: formal analysis, writing-review & editing, visualization; NSP: data curation, project administration; JT: writing-review & editing; RS: funding acquisition, resources, writing-review & editing; RPC: resources; ONK: resources; CRR: resources; BN: resources; MLG: resources, writing-review & editing; SMG: resources, writing-review & editing, funding acquisition; MA: resources; ADP: resources; BAM: resources; AP: resources, funding acquisition; DJP: resources, funding acquisition, writing-review & editing; SP: conceptualization, funding acquisition, methodology, writing-review & editing, supervision

Corresponding author

Correspondence to Helen Y. Hougen.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

The University of Miami Institutional Review Board approved the study (#20140372). All methods were performed in accordance with relevant guidelines and regulations. Informed consent was obtained from all participants.

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Hougen, H.Y., Reis, I.M., Han, S. et al. Evaluating 4Kscore’s role in predicting progression on active surveillance for prostate cancer independently of clinical information and PIRADS score. Prostate Cancer Prostatic Dis 28, 180–186 (2025). https://doi.org/10.1038/s41391-024-00898-w

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