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Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance

Prostate Cancer and Prostatic Diseases volume 22, pages 84–90 (2019)Cite this article

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Abstract

Background

Management of active surveillance (AS) in low-risk prostate cancer (PCa) patients could be improved with new biomarkers, such as the 4Kscore test. We analyze its ability to predict tumor reclassification by upgrading at the confirmatory biopsy at 6 months.

Methods

Observational, prospective, blinded, and non-randomized study, within the Spanish National Registry on AS (AEU/PIEM/2014/0001; NCT02865330) with 181 patients included after initial Bx and inclusion criteria: PSA ≤10 ng/mL, cT1c-T2a, Grade group 1, ≤2 cores, and ≤5 mm/50% length core involved. Central pathological review of initial and confirmatory Bx was performed on all biopsy specimens. Plasma was collected 6 months after initial Bx and just before confirmatory Bx to determine 4Kscore result. In order to predict reclassification defined as Grade group ≥2, we analyzed 4Kscore, percent free to total (%f/t) PSA ratio, prostate volume, PSA density, family history, body mass index, initial Bx, total cores, initial Bx positive cores, initial Bx % of positive cores, initial Bx maximum cancer core length and initial Bx cancer % involvement. Wilcoxon rank-sum test, non-parametric trend test or Fisher’s exact test, as appropriate established differences between groups of reclassification.

Results

A total of 137 patients met inclusion criteria. Eighteen patients (13.1%) were reclassified at confirmatory Bx. The %f/t PSA ratio and 4Kscore showed differences between the groups of reclassification (Yes/No). Using 7.5% as cutoff for the 4Kscore, we found a sensitivity of 89% and a specificity of 29%, with no reclassifications to Grade group 3 for patients with 4Kscore below 7.5% and 2 (6%) missed Grade group 2 reclassified patients. Using this threshold value there is a biopsy reduction of 27%. Additionally, 4Kscore was also associated with changes in tumor volume.

Conclusions

Our preliminary findings suggest that the 4Kscore may be a useful tool in the decision-making process to perform a confirmatory Bx in active surveillance management.

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Authors and Affiliations

  1. Department of Urology, Hospital Universitario Miguel Servet. IIS Aragon., Zaragoza, Spain

    Ángel Borque-Fernando

  2. Department of Urology, Instituto Valenciano de Oncología, Valencia, Spain

    José Rubio-Briones

  3. Escuela Universitaria Politécnica La Almunia, Universidad de Zaragoza, Zaragoza, Spain

    Luis M. Esteban

  4. OPKO Diagnostics, Woburn, MA, USA

    Yan Dong

  5. Department of Pathology, Instituto Valenciano de Oncología, Valencia, Spain

    Ana Calatrava

  6. Department of Urology, Instituto Valenciano de Oncología, Valencia, Spain

    Álvaro Gómez-Ferrer

  7. Department of Urology, Hospital Reina Sofía. IMIBIC, Córdoba, Spain

    Enrique Gómez-Gómez

  8. Department of Urology, Hospital Universitario Miguel Servet. IIS Aragon., Zaragoza, Spain

    Jesús M. Gil Fabra

  9. Department of Urology, Hospital Son Llàtzer, Palma de Mallorca, Spain

    Nuria Rodríguez-García

  10. Department of Urology, Hospital Universitario Virgen de la Arrixaca, Murcia, Spain

    Pedro Á. López González

  11. Department of Urology, Hospital Universitario Central de Asturias, Oviedo, Spain

    Jorge García-Rodríguez

  12. Department of Urology, Hospital General Universitario de Castellón, Castellón de La Plana, Spain

    Miguel Rodrigo-Aliaga

  13. Department of Urology, Hospital Universitario Virgen de la Victoria, Málaga, Spain

    Bernardo Herrera-Imbroda

  14. Department of Urology, Hospital Universitario Puerta del Mar, Cádiz, Spain

    Juan Soto-Villalba

  15. Department of Urology, Complejo Hospitalario Universitario de A Coruña, A Coruña, Spain

    Sara Martínez-Breijo

  16. Department of Urology, Hospital Universitario Fundación Alcorcón, Madrid, Spain

    Virginia Hernández-Cañas

  17. Department of Urology, Hospital de Manises, Valencia, Spain

    Ana M. Soto-Poveda

  18. Department of Urology, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain

    Carlos Sánchez-Rodríguez

  19. Department of Urology, Hospital General Universitario Morales Meseguer, Murcia, Spain

    Carlos Carrillo-George

  20. Department of Urology, Hospital de Manacor, Manacor, Spain

    Yumaira E. Hernández-Martínez

  21. OPKO Diagnostics, Miami, FL, USA

    David Okrongly

Authors
  1. Ángel Borque-Fernando
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  2. José Rubio-Briones
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  3. Luis M. Esteban
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  4. Yan Dong
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  5. Ana Calatrava
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  6. Álvaro Gómez-Ferrer
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  8. Jesús M. Gil Fabra
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  9. Nuria Rodríguez-García
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  10. Pedro Á. López González
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  11. Jorge García-Rodríguez
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  12. Miguel Rodrigo-Aliaga
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  13. Bernardo Herrera-Imbroda
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  14. Juan Soto-Villalba
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  15. Sara Martínez-Breijo
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  16. Virginia Hernández-Cañas
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  17. Ana M. Soto-Poveda
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  18. Carlos Sánchez-Rodríguez
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  19. Carlos Carrillo-George
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  20. Yumaira E. Hernández-Martínez
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  21. David Okrongly
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Corresponding author

Correspondence to Ángel Borque-Fernando.

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The authors declare that they have no conflict of interest.

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Borque-Fernando, Á., Rubio-Briones, J., Esteban, L.M. et al. Role of the 4Kscore test as a predictor of reclassification in prostate cancer active surveillance. Prostate Cancer Prostatic Dis 22, 84–90 (2019). https://doi.org/10.1038/s41391-018-0074-5

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