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Urine spermine and multivariable Spermine Risk Score predict high-grade prostate cancer

Prostate Cancer and Prostatic Diseases volume 24, pages 542–548 (2021)Cite this article

Subjects

Abstract

Background

To investigate the role of urine spermine and Spermine Risk Score in prediction of high-grade prostate cancer (HGPCa, ISUP grade group ≥2).

Methods

Nine hundred and five consecutive men with elevated PSA were prospectively recruited from two hospitals. Core analyses focused on consecutive men with PSA 4–20 ng/mL (n = 600). Pre-biopsy urine without prior prostatic massage was analyzed for spermine level with ultra-high performance liquid chromatography with triple quadrupole mass spectrometer (UPLC-MS/MS). The proportions of PCa and HGPCa were compared across different spermine ranges. Logistic regressions were used to form different models, and their performances were compared using area under curve (AUC) and decision curve analysis (DCA).

Results

PCa and HGPCa were diagnosed in 30.8% (185/600) and 17.2% (103/600) men, respectively, and were significantly associated with lower urine spermine levels. Between the lowest and highest quartiles of spermine results, a threefold increase in PCa risk (49.3% vs. 16.7%) and 3.5-fold increase in ISUP grade group ≥2 PCa risk (31.3% vs. 8.7%) were observed. Multivariate analysis showed PSA, prostate volume (PV), digital rectal examination (DRE), and spermine, which were independent predictors for PCa and HGPCa, and a Spermine Risk Score with these factors achieved the highest AUC of 0.78 for PCa and 0.82 for HGPCa. At 90% sensitivity for HGPCa, 36.7% biopsies and 24.4% ISUP grade group 1 diagnoses could have been avoided, with a negative predictive value of 95.4%. DCA revealed net clinical benefit of the Spermine Risk Score. Internal validation with bootstrapping showed good discrimination and calibration.

Conclusion

Urine spermine and Spermine Risk Score identified men at higher risk of HGPCa and reduced unnecessary biopsies.

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References

  1. Hugosson J, Roobol MJ, Månsson M, Tammela TLJ, Zappa M, Nelen V, et al. A 16-yr follow-up of the European Randomized study of screening for prostate cancer. Eur Urol. 2019;76:43–51.

    Article  Google Scholar 

  2. Chiu PK, Ng CF, Semjonow A, Zhu Y, Vincendeau S, Houlgatte A, et al. A multicentre evaluation of the role of the Prostate Health Index (PHI) in regions with differing prevalence of prostate cancer: adjustment of PHI reference ranges is needed for European and Asian settings. Eur Urol. 2019;75:558–61.

    Article  Google Scholar 

  3. Braun K, Sjoberg DD, Vickers AJ, Lilja H, Bjartell AS. A four-kallikrein panel predicts high-grade cancer on biopsy: independent validation in a community cohort. Eur Urol. 2016;69:505–11.

    Article  Google Scholar 

  4. Rodríguez SVM. Diagnostic accuracy of prostate cancer antigen 3 (PCA3) prior to first prostate biopsy: a systematic review and meta-analysis. Can Urol Assoc J. 2020;14:E214–9.

    PubMed  Google Scholar 

  5. Van Neste L, Hendriks RJ, Dijkstra S, Trooskens G, Cornel EB, Jannink SA, et al. Detection of high-grade prostate cancer using a urinary molecular biomarker-based risk score. Eur Urol. 2016;70:740–48.

    Article  Google Scholar 

  6. Kasivisvanathan V, Rannikko AS, Borghi M, Panebianco V, Mynderse LA, Vaarala MH, et al. MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med. 2018;378:1767–77.

    Article  Google Scholar 

  7. Schipper RG, Romijn JC, Cuijpers VM, Verhofstad AA. Polyamines and prostatic cancer. Biochem Soc Trans. 2003;31:375–80.

    Article  CAS  Google Scholar 

  8. van der Graaf M, Schipper RG, Oosterhof GO, Schalken JA, Verhofstad AA, Heerschap A. Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer. MAGMA. 2000;10:153–9.

    PubMed  Google Scholar 

  9. Tsoi TH, Chan CF, Chan WL, Chiu KF, Wong WT, Ng CF, et al. Urinary polyamines: a pilot study on their roles as prostate cancer detection biomarkers. PLoS ONE. 2016;11:e0162217.

    Article  Google Scholar 

  10. Russell DH. Increased polyamine concentrations in the urine of human cancer patients. Nat N Biol. 1971;233:144–5.

    Article  CAS  Google Scholar 

  11. Fair WR, Wehner N, Brorsson U. Urinary polyamine levels in the diagnosis of carcinoma of the prostate. J Urol. 1975;114:88–92.

    Article  CAS  Google Scholar 

  12. Hradec E, Jiránek J, Macek K. Urinary spermidine levels in cases of carcinoma of the prostate. Preliminary report. Scand J Urol Nephrol Suppl. 1980;55:71–3.

    CAS  PubMed  Google Scholar 

  13. Horn Y, Beal SL, Walach N, Lubich WP, Spigel L, Marton LJ. Further evidence for the use of polyamines as biochemical markers for malignant tumors. Cancer Res. 1982;42:3248–51.

    CAS  PubMed  Google Scholar 

  14. Horn Y, Beal SL, Walach N, Lubich WP, Spigel L, Marton LJ. Relationship of urinary polyamines to tumor activity and tumor volume in patients. Cancer Res. 1984;44:4675–8.

    CAS  PubMed  Google Scholar 

  15. Sakai S, Ito Y, Koide T, Tei K, Hara A, Sawada H. Detection of urinary polyamine by a new enzymatic differential assay. (III). Studies on urinary polyamines in patients with malignant genitourinary diseases. Hinyokika Kiyo. 1986;32:343–50.

    CAS  PubMed  Google Scholar 

  16. Sakai S, Koide T, Ito Y, Tei K, Deguchi T, Matsuda S, et al. Urine polyamine in patients with malignant urological diseases using a polyamine-test enzyme kit. Hinyokika Kiyo. 1986;32:661–5.

    CAS  PubMed  Google Scholar 

  17. Chen R, Ren S, Chinese Prostate Cancer Consortium, Yiu MK, Fai NC, Cheng WS, et al. Prostate cancer in Asia: a collaborative report. Asian J Urol. 2014;1:15–29.

    Article  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Ms Shaz Cheng for her help in this project.

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Authors and Affiliations

  1. SH Ho Urology Centre, Division of Urology, Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, China

    Peter Ka-Fung Chiu, Jeremy Yuen-Chun Teoh, Chun-Hong Chan, Ryan Tsz-Hei Tse, Chi-Ho Leung, Yim-Ping Wong & Chi-Fai Ng

  2. Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR, China

    Yan-Ho Fung & Ka-Leung Wong

  3. Division of Urology, Department of Surgery, North District Hospital, Hong Kong SAR, China

    Ka-Lun Lo & Kai-Man Li

  4. Department of Urology, Erasmus MC, Rotterdam, The Netherlands

    Monique J. Roobol

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  1. Peter Ka-Fung Chiu
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Correspondence to Ka-Leung Wong or Chi-Fai Ng.

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Conflict of interest

K-LW holds a patent for urinary polyamines as prostate cancer detection biomarkers (patent no. US20180172695A1). The other authors declare that they have no conflict of interest.

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Chiu, P.KF., Fung, YH., Teoh, J.YC. et al. Urine spermine and multivariable Spermine Risk Score predict high-grade prostate cancer. Prostate Cancer Prostatic Dis 24, 542–548 (2021). https://doi.org/10.1038/s41391-020-00312-1

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