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Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts

British Journal of Cancervolume 119pages14451450 (2018) | Download Citation




Active surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa.


We used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3: Gleason 3 + 3 only, index tumour volume < 1.3 cm3 and total tumour volume < 2.5 cm3). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). We compared the accuracy of existing predictive tools and the NRS in these cohorts.


The NRS (incorporating PSA, prostate volume, age, clinical T Stage, percent and number of positive biopsy cores) outperformed pre-existing predictive tools in derivation and validation cohorts (AUC 0.755 and 0.76, respectively). Selection bias due to analysis of a surgical cohort is acknowledged.


The advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making.

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Data availability

Patient data is stored in the database of the Prostatazentrum Nordwest, St. Antonius-Hospital, Klinik für Urologie, Kinderurologie und Urologische Onkologie, Gronau, Germany.


  1. 1.

    Albertsen, P. C., Hanley, J. A. & Fine, J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA 293, 2095–2101 (2005).

  2. 2.

    Wolters, T. et al. A critical analysis of the tumor volume threshold for clinically insignificant prostate cancer using a data set of a randomized screening trial. J. Urol. 185, 121–125 (2011).

  3. 3.

    Van den Bergh, R. C. et al. Outcomes of men with screen-detected prostate cancer eligible for active surveillance who were managed expectantly. Eur. Urol. 55, 1–8 (2009).

  4. 4.

    Iremashvili, V. et al. Pathologic prostate cancer characteristics in patients eligible for active surveillance: a head-to-head comparison of contemporary protocols. Eur. Urol. 62, 462–468 (2012).

  5. 5.

    Carter, H. B. et al. Early detection of prostate cancer: AUA guideline. J. Urol. 190, 419–426 (2013).

  6. 6.

    Adamy, A. et al. Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer. J. Urol. 185, 477–482 (2011).

  7. 7.

    Ochiai, A., Troncoso, P., Chen, M. E., Lloreta, J. & Babaian, R. J. The relationship between tumor volume and the number of positive cores in men undergoing multisite extended biopsy: implication for expectant management. J. Urol. 174, 2164–2168 (2005).

  8. 8.

    Parker, C., Muston, D., Melia, J., Moss, S. & Dearnaley, D. A model of the natural history of screen-detected prostate cancer, and the effect of radical treatment on overall survival. Br. J. Cancer 94, 1361–1368 (2006).

  9. 9.

    Selvadurai, E. D. et al. Medium-term outcomes of active surveillance for localised prostate cancer. Eur. Urol. 64, 981–987 (2013).

  10. 10.

    Soloway, M. S. et al. Careful selection and close monitoring of low-risk prostate cancer patients on active surveillance minimizes the need for treatment. Eur. Urol. 58, 831–835 (2010).

  11. 11.

    Stamey, T. A. et al. Localized prostate cancer. Relationship of tumor volume to clinical significance for treatment of prostate cancer. Cancer 71, 933–938 (1993).

  12. 12.

    Tosoian, J. J. et al. Active surveillance program for prostate cancer: an update of the Johns Hopkins experience. J. Clin. Oncol. 29, 2185–2190 (2011).

  13. 13.

    Whitson, J. M. et al. The relationship between prostate specific antigen change and biopsy progression in patients on active surveillance for prostate cancer. J. Urol. 185, 1656–1660 (2011).

  14. 14.

    Shaw, G. L. et al. Identification of pathologically insignificant prostate cancer is not accurate in unscreened men. Br. J. Cancer 110, 2405–2411 (2014).

  15. 15.

    Shah, N., Huebner, T., Ioffe, V. & Hum, R. Prostate biopsy characteristics: a comparison between pre- and post-United States Preventive Service Task Force Prostate Cancer Screening Guidelines of 2012. Rev. Urol. 19, 25–31 (2017).

  16. 16.

    Draisma, G. et al. Lead times and overdetection due to prostate-specific antigen screening: estimates from the European Randomized Study of Screening for Prostate Cancer. J. Natl. Cancer Inst. 95, 868–878 (2003).

  17. 17.

    Moyer V. A. U. S. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann. Intern. Med. 157, 120–34 (2012).

  18. 18.

    Mottet, N. et al. P. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: screening, diagnosis, and local treatment with curative intent. Eur. Urol. 71, 618–629 (2017).

  19. 19.

    R Core Team. R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2016).

  20. 20.

    Janssen, K. J. M. et al. Missing covariate data in medical research: to impute is better than to ignore. J. Clin. Epidemiol. 63, 721–727 (2010).

  21. 21.

    Delong, E. R., Delong, D. M. & Clarkepearson, D. I. Comparing the areas under 2 or more correlated receiver operating characteristic curves—a nonparametric approach. Biometrics 44, 837–845 (1988).

  22. 22.

    Klotz, L. Strengthening evidence for active surveillance for prostate cancer. Eur. Urol. 63, 108–110 (2013).

  23. 23.

    Klotz, L. et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J. Clin. Oncol. 33, 272–277(2015).

  24. 24.

    Ahmed, H. U. et al. PROMIS study group. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 389, 815–822 (2017).

  25. 25.

    Kattan, M. W., Eastham, J. A., Stapleton, A. M., Wheeler, T. M. & Scardino, P. T. A preoperative nomogram for disease recurrence following radical prostatectomy for prostatecancer. J. Natl. Cancer Inst. 90, 766–771 (1998).

  26. 26.

    D’Amico, A. V. et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA 280, 969–974 (1998).

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  1. Prostatazentrum Nordwest, St. Antonius-Hospital, Klinik für Urologie, Kinderurologie und Urologische Onkologie, Gronau, Germany

    • Lorenzo Dutto
    • , Katerina Urbanova
    • , Christian Wagner
    • , Andreas Schuette
    • , Mustafa Addali
    •  & Joern H. Witt
  2. Department of Urology, Queen Elisabeth University Hospital, Glasgow, UK

    • Lorenzo Dutto
  3. Wolfson Institute of Preventive Medicine, Barts and The London School of Medicine, Queen Mary University of London, Centre for Cancer Prevention, London, UK

    • Amar Ahmad
  4. Department of Urology, University College London Hospital, London, UK

    • John D. Kelly
    • , Ashwin Shridhar
    • , Senthil Nathan
    • , Timothy P. Briggs
    •  & Gregory Shaw


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Study concept: L.D., A.A. and G.S. Manuscript: L.D. Statistical analysis: A.A. Manuscript revision: J.H.W., J.D.K., S.N. Data handling and interpretation: K.U., A.S., C.W., A.S., M.A., T.P.B. Study coordinators: G.S., J.H.W.

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

All patients were consented for collection of data. Full ethical approval for data collection and storage was obtained from the University of Münster, Germany (2015-533-f-S).

Data were collected strictly in accordance with University College London- and Cambridge Hospitals governance policies and in line with the clinical governance processes at the respective institutions.

The study was performed in accordance with the Declaration of Helsinki.


This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0)

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Correspondence to Lorenzo Dutto.

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