Skip to main content
SpringerLink
Log in

Risk-based MRI-directed diagnostic pathway outperforms non-risk-based pathways in suspected prostate cancer biopsy-naïve men: a large cohort validation study

  • Urogenital
  • Published:
European Radiology Aims and scope Submit manuscript

An Editorial Comment to this article was published on 01 February 2022

Abstract

Objectives

To investigate and compare the performance of different proposed diagnostic pathways in a cohort of biopsy-naïve men at risk for prostate cancer (PCa), in terms of biopsy avoidance, accurate diagnosis of clinically significant prostate cancer (csPCa), and reduction in overdiagnosis of clinically insignificant cancer (cisPCa), with particular focus on a recently suggested “risk-based” MRI-directed diagnostic pathway.

Methods

Single-center, retrospective cohort study, including 499 biopsy-naïve men at risk for PCa. All men underwent PI-RADS-compliant prostate MRI, transrectal ultrasound fusion-guided targeted (TBx), and systematic biopsy (SBx). Five diagnostic pathways were retrospectively evaluated and compared for. Outcome measures were biopsy avoidance, combined with missed csPCa and detected cisPCa. csPCa and cisPCa were defined as ISUP grade group ≥ 2 and grade = 1, respectively. Chi-square test was used for statistical analysis. Decision curve analyses were used to compare the benefits of the pathways across a range of biopsy thresholds.

Results

The prevalence (detection-focused [reference] pathway) of csPCa and cisPCa was 52.9% (264/499) and 23.0% (115/499). MRI-focused pathway (no biopsy in PI-RADS 1–2 men) did not significantly reduce ISUP ≥ 2 cancer detection (52.1% (260/499); p = 0.13), but significantly reduced ISUP 1 cancers diagnosed (20.6% (103/499); p < 0.01), and biopsy avoidance was 11.8% (59/499). The risk-based MRI-directed pathway (no biopsy in low-risk PI-RADS 1–3 men) resulted in a small reduction of ISUP ≥ 2 diagnosed (51.7% (258/499); p = 0.04), however non-significant when compared to MRI-focused pathway (p = 0.625). Moreover, the risk-based pathway further reduced detection of ISUP 1 (18.6% (93/499); p < 0.01), and biopsy avoidance was 19.2% (96/499). Decision curve analysis showed maximized net benefit of the risk-based pathway, for the range of threshold probabilities between 6.25 and 65%.

Conclusion

The risk-based MRI-directed pathway for prostate cancer diagnosis was optimal in balancing accurate diagnosis, reducing overdiagnosis, and maximizing biopsy avoidance. This substantial evidence should inform guideline recommendations towards using “risk-based” MRI-directed biopsy decisions in biopsy-naïve men at risk of significant prostate cancer.

Key Points

• Our study recognizes the added value of prostate MRI and MR-targeted biopsies in order to propose clinical diagnostic pathways for prostate cancer, towards maximizing the potential avoidance of unnecessary biopsies, while maintaining optimal detection rate of clinically significant prostate cancer.

• The risk-based MRI-directed pathway incorporates risk factors such as PSA density, digital rectal examination, and family history to further refine the initial stratification of patients based on PI-RADS scores.

• In this study, the risk-based pathway had the most optimal performance in terms of combination of outcomes, with the highest rate of biopsy avoidance (19.2%), while keeping a high detection rate of clinically significant prostate cancer (51.7%), when compared to the reference standard (52.9%).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Abbreviations

cisPCa:

Clinically insignificant prostate cancer

csPCa:

Clinically significant prostate cancer

ISUP:

International Society of Urogenital Pathology

MRI:

Magnetic resonance imaging

PCa:

Prostate cancer

PI-RADS:

Prostate Imaging Reporting and Data System

PSA:

Prostate-specific antigen

PSAd:

PSA density

PZ:

Peripheral zone

SBx:

Systematic biopsy

TBx:

Targeted biopsy

TRUS:

Transrectal ultrasound

TZ:

Transition zone

References

  1. Weinreb JC, Barentsz JO, Choyke PL et al (2016) PI-RADS prostate imaging–reporting and data system: 2015, version 2. Eur Urol 69:16–40

    Article  Google Scholar 

  2. Turkbey B, Rosenkrantz AB, Haider MA et al (2019) Prostate Imaging Reporting and Data System version 2.1: 2019 update of Prostate Imaging Reporting and Data System version 2. Eur Urol 76:340–351

    Article  Google Scholar 

  3. Kasivisvanathan V, Rannikko AS, Borghi M et al (2018) MRI-targeted or standard biopsy for prostate-cancer diagnosis. N Engl J Med 378:1767–1777

    Article  Google Scholar 

  4. Rouvière O, Puech P, Renard-Penna R et al (2019) Use of prostate systematic and targeted biopsy on the basis of multiparametric MRI in biopsy-naive patients (MRI-FIRST): a prospective, multicentre, paired diagnostic study. Lancet Oncol 20:100–109

    Article  Google Scholar 

  5. Mottet N, Bellmunt J, Briers E, et al (2018) EAU-ESTRO-ESUR-SIOG guidelines on prostate cancer. European Association of Urology. Available at: https://uroweb.org/wp-content/uploads/Prostate-Cancer-2017-pocket.pdf

  6. Mohler JL, Antonarakis ES, Armstrong AJ et al (2019) Prostate cancer, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 17:479–505

    Article  CAS  Google Scholar 

  7. Bjurlin MA, Carroll PR, Eggener S et al (2019) Update of the AUA policy statement on the use of multiparametric magnetic resonance imaging in the diagnosis, staging and management of prostate cancer. J Urol 198:832–838

    Google Scholar 

  8. Borghesi M, Ahmed H, Nam R et al (2017) Complications after systematic, random, and image-guided prostate biopsy. Eur Urol 71:353–365

    Article  Google Scholar 

  9. Drost F-JH, Osses D, Nieboer D et al (2020) Prostate magnetic resonance imaging, with or without magnetic resonance imaging-targeted biopsy, and systematic biopsy for detecting prostate cancer: a Cochrane systematic review and meta-analysis. Eur Urol 77:78–94

    Article  Google Scholar 

  10. Kasivisvanathan V, Stabile A, Neves JB et al (2019) Magnetic resonance imaging-targeted biopsy versus systematic biopsy in the detection of prostate cancer: a systematic review and meta-analysis. Eur Urol 76:284–303

    Article  Google Scholar 

  11. Schoots IG, Padhani AR, Rouvière O et al (2020) Analysis of magnetic resonance imaging–directed biopsy strategies for changing the paradigm of prostate cancer diagnosis. Eur Urol Oncol 3:32–41. https://doi.org/10.1016/j.euo.2019.10.001

    Article  PubMed  Google Scholar 

  12. Padhani AR, Barentsz J, Villeirs G et al (2019) PI-RADS Steering Committee: the PI-RADS multiparametric MRI and MRI-directed biopsy pathway. Radiology 292:464–474. https://doi.org/10.1148/radiol.2019182946

    Article  PubMed  Google Scholar 

  13. Boesen L, Nørgaard N, Løgager V et al (2019) Prebiopsy biparametric magnetic resonance imaging combined with prostate-specific antigen density in detecting and ruling out Gleason 7–10 prostate cancer in biopsy-naïve men. Eur Urol Oncol 2:311–319

    Article  Google Scholar 

  14. Knaapila J, Jambor I, Perez IM et al (2020) Prebiopsy IMPROD biparametric magnetic resonance imaging combined with prostate-specific antigen density in the diagnosis of prostate cancer: an external validation study. Eur Urol Oncol 3:648–656

    Article  Google Scholar 

  15. Schoots IG, Padhani AR (2021) Risk-adapted biopsy decision based on prostate magnetic resonance imaging and prostate-specific antigen density for enhanced biopsy avoidance in first prostate cancer diagnostic evaluation. BJU Int 127:175–178. https://doi.org/10.1111/bju.15277

    Article  PubMed  Google Scholar 

  16. Moore CM, Kasivisvanathan V, Eggener S et al (2013) Standards of reporting for MRI-targeted biopsy studies (START) of the prostate: recommendations from an international working group. Eur Urol 64:544–552. https://doi.org/10.1016/j.eururo.2013.03.030

    Article  PubMed  Google Scholar 

  17. Vickers AJ, Van Calster B, Steyerberg EW (2016) Net benefit approaches to the evaluation of prediction models, molecular markers, and diagnostic tests. BMJ 352:i6. https://doi.org/10.1136/bmj.i6

  18. Fitzgerald M, Saville BR, Lewis RJ (2015) Decision curve analysis. JAMA 313:409. https://doi.org/10.1001/jama.2015.37

    Article  CAS  PubMed  Google Scholar 

  19. Vickers AJ, van Calster B, Steyerberg EW (2019) A simple, step-by-step guide to interpreting decision curve analysis. Diagn Progn Res 3:18. https://doi.org/10.1186/s41512-019-0064-7

    Article  PubMed  PubMed Central  Google Scholar 

  20. Van Calster B, Wynants L, Verbeek JFM et al (2018) Reporting and interpreting decision curve analysis: a guide for investigators. Eur Urol 74:796–804. https://doi.org/10.1016/j.eururo.2018.08.038

    Article  PubMed  PubMed Central  Google Scholar 

  21. Andriole GL, Crawford ED, Grubb RL III et al (2009) Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 360:1310–1319

    Article  CAS  Google Scholar 

  22. Schröder FH, Hugosson J, Roobol MJ et al (2009) Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 360:1320–1328

    Article  Google Scholar 

  23. Ahmed HU, Bosaily AE-S, Brown LC et al (2017) Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet 389:815–822

    Article  Google Scholar 

  24. van der Leest M, Cornel E, Israël B et al (2019) Head-to-head comparison of transrectal ultrasound-guided prostate biopsy versus multiparametric prostate resonance imaging with subsequent magnetic resonance-guided biopsy in biopsy-naive men with elevated prostate-specific antigen: a large prospective multicenter clinical study. Eur Urol 75:570–578

    Article  Google Scholar 

  25. Klotz L, Chin J, Black PC et al (2021) Comparison of multiparametric magnetic resonance imaging-targeted biopsy with systematic transrectal ultrasonography biopsy for biopsy-naive men at risk for prostate cancer: a phase 3 randomized clinical trial. JAMA Oncol 7(4):534–542. https://doi.org/10.1001/jamaoncol.2020.7589

  26. Sathianathen NJ, Omer A, Harriss E et al (2020) Negative predictive value of multiparametric magnetic resonance imaging in the detection of clinically significant prostate cancer in the prostate imaging reporting and data system era: a systematic review and meta-analysis. Eur Urol 78(3):402–414. https://doi.org/10.1016/j.eururo.2020.03.048

  27. Guidance N (2019) Prostate cancer: diagnosis and management. BJU Int 124:9–26

    Article  Google Scholar 

  28. Siddiqui MM, Rais-Bahrami S, Turkbey B et al (2015) Comparison of MR/ultrasound fusion–guided biopsy with ultrasound-guided biopsy for the diagnosis of prostate cancer. JAMA 313:390–397

    Article  CAS  Google Scholar 

  29. Schoots IG, Roobol MJ (2020) Multivariate risk prediction tools including MRI for individualized biopsy decision in prostate cancer diagnosis: current status and future directions. World J Urol 38:517–529

    Article  Google Scholar 

  30. Punnen S, Nahar B, Soodana-Prakash N et al (2018) Optimizing patient’s selection for prostate biopsy: a single institution experience with multi-parametric MRI and the 4Kscore test for the detection of aggressive prostate cancer. PLoS One 13:e0201384

    Article  Google Scholar 

  31. Druskin SC, Tosoian JJ, Young A et al (2018) Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer. BJU Int 121:619–626

    Article  Google Scholar 

  32. Porpiglia F, Russo F, Manfredi M et al (2014) The roles of multiparametric magnetic resonance imaging, PCA3 and Prostate Health Index—which is the best predictor of prostate cancer after a negative biopsy? J Urol 192:60–66

    Article  Google Scholar 

  33. Hendriks RJ, van der Leest MMG, Dijkstra S et al (2017) A urinary biomarker-based risk score correlates with multiparametric MRI for prostate cancer detection. Prostate 77:1401–1407. https://doi.org/10.1002/pros.23401

    Article  CAS  PubMed  Google Scholar 

  34. Falagario UG, Martini A, Wajswol E et al (2020) Avoiding unnecessary magnetic resonance imaging (MRI) and biopsies: negative and positive predictive value of MRI according to prostate-specific antigen density, 4Kscore and risk calculators. Eur Urol Oncol 3:700–704. https://doi.org/10.1016/j.euo.2019.08.015

    Article  PubMed  Google Scholar 

  35. de Rooij M, Israël B, Tummers M et al (2020) ESUR/ESUI consensus statements on multi-parametric MRI for the detection of clinically significant prostate cancer: quality requirements for image acquisition, interpretation and radiologists’ training. Eur Radiol 30:5404–5416. https://doi.org/10.1007/s00330-020-06929-z

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

The authors state that this work has not received any funding.

Author information

Authors and Affiliations

  1. Department of Radiology, University Hospitals Cleveland Medical Center and Case Western Reserve University, 11100 Euclid Ave, Cleveland, OH, 44106, USA

    Leonardo Kayat Bittencourt

  2. Alta Excelencia Diagnostica, Dasa Company, Sao Paulo, Brazil

    Leonardo Kayat Bittencourt

  3. Department of Radiation Therapy, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Karolina Guricova

  4. Herbert Wertheim College of Medicine at Florida International University, Miami, FL, USA

    Isaac Zucker

  5. Department of Radiology and Center for Clinical Research, University Hospitals Cleveland Medical Center, Cleveland, OH, USA

    Jared C. Durieux

  6. Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

    Ivo G. Schoots

  7. Department of Radiology, Netherlands Cancer Institute, Amsterdam, The Netherlands

    Ivo G. Schoots

Authors
  1. Leonardo Kayat Bittencourt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karolina Guricova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Isaac Zucker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jared C. Durieux
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ivo G. Schoots
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leonardo Kayat Bittencourt.

Ethics declarations

Guarantor

The scientific guarantor of this publication is Leonardo Kayat Bittencourt.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

Karolina Guricova and Jared C. Durieux (co-authors) kindly provided statistical advice for this manuscript.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional Review Board approval was obtained.

Methodology

• retrospective

• diagnostic or prognostic study

• performed at one institution

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1937 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bittencourt, L.K., Guricova, K., Zucker, I. et al. Risk-based MRI-directed diagnostic pathway outperforms non-risk-based pathways in suspected prostate cancer biopsy-naïve men: a large cohort validation study. Eur Radiol 32, 2330–2339 (2022). https://doi.org/10.1007/s00330-021-08407-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-021-08407-6

Keywords

Search

Navigation