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Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test

Prostate Cancer and Prostatic Diseases volume 24, pages 457–464 (2021)Cite this article

Subjects

Abstract

Background

The validated Stockholm3 test is used to improve PC detection. Stockholm3, however, was developed using systematic biopsies. We aimed to assess Stockholm3 operating performance when using MRI-targeted biopsies for PC detection.

Methods

A prospective cohort of 532 men was considered for prostate biopsy during 2016–2017. All men underwent Stockholm3 testing and MRI before biopsy. All PIRADs ≥3 lesion underwent targeted biopsy; all men underwent systematic biopsy. The primary outcome was ISUP Grade Group ≥2 (GG ≥ 2) PC. Detection strategies included: (1) systematic biopsies alone, (2) targeted biopsies alone, (3) targeted with associated systematic biopsies for MRI+, and (4) all biopsies in all men. For each strategy, the Stockholm3 operating characteristics were assessed with discrimination, calibration, and decision curve analysis (DCA).

Results

Median age was 65 years, median PSA was 6.2 ng/mL, median Stockholm3 score was 16.5%, and overall detection of GG ≥ 2 PC was 36% (193/532). Stockholm3 showed accurate discrimination for separating GG ≥ 2 cancer from benign and GG1, with an area under the curve of 0.84–0.86 depending on the biopsy strategy. Calibration analysis showed that Stockholm3 underestimated risks for GG ≥ 2 PC risk using MRI-targeted biopsies: there was a net benefit over biopsies in all men for Stockholm3 at risk thresholds varying from >3% in systematic biopsies to >15% in targeted with systematic biopsies in MRI+ men. When using a Stockholm3 score of >10% cutoff, a range of 32–38% of biopsies could be avoided while missing 5–11% of GG ≥ 2 PC and 0–3% of GG ≥ 3 PC.

Conclusions

Stockholm3 shows high discriminatory performance in an MRI-targeted biopsy setting, however risks are underpredicted due to MRI-targeted biopsies being more sensitive than the systematic biopsies for which Stockholm3 was developed. Stockholm3, along with any risk prediction model developed for systematic prostate biopsy decisions, will need recalibration for optimal use in an MRI-driven biopsy setting.

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Fig. 1: Discrimination analysis for the four different biopsy methods.
Fig. 2: Calibration analysis for the four different biopsy methods.
Fig. 3: Decision curve analysis for the four different biopsy methods.

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Code availability

The code generated during the current study is available from the corresponding author on reasonable request.

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Funding

Swedish Cancer Society (Cancerfonden) (Grönberg, Eklund, Nordström), Swedish Research Council (Vetenskapsrådet) (Grönberg, Eklund), Swedish Research Council for Health Working Life and Welfare (FORTE) (Eklund), Strategic Research Programme on Cancer (StratCan) (Nordström), and Swedish e-Science Research Center (SeRC) (Eklund).

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Authors and Affiliations

  1. Department of Urology, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA

    Hari T. Vigneswaran

  2. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

    Hari T. Vigneswaran, Thorgerdur Palsdottir, Henrik Olsson, Henrik Grönberg, Martin Eklund & Tobias Nordström

  3. Department of Urology, Vestfold Hospital Trust, Tønsberg, Norway

    Erik S. Haug & Sven Löffeler

  4. Oslo University Hospital, Institute of Cancer Genomics and Informatics, Oslo, Norway

    Erik S. Haug

  5. Department of Radiology, Aleris Cancer Center, Oslo, Norway

    Wolfgang Picker

  6. Department of Clinical Sciences at Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden

    Tobias Nordström

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  1. Hari T. Vigneswaran
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Corresponding author

Correspondence to Hari T. Vigneswaran.

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Conflict of interest

HG has five prostate cancer diagnostic-related patents pending, has patent applications licensed to Thermo Fisher Scientific, and might receive royalties from sales related to these patents. ME has five prostate cancer diagnostic-related patents pending. Karolinska Institutet collaborates with Thermo Fisher Scientific in developing the technology for the Stockholm3 test. The other authors declare that they have no conflict of interest.

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Vigneswaran, H.T., Palsdottir, T., Olsson, H. et al. Biomarker discrimination and calibration with MRI-targeted biopsies: an analysis with the Stockholm3 test. Prostate Cancer Prostatic Dis 24, 457–464 (2021). https://doi.org/10.1038/s41391-020-00297-x

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