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The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort

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Abstract

Background

Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort.

Methods

The study-population consisted of 533 men in ages 45–75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP).

Results

263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7–89.2) and AUC 74.8 (95% CI 70.3–79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer.

Conclusion

A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.

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Acknowledgements

We thank all the study participants, the STHLM3 core management group for taking care of all contact with participants and organizing the databases, KI Biobank at Karolinska Institutet for taking care of all blood samples, aliquoting plasma, extracting DNA, and doing all genotyping, Karolinska University Hospital Laboratory for organizing sample handling and performing analyses, all personnel at Aleris Cancer Centrum in Oslo and Siv Tönsberg for their dedicated and invaluable work, participating radiologists Wolfgang Picker, Tom Werner Olsen (Aleris Cancer Centrum) and Beata Gajdzik (SiV Tönsberg) and finally the participating urologists Sven Löffeler, Adrian Halland, Dag Gullan (SiV Tönsberg); Espen Kvan, Leif Erik Grønning (Aleris Cancer Centrum); Stefan Knutsson, Magnus Annerstedt (Urologi STHLM); Olof Jansson, Xiaoli Fang, Magnus Törnblom (UroClinic), Dushanka Kristiansson (UroPraxis) Stefan Carlsson and Rodolfo Sanchez Sala (Karolinska University Hospital) taking care of and doing prostate biopsies in STHLM3MR participants.

Funding

Funding was provided by the Swedish Cancer Society, (Cancerfonden), the Swedish Research Council (Vetenskapsrådet), Swedish Research Council for Health Working Life and Welfare (FORTE), The Strategic Research Program on Cancer (StratCan), Karolinska Institutet and Swedish e-Science Research Center (SeRC). The STHLM3 study is a part of the Linnaeus Center CRISP “Predication and prevention of breast and prostate cancer” funded by the Swedish Research Council.

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Authors and Affiliations

  1. Department of Urology, Karolinska University Hospital Solna, Stockholm, Sweden

    Axel Möller & Markus Aly

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

    Henrik Olsson, Henrik Grönberg, Martin Eklund, Markus Aly & Tobias Nordström

  3. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden

    Axel Möller & Markus Aly

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

    Tobias Nordström

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  1. Axel Möller
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  4. Martin Eklund
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Corresponding author

Correspondence to Axel Möller.

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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 is named on four of these five patent applications. Karolinska Institutet collaborates with Thermo Fisher Scientific in developing the technology for the Stockholm3 test. The remaining authors declare that they have no conflict of interest.

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Möller, A., Olsson, H., Grönberg, H. et al. The Stockholm3 blood-test predicts clinically-significant cancer on biopsy: independent validation in a multi-center community cohort. Prostate Cancer Prostatic Dis 22, 137–142 (2019). https://doi.org/10.1038/s41391-018-0082-5

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