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A randomized trial of early detection of clinically significant prostate cancer (ProScreen): study design and rationale

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Abstract

The current evidence of PSA-based prostate cancer screening shows a reduction in cause-specific mortality, but with substantial overdiagnosis. Recently, new developments in detection of clinically relevant prostate cancer include multiple kallikreins as biomarkers besides PSA, and multiparametric magnetic resonance imaging (mpMRI) for biopsy decision. They offer opportunities for improving the outcomes in screening, particularly reduction in overdiagnosis and higher specificity for potentially lethal cancer. A population-based randomized screening trial will be started, with 67,000 men aged 55–67 years at entry. A quarter of the men will be allocated to the intervention arm, and invited to screening. The control arm will receive no intervention. All men in the screening arm will be offered a serum PSA determination. Those with PSA of 3 ng/ml or higher will have an additional multi-kallikrein panel and those with indications of increased risk of clinically relevant prostate cancer will undergo mpMRI. Men with a malignancy-suspect finding in MRI are referred to targeted biopsies. Screening interval is 6 years for men with baseline PSA < 1.5 ng/ml, 4 years with PSA 1.5–3.0 and 2 years if initial PSA > 3. The main outcome of the trial is prostate cancer mortality, with analysis at 10 and 15 years. The statistical power is sufficient for detecting a 28% reduction at 10 years and 22% at 15 years. The proposed study has the potential to provide the evidence to justify screening as a public health policy if mortality benefit can be sustained with substantially reduced overdiagnosis.

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Acknowledgements

The study has been funded by Academy of Finland (Grant No. 311336) and Pirkanmaa Cancer Society.

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Authors and Affiliations

  1. Faculty of Social Sciences, University of Tampere, Arvo B335, Box 100, 33014, Tampere, Finland

    Anssi Auvinen

  2. Department of Urology, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

    Antti Rannikko & Kimmo Taari

  3. Fimlab Laboratories, Department of Pathology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    Paula Kujala

  4. Department of Pathology, Faculty of Medicine, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

    Tuomas Mirtti

  5. HUS Medical Imaging Center, Helsinki University Hospital, Helsinki, Finland

    Anu Kenttämies

  6. Department of Radiology, Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland

    Irina Rinta-Kiikka

  7. Fimlab Laboratories, Department of Clinical Chemistry, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland

    Terho Lehtimäki

  8. Department of Surgery, Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland

    Niku Oksala

  9. Division of Biotechnology, Department of Biochemistry, University of Turku, Turku, Finland

    Kim Pettersson

  10. Department of Urology, Faculty of Medicine and Life Sciences, Tampere University Hospital, University of Tampere, Tampere, Finland

    Teuvo L. Tammela

Authors
  1. Anssi Auvinen
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  2. Antti Rannikko
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  4. Paula Kujala
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  9. Niku Oksala
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  11. Teuvo L. Tammela
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Corresponding author

Correspondence to Anssi Auvinen.

Appendix: MRI protocol

Appendix: MRI protocol

The patient preparation includes the evacuation of the rectum and administration of antispasmolytic.

The mpMRI consists of T2WI, DWI with ADC maps and DCE performed by 3T scanners, using a protocol in accordance with PI-RADS v2 published by the American College of Radiology in 2015. Slice thickness is 3 mm for T2WI and DWI, and 4 mm for DCE. The T2WI are obtained with turbo-spin-echo (TSE) sequences covering the whole prostate gland and the seminal vesicles. The DWI utilize b-values up to 800 for calculating ADC-maps and b-values up to 2000 for tumor detection. High b-value images are obtained by calculating those images by extrapolation up to b1400 from the acquired lower b-value data. Pre-contrast enhancement T1W images with fat suppression are obtained to detect haemorrhages. The DCE imaging, T1WI is performed with intravenous administration of gadolinium-based contrast agent with the temporal resolution of 7 s and total observation time 2 min 30 s to detect possible early enhancement. The DCE data are visually assessed and further analyzed by using DynaCad software to produce signal intensity curves of each lesion detected.

All uroradiologists who read the prostate MRI scans have attended the European Society of Uroradiology two-day Prostate MRI course at least once, and most of them have more than 5 years of experience in interpreting prostate MRIs. Currently, each of them read at least 300 prostate MRIs annually.

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Auvinen, A., Rannikko, A., Taari, K. et al. A randomized trial of early detection of clinically significant prostate cancer (ProScreen): study design and rationale. Eur J Epidemiol 32, 521–527 (2017). https://doi.org/10.1007/s10654-017-0292-5

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  • DOI: https://doi.org/10.1007/s10654-017-0292-5

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