Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2024 May 7;331(17):1452-1459.
doi: 10.1001/jama.2024.3841.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial

Anssi Auvinen  1 , Teuvo L J Tammela  2   3 , Tuomas Mirtti  4   5   6   7   8 , Hans Lilja  9   10 , Teemu Tolonen  2   11 , Anu Kenttämies  12 , Irina Rinta-Kiikka  2   13 , Terho Lehtimäki  2   14 , Kari Natunen  1 , Jaakko Nevalainen  1 , Jani Raitanen  1   15 , Johanna Ronkainen  13 , Theodorus van der Kwast  16 , Jarno Riikonen  3 , Anssi Pétas  17 , Mika Matikainen  17 , Kimmo Taari  5   17 , Tuomas Kilpeläinen  7   17 , Antti S Rannikko  5   6   7   17 ; ProScreen Trial Investigators
Collaborators, Affiliations
Randomized Controlled Trial

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial

Anssi Auvinen et al. JAMA. .

Abstract

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important.

Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan.

Design, setting, and participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020.

Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023.

Main outcomes and measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group.

Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer.

Conclusions and relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome.

Trial registration: ClinicalTrials.gov Identifier: NCT03423303.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Tammela reported receiving nonfinancial support from Tay Ja Tays during the conduct of the study and having served as an investigator for trials sponsored by Astellas, Bayer, Lidds Ab, and MSD. Dr Lilja reported serving on the scientific advisory board of Fujirebio Diagnostics Inc outside the submitted work; having patents US 9,672,329 B2 and US 7,872,104 B2 with royalties paid from OPKO Health Inc, patent US 0,308,204 A1 with royalties paid from Radiopharm Theranostics, which is not relevant to the current work; is named on a patent on assays to measure intact PSA and on a patent for a statistical method to detect prostate cancer assigned to Arctic Partners, and licensed to and commercialized by OPKO Health (4KScore); receiving royalties from sales of this test; and owning stock in Arctic Partners and OPKO Health. Dr Matikainen reported receiving lecture fees from Amgen, Astellas, and Orion Corp. Dr Rannikko reported serving as a consultant to Bayer, Janssen Pharmaceuticals, and Orion Corp. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Flow Diagram of the ProScreen Trial
MRI indicates magnetic resonance imaging; PI-RADS, Prostate Imaging and Data Reporting System; and PSA, prostate-specific antigen.
Figure 2.
Figure 2.. Summary of the Results
Screening results expressed per 1000 invited men (upper panel) and per 1000 screened men (lower panel). PSA indicates prostate-specific antigen.
See this image and copyright information in PMC

Comment on

References

    1. Ilic D, Djulbegovic M, Jung JH, et al. Prostate cancer screening with prostate-specific antigen (PSA) test: a systematic review and meta-analysis. BMJ. 2018;362:k3519. doi: 10.1136/bmj.k3519 - DOI - PMC - PubMed
    1. Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Melnikow J. Prostate-specific antigen-based screening for prostate cancer. JAMA. 2018;319(18):1914-1931. doi: 10.1001/jama.2018.3712 - DOI - PubMed
    1. Paschen U, Sturtz S, Fleer D, Lampert U, Skoetz N, Dahm P. Assessment of prostate-specific antigen screening: an evidence-based report by the German Institute for Quality and Efficiency in Health Care. BJU Int. 2022;129(3):280-289. doi: 10.1111/bju.15444 - DOI - PubMed
    1. Braun K, Sjöberg DD, Vickers AJ, Lilja H, Bjartell AS. A four-kallikrein panel predicts high-grade cancer on biopsy: independent validation in a community cohort. Eur Urol. 2016;69(3):505-511. doi: 10.1016/j.eururo.2015.04.028 - DOI - PMC - PubMed
    1. Vickers A, Vertosick EA, Sjöberg DD, et al. Value of intact prostate specific antigen and human kallikrein 2 in the 4 kallikrein predictive model: an individual patient data meta-analysis. J Urol. 2018;199(6):1470-1474. doi: 10.1016/j.juro.2018.01.070 - DOI - PMC - PubMed

Publication types

MeSH terms

Associated data