Condition category
Cancer
Date applied
26/04/2017
Date assigned
10/07/2017
Last edited
10/07/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Prostate cancer is the most common cancer among Swedish men, and Sweden has one of the highest prostate cancer mortality (death) rates in the world. 10,000 men are diagnosed with the disease each year and 2,400 die from it. Prostate-specific antigen (PSA) is a protein made by the prostate gland. A PSA test looks for raised levels of PSA in the blood which may be a sign of prostate cancer in its early stages. Screening with PSA testing can reduce prostate cancer mortality, but the major drawback is that many men are diagnosed with small insignificant tumours that would never cause neither disease nor death within the patient’s lifetime (overdiagnosis). This dilemma is the main reason to why there is no public prostate cancer screening program for men. By using Magnetic Resonance Imaging (MRI) scans in men with high PSA in combination with targeted biopsies (tissue samples) of suspected tumours, screening could be more efficient and overdiagnosis might be reduced. The aim of this study is to find out whether prostate cancer screening with PSA followed by an MRI scan of the prostate reduces the risk of overdiagnosis.

Who can participate?
Men aged 50-60 from West Sweden

What does the study involve?
Participants are randomly allocated to either be invited for testing or not (control group). Men allocated to testing are randomly allocated in a second step into three groups. If their PSA level is normal, no further testing or examination is performed and the participant is re-invited for screening after 1, 2, 4 or 8 years depending on their PSA level. All men with high PSA, regardless of group, are offered an MRI scan of their prostate. If the MRI scan is positive, men from two of the groups are further examined with targeted biopsies. In the third group, standard biopsies are taken regardless of the MRI result. Rates of overdiagnosis, prostate biopsy and prostate cancer mortality are measured on a regular basis throughout the study using data from the Regional Cancer Registry.

What are the possible benefits and risks of participating?
The combination of PSA and MRI may improve prostate cancer diagnosis, reduce the number of men who need prostate biopsies, and reduce overdiagnosis and prostate cancer mortality. The possible risks are overdiagnosis and infection after the biopsy.

Where is the study run from?
University of Gothenburg/Sahlgrenska University Hospital (Sweden)

When is the study starting and how long is it expected to run for?
September 2015 to December 2040

Who is funding the study?
1. Swedish Cancer Society (Sweden)
2. Swedish Government (Sweden)
3. BioCARE (Sweden)
4. Regional Cancer Center West (Sweden)
5. Swedish Research Council (Sweden)

Who is the main contact?
Prof. Jonas Hugosson

Trial website

http://g2screening.se/

Contact information

Type

Scientific

Primary contact

Prof Jonas Hugosson

ORCID ID

http://orcid.org/0000-0002-2324-2817

Contact details

Department of Urology
Institute of Clinical Sciences
University of Gothenburg
Bruna stråket 11B
Sahlgrenska University Hospital
Göteborg
413 45
Sweden

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

N/A

Study information

Scientific title

The GÖTEBORG Prostate Cancer Screening 2 trial (G2): a prospective, randomized, large-scale, population-based prostate cancer screening trial using PSA followed by magnetic resonance imaging of the prostate

Acronym

Study hypothesis

The study intends to analyze the value of PSA combined with Magnetic Resonance Tomography (MR) of the prostate for early detection of Prostate Cancer (PC). By using MR and only biopsying MR-positive men with targeted biopsies (in contrast to 10-12 systematic biopsies which is clinical practice today), the hypothesis is that overdiagnosis can be reduced by half and still keep the same sensitivity.

Ethics approval

Regional Ethical Review Board, 28/01/2015, ref: 890-14

Study design

Population-based randomized controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

See website (in Swedish)

Condition

Prostate cancer

Intervention

By computerized randomization, a random sample of 40,000 men living in Västra Götalandsregionen will gradually be randomized and form the database. If a man decides to participate he visits a clinic to have a regular blood draw (PSA). The analysis of PSA is carried out at a central lab. Men who choose to participate are randomized, by blinded computer randomization, in a 1:1:1 ratio (equal sizes) into three different screening strategies:

Arm 1: Reference arm: PSA cut-off 3 ng/mL, standard biopsies for all men with PSA >=3 plus targeted biopsies for MR+
“Screen-negative”: If the Total-PSA level is “normal”, i.e. below 3.0 ng/mL, no further testing or examination will be performed but all men will be re-invited (see below).
“Screen-positive”: If the PSA level is “elevated” above the cut-off i.e. 3.0 ng/mL, the man will be invited for a multi-parametric MRI (mpMRI). Irrespective of the MRI result all men will be recommended “STANDARD BIOPSY”, i.e. digital rectal exam followed by TRUS-guided 10-core standard prostate biopsy according to the screening protocol (as is also clinical practice). These standard biopsies will be taken blindly to the MRI result. During the same investigation after the standard biopsies the urologist will be shown the result from MRI and in case of a suspicious lesion at MRI also targeted biopsies (4 cores) will be added (same procedure as in the performed pilot study. The results from the reference arm could be divided into those detected by standard biopsy alone (pure PSA detected – common practice today) and those also detected by targeted biopsies (false negatives).

Arm 2: Experimental arm I: PSA cut-off 3 ng/mL, only targeted biopsies for MR+
“Screen-negative”: If the PSA level is “normal”, i.e. below 3.0 ng/mL, no further testing or examination will be performed. The man will be re-invited for screening identical to arm 1.
“Screen-positive”: If the PSA level is “elevated” ≥ 3.0 ng/mL, he will be offered mpMRI.
If the mpMRI is positive, only “TARGETED BIOPSIES” will be performed, i.e. 4 biopsy cores targeted against each suspicious lesion, but no systematic biopsies
If the mpMRI is negative, no biopsies will be performed.

Arm 3: Experimental arm II: PSA cut-off 1.8 ng/mL, only targeted biopsies for MR+
Identical to arm 2, except that the PSA-cut off is lower, 1.8 ng/mL.

Reinvitation (all arms):
The men will be re-invited to screening, with the interval length determined by the PSA level.

Reinvitation interval:
If PSA<0.6 ng/mL: 8-year interval
If PSA 0.6-1.2 ng/mL: 4-year interval
If PSA 1.2-2.4 ng/mL: 2-year interval
If PSA 2.4-3.0 ng/mL: 1-year interval

Regardless of age at first invitation all men will be invited twice, thereafter the following upper age limits for participation in combination with PSA values will be used:
If PSA <0.51 ng/mL: age 62
If PSA 0.51-1.00 ng/mL: age 65
If PSA 1.01-1.80 ng/mL: age 70
Non responder: age 70
Irrespective: age 75

Intervention type

Other

Phase

Drug names

Primary outcome measures

Rate of overdiagnosis, measured by linking the study population/study database with the Regional Cancer Registry every third month until the study ends

Secondary outcome measures

Rate of prostate biopsy, defined as the number of events per randomized men measured continuously throughout the study

Tertiary outcome measure:
Prostate cancer mortality, measured by linkage with the Swedish Causes of Death Registry twice a year until the study ends

Overall trial start date

01/09/2015

Overall trial end date

31/12/2040

Reason abandoned

Eligibility

Participant inclusion criteria

1. Male
2. Age 50-60
3. Living in selected municipalities in Västra Götaland, Sweden

Participant type

All

Age group

Adult

Gender

Male

Target number of participants

40,000

Participant exclusion criteria

Men with prior diagnosis of prostate cancer

Recruitment start date

01/09/2015

Recruitment end date

31/12/2019

Locations

Countries of recruitment

Sweden

Trial participating centre

University of Gothenburg/Sahlgrenska University Hospital
Departments of Urology and Radiology Bruna stråket 11B
Göteborg
41345
Sweden

Sponsor information

Organisation

University of Gothenburg

Sponsor details

Box 100
Göteborg
405 30
Sweden

Sponsor type

University/education

Website

http://www.gu.se/

Funders

Funder type

Research organisation

Funder name

Cancerfonden

Alternative name(s)

Swedish Cancer Society

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

Sweden

Funder name

Swedish Government

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Biocare

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Regional Cancer Center West

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Vetenskapsrådet

Alternative name(s)

Swedish Research Council, VR

Funding Body Type

government organisation

Funding Body Subtype

government non-federal

Location

Sweden

Results and Publications

Publication and dissemination plan

Primary outcome is planned to be published in Autumn 2020.

IPD sharing plan
The current data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

01/09/2020

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes