The GÖTEBORG prostate cancer screening 2 trial: a prospective, randomised, population-based prostate cancer screening trial with prostate-specific antigen testing followed by magnetic resonance imaging of the prostate

Figures & data

Table 1. Primary and secondary outcomes in Göteborg-2 trial.

Outcome	Definition	Time of assessment
Primary	Proportions of clinically insignificant cancers^a Arm 1 vs Arm 2 + 3^b.	After completion of SR 1.
Primary	Proportions of clinically insignificant cancers^a Arm 1 vs. Arm 2.	After completion of each SR after SR 1 (every 2 years).
Secondary	Proportions of clinically significant cancers^a Arm 1 vs. Arm 2 + 3^b.	After completion of SR 1, 2 (at 2 and 4 years) and 8 years after SR 1.
Secondary	Cancer detection rate^c bpMRI vs mpMRI.	After completion of SR 1.
Secondary	Proportion of clinically significant cancers Arm 2 vs. Arm 3.	After completion of each SR with start after SR 2.
Secondary	Cancer-specific incidence and mortality SG vs. CG (intention to screen analysis).	12 years after randomisation (31 December 2027) and every third year after.

SR: screening round; SG: screening group; CG: control group; bpMRI: bi-parametric MRI; mpMRI: multiparametric MRI

^a Clinically insignificant cancer is primarily defined as Gleason score 3 + 3 in prostate biopsy and clinically significant cancer as Gleason score >3 + 3.

^b The number of insignificant and significant cancers are only related to the number of men with PSA ≥ 3 ng/mL. Thus, cancers diagnosed in Arm 3 in men with PSA 1.8–3 will not be included in the statistical analysis.

^c Cancer detection rate is defined as the ratio between number of men who are diagnosed with PC at biopsy and the total number of men who underwent MRI.

Table 2. Definitions of clinically significant cancer.

	Clinically significant cancer	Clinically insignificant cancer
Primary definition	Gleason score $\ge$ 3 + 4	Gleason score = 3 + 3
Definition 2^a		Gleason score = 3 + 3, Clinical stage T1C, PSA-density < 0.15, $\le$ 2 positive sectors and unilateral cancer
Definition 3^b	Gleason score $\ge$ 4 + 3, or cancer core $\ge$ 6 mm
Definition 4^b	Gleason score $\ge$ 3 + 4, or cancer core $\ge$ 4 mm

^a In definition 2, the modified Epstein criteria is used. In order to not overestimate cancer extent in men who underwent targeted biopsies, the number of positive cores is translated into positive sectors.

^b Definitions 3 and 4 are adapted from the PROMIS trial [17]. For cancer core length in targeted biopsies a mean value is calculated from the three to four cores of targeted biopsies.

Table 3. Eligibility criteria.

Inclusion criteria	Exclusion criteria
Alive on randomisation date A registered address in the county of Gothenburg or any of six specified surrounding municipalities in Sweden Age 50–60 years	Previous diagnosis of prostate cancer Emigration during the period between randomisation and update of the Total Population Register, to which the study participants’ unique personal identification numbers are linked. Death during the period between randomisation and update of the Total Population Register, to which the study participants’ unique personal identification numbers are linked.

Figure 1. Study Schema of the Göteborg-2 trial. Figure 1 shows the study layout of the Göteborg-2 trial. MRI interpretation is performed according to Prostate Imaging-Reporting and Data System (PI-RADS), v.2.1. MRI +: positive MRI defined as PI-RADS 3, 4 or 5. MRI−: negative MRI defined as PI-RADS 1 or 2. *All men with PSA ≥ 10.0 ng/mL are recommended 12-core systematic TRUS biopsy plus additional targeted biopsy if positive MRI. **All men with an MRI showing PI-RADS 5 are recommended 12-core systematic TRUS biopsy.

Figure 3. (A) Reasons for MRI not performed or MRI of non-diagnostic quality.Of the planned MR exams, 6% were not performed (due to participant declining or having a medical contraindication) or of non-diagnostic quality (mainly due to hip-prostheses or other osteosynthesis material distorting the diffusion-weighted sequence but also due to claustrophobia rendering incomplete examinations). (B) Reasons for TRUS biopsies not performed. Of the planned TRUS biopsies, 15% were not performed.

Figure 4. Age distribution at randomisation. Due to time delay between the identification of the first random sample from the Total Population Register and the randomisation to control or screening group, some men turn 61. They make 1% of the randomised men up-until 31 December 2019.

Ahmed HU, El-Shater Bosaily A, Brown LC, et al. Diagnostic accuracy of multi-parametric MRI and TRUS biopsy in prostate cancer (PROMIS): a paired validating confirmatory study. Lancet. 2017;389(10071):815–822.

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