PCa trial updates: Finding the best way to screen men
During the Thematic Session ‘Early detection and diagnosis pathways in prostate cancer revisited’, presentations covered ongoing trials seeking the best way to screen men for prostate cancer (PCa). These trials include Göteborg, STHLM3 MRI, ProScreen, PROBASE, and TRANSFORM.
Göteborg 2 (G2) trial
The Göteborg 2 (G2) prostate cancer screening trial evaluates screening with prostate-specific antigen (PSA) followed by magnetic resonance imaging (MRI) in case of elevated PSA levels. G2 started in 2015, inviting men aged 50-60 years, with invitations repeated at two, four, and eight years, with the ratio of clinically insignificant cancer (ISUP grade 1) being the main endpoint.
Prof. Hugosson concluded from the results he presented, “MRI seems to have a very high sensitivity to detect clinically significant cancers while they are still in the window of cure. Avoiding routine systematic biopsies will lead to a more acceptable rate of overdiagnosis which will shift the benefit/harm balance in a direction that may convince healthcare authorities to introduce population based PCa screening.”
Prof. Hugosson outlined future plans for the G2 trial, including an extended six-year follow-up to compare cumulative incidences across arm 1, arm 2, and the control group. The study will also assess anxiety and quality of life during screening. Additionally, a first comparison will be made between arm 2 (PSA cut off 3 for MRI and targeted biopsies only) and arm 3 (PSA cut off 1.8 with targeted biopsies only). A key analysis comparing the non-invited control group with the three screening groups, focusing on PCa mortality, is scheduled for 2028.
STHLM3 MRI: Repeated screening with biomarkers and MRI
Prof. Tobias Nordström (SE) presented details of the STHLM3 MRI trial that compares the traditional screening approach with a diagnostic strategy of blood-based prediction combined with MRI-targeted biopsies.
According to Prof. Nordström, two thirds of men have a negative MRI in screening cohorts, especially in repeat screening rounds. “Results showed that risk stratification can inform decisions to perform MRI in both initial and repeat screening. Moving forward, STHLM3 MRI will report long-term outcomes including comparisons with opportunistic screening.”
ProScreen: Repeated screening with biomarkers and MRI
Prof. Anssi Auvinen (FI) presented the second-round results of the ProScreen trial, which investigates the effectiveness of a screening strategy combining PSA, kallikrein panel, and MRI in reducing PCa mortality over a 15-year period from randomisation.
He stated, “Overall detection was higher in the second screening round compared to the first round, with rates exceeding 5% versus 2%. This increase is likely due to only high-risk men with PSA ≥ 3 or 1.5-2.99 ng/ml being invited for follow-up screening at two or four years. The detection rate was slightly lower in men whose initial PSA was between 1.5-2.99 compared to those with PSA >3. However, the positive predictive value (PPV) at biopsy was clearly higher. There was a similar or slightly lower proportion of GG2-5 cases than at the first round (65-86%).
PROBASE trial – PSA
In his update on the PROBASE screening trial, Prof. Peter Albers (DE) emphasised that this risk-adapted PCa screening trial began in 2014, is PSA-based only screening and has a significantly lower base age of 45 for men enrolled, compared to other trials.
Prof. Albers: “With follow-up currently up to 10-years, the most important results from PROBASE to date are that confirmatory second PSA reduced the group of men classified at ‘high-risk’ by nearly half, and thereby, reduced the number of MRIs and biopsies. Men with first of second PSA <1.5ng/ml and those with negative biopsy are at extremely low PCa risk and may need only re-testing every five years. At ages 45-50, combined systematic/MRI-targeted biopsies may remain necessary.”
TRANSFORM trial – IP1-Postagram and ReIMAGINE
“TRANSFORM aims to close the evidence gaps between the uncertainty of historical screening studies, our current practice and future proofing for upcoming developments,” stated Prof. Hashim Ahmed (GB) in his presentation unveiling the design of the TRANSFORM trial.
He explained that the trial will be informed by IP1-Prostagram and ReIMAGINE screening, and use the Zelen design. “Men will be randomised to either a prostate health check or a control group before receiving an invitation.” According to Prof. Ahmed, this is the most effective design to avoid contamination. Those randomised to the control group who are not invited, will remain unaware of their involvement in the trial and will continue with their usual care. “The TRANSFORM population will be men between 50 – 70 years of age (45 – 74 age group if Black ethnicity or with learning disability), with no previous PCa, No PSA test, prostate MRI scan, prostate biomarker test or prostate biopsy. Men will be identified through primary care records. A data-driven sampling approach will be used, with a targeted age distribution towards of over 50 years of age and 10% of the invited population will be of Black ethnicity”.
You can watch the full webcast via the EAU25 Resource Centre.