(UroToday.com) The 2024 European Association of Urology (EAU) annual meeting featured a game changing session for guideline changes in screening and diagnosis for prostate cancer, and a presentation by Dr. Anssi Auvinen discussing results from the first screening round of the ProScreen screening trial with PSA, kallikrein panel and MRI. PSA-based screening can reduce prostate cancer mortality, with the ERSPC trial showing a mortality reduction, while the PLCO and CaP trials did not. The balance of benefits and harms is dubious due to extensive overdiagnosis of low-risk, low-grade cases of limited clinical relevance. MRI has reduced detection of Grade Group 1 cases in diagnostic accuracy studies, but retained high sensitivity for Grade Group 2-5 cases. The Goteborg-2 trial and STHLM3-MRI study have compared systematic biopsy with MRI-targeted biopsy in the screening setting, but have not reported findings for a control group without screening. As such. Dr. Auvinen and colleagues described cancer detection at the first screening round and compared these men with a control arm that was not offered screening.
The primary outcome of the ProScreen trial is prostate cancer mortality, with analyses planned at 10 and 15 years. The target sample size is 115,000 men, giving >80% power to detect a 25% reduction in prostate cancer mortality. The screening protocol involves first a PSA, followed by men with a PSA >=3 ng/mL having a four-kallikrein panel, those with a score >= 7.5% are referred for mpMRI, and finally men with PI-RADS scores >= 3 undergo a prostate biopsy. As a safety feature, men with a PSA density >= 0.15 also have a systematic biopsy. The screening interval is two years if the PSA is >= 3 ng/mL, four years if the PSA is 1.5-3 ng/mL, and six years if PSA is < 1.5 ng/mL. At EAU 2024, Dr. Auvinen reported the first round results for the initial cohort of 60,745 men from Helsinki and Tampere, Finland.
Of the 15,201 invited men, 7,744 (51%) participated, and of the participants, 44% reported >1 previous PSA test, with 14% of men having a positive family history. There were 752 men (9.7%) with a PSA >= 3 ng/mL, 526 men (72%) had a kallikrein panel score >= 7.5%, and 211 (41%) had a PI-RADS score of 3-5. Targeted biopsies were performed on 209 men (2.7% of participants), with 22 Gleason Grade Group 1 cases (11% of biopsies), and 113 Gleason Grade Group 2-5 cases (54% of biopsies). Systematic biopsies in 53 men with PIRADS <3 but PSA density >= 0.15 led to the detection of 10 Gleason Grade Group 1 and 15 Gleason Grade Group 2-5 cancers. Among 7,457 men in the screening arm who did not participate, there were 7 Gleason Grade 1 and 44 Gleason Grade Group 2-5 cancers diagnosed (ascertained from the cancer registry). In the control arm, 65 Gleason Grade Group 1 cancers and 28 Gleason Grade Group 2-5 cancers were diagnosed among 45,544 men during a median follow-up of 3.4 years. The cancers by trial arm and Grade Group are as follows:
Furthermore, the cancer detected by detailed Grade Group is as follows:
Dr. Auvinen concluded his presentation by discussing results from the first screening round of the ProScreen screening trial with PSA, kallikrein panel and MRI with the following concluding statements:
- The ProScreen trial showed a substantially higher detection of high-grade than low-grade cancer at the first screening round
- This was also shown in comparison with a control arm not offered screening
- Assuming that high grade cancers represent benefit and low-grade cancer harm (overdiagnosis), the results suggest a materially improved balance of benefits and harms compared with PSA–based screening
- The Goteborg-2 trial detection of high-grade cancer was 0.9% with MRI (ProScreen 1.6%) and low grade cancer was 0.6% (ProScreen 0.4%). In the STHLM3-MRI study with targeted + systematic biopsies, 12% of biopsies showed a Gleason Grade Group 1 cancer (ProScreen 11% targeted/12% overall) and 57% Gleason Grade Group 2-5 cancers (ProScreen 54%/49%)
- The investigators have started the second and third screening rounds, and they will evaluate kallikrein panel and PI-RADS cutoffs, as well as simplified MRI protocols
- Mortality analyses are expected at 10 and 15 years
Following this presentation by Dr. Auvinen, this study was published concomitantly in JAMA1
Presented by: Anssi P. Auvinen, MD, PhD, Tampere University, Tampere, Finland
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 European Association of Urology (EAU) annual congress, Paris, France, April 5th – April 8th, 2024
References:
- Auvinen A, Tammela TLJ, Mirtti T, et al. Prostate Cancer Screening with PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial. JAMA 2024 Apr 6 [Epub ahead of print].