EAU 2021: Risk-Adapted Screening with Genomics and MRI: STHLM3 MR Phase 2 Trial

(UroToday.com) Dr. Tobias Nordstrom presented on the Stockholm3 MRI trial, which is a risk-adapted screening protocol incorporating genomics and MRI. The aim of this study was to compare traditional screening with web-based risk prediction combined with MRI-targeted biopsies for prostate cancer screening. This was a population-based screening-by-invitation noninferiority trial. The trial flow diagram is listed below.


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- The STHLM3RS marker was created at the Karolinska Institutet, a world-leading medical university, and Thermo Fisher Scientific. It is a blood-based test including analyses of PSA and four other proteins, 101 genetic markers (single nucleotide polymorphisms), and clinical information (age, family history, earlier biopsies, and use of 5-alpha reductase inhibitors).

- The MRI was a 1.5/3T MRI (mostly 1.5T), 16-minute protocol without DCE

- Biopsies were 3-4 targeted biopsies of PIRADS3-5 lesions, standard bx was 10-12 cores

Analysis was an intention-to-treat (ITT).

Baseline characteristics stratified by arm are listed below:

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Most MRIs were essentially negative (59%). Median PSA was 3.5 in both arms.

Ultimately the MRI targeted biopsy pathway was non-inferior for detection of significant prostate cancer and was associated with the lower detection of insignificant prostate cancer. Results are seen below:

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In fact, it detected more clinically significant prostate cancer (21% vs. 18%) and much less insignificant prostate cancer (4% vs. 12%).

The Stockholm3 test, similar to prior studies, discriminated for significant prostate cancer better than PSA (AUC 0.76 vs. 0.60).

Looking at the different diagnostic strategies and various outcomes below:

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  • Strategy 3 (MRI enhanced in men with Stockholm3 score >0.15) had less MRI procedures, less biopsies procedures, better detection of clinically significant prostate cancer, and less detection of insignificant prostate cancer
Based on this the authors conclude the following:

  1. MRI with targeted and systematic biopsy in MRI positive men was non-inferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation setting and markedly reduced detection of clinically insignificant cancer
  2. The Stockholm3 test can inform risk ratification before MRI and targeted biopsies in prostate cancer screening
  3. Combining the Stockholm3 test with an MRI target biopsy approach for prostate cancer screening decreases over detection while maintaining detection of significant cancer

Presented by: Tobias Nordstrom, MD, PhD, Karolinska Institutet, Stockholm, Sweden

Written by: Thenappan (Thenu) Chandrasekar, MD – Urologic Oncologist, Assistant Professor of Urology, Sidney Kimmel Cancer Center, Thomas Jefferson University, @tchandra_uromd on Twitter during the 2021 European Association of Urology, EAU 2021- Virtual Meeting, July 8-12, 2021.