MRI-targeted biopsy + new risk score cuts unnecessary biopsies in prostate cancer

An MRI-targeted biopsy* plus a new risk score cuts unnecessary biopsies by half in men with positive MRI results and elevated PSA** levels in the STHLM3-MRI study. This benefit comes without missing clinically significant cancers, experts report at EAU 2021.

The combined strategy was as effective as standard biopsy in detecting clinically significant prostate cancer. However, MRI-targeted biopsy was associated with a 52-percent reduction in biopsy procedures and a 69-percent reduction in low-grade (Gleason score 6) cancer detection vs standard biopsy alone.

“The benefits of screening were maintained, and potential harms were reduced substantially,” said study author Dr Tobias Nordström from the Danderyd Hospital at Karolinska Institute in Stockholm, Sweden.

Drawbacks of current screening strategies

Current screening methods – PSA** testing followed by standard systematic, ultrasonography-guided transrectal biopsy in men with elevated PSA levels –  reduce mortality from prostate cancer. Conversely, PSA-based screening also leads to unnecessary biopsies, biopsy-related side effects,  detection of low-risk tumours, overdiagnosis, and overtreatment,” said principal investigator Associate Professor Martin Eklund from the Department of Medical Epidemiology and Biostatistics, Karolinska Institute. “Newer, refined screening methods could help reduce prostate cancer overdiagnosis and overtreatment.”

A closer look at STHLM3-MRI

STHLM3-MRI enrolled 12,750 men from Stockholm County from 2018 to 2020. PSA was analysed for all men. Those with PSA levels of ≥1.5 ng/mL underwent a Stockholm 3 test. Those with PSA levels of ≥3 ng/mL (n=1,532), irrespective of the Stockholm 3 scores, were randomly assigned to undergo standard biopsy (n=603), or combined MRI-targeted and standard biopsy (n=929) if MRI results were suggestive of prostate cancer. [EAU 2021, abstract P1014; N Engl J Med 2021;doi:10.1056/NEJMoa2100852]

Biopsies were not performed in patients without clinically significant lesions identified, except in cases of Stockholm 3 test scores of 25 percent or greater, which suggest a high risk of clinically significant cancer despite a negative MRI finding.

Stockholm 3 better than PSA testing

The Stockholm 3 test discriminated for significant prostate cancer better than PSA (area under the curve [AUC], 0.76 vs 0.60).

“The score was able to inform risk stratification before MRI-targeted biopsies during prostate cancer screening,” Nordström said. “Combining the Stockholm 3 score with the MRI-targeted biopsy approach reduced overdetection while maintaining detection of significant prostate cancer,” he added.

Stockholm 3 is a blood-based test that includes analyses of PSA and four other proteins, 101 genetic markers (single nucleotide polymorphisms), and clinical variables (age, family history, previous biopsies, and use of 5-alpha reductase inhibitors).

ITT population

In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21 percent) in the MRI-targeted biopsy group vs 106 men (18 percent) in the standard biopsy group (difference of 3 percentage points; p<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the MRI-targeted biopsy group than the control group (4 percent vs 12 percent).

Among men with PSA levels of ≥3 ng/mL, the detection of clinically insignificant tumours and benign lesions were lower by 64 percent and 74 percent, respectively, when the biopsy was performed with positive MRI results.

“Finally, we’re able to show that men over age 50 can reduce their risk of malignant cancer through nationwide prostate-cancer screening that utilizes modern methods,” said Nordström.

The future of cancer diagnostics

Commenting on the study, Professor Hendrik Van Poppel, Adjunct Secretary-General of the EAU, said it is exciting to see breakthroughs in the early detection of prostate cancer. “An innovation such as the STHLM3-MRI makes an even more compelling case for the European Commission to ensure that a risk-stratified approach to early detection of prostate cancer is adopted across Europe.”