Standard biopsy only after suspicious MRI biopsy may be the way to go

In men with elevated prostate-specific antigen (PSA) levels (≥3 ng/mL), MRI-targeted biopsy combined with standard biopsy was as good as standard biopsy in detecting clinically significant prostate cancer and reduced the detection of clinically insignificant cancers, according to researchers of the STHLM3-MRI trial.

“Organized prostate cancer screening in which prostate-specific antigen (PSA) testing is followed by standard systematic, ultrasonography-guided, transrectal biopsy of the prostate in men with elevated PSA levels reduces prostate cancer mortality. However, PSA-based screening also leads to high rates of overdiagnosis and overtreatment of clinically insignificant prostate cancer and to many unnecessary biopsies. As a result, no country except Lithuania has instituted an organized prostate cancer screening program,” Martin Eklund, PhD, of the Karolinska Institutet in Stockholm, Sweden, and colleagues for the STHLM3 consortium wrote in The New England Journal of Medicine.

“Magnetic resonance imaging (MRI) has generated interest as a method for improving prostate cancer diagnostics. MRI can identify areas of the prostate suggestive of cancer, which allows prostate biopsies to be targeted toward those areas while unnecessary biopsies can be avoided in men with no visible lesions,” they added.

For this population-based noninferiority trial, Eklund and colleagues included 12,750 men ages 50-74 years from the Swedish general population. After using PSA and Stockholm3 testing to determine participant risk of prostate cancer, they randomized only the 1,532 men with positive results on either (≥3 ng/mL on PSA, or ≥11% on Stockholm3) to biopsy groups: 603 to standard biopsy and 929 to MRI targeted biopsy followed by standard biopsy only if results suggested prostate cancer (the experimental biopsy group).

“The Stockholm3 test is a risk-prediction model that is based on clinical variables (age, first-degree family history of prostate cancer, and previous biopsy), blood biomarkers (total PSA, free PSA, ratio of free PSA to total PSA, human kallikrein 2, macrophage inhibitory cytokine-1, and MSMB), and a polygenic risk score for predicting the risk of prostate cancer with a Gleason score of 7 or higher,” explained Eklund et al.

Upon intention-to-treat analysis, 21% of men in the experimental biopsy group were diagnosed with clinically significant cancer, compared with 18% in the standard biopsy group (difference: 3 percentage points; 95% CI: −1 to −7; P˂0.001 for noninferiority). In addition, the percentage of clinically insignificant cancers was lower in the experimental biopsy group compared with the standard biopsy group (4% vs 12%, respectively; difference: −8 percentage points; 95% CI: −11 to −5).

Infection occurred in 2% of men in the experimental biopsy group and 4% in the standard biopsy group—1% and 3%, respectively, were hospitalized.

“An important question is whether men who have positive MRI results should undergo standard biopsy in addition to targeted biopsy. In our trial, 30 fewer clinically significant cancers would have been detected among the 929 men in the experimental biopsy group if the additional standard biopsy had not been performed, while 18 fewer clinically insignificant cancers would have been found; thus, detection of 1.7 clinically significant cancers would be delayed for each clinically insignificant cancer avoided. Our results therefore support the use of standard biopsy in addition to targeted biopsy for men who have positive MRI results, an observation that is in line with previous findings,” noted Eklund et al.

“When normalized to a population of 10,000 men 50 to 74 years of age in which those with elevated PSA levels (≥3 ng per milliliter) are referred for biopsy, the combined biopsy approach in men with positive MRI scans would result in 409 fewer men undergoing biopsy, 366 fewer biopsies with benign findings, and 88 fewer clinically insignificant cancers detected than with the standard biopsy approach. These numbers represent 48%, 73%, and 62% lower incidences, respectively, with the use of MRI and the combined biopsy approach. The reduced biopsy rate and potential downstream savings that result from less overtreatment offer potential cost savings that may offset the additional costs of MRI,” concluded Eklund and fellow researchers.

Study limitations include the use of biparametric 1.5T and 3T MRI protocols may have “contributed to the somewhat lower relative detection probability of targeted biopsies than that observed in previous studies,” noted the authors. Other limitations include that it was performed in Sweden and thus limits generalizability of results, the use of only one round of screening, and the limited availability of Stockholm3 testing.

  1. Among men with elevated PSA levels, combined biopsy performed only in those with positive results on MRI was noninferior to standard biopsy for detecting clinically significant prostate cancer.

  2. This approach may reduce the incidence of unnecessary biopsies as well as diagnosis of clinically insignificant cancers.

Liz Meszaros, Deputy Managing Editor, BreakingMED™

This study was funded by the Swedish Research Council (Vetenskapsrådet), the Swedish Cancer Society (Cancerfonden), the Percy Falk Foundation, the Magnus Bergvall Foundation, the Strategic Research Program on Cancer (StratCan) at Karolinska Institutet, the Hagstrand Memorial Fund (Hagstrandska Minnesfonden), Region Stockholm, Svenska Druidorden, Åke Wibergs Stiftelse, and Swedish e-Science Research Center (SeRC), Karolinska Institutet, and the Swedish Prostate Cancer Foundation (Prostatacancerförbundet).

Eklund reported stock ownership in A3P Biomedical AB, where he has four pending patent applications related to prostate cancer diagnostics.

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