Prostate cancer screening using a combination of risk-prediction, MRI, and targeted prostate biopsies (STHLM3-MRI): a prospective, population-based, randomised, open-label, non-inferiority trial.
Screening for prostate cancer using prostate-specific antigen (PSA) reduces prostate cancer mortality but can lead to adverse outcomes. We aimed to compare a traditional screening approach with a diagnostic strategy of blood-based risk prediction combined with MRI-targeted biopsies.
We did a prospective, population-based, randomised, open-label, non-inferiority trial (STHLM3-MRI) in Stockholm county, Sweden. Men aged 50-74 years were randomly selected by Statistics Sweden and invited by mail to participate in screening; those with an elevated risk of prostate cancer, defined as either a PSA of 3 ng/mL or higher or a Stockholm3 score of 0·11 or higher were eligible for randomisation. Men with a previous prostate cancer diagnosis, who had undergone a prostate biopsy within 60 days before the invitation to participate, with a contraindication for MRI, or with severe illness were excluded. Eligible participants were randomly assigned (2:3) using computer-generated blocks of five, stratified by clinically significant prostate cancer risk, to receive either systematic prostate biopsies (standard group) or biparametric MRI followed by MRI-targeted and systematic biopsy in MRI-positive participants (experimental group). The primary outcome was the detection of clinically significant prostate cancer at prostate biopsy, defined as a Gleason score of 3 + 4 or higher. We used a margin of 0·78 to assess non-inferiority for the primary outcome. Key secondary outcome measures included the proportion of men with clinically insignificant prostate cancer (defined as a Gleason score of 3 + 3), and the number of any prostate MRI and biopsy procedures done. We did two comparisons: Stockholm3 (using scores of 0·11 and 0·15 as cutoffs) versus PSA in the experimental group (paired analyses) and PSA plus standard biopsy versus Stockholm3 plus MRI-targeted and systematic biopsy (unpaired, randomised analyses). All analyses were intention to treat. This study is registered with ClinicalTrials.gov, NCT03377881.
Between Feb 5, 2018, and March 4, 2020, 49 118 men were invited to participate, of whom 12 750 were enrolled and provided blood specimens, and 2293 with elevated risk were randomly assigned to the experimental group (n=1372) or the standard group (n=921). The area under the receiver-operating characteristic curve for detection of clinically significant prostate cancer was 0·76 (95% CI 0·72-0·80) for Stockholm3 and 0·60 (0·54-0·65) for PSA. In the experimental group, a Stockholm3 of 0·11 or higher was non-inferior to a PSA of 3 ng/mL or higher for detection of clinically significant prostate cancer (227 vs 192; relative proportion [RP] 1·18 [95% CI 1·09-1·28], p<0·0001 for non-inferiority), and also detected a similar number of low-grade prostate cancers (50 vs 41; 1·22 [0·96-1·55], p=0·053 for superiority) and was associated with more MRIs and biopsies. Compared with PSA of 3 ng/mL or higher, a Stockholm3 of 0·15 or higher provided identical sensitivity to detect clinically significant cancer, and led to fewer MRI procedures (545 vs 846; 0·64 [0·55-0·82]) and fewer biopsy procedures (311 vs 338; 0·92 (0·86-1·03). Compared with screening using PSA and systematic biopsies, a Stockholm3 of 0·11 or higher combined with MRI-targeted and systematic biopsies was associated with higher detection of clinically significant cancers (227 [3·0%] men tested vs 106 [2·1%] men tested; RP 1·44 [95% CI 1·15-1·81]), lower detection of low-grade cancers (50 [0·7%] vs 73 [1·4%]; 0·46 [0·32-0·66]), and led to fewer biopsy procedures. Patients randomly assigned to the experimental group had a lower incidence of prescription of antibiotics for infection (25 [1·8%] of 1372 vs 41 [4·4%] of 921; p=0·0002) and a lower incidence of admission to hospital (16 [1·2%] vs 31 [3·4%]; p=0·0003) than those in the standard group.
The Stockholm3 test can inform risk stratification before MRI and targeted biopsies in prostate cancer screening. Combining the Stockholm3 test with an MRI-targeted biopsy approach for prostate cancer screening decreases overdetection while maintaining the ability to detect clinically significant cancer.
The Swedish Cancer Society, the Swedish Research Council, and Stockholm City Council.
Nordström T
，Discacciati A
，Bergman M
，Clements M
，Aly M
，Annerstedt M
，Glaessgen A
，Carlsson S
，Jäderling F
，Eklund M
，Grönberg H
，STHLM3 study group
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Adoption of Prebiopsy Magnetic Resonance Imaging for Men Undergoing Prostate Biopsy in the United States.
To assess adoption of prebiopsy prostate magnetic resonance imaging (MRI) in the United States and to evaluate factors associated with magnetic resonance imaging-guided prostate biopsy (MRI-Bx) use. Prior reports have shown improved cancer detection with MRI-Bx vs transrectal ultrasound-guided methods (transrectal ultrasound-guided biopsy [TRUS-Bx]). Population-based trends of their use and outcomes have not been previously characterized.
Using private insurance claims (2009-2015), we identified men who underwent prostate biopsy. Exposures were biopsy year and geographic region defined by metropolitan statistical area. Outcomes included biopsy type (MRI-Bx, TRUS-Bx, or transperineal biopsy) based on procedure codes and cancer detection based on a new diagnosis for prostate cancer (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] 185). Hierarchical mixed-effects multivariable regression estimated odds of undergoing MRI-Bx.
We identified 241,681 men (mean age 57.5 ± 5.4 years) who underwent biopsy. The use of MRI-Bx rose rapidly (0.2% in 2009 to 6.5% in 2015, P <.001). Overall, 3429 men underwent MRI before biopsy, more commonly in metropolitan statistical areas (odds ratio 1.90, 95% confidence interval 1.66-2.19). In 2015, nearly 18% of men with prior negative biopsy underwent a prebiopsy MRI. Patients with prior negative biopsies were over 4 times more likely to use MRI guidance (vs no prior biopsies, odds ratio 4.63, 95% confidence interval 4.27-5.02) and had a greater chance of cancer detection with MRI-Bx (25.2%) vs TRUS-Bx (19.7%, P = .010).
Among men undergoing prostate biopsy, prebiopsy prostate MRI utilization was concentrated within urban areas and among patients with prior negative biopsies, where its use was associated with superior cancer detection compared with traditional TRUS-Bx.
Liu W
，Patil D
，Howard DH
，Moore RH
，Wang H
，Sanda MG
，Filson CP
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Risk-stratification based on magnetic resonance imaging and prostate-specific antigen density may reduce unnecessary follow-up biopsy procedures in men on active surveillance for low-risk prostate cancer.
To assess the value of risk-stratification based on magnetic resonance imaging (MRI) and prostate-specific antigen density (PSA-D) in reducing unnecessary biopsies without missing Gleason pattern 4 prostate cancer in men on active surveillance (AS).
In all, 210 men on AS with Gleason score 3 + 3 prostate cancer received a first MRI and if indicated [Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] targeted biopsy (TBx) using MRI-transrectal ultrasonography (TRUS) fusion. The MRI was performed 3 months after diagnosis (group A: n = 97), at confirmatory biopsy (group B: n = 39) or at surveillance biopsy after one or more repeat TRUS-guided systematic biopsies (TRUS-Bx) (group C: n = 74). The primary outcome was upgrading to Gleason score ≥3 + 4 prostate cancer based on MRI ± TBx in groups A, B and C. Biopsy outcomes were stratified for the overall PI-RADS score and PSA-D to identify a subgroup of men in whom a biopsy could have been avoided as no Gleason score upgrading was detected.
In all, 134/210 (64%) men had a positive MRI and 51/210 (24%) men had Gleason score upgrading based on MRI-TBx. The percentage of Gleason score upgrading based on MRI-TBx was 23% (22/97), 23% (9/39) and 27% (20/74) in respectively groups A, B and C. Additional Gleason score upgrading detected by TRUS-Bx occurred in 8% (3/39) of men in group B and 6% (1/17) of men who received TRUS-Bx in group C. No Gleason score upgrading was detected by MRI-TBx in men with a PI-RADS score of 3 and a PSA-D of <0.15 ng/mL2 (n = 15), nor by TRUS-Bx in men with a PI-RADS score of 1-3 and a PSA-D of <0.15 ng/mL2 (n = 15).
At least one out of five men on AS with Gleason score 3 + 3 prostate cancer at diagnostic TRUS-Bx show Gleason score upgrading based on first MRI ± TBx at baseline, confirmatory or surveillance biopsy. Men with a PI-RADS score of 1-3 and PSA-D of <0.15 ng/mL2 did not show Gleason score upgrading at MRI ± TBx or TRUS-Bx at each time point of surveillance. Thus risk-stratification based on PI-RADS and PSA-D may reduce unnecessary follow-up biopsy procedures in men on AS.
Alberts AR
，Roobol MJ
，Drost FH
，van Leenders GJ
，Bokhorst LP
，Bangma CH
，Schoots IG
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Prebiopsy multiparametric MRI-based risk score for predicting prostate cancer in biopsy-naive men with prostate-specific antigen between 4-10 ng/mL.
Risk calculators have traditionally utilized serum prostate-specific antigen (PSA) values in addition to clinical variables to predict the likelihood of prostate cancer (PCa).
To develop a prebiopsy multiparametric MRI (mpMRI)-based risk score (RS) and a statistical equation for predicting the risk of PCa in biopsy-naive men with serum PSA between 4-10 ng/mL that may help reduce unnecessary biopsies.
Prospective cross-sectional study.
In all, 137 consecutive men with PSA between 4-10 ng/mL underwent prebiopsy mpMRI (diffusion-weighted [DW]-MRI and MR spectroscopic imaging [MRSI]) during 2009-2015 were recruited for this study.
1.5T (Avanto, Siemens Health Care, Erlangen, Germany); T1 -weighted, T2 -weighted, DW-MRI, and MRSI sequences were used.
All eligible patients underwent mpMRI-directed, cognitive-fusion transrectal ultrasound (TRUS)-guided biopsies.
An equation model and an RS were developed using receiver operating characteristic (ROC) curve analysis and a multivariable logistic regression approach. A 10-fold crossvalidation and simulation analyses were performed to assess diagnostic performance of various combinations of mpMRI parameters.
Of 137 patients, 32 were diagnosed with PCa on biopsy. Multivariable analysis, adjusted with positive pathology, showed apparent diffusion coefficient (ADC), metabolite ratio, and PSA as significant predictors of PCa (P < 0.05). A statistical equation was derived using these predictors. A simple 6-point mpMRI-based RS was derived for calculating the risk of PCa and it showed that it is highly predictive for PCa (odds ratio = 3.74, 95% confidence interval [CI]: 2.24-6.27, area under the curve [AUC] = 0.87). Both models (equation and RS) yielded high predictive performance (AUC ≥0.85) on validation analysis.
A statistical equation and a simple 6-point mpMRI-based RS can be used as a point-of-care tool to potentially help limit the number of negative biopsies in men with PSA between 4 and 10 ng/mL.
1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:1227-1236.
Dwivedi DK
，Kumar R
，Dwivedi AK
，Bora GS
，Thulkar S
，Sharma S
，Gupta SD
，Jagannathan NR
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ResearchGate
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