Björnebo Lars, Discacciati Andrea, Abbadi Ahmad, Falagario Ugo Giovanni, Engel Jan Chandra, Vigneswaran Hari T, Jäderling Fredrik, Grönberg Henrik, Eklund Martin, Lantz Anna, Nordström Tobias
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Eur Urol Focus. 2025 Jul 29. doi: 10.1016/j.euf.2025.06.008.
Prostate cancer screening is challenged by overdetection, overtreatment, and high resource use. Prostate-specific antigen (PSA) density (PSAD) correlates more strongly with clinically significant cancer than PSA alone. We compare outcomes using various PSAD cutoffs to select men for magnetic resonance imaging (MRI).
STHLM3MRI is a screening-by-invitation trial with 49 118 men invited and 12 750 screened. In the experimental arm, participants with elevated PSA (≥3 ng/ml) had MRI and, if positive [PI-RADS] score ≥3), systematic and targeted biopsies. Evaluated PSAD cutoffs were 0.075, 0.10, 0.125, and 0.15 ng/ml. Prostate volume was measured by MRI or transrectal ultrasound. The primary endpoint was Gleason ≥3 + 4 cancer detection. The secondary endpoints were Gleason 6 and ≥4 + 3 cancer detection, and the number of MRI scans and biopsies. Relative positive fractions (RPFs) compared the outcomes using PSA ≥3 ng/ml alone.
Of 7609 men in the experimental arm, 929 (12.2%) had PSA ≥3 ng/ml, and 846 (91%) underwent MRI, with 38% having a PI-RADS score of ≥3. The median prostate volume was 45 ml (interquartile range [IQR], 33-62 ml) and PSAD 0.10 ng/ml (IQR, 0.07-0.14 ng/ml). A PSAD cutoff of 0.075 ng/ml reduced Gleason 6 cancer detection by 17% (RPF, 0.83; 95% confidence interval [CI], 0.72-0.96), lowered MRI use by 28% (RPF, 0.72; 95% CI, 0.69-0.75), and missed 5% (RPF, 0.95; 95% CI, 0.92-0.98) of Gleason ≥3 + 4 cancer cases, with no difference in Gleason ≥4 + 3 cancer detection. Higher PSAD thresholds reduced Gleason 6 cancer detection and MRI use, but lowered Gleason ≥3 + 4 cancer detection. Limitations include assumed equivalency between MRI and ultrasound volume.
The use of PSAD before MRI lowers overdiagnosis and resource use, while maintaining detection of significant cancer cases. Our results suggest that a PSAD cutoff above 0.075 ng/ml is not advisable, regardless of age, due to the increased risk of missing cancer cases with Gleason scores ≥3 + 4.
前列腺癌筛查面临过度检测、过度治疗以及高资源消耗等挑战。前列腺特异性抗原（PSA）密度（PSAD）与临床显著癌症的相关性比单独的PSA更强。我们比较使用各种PSAD临界值来选择男性进行磁共振成像（MRI）的结果。
STHLM3MRI是一项邀请式筛查试验，邀请了49118名男性，12750名接受了筛查。在试验组中，PSA升高（≥3 ng/ml）的参与者进行了MRI检查，如果结果为阳性（[PI-RADS]评分≥3），则进行系统和靶向活检。评估的PSAD临界值为0.075、0.10、0.125和0.15 ng/ml。前列腺体积通过MRI或经直肠超声测量。主要终点是Gleason≥3 + 4癌症的检测。次要终点是Gleason 6和≥4 + 3癌症的检测，以及MRI扫描和活检的次数。相对阳性率（RPFs）比较了仅使用PSA≥3 ng/ml的结果。
在试验组的7609名男性中，929名（12.2%）PSA≥3 ng/ml，846名（91%）接受了MRI检查，其中38%的PI-RADS评分为≥3。前列腺体积中位数为45 ml（四分位间距[IQR]，33 - 62 ml），PSAD为0.10 ng/ml（IQR，0.07 - 0.14 ng/ml）。PSAD临界值为0.075 ng/ml可使Gleason 6癌症检测减少17%（RPF，0.83；95%置信区间[CI]，0.72 - 0.96），MRI使用减少28%（RPF，0.72；95% CI，0.69 - 0.75），但会遗漏5%（RPF，0.95；95% CI，0.92 - 0.98）的Gleason≥3 + 4癌症病例，Gleason≥4 + 3癌症检测无差异。更高的PSAD阈值可减少Gleason 6癌症检测和MRI使用，但会降低Gleason≥3 + 4癌症检测。局限性包括假设MRI和超声测量的体积等效。
在MRI检查前使用PSAD可降低过度诊断和资源消耗，同时保持对显著癌症病例的检测。我们的结果表明，无论年龄如何，PSAD临界值高于0.075 ng/ml都不可取，因为Gleason评分≥3 + 4的癌症病例漏诊风险增加。
