Department of Urology, Karolinska University Hospital Solna, Stockholm, Sweden.
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
Prostate Cancer Prostatic Dis. 2019 Mar;22(1):137-142. doi: 10.1038/s41391-018-0082-5. Epub 2018 Aug 31.
Several blood-based tests have been suggested to improve prostate cancer testing. The Stockholm3 test has been shown to reduce the number of prostate biopsies, to decrease detection of low-grade cancer and to maintain the detection rate of ISUP Gleason Group (GG) ≥ 2 cancer in a screening-by-invitation setting. We aimed to validate the performance of the Stockholm3 test in an independent, clinical practice cohort.
The study-population consisted of 533 men in ages 45-75 without previous diagnosis of prostate cancer scheduled for prostate biopsy at any of three centers in Norway and Sweden. Blood samples for Stockholm3 analysis were drawn prior to systematic prostate biopsies. Clinically significant prostate cancer was defined as any finding of ISUP Grade Group (GG) 2 or higher. We calculated area under the curve (AUC) for predicting prostate cancer at biopsy and calculated. Models including PSA and PSA-density (PSA/prostate volume) were compared to a model including also clinical information, protein levels and single nucleotide polymorphisms (SNP).
263 of 533 (49%) participants were diagnosed with prostate cancer. 162 men had prostate cancer with GG ≥ 2. The Stockholm3 test discriminated better for GG ≥ 2 prostate cancer than PSA in combination with PSA-density AUC 8.9 (95% CI 82.7-89.2) and AUC 74.8 (95% CI 70.3-79.3). Using a Stockholm3 cut-off of 10% risk of GG ≥ 2 cancer, 38% of the biopsy procedures were saved, however delaying diagnosis for 6% (n = 10) of men with GG ≥ 2 cancer. Using PSA-density 0.1 as cut-off for biopsy saved 35% of biopsies, delaying diagnosis for 16% (n = 26) of men with GG ≥ 2 cancer.
A prediction model including clinical information, protein levels and SNPs was independently validated in a clinical practice cohort and reduces the number of un-necessary biopsies while delaying diagnosis for a limited number of men.
已有多种血液检测方法被建议用于改善前列腺癌检测。Stockholm3 检测已被证实可减少前列腺活检的数量，降低低级别癌症的检出率，并在邀请筛查模式下维持 ISUP 分级组（GG）≥2 癌症的检出率。我们旨在验证 Stockholm3 检测在独立的临床实践队列中的表现。
研究人群由挪威和瑞典三个中心的 533 名年龄在 45-75 岁之间、既往无前列腺癌诊断、计划接受前列腺活检的男性组成。在进行系统前列腺活检前抽取 Stockholm3 分析的血样。临床显著的前列腺癌定义为任何 ISUP 分级组（GG）2 级或更高的发现。我们计算了活检时预测前列腺癌的曲线下面积（AUC），并计算了包括 PSA 和 PSA 密度（PSA/前列腺体积）的模型与包括临床信息、蛋白水平和单核苷酸多态性（SNP）的模型之间的 AUC。
533 名参与者中有 263 名（49%）被诊断为前列腺癌。162 名男性患有 GG≥2 的前列腺癌。与 PSA 联合 PSA 密度相比，Stockholm3 检测对 GG≥2 前列腺癌的诊断效果更好，AUC 为 8.9（95%CI 82.7-89.2）和 AUC 为 74.8（95%CI 70.3-79.3）。使用 Stockholm3 截断值为 10% GG≥2 癌症的风险，可减少 38%的活检程序，但会使 6%（n=10）的 GG≥2 癌症男性延迟诊断。使用 PSA 密度 0.1 作为活检的截断值，可减少 35%的活检，使 16%（n=26）的 GG≥2 癌症男性延迟诊断。
包含临床信息、蛋白水平和 SNP 的预测模型在临床实践队列中得到了独立验证，可减少不必要的活检数量，同时使有限数量的男性延迟诊断。
