Scott Eggener, Adolfsson J, Aly M, Nordström T, Wiklund P, Brandberg Y, Thompson J, Wiklund F, Lindberg J, Clements M, Egevad L, Eklund M
Urol Oncol. 2017 Mar;35(3):120. doi: 10.1016/j.urolonc.2016.03.013.
The prostate-specific antigen (PSA) test is used to screen for prostate cancer but has a high false-positive rate that translates into unnecessary prostate biopsies and overdiagnosis of low-risk prostate cancers. We aimed to develop and validate a model to identify high-risk prostate cancer (with a Gleason score of at least 7) with better test characteristics than that provided by PSA screening alone.
The Stockholm 3 (STHLM3) study is a prospective, population-based, paired, screen-positive, diagnostic study of men without prostate cancer aged 50 to 69 years randomly invited by date of birth from the Swedish Population Register kept by the Swedish Tax Agency. Men with prostate cancer at enrolment were excluded from the study. The predefined STHLM3 model (a combination of plasma protein biomarkers [PSA, free PSA, intact PSA, hK2, MSMB, MIC1], genetic polymorphisms [232 SNPs], and clinical variables [age, family, history, previous prostate biopsy, prostate exam]), and PSA concentration were both tested in all participants enrolled. The primary aim was to increase the specificity compared with PSA without decreasing the sensitivity to diagnose high-risk prostate cancer. The primary outcomes were number of detected high-risk cancers (sensitivity) and the number of performed prostate biopsies (specificity). The STHLM3 training cohort was used to train the STHLM3 model, which was prospectively tested in the STHLM3 validation cohort. Logistic regression was used to test for associations between biomarkers and clinical variables and prostate cancer with a Gleason score of at least 7. This study is registered with ISCRTN.com, number ISRCTN84445406.
The STHLM3 model performed significantly better than PSA alone for detection of cancers with a Gleason score of at least 7 (P<0.0001), the area under the curve was 0·56 (95% CI: 0·55-0·60) with PSA alone and 0·74 (95% CI: 0·72-0·75) with the STHLM3 model. All variables used in the STHLM3 model were significantly associated with prostate cancers with a Gleason score of at least 7 (P<0·05) in a multiple logistic regression model. At the same level of sensitivity as the PSA test using a cutoff of≥3ng/ml to diagnose high-risk prostate cancer, use of the STHLM3 model could reduce the number of biopsies by 32% (95% CI: 24-39) and could avoid 44% (35-54) of benign biopsies.
The STHLM3 model could reduce unnecessary biopsies without compromising the ability to diagnose prostate cancer with a Gleason score of at least 7, and could be a step towards personalised risk-based prostate cancer diagnostic programmes.
Stockholm County Council (Stockholms Läns Landsting).
前列腺特异性抗原（PSA）检测用于筛查前列腺癌，但假阳性率较高，这导致了不必要的前列腺活检以及低风险前列腺癌的过度诊断。我们旨在开发并验证一种模型，以识别高危前列腺癌（Gleason评分至少为7分），其检测特征要优于单独的PSA筛查。
斯德哥尔摩3（STHLM3）研究是一项基于人群的前瞻性配对筛查阳性诊断研究，研究对象为年龄在50至69岁之间、未患前列腺癌的男性，他们由瑞典税务机构保存的瑞典人口登记册按出生日期随机邀请。入组时患有前列腺癌的男性被排除在研究之外。预定义的STHLM3模型（血浆蛋白生物标志物[PSA、游离PSA、完整PSA、hK2、MSMB、MIC1]、基因多态性[232个单核苷酸多态性]和临床变量[年龄、家族史、既往前列腺活检、前列腺检查]的组合）以及PSA浓度在所有入组参与者中均进行了检测。主要目的是在不降低诊断高危前列腺癌敏感性的情况下提高与PSA相比的特异性。主要结局为检测到的高危癌症数量（敏感性）和进行的前列腺活检数量（特异性）。STHLM3训练队列用于训练STHLM3模型，该模型在前瞻性的STHLM3验证队列中进行测试。采用逻辑回归检验生物标志物、临床变量与Gleason评分至少为7分的前列腺癌之间的关联。本研究已在ISCRTN.com注册，注册号为ISRCTN84445406。
对于检测Gleason评分至少为7分的癌症，STHLM3模型的表现明显优于单独的PSA（P<0.0001），单独使用PSA时曲线下面积为0.56（95%CI：0.55 - 0.60），使用STHLM3模型时为0.74（95%CI：0.72 - 0.75）。在多逻辑回归模型中，STHLM3模型中使用的所有变量均与Gleason评分至少为7分的前列腺癌显著相关（P<0.05）。在使用≥3ng/ml的临界值诊断高危前列腺癌时，与PSA检测具有相同敏感性的情况下，使用STHLM3模型可将活检数量减少32%（95%CI：24 - 39），并可避免44%（35 - 54）的良性活检。
STHLM3模型可以减少不必要的活检，同时不影响诊断Gleason评分至少为7分的前列腺癌的能力，并且可能朝着基于个性化风险的前列腺癌诊断方案迈出了一步。
斯德哥尔摩郡议会（Stockholms Läns Landsting）。
