Department of Urology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, USA.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
BJU Int. 2021 Aug;128(2):218-224. doi: 10.1111/bju.15320. Epub 2020 Dec 28.
To prospectively evaluate the performance of a pre-specified statistical model based on four kallikrein markers in blood (total prostate-specific antigen [PSA], free PSA, intact PSA, and human kallikrein-related peptidase 2), commercially available as the 4Kscore, in predicting Gleason Grade Group (GG) ≥2 prostate cancer at biopsy in an international multicentre study at three academic medical centres, and whether microseminoprotein-β (MSP) adds predictive value.
A total of 984 men were prospectively enrolled at three academic centres. The primary outcome was GG ≥2 on prostate biopsy. Three pre-specified statistical models were used: a base model including PSA, age, digital rectal examination and prior negative biopsy; a model that added free PSA to the base model; and the 4Kscore.
A total of 947 men were included in the final analysis and 273 (29%) had GG ≥2 on prostate biopsy. The base model area under the receiver operating characteristic curve of 0.775 increased to 0.802 with the addition of free PSA, and to 0.824 for the 4Kscore. Adding MSP to the 4Kscore model yielded an increase (0.014-0.019) in discrimination. In decision-curve analysis of clinical utility, the 4Kscore showed a benefit starting at a 7.5% threshold.
A prospective multicentre evaluation of a pre-specified model based on four kallikrein markers (4Kscore) with the addition of MSP improves the predictive discrimination for GG ≥2 prostate cancer on biopsy and could be used to inform biopsy decision-making.
前瞻性评估基于四项血液激肽释放酶标志物（总前列腺特异性抗原[PSA]、游离 PSA、完整 PSA 和人激肽释放酶相关肽酶 2）的预定义统计模型在预测活检中格里森分级组（GG）≥2 前列腺癌方面的表现，该模型可作为商业产品 4Kscore 使用，该研究在三个学术医疗中心的国际多中心研究中进行，并且研究了微 Seminoprotein-β（MSP）是否增加预测价值。
总共前瞻性招募了 984 名男性，在三个学术中心进行。主要结局是前列腺活检中 GG≥2。使用了三种预定义的统计模型：一个包含 PSA、年龄、直肠指检和既往阴性活检的基本模型；一个在基本模型中添加游离 PSA 的模型；以及 4Kscore。
共有 947 名男性纳入最终分析，273 名（29%）前列腺活检中 GG≥2。基本模型的受试者工作特征曲线下面积从 0.775 增加到添加游离 PSA 后的 0.802，增加到 4Kscore 的 0.824。将 MSP 添加到 4Kscore 模型中可提高判别力（0.014-0.019）。在临床效用的决策曲线分析中，4Kscore 从 7.5%的阈值开始具有获益。
基于四项激肽释放酶标志物（4Kscore）的预定义模型的前瞻性多中心评估，加上 MSP，可提高活检中 GG≥2 前列腺癌的预测判别能力，并可用于指导活检决策。
