Robinson Hunter S, Lee Sangmyung S, Barocas Daniel A, Tosoian Jeffrey J
Department of Urology, Vanderbilt University Medical Center, Nashville, TN, USA.
Vanderbilt-Ingram Cancer Center, Nashville, TN, USA.
Prostate Cancer Prostatic Dis. 2025 Mar;28(1):45-55. doi: 10.1038/s41391-024-00840-0. Epub 2024 Jun 10.
Recognizing the limitations of prostate-specific antigen (PSA) screening and the morbidity of prostate biopsies, several blood- and urine-based biomarkers have been proposed for pre-biopsy risk stratification. These assays aim to reduce the frequency of unnecessary biopsies (i.e., negative or Grade Group 1 [GG1]) while maintaining highly sensitive detection of clinically significant cancer (GG ≥ 2) prostate cancer.
We reviewed the literature describing the use of currently available blood- and urine-based biomarkers for detection of GG ≥ 2 cancer, including the Prostate Health Index (PHI), 4Kscore, MyProstateScore (MPS), SelectMDx, ExoDx Prostate Intelliscore (EPI), and IsoPSA. To facilitate clinical application, we focused on the use of biomarkers as a post-PSA secondary test prior to biopsy, as proposed in clinical guidelines. Our outcomes included test performance measures-sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV)-as well as clinical outcomes resulting from biomarker use (i.e., unnecessary biopsies avoided, GG ≥ 2 cancers missed).
Contemporary validation data (2015-2023) reveal that currently available biomarkers provide ~15-50% specificity at a sensitivity of 90-95% for GG ≥ 2 PCa. Clinically, this indicates that secondary use of biomarker testing in men with elevated PSA could allow for avoidance of up to 15-50% of unnecessary prostate biopsies, while preserving detection of 90-95% of GG ≥ 2 cancers that would be detected under the traditional "biopsy all" approach.
The contemporary literature further supports the proposed role of post-PSA biomarker testing to reduce the use of invasive biopsy while maintaining highly sensitive detection of GG ≥ 2 cancer. Questions remain regarding the optimal application of biomarkers in combination or in sequence with mpMRI.
认识到前列腺特异性抗原（PSA）筛查的局限性以及前列腺活检的发病率，已经提出了几种基于血液和尿液的生物标志物用于活检前风险分层。这些检测旨在减少不必要活检（即阴性或1级[GG1]）的频率，同时保持对临床显著癌症（GG≥2）前列腺癌的高灵敏度检测。
我们回顾了描述使用当前可用的基于血液和尿液的生物标志物检测GG≥2癌症的文献，包括前列腺健康指数（PHI）、4Kscore、MyProstateScore（MPS）、SelectMDx、ExoDx Prostate Intelliscore（EPI）和IsoPSA。为便于临床应用，我们重点关注生物标志物作为活检前PSA后的二次检测的使用，如临床指南中所提议的。我们的结果包括检测性能指标——灵敏度、特异性、阴性预测值（NPV）和阳性预测值（PPV）——以及使用生物标志物产生的临床结果（即避免不必要的活检、漏诊GG≥2癌症）。
当代验证数据（2015 - 2023年）显示，目前可用的生物标志物在对GG≥2前列腺癌的灵敏度为90 - 95%时，提供约15 - 50%的特异性。在临床上，这表明在PSA升高的男性中二次使用生物标志物检测可避免高达15 - 50%的不必要前列腺活检，同时保留对90 - 95%在传统“全部活检”方法下会被检测到的GG≥2癌症的检测。
当代文献进一步支持了PSA后生物标志物检测在减少侵入性活检使用同时保持对GG≥2癌症高灵敏度检测方面的提议作用。关于生物标志物与多参数磁共振成像（mpMRI）联合或序贯的最佳应用仍存在问题。
