Dept. of Urology, Erasmus Medical Centre, Rotterdam, The Netherlands.
Eur J Cancer. 2010 Nov;46(17):3109-19. doi: 10.1016/j.ejca.2010.09.031.
Prostate-specific antigen (PSA) has been the main drive for early detection of prostate cancer (PCa), including in population-based screening as in the European Randomised Study for Screening of Prostate Cancer (ERSPC). The specificity of PSA to indicate men with biopsy detectable prostate cancer can be improved by adding information obtained by new biomarkers, such as PSA isoforms. This improvement is needed to increase the efficacy of the screening procedure for the population-based as well as the individual screening. Various PSA isoforms, kallikreins and molecular markers have been validated in various cohorts from ERSPC of men with and without PCa in order to design the optimal diagnostic procedure for screening asymptomatic men. So far, most promising results have been obtained from the analysis of free PSA, proPSA, nicked PSA and hK2. The use of free PSA in addition to total PSA reduces the number of negative sextant biopsies at a PSA cut-off level of 3 ng/ml at initial screening with 30%, at the cost of losing 10% of detectable cancers that are predominantly well differentiated on histology. Further addition of PSA isoforms and hK2 only improve ROC curves in selected samples by a maximum of 5%. Molecular markers like PCA3 and TMPRSS2 in urine do not appear to be useful but they have been assessed insufficiently so far. The level of PSA at initial screening is highly predictive for the chance of being diagnosed with PCa later on in life. The changes in PSA over time after initial screening (like PSA-velocity and PSA-doubling time) are statistically different between men with detectable cancers versus those without (PSA-doubling time 5.1 versus 6.1 years), but this does not contribute significantly to population-based screening overall. Changes in specificity need to be related to a cost efficacy evaluation in the final analysis of ERSPC.
前列腺特异性抗原（PSA）一直是前列腺癌（PCa）早期检测的主要手段，包括在基于人群的筛查中，如欧洲前列腺癌筛查随机研究（ERSPC）。通过添加新的生物标志物（如 PSA 同工型）获得的信息，可以提高 PSA 检测活检可检测前列腺癌的特异性。这种改进对于提高基于人群和个体筛查的筛查程序的效果是必要的。已经在 ERSPC 的各种队列中验证了各种 PSA 同工型、激肽释放酶和分子标志物，以便为无症状男性设计最佳的筛查诊断程序。到目前为止，从分析游离 PSA、前列腺特异抗原、nicked PSA 和 hK2 中获得了最有前途的结果。在初始筛查时，在 PSA 截断值为 3ng/ml 时，与总 PSA 相比，使用游离 PSA 可将阴性六分区活检的数量减少 30%，但代价是失去 10%的组织学上主要为低分化的可检测癌症。进一步增加 PSA 同工型和 hK2 只能在特定样本中通过最大 5%的方式提高 ROC 曲线。尿液中的分子标志物如 PCA3 和 TMPRSS2 似乎没有用，但到目前为止还没有充分评估。初始筛查时 PSA 水平高度预测以后一生中患前列腺癌的机会。与无癌症可检测的男性相比，初始筛查后 PSA 随时间的变化（如 PSA 速度和 PSA 倍增时间）在统计学上存在差异（PSA 倍增时间为 5.1 年与 6.1 年），但这并没有对总体人群筛查产生重大贡献。特异性的变化需要与成本效益评估相关，最终在 ERSPC 的分析中进行评估。
