Institute of Health Informatics, 4919University College London, London, UK.
Population Health Research Institute, 4915St George's University of London, London, UK.
J Med Screen. 2022 Jun;29(2):123-133. doi: 10.1177/09691413221076415. Epub 2022 Mar 7.
To determine prostate cancer screening performance using prostate specific antigen (PSA) along with other markers, expressing markers in age-specific multiples of the median (MoM), and age.
A prospective nested case-control study used stored serum from 571 men who died of, or with history of, prostate cancer (cases), and 2169 matched controls. Total, free and intact PSA, human kallikrein-related peptidase 2 (hK2), and microseminoprotein were measured and converted into MoM values. Screening marker distribution parameters were estimated in cases and controls. Monte Carlo simulation used these in a risk-based algorithm to estimate screening performance (detection rates [DRs] and false-positive rates [FPRs]).
Almost all (99%) cases occurred aged ≥55. Marker values were similar in cases who did and did not die of prostate cancer. Combining age, total PSA and hK2 MoM values (other markers added little or no discrimination) yielded a 1.2% FPR (95% CI 0.2-4.8%) for a 90% DR (59-98%) in men who died of or with a prostate cancer diagnosis within 5 years of blood collection (risk cut-off 1 in 20), two-thirds less than the 4.5% FPR using total PSA alone measured in ng/ml for the same 90% DR (cut-off 3.1 ng/ml). Screening performance over 10 years yielded a 33% (22-46%) FPR for a 90% DR.
Screening performed up to every 5 years from age 55 using the multi-marker risk-based screening algorithm for future prostate cancer achieves a high DR and a much lower FPR than using PSA alone, resulting in reductions in overdiagnosis and overtreatment.
通过前列腺特异性抗原（PSA）以及其他标志物来确定前列腺癌筛查的性能，以年龄特异性中位数倍数（MoM）和年龄表示标志物，并评估其性能。
采用前瞻性巢式病例对照研究，使用 571 名死于前列腺癌或有前列腺癌病史的男性（病例）以及 2169 名匹配对照者的储存血清。测量总前列腺特异性抗原、游离前列腺特异性抗原、人激肽释放酶相关肽 2（hK2）和微精囊蛋白，并将其转换为 MoM 值。在病例和对照者中估计筛查标记物分布参数。蒙特卡罗模拟使用这些参数在基于风险的算法中估计筛查性能（检出率[DR]和假阳性率[FPR]）。
几乎所有（99%）病例发生于年龄≥55 岁的男性。发生和未发生前列腺癌死亡的病例之间的标志物值相似。结合年龄、总前列腺特异性抗原和 hK2 MoM 值（其他标志物增加的差异不大或无差异），在采集血液后 5 年内死于或诊断为前列腺癌的男性中，得出 1.2%的 FPR（95%CI 0.2-4.8%）和 90%的 DR（59-98%）（风险截止值为 1/20），比使用 ng/ml 单位测量的总前列腺特异性抗原进行同样的 90%DR（截止值为 3.1ng/ml）的 FPR 低 2/3。10 年内的筛查性能得出 33%（22-46%）的 FPR 和 90%的 DR。
从 55 岁起每 5 年使用多标记物基于风险的筛查算法筛查前列腺癌，可获得较高的 DR 和较低的 FPR，与单独使用 PSA 相比，可降低过度诊断和过度治疗的风险。
