We investigated whether adding 4Kscore as a reflex test to prostate-specific antigen (PSA) could improve the screening algorithm for prostate cancer (PC). In the GÖTEBORG-2 PC screening trial, 38 000men (50–60 yr) were invited to PSA testing and, if elevated, followed by magnetic resonance imaging (MRI). For 571 men with PSA ≥3.0 ng/ml and evaluable outcomes, 4Kscore was calculated. The performance using a prespecified 4Kscore cutoff of 7.5% was evaluated. The area under the curve for 4Kscore to identify intermediate- and high-risk PC was 0.84 (95% confidence interval 0.79–0.89), and the positive predictive value, and negative predictive value were 15% (0.12–0.20) and 99% (97–100%), respectively. Of the 54 men diagnosed with intermediate- or high-grade PC, two had a 4Kscore cutoff below 7.5%, both with organ-confined intermediate-risk PC. Per 1000 men with elevated PSA, adding 4Kscore would have resulted in avoidance of MRI for 408 (41%) men, biopsies for 95 (28% reduction) men, and diagnosis of 23 low-grade cancers (23% reduction) while delaying the diagnosis of four men with intermediate-grade cancers (4%). Including 4Kscore as a reflex test for men with elevated PSA reduces the need for MRI and biopsy markedly, and results in less overdiagnosis of low-grade PC at the cost of delaying the diagnosis of intermediate-grade PC in a few men. These results add further evidence for including new blood-based biomarkers in addition to PSA to improve the harm and benefit ratio of PC screening and reduce the need for resource-demanding MRI and biopsies.

中文翻译：

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4Kscore 在哥德堡 2 前列腺癌筛查试验中作为前列腺特异性抗原反射测试的性能


我们研究了将 4Kscore 作为反射测试添加到前列腺特异性抗原 （PSA） 是否可以改善前列腺癌 （PC） 的筛查算法。在哥德堡 2 号 PC 筛查试验中，邀请了 38 000 名男性（50-60 岁）进行 PSA 检测，如果升高，则进行磁共振成像 （MRI）。对于 571 名 PSA ≥3.0 ng/ml 且结局可评估的男性，计算 4Kscore。使用预先设定的 7.5% 的 4Kscore 临界值评估了性能。4Kscore 识别中高危 PC 的曲线下面积为 0.84 （95% 置信区间 0.79-0.89），阳性预测值和阴性预测值分别为 15% （0.12-0.20） 和 99% （97-100%）。在 54 名被诊断患有中度或高度 PC 的男性中，两名的 4Kscore 临界值低于 7.5%，两人都患有器官局限的中等风险 PC。每 1000 名 PSA 升高的男性中，增加 4Kscore 将导致 408 名 （41%） 男性避免 MRI，95 名 （减少 28%） 男性避免活检，诊断出 23 种低级别癌症 （减少 23%），同时延迟诊断 4 名患有中级别癌症的男性 （4%）。将 4Kscore 作为 PSA 升高男性的反射测试显着减少了对 MRI 和活检的需求，并减少了对低级别 PC 的过度诊断，但代价是延迟了少数男性中级 PC 的诊断。这些结果为在 PSA 之外包括新的基于血液的生物标志物提供了进一步的证据，以提高 PC 筛查的危害和收益比，并减少对资源需求 MRI 和活检的需求。