Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Department of Urology, Erasmus University Medical Centre, Rotterdam, the Netherlands.
J Med Screen. 2021 Dec;28(4):480-487. doi: 10.1177/0969141321989738. Epub 2021 Feb 9.
Trials of cancer screening present results in terms of deaths prevented, but metastasis is also a key endpoint that screening seeks to prevent. We developed a framework for projecting overall (de novo and progressive) metastases prevented in a screening trial using prostate cancer screening as a case study.
Mechanistic simulation model in which screening shifts a fraction of cases that would be metastatic at diagnosis to being non-metastatic. This shift increases the incidence of non-overdiagnosed, organ-confined cases. We use estimates of the risk of metastatic progression for these cases to project how many progress to metastasis after diagnosis and tally the projected de novo and progressive metastatic cases with and without screening. We use data on stage shift from the European Randomized Study of Screening for Prostate Cancer (ERSPC) and data on the risk of metastatic progression from the Scandinavian Prostate Cancer Group-4 trial. We estimate the relative risk and absolute risk reductions in metastatic disease at diagnosis and compare these with reductions in overall metastases.
Assuming no effect of screening beyond initial stage shift at diagnosis, the model projects a 43% reduction in metastasis at diagnosis but a 22% reduction in the cumulative probability of metastasis over 12 years in favor of screening. These results are consistent with the empirical findings from the ERSPC.
Any reduction in metastatic disease at diagnosis under screening is likely to be an overly optimistic predictor of the impact of screening on overall metastasis and disease-specific mortality.
癌症筛查试验以预防的死亡人数来呈现结果，但转移也是筛查试图预防的关键终点。我们开发了一个框架，以通过前列腺癌筛查作为案例研究，来预测筛查试验中预防的总体（新发和进展性）转移。
机制模拟模型，其中筛查将一部分在诊断时就会转移的病例转移到非转移性病例中。这种转移增加了非过度诊断、器官局限病例的发病率。我们使用这些病例的转移进展风险估计值来预测有多少病例在诊断后会进展为转移，并在有和没有筛查的情况下计算预测的新发和进展性转移病例。我们使用欧洲前列腺癌筛查随机研究（ERSPC）中的分期转移数据和斯堪的纳维亚前列腺癌组-4 试验中的转移进展风险数据。我们估计了诊断时转移性疾病的相对风险和绝对风险降低，并将其与总体转移的降低进行了比较。
假设除了初始诊断时的分期转移之外，筛查没有其他影响，该模型预测诊断时转移的风险降低了 43%，但在 12 年内转移的累积概率降低了 22%，支持筛查。这些结果与 ERSPC 的经验发现一致。
筛查下诊断时转移性疾病的任何减少都可能是对筛查对总体转移和疾病特异性死亡率影响的过于乐观的预测。
