Hu Ping, Prorok Philip C, Katki Hormuzd A
Division of Cancer Prevention, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
J Natl Cancer Inst. 2025 Feb 1;117(2):303-311. doi: 10.1093/jnci/djae247.
Determining whether screening with multicancer detection (MCD) tests saves lives requires randomized controlled trials (RCTs). To inform RCT design, we estimated cancer-mortality outcomes from hypothetical MCD RCTs.
We used the Hu-Zelen model, previously used to plan the National Lung Screening Trial (NLST), to estimate mortality reductions, sample size, and power for 9 cancers for different RCT design parameters and MCD test parameters.
Our base-case RCT with 5 yearly screens and 100 000 people ages 60-74 in each arm, who also undergo standard-of-care screens, has 87%-89% power to detect a 9%-10% mortality reduction (Number Needed to Screen [NNS] = 578-724) over 7-9 years. The majority of prevented deaths were from lung cancers (base-case [64%-66%] and all sensitivity analyses), 8%-10% from colorectal cancer, and 26% from the other 7 cancers, mostly from stomach or ovary or esophagus (due to excellent stage 1 survival) and less from liver or pancreas (poor stage 1 survival) or head and neck or lymphoma (excellent stage 4 survival). There was limited power for mortality reductions at most individual cancer sites. Base-case findings were sensitive to test sensitivity, stage shifts, and mean sojourn times in the preclinical state (especially for lung cancer), but 90% power could be recovered by recruiting a substantially higher risk population.
Large-scale MCD RCTs would have 89% power to detect an approximate 10% cancer mortality reduction over a relatively short 7-9 year timeframe from trial entry. The estimated NNS for MCD RCTs compares favorably with mammographic screening. Most prevented cancer deaths in a well-powered MCD RCT would likely be from lung cancer. Non-lung and non-colorectal cancer sites could be a meaningful proportion of prevented cancer deaths, but power is insufficient to isolate non-lung-cancer mortality reductions.
确定多癌检测（MCD）筛查是否能挽救生命需要进行随机对照试验（RCT）。为指导RCT设计，我们估计了假设的MCD RCT的癌症死亡率结果。
我们使用先前用于规划国家肺癌筛查试验（NLST）的Hu-Zelen模型，针对不同的RCT设计参数和MCD检测参数，估计9种癌症的死亡率降低情况、样本量和检验效能。
我们的基础病例RCT，每组有5次年度筛查，各有100000名60 - 74岁的参与者，他们也接受标准护理筛查，在7 - 9年内有87% - 89%的检验效能检测到死亡率降低9% - 10%（筛查需治人数[NNS]=578 - 724）。大多数预防的死亡来自肺癌（基础病例[64% - 66%]以及所有敏感性分析），8% - 10%来自结直肠癌，26%来自其他7种癌症，主要是胃癌、卵巢癌或食管癌（由于1期生存率高），而肝癌、胰腺癌（1期生存率低）或头颈癌、淋巴瘤（4期生存率高）导致的死亡较少。大多数个体癌症部位降低死亡率的检验效能有限。基础病例结果对检测敏感性、分期变化以及临床前状态的平均停留时间敏感（尤其是肺癌），但通过招募风险显著更高的人群可恢复90%的检验效能。
大规模MCD RCT在从试验入组起相对较短的7 - 9年时间范围内，有89%的检验效能检测到癌症死亡率降低约10%。MCD RCT的估计NNS与乳腺钼靶筛查相比具有优势。在检验效能充足的MCD RCT中，大多数预防的癌症死亡可能来自肺癌。非肺癌和非结直肠癌部位可能在预防的癌症死亡中占相当比例，但检验效能不足以单独分离出非肺癌死亡率的降低情况。
