Stage Shift as an Endpoint in Cancer Screening Trials: Implications for Evaluating Multicancer Early Detection Tests.
Stage Shift as an Endpoint in Cancer Screening Trials: Implications for Evaluating Multicancer Early Detection Tests.
复制标题
作为癌症筛查试验终点的分期变化：对评估多癌早期检测试验的意义。
DOI：
10.1158/1055-9965.epi-22-0024
复制
发表时间：
2022-07-01
影响因子：
3.8
通讯作者：
Etzioni, Ruth
中科院分区：
文献类型：
--
作者：
Owens, Lukas;Gulati, Roman;Etzioni, Ruth
疾病特异性死亡率是癌症筛查试验的共识终点。新的基于液体活检的筛查测试，包括多癌症早期检测（MCED）测试，正在创造一种需要，以减少通常冗长的筛查试验过程。已经提出了基于晚期疾病减少（阶段转移）的终点，但目前尚不清楚它们如何预测筛查对MCED检测可能检测到的各种癌症的疾病特异性死亡率的影响。我们开发了一种数学公式，将晚期癌症的减少与通过筛查早期诊断的病例的死亡率发生相应变化时特定疾病死亡率的预期减少联系起来。我们研究了预期死亡率降低与已发表的乳腺癌、肺癌、卵巢癌和前列腺癌筛查试验中观察到的死亡率降低之间的相似性。对于给定的阶段转移，预期的死亡率降低显著地取决于癌症和阶段特异性生存分布，某些癌症类型即使在实质性阶段转移下也几乎不可能显示死亡率改善。预期的死亡率降低未能与已发表试验的死亡率结局一致。在MCED中，任何死亡率益处都可能在靶癌症之间有很大差异。阶段转移似乎不是推断MCED测试可能检测到的癌症死亡率降低的可靠基础。阶段转变可能是评估癌症筛查测试的一个有吸引力的终点，但它似乎是死亡率获益的一个不可靠的预测因素;此外，相同的阶段转变对不同的癌症可能意味着不同的事情。
Disease-specific mortality is a consensus endpoint in cancer screening trials. New liquid biopsy-based screening tests, including multi-cancer early detection (MCED) tests, are creating a need to reduce the typically lengthy screening trial process. Endpoints based on the reduction in late-stage disease (stage shift) have been proposed but it is unclear how well they predict the impact of screening on disease-specific mortality across a variety of cancers potentially detectable by MCED tests. We develop a mathematical formulation relating the reduction in late-stage cancer to the expected reduction in disease-specific mortality if cases diagnosed early via screening receive a corresponding shift in mortality. We investigate the similarity between the expected mortality reduction and the observed mortality reduction in published trials of screening for breast, lung, ovarian, and prostate cancer. The expected mortality reduction for a given stage shift varies significantly depending on cancer- and stage-specific survival distributions, with some cancer types showing little possibility for mortality improvement even under substantial stage shift. The expected mortality reduction fails to consistently match the mortality outcomes of published trials. In MCED, any mortality benefit is likely to vary substantially across target cancers. Stage shift does not appear to be a reliable basis for inference about mortality reduction across cancers potentially detectable by MCED tests. Stage shift may be an appealing endpoint for evaluation of cancer screening tests but it appears to be an unreliable predictor of mortality benefit; further, the same stage shift can mean different things for different cancers.