Program in Biostatistics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Cancer Epidemiol Biomarkers Prev. 2022 Jul 1;31(7):1298-1304. doi: 10.1158/1055-9965.EPI-22-0024.
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; furthermore, the same stage shift can mean different things for different cancers.
疾病特异性死亡率是癌症筛查试验的共识终点。基于液体活检的新型筛查检测方法，包括多癌种早期检测（MCED）检测，正在推动减少通常冗长的筛查试验过程。基于晚期疾病减少的终点（分期转移）已经被提出，但尚不清楚它们在多大程度上可以预测通过 MCED 检测潜在可检测的各种癌症的筛查对疾病特异性死亡率的影响。
我们开发了一个数学公式，将晚期癌症的减少与通过筛查早期诊断的病例的预期死亡率减少相关联，如果这些病例的死亡率相应转移。我们研究了发表的乳腺癌、肺癌、卵巢癌和前列腺癌筛查试验中观察到的死亡率减少与预期死亡率减少之间的相似性。
给定分期转移的预期死亡率减少因癌症和分期特异性生存分布而有很大差异，某些癌症类型即使在大量分期转移的情况下，死亡率改善的可能性也很小。预期死亡率减少与发表的试验的死亡率结果不一致。
在 MCED 中，任何死亡率获益都可能因目标癌症而异。分期转移似乎不是基于 MCED 检测潜在可检测的癌症的死亡率减少推断的可靠依据。
分期转移可能是评估癌症筛查试验的一个有吸引力的终点，但它似乎是死亡率获益的不可靠预测指标；此外，相同的分期转移对不同的癌症可能意味着不同的事情。
