Memorial Sloan Kettering Cancer Center, New York, New York.
Massachusetts General Hospital, Boston, Massachusetts.
Cancer Epidemiol Biomarkers Prev. 2022 Jun 1;31(6):1139-1145. doi: 10.1158/1055-9965.EPI-21-1443.
More than 75% of cancer-related deaths occur from cancers for which we do not screen. New screening liquid biopsies may help fill these clinical gaps, although evidence of benefit still needs to be assessed. Which lessons can we learn from previous efforts to guide those of the future? Screening trials for ovarian, prostate, pancreatic, and esophageal cancers are revisited to assess the evidence, which has been limited by small effect sizes, short duration of early-stage disease relative to screening frequency, study design, and confounding factors. Randomized controlled trials (RCT) to show mortality reduction have required millions of screening-years, two-decade durations, and been susceptible to external confounding. Future RCTs with late-stage incidence as a surrogate endpoint could substantially reduce these challenges, and clinical studies demonstrating safety and effectiveness of screening in high-risk populations may enable extrapolation to broader average-risk populations. Multicancer early detection tests provide an opportunity to advance these practical study designs. Conditional approvals based on RCTs with surrogate endpoints, contingent upon real world evidence generation and continuation of trials to definitive endpoints, may lower practical barriers to innovation in cancer screening and enable greater progress.
超过 75%的癌症相关死亡发生在我们未进行筛查的癌症中。新的筛查液体活检可能有助于填补这些临床空白，但仍需要评估其获益证据。我们可以从之前的努力中吸取哪些经验教训来指导未来的工作？本文重新回顾了卵巢癌、前列腺癌、胰腺癌和食管癌的筛查试验，以评估证据，这些证据受到小效应量、早期疾病与筛查频率的相对持续时间短、研究设计和混杂因素的限制。为了证明死亡率降低，需要进行随机对照试验（RCT），这需要数百万的筛查年、二十年的持续时间，并且容易受到外部混杂因素的影响。未来以晚期发病率作为替代终点的 RCT 可能会大大降低这些挑战，而在高危人群中进行的临床研究表明筛查的安全性和有效性可能会推广到更广泛的一般风险人群。多癌种早期检测试验为推进这些实用研究设计提供了机会。基于具有替代终点的 RCT 的有条件批准，取决于真实世界证据的产生和继续进行到明确终点的试验，可能会降低癌症筛查创新的实际障碍，并促进更大的进展。
