NEW YORK – Researchers from the Stanford University School of Medicine have used decision analytic modeling to determine the potential long-term clinical and economic impacts of novel blood- and stool-based colorectal cancer screening tests, such as those from Guardant Health and Exact Sciences.

纽约——斯坦福大学医学院的研究人员使用决策分析模型来确定新型基于血液和粪便的结直肠癌筛查测试（例如来自Guardant Health and Exact Sciences的测试）的潜在长期临床和经济影响。

In a study published in Annals of Internal Medicine on Monday, the researchers described their findings, which compared blood-based and stool-based screening tests to fecal immunochemical tests and colonoscopies. The researchers used their Model of Screening and Surveillance for Colorectal Cancer (MOSAIC), which the team has previously utilized for other studies looking at different aspects of colorectal cancer screening, such as the potential impact of lowering the initial screening age from 50 to 45 years old, said Uri Ladabaum, director of the Gastrointestinal Cancer Prevention Program at Stanford and one of the paper's authors..

在周一发表在《内科年鉴》上的一项研究中，研究人员描述了他们的发现，该研究将基于血液和粪便的筛查测试与粪便免疫化学测试和结肠镜检查进行了比较。斯坦福大学胃肠道癌症预防项目主任、论文作者之一乌里·拉达鲍姆（UriLadabaum）说，研究人员使用了他们的结直肠癌筛查和监测模型（MOSAIC），该团队之前曾将该模型用于其他研究结直肠癌筛查的不同方面，例如将初始筛查年龄从50岁降低到45岁的潜在影响。。

The team decided to perform the newest study after the 'very exciting scientific development of blood tests that can detect colorectal cancer with various degrees of sensitivity,' he said. However, many of these tests do not perform as well when detecting advanced precancerous polyps, so the researchers wanted to see how the performance characteristics would potentially stack up in the long term.

他说，在“能够以不同程度的敏感性检测结直肠癌的血液检测技术取得了非常令人兴奋的科学发展”之后，该团队决定进行这项最新研究。然而，这些测试中的许多在检测晚期癌前息肉时表现不佳，因此研究人员想看看这些性能特征在长期内可能会如何累积。

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Without modeling, it is 'difficult to know how to interpret [test performance characteristics] when you're talking about colorectal cancer screening being a long-term programmatic endeavor where people are supposed to come in every few years over decades, and when there's a certain cost of testing that could potentially be traded off against potential savings, if you prevent cancers or find cancers early,' he said..

他说，如果没有建模，当你谈论结直肠癌筛查是一项长期的计划性工作时，人们应该在几十年内每隔几年就来进行一次筛查，并且如果你预防癌症或尽早发现癌症，有一定的测试成本可能会与潜在的节省进行权衡，那么很难理解如何解释[测试性能特征]。。

According to Ladabaum, novel screening tests 'have some potential upsides and some potential downsides.' The question is, 'How does the whole story play out over the long term, in terms of the population-level impact, the population-level downsides, and the economic balance sheet compared to the current established alternatives of stool-based testing and colonoscopy?' .

拉达鲍姆说，新的筛查测试“有一些潜在的优点和一些潜在的缺点”问题是，“与目前建立的粪便检测和结肠镜检查替代方案相比，从人口水平的影响，人口水平的下降以及经济资产负债表来看，整个故事从长远来看是如何发展的？”。

He and his colleagues looked at novel tests that have high-quality data in the public domain, including Exact Sciences' stool-based Cologuard test and its next-generation Cologuard Plus test, Geneoscopy's stool-based ColoSense test, Guardant's blood-based Shield assay, and Freenome's blood-based test that is under development, and modeled the relative rate of colorectal cancer and deaths among 100,000 average-risk people who used each screening method.

他和他的同事研究了在公共领域拥有高质量数据的新型测试，包括Exact Sciences基于粪便的Cologuard测试及其下一代Cologuard Plus测试，Geneoscopy基于粪便的ColoSense测试，Guardant基于血液的Shield测试，以及Freenome正在开发的基于血液的测试，并模拟了使用每种筛查方法的100000名平均风险人群中结直肠癌和死亡率的相对比率。

Guardant's Shield test received approval from the US Food and Drug Administration in July, while Cologuard Plus received FDA approval earlier this month, and ColoSense nabbed FDA approval in May..

Guardant的Shield测试于7月获得美国食品和药物管理局的批准，而Cologuard Plus于本月早些时候获得了FDA的批准，ColoSense于5月获得了FDA的批准。。

In addition to the blood-based testing data, the researchers validated the model with data for cancer and cancer death in people who undergo colonoscopies and calibrated it with contemporary data for precancerous polyps found during colonoscopies. They wanted to do a 'rigorous synthesis of all the information that's out there in an organized way, in a validated model, to try to make long-term projections that can inform the application of these new tests,' Ladabaum said..

除了基于血液的测试数据外，研究人员还用结肠镜检查患者的癌症和癌症死亡数据验证了该模型，并用结肠镜检查中发现的癌前息肉的当代数据对其进行了校准。拉达鲍姆说，他们想“在一个经过验证的模型中，以有组织的方式对所有信息进行严格的综合，试图做出长期预测，为这些新测试的应用提供信息。”。。

Among 100,000 people who receive a colonoscopy every 10 years, 1,543 would develop colorectal cancer and 672 would die from the disease, the researchers found. For patients who undergo stool-based testing every one to three years depending on the test, the incidence of colorectal cancer was between 2,181 when using FIT every year and 2,498 cases when using Cologuard Plus every three years.

研究人员发现，在每10年接受结肠镜检查的10万人中，有1543人会患结直肠癌，672人会死于这种疾病。对于每一到三年进行一次粪便检测的患者，根据检测结果，结直肠癌的发病率在每年使用FIT时为2181例，每三年使用Cologuard Plus时为2498例。

The number of deaths with FIT was 904, while the number of deaths with Cologuard Plus was 1,025. .

FIT导致的死亡人数为904人，而Cologuard Plus导致的死亡人数为1025人。

For the new blood-based tests, which are recommended for use every three years, the number of colorectal cancer cases was 4,310 for the Freenome test and 4,365 for Guardant Shield, and the number of deaths was 1,679 for Freenome's assay and 1,604 for Guardant Shield.

对于建议每三年使用一次的新的基于血液的检测，Freenome检测的结直肠癌病例数为4310例，Guardant Shield为4365例，Freenome检测的死亡人数为1679例，Guardant Shield为1604例。

Among those who receive no screening, 7,470 would develop colorectal cancer and 3,624 would die from it.

在那些没有接受筛查的人中，7470人会患结直肠癌，3624人会死于结直肠癌。

According to the model's predictions, 'the blood tests aren't really stacking up yet compared to alternatives,' but one potential advantage could be increased participation in patients who are not willing to do a stool test or colonoscopy, Ladabaum said.

拉达鲍姆说，根据该模型的预测，“与替代品相比，血液检查还没有真正积累起来”，但一个潜在的优势可能是增加不愿意做大便检查或结肠镜检查的患者的参与。

The researchers found that if three people replaced colonoscopy or stool-based testing with a blood-based test, two people who wouldn’t have been screened with other methods would also have to use a blood-based test for the current number of colorectal cancer deaths to remain even. This assumes the patients who use blood-based tests undergo a follow-up colonoscopy if their results indicate need for follow-up..

研究人员发现，如果三个人用血液检测代替结肠镜检查或粪便检测，那么两个不会用其他方法筛查的人也必须使用血液检测来保持目前结直肠癌死亡人数的平衡。这假设使用血液检测的患者如果结果表明需要随访，则需要进行随访结肠镜检查。。

The research team also determined that as the colonoscopy follow-up rate after an abnormal blood-based test result decreased, the effectiveness of screening 'eroded substantially,' according to the study. Failure to follow up with colonoscopy also eroded cost-effectiveness.

研究小组还确定，根据该研究，随着血液检测结果异常后结肠镜检查的随访率下降，筛查的有效性“大大降低”。未能进行结肠镜检查也降低了成本效益。

When 5 percent of the population shifted from no screening to Guardant Shield, the additional number of deaths prevented was 70 per 100,000 people. When 25 percent shifted, the additional number of deaths prevented was 348 per 100,000 people.

当5%的人口从不筛查转移到Guardant Shield时，预防的额外死亡人数为每10万人中有70人。当25%的人转移时，预防的额外死亡人数为每10万人348人。

A spokesperson for Guardant noted via email that colonoscopy is still the gold standard, but many patients remain unscreened. The company has collaborated with the FDA and developed physician brochures and patient fact sheets to 'clearly outline' the benefits and limitations of Shield for CRC screening.

。该公司与FDA合作，开发了医生手册和患者情况说明书，以“清楚地概述”Shield对CRC筛查的益处和局限性。

'As a result, through shared decision-making, clinicians and patients can determine the best screening option that is likely to be completed,' the spokesperson added..

这位发言人补充说：“因此，通过共同决策，临床医生和患者可以确定可能完成的最佳筛查选择。”。。

'The best test is the one that gets done,' the spokesperson added. Data from Guardant has shown that in the two years since Shield has been available as a laboratory-developed test, the adherence rate has been greater than 90 percent with the test, considerably higher than the 28 percent to 71 percent with other current methods..

这位发言人补充说：“最好的测试是完成的测试。”。。。

In a study published earlier this year, researchers at Kaiser Permanente Northwest showed a three times increase in the odds of completing colorectal cancer screening when Shield was integrated as a screening option alongside stool-based tests and colonoscopy, the spokesperson noted.

这位发言人指出，在今年早些时候发表的一项研究中，凯撒永久西北大学的研究人员表明，将Shield作为筛查选择与粪便检测和结肠镜检查相结合，完成结直肠癌筛查的几率增加了三倍。

Ladabaum noted that if the next generation of blood-based screening tests have better performance characteristics, 'the calculus changes.'

拉达鲍姆指出，如果下一代基于血液的筛查测试具有更好的性能特征，“微积分就会改变。”

'For the future, if it's possible scientifically to have noninvasive tests that get better at stage I cancer, they get substantially better at advanced polyps,' he said, 'and where the cost is much more competitive, that could really be a change in the paradigm.'

他说：“未来，如果科学上有可能在I期癌症中进行更好的无创检测，那么在晚期息肉中的检测效果会更好，而且在成本更具竞争力的地方，这可能真的是范式的改变。”

Paul Limburg, Exact Sciences' chief medical officer for screening, said via email that both Cologuard and Cologuard Plus have high sensitivity for detecting stage I colorectal cancer, and both detect stages I, II, and III colorectal cancer at 94 percent sensitivity. Cologuard Plus also detects high-grade dysplasia in advanced pre-cancers at 74 percent.

精准科学公司负责筛查的首席医疗官保罗·林伯格（PaulLimburg）通过电子邮件表示，Cologuard和Cologuard Plus对检测I期结直肠癌具有很高的敏感性，对检测I、II和III期结直肠癌的敏感性均为94%。Cologuard Plus还检测到晚期癌症前期的高度不典型增生，占74%。

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Modeling data presented this week at the American College of Gastroenterology annual meeting show that Cologuard Plus 'delivers the highest life-years gained with fewest number of colonoscopies among noninvasive colorectal cancer screening strategies,' he added.

他补充道，本周在美国胃肠病学会年会上提供的建模数据显示，Cologuard Plus“在无创性结直肠癌筛查策略中，结肠镜检查次数最少，获得的寿命最高。”。

Limburg also noted that 'to increase screening participation, patients and providers need to have full understanding and clear conversations about the benefits and limitations of the available test options.'

Limburg还指出，“为了增加筛查参与率，患者和提供者需要充分了解和明确讨论可用测试选项的益处和局限性。”

'Healthcare providers should counsel people about the limitations of current blood tests with respect to early detection of cancers and pre-cancers to achieve the full benefits of colorectal cancer screening,' he added.

他补充说：“医疗保健提供者应该就目前血液检测在早期发现癌症和癌症前期方面的局限性向人们提供咨询，以实现结直肠癌筛查的全部益处。”。

Cologuard 'far outperforms blood-based screening in pre-cancer and early-stage cancer sensitivity.' In addition, it can be completed at home with no special diet or preparation, Limburg said.

Cologuard“在癌症前期和早期癌症敏感性方面远远优于基于血液的筛查。”此外，它可以在家里完成，不需要特殊的饮食或准备，林伯格说。

Exact Sciences is also developing a blood-based screening test, for which it presented data at the European Society for Medical Oncology Congress in September. Limburg noted that Exact's test is intended as 'an additional option to get more people screened, particularly those who are unable or unwilling to complete any of the other tests that are currently recommended in national screening guidelines, which include colonoscopy, Cologuard, or other stool tests.'.

Exact Sciences还开发了一种基于血液的筛查测试，并于9月在欧洲肿瘤内科学会大会上提交了该测试的数据。Limburg指出，Exact的测试旨在“作为一种额外的选择，让更多的人接受筛查，特别是那些无法或不愿意完成国家筛查指南中目前推荐的任何其他测试的人，包括结肠镜检查，结肠保护或其他粪便测试。”。

'Currently, FDA-approved blood-based tests are limited in sensitivity for both early-stage cancers and advanced pre-cancers, limiting the opportunities for maximally effective cancer treatment and prevention interventions,' he noted.

他指出：“目前，FDA批准的血液检测对早期癌症和晚期癌症前期的敏感性有限，限制了最大限度有效的癌症治疗和预防干预的机会。”。

The Stanford researchers also found that colonoscopies and stool-based tests are more cost-effective than blood-based tests. According to the study, in people who will absolutely not take up screening colonoscopy or stool tests, blood-based testing 'emerges as cost-effective versus no screening, assuming a high colonoscopy follow-up rate.' They noted that the costs of various emerging blood-based tests are yet to be established, and competition may affect test costs..

斯坦福大学的研究人员还发现，结肠镜检查和粪便检查比血液检查更具成本效益。根据这项研究，在绝对不接受结肠镜检查或粪便检查筛查的人群中，假设结肠镜检查的随访率很高，基于血液的检测“与不进行筛查相比具有成本效益”他们指出，各种新兴的血液检测的成本尚未确定，竞争可能会影响检测成本。。

But Ladabaum added that blood-based tests are 'an incredible development in the colorectal cancer screening world' and that 'even with their limitations, it's a tremendous scientific advance.'

但拉达鲍姆补充说，基于血液的检测是“结直肠癌筛查领域令人难以置信的发展”，“即使有其局限性，这也是一项巨大的科学进步。”