抓住癌早期篩查的變革機遇

1、Seizing the Transformative Opportunity of Multi-cancer Early DetectionSTEPHEN EZELL | APRIL 2021Blood-based multi-cancer early detection (MCED) technologies hold the promise to revolutionize Americas cancer-screening paradigm, dramatically expanding the range of detectable cancers and identifying th

2、em at earlier stages when cancers are more treatable. Policymakers should provide a supportive regulatory and coverage environment.KEY TAKEAWAYSMulti-cancer early detection approaches merge emerging biological and information technologiesincluding next-generation gene sequencing, artificial intellig

3、ence, and big datain a revolutionary new approach to cancer detection.MCED can detect signals for dozens of different types of cancers with a very high rate of accuracy, a low false-positive rate, and the ability to trace the detected cancer to its likely tissue of origin with a high degree of confi

4、dence.MCED holds the potential, over time, to transform Americas cancer-detection paradigm from one in which most cancers are detected when patients present symptomatically to one in which they can be screen-detected in advance.If U.S. enterprises are to lead in this fast-emerging, intensely globall

5、y competitive technology fieldand if citizens are to enjoy the benefitsthen policymakers will need to get the regulatory and coverage environment right.Congress should pass the Medicare Multi-Cancer Early Detection Screening Coverage Act, which authorizes the Centers for Medicare & Medicaid Services

6、 to use an evidence-based process to cover blood-based MCED tests.INFORMATION TECHNOLOGY & INNOVATION FOUNDATION | APRIL 2021INTRODUCTIONCancer remains one of humanitys most intractable diseases, and is expected to surpass heart disease as the leading annual cause of American fatalities by 2030. The

7、 individual, social, and economic costs cancer inflict are enormous, meaning the need for both effective cancer screening and therapeutic options remains paramount. Fortunately, a new slate of biological and informational technologiesincluding genome sequencing, big data analytics, artificial intell

8、igence/machine learning (AI/ML), and nanotechnologyare enabling breakthrough innovations in cancer detection and treatment.In detection, blood-based approaches hold the potential to screen for signals of over 50 cancers simultaneously with a very high rate of accuracy and the ability to trace the de

9、tected cancer to its likely tissue of origin with a high degree of confidence. Multi-cancer early detection (MCED) screening holds the promise to radically expand the number of cancers for which there are available screening options and to broaden cancer detection to the asymptomatic population. It

10、heralds a potential paradigm shift from trying to treat cancer in later stages to detecting and treating the disease in its earliest ones. But if the promise of multi-cancer early detection screening approaches is to be realized, policymakers will have to get the regulatory and coverage policies rig

11、ht to support deployment and uptake of this transformative technology.Multi-cancer early detection (MCED) screening holds the promise to radically expand the number of cancers for which there are available screening options and to broaden cancer detection to the asymptomatic population.This report b

12、egins by examining the social and economic costs cancer inflicts. It discusses the importance of early cancer detection and moves on to an exploration of how MCED technologies work, evidence of their effectiveness to date, the benefits they are capable of providing, and why its important the United

13、States remain the global leader in this field. It then analyzes the regulatory and coverage environment before concluding by providing recommendations for how policymakers can enact policies enabling this transformative technology to flourish, includingby passing legislation creating a pathway to en

14、sure timely Medicare coverage of MCED screening exams.THE INDIVIDUAL, SOCIAL, AND ECONOMIC COSTS OF CANCERCancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells. HYPERLINK l _bookmark4 1 It remains one of Americas, and global societies, greatest he

15、alth challenges. Cancer is responsible for almost one in six deaths globally. HYPERLINK l _bookmark5 2 The global cancer burden is expected to surpass 20 million new yearly cases by 2025. HYPERLINK l _bookmark6 3 Cancer is the second-most common cause of death in the United States, exceeded only by

16、heart disease, although cancer is expected to become the leading cause of American fatalities by 2030. Likewise, among adults ages 35 to 70, while cardiovascular disease remains the leading cause of mortality globally, “mortality from cancer will probably become the leading cause of death” in the ne

17、ar future. HYPERLINK l _bookmark7 4 Experts predict the year 2021 will see 1.9 million new cancer cases diagnosed in the United States, with over 600,000 Americans expected to perish from the disease, which translates to about 1,650 deaths per day. HYPERLINK l _bookmark8 5 Approximately 1 out of eve

18、ry 200 Americansreceive a cancer diagnosis each year. For Americans born today, one in two women, and one in three men, are likely to develop cancer at some point in their lifetimes (with one in five perishing from them). HYPERLINK l _bookmark9 6 One in eight U.S. women will be diagnosed with breast

19、 cancer in their lifetimes. HYPERLINK l _bookmark10 7 One reason cancer rates are increasing is because cancer is primarily a disease of old age, and as Americans live longer in general, the likelihood of their developing a cancer grows. In the United States, 60 percent of all cancer cases diagnosed

20、 are in people above age 65, while 80 percent of all cancers in the United States are diagnosed in people 55 years of age or older. HYPERLINK l _bookmark11 8 Americans ages 65 and older are more than seven times more likely than younger Americans to be diagnosed with cancer. HYPERLINK l _bookmark12

21、9 Seventy percent of all American cancer deaths occur with people ages 65 or older. HYPERLINK l _bookmark13 10 Yet, despite being more prevalent in the older population, cancer is actually the leading cause of death for Americans under age 65. HYPERLINK l _bookmark14 11 In the United States, health

22、experts predict that breast, prostate, and lung cancers will account for the most new cases diagnosed among American men and women in 2021. (See HYPERLINK l _bookmark0 figure 1.) However, in terms of cancer fatalities, lung cancer is now the leading cause of death for American men and women alike, s

23、econd is prostate cancer for men and breast cancer for women, followed by colorectal and pancreatic cancer. (See HYPERLINK l _bookmark1 figure 2.)Figure 1: Estimated new U.S. cancer cases, 2021 (by cancer type, both sexes combined) HYPERLINK l _bookmark15 12Figure 2: Estimated U.S. cancer fatalities

24、, 2021 HYPERLINK l _bookmark16 13Fortunately, American cancer fatality rates have decreased over the past half-century, largely the result of a combination of more-effective screening approaches, an overall decrease in smoking in the population, and more-effective treatment and therapeutic options.

25、For some of the most common cancerslung, colorectal, breast, and prostatereductions in smoking and improvements in screening have led to 36 percent fewer deaths than would have occurredotherwise. HYPERLINK l _bookmark17 14 Americans deaths from cancer have fallen from 193.9 per 100,000 population in

26、 1950 to 152.5 today. HYPERLINK l _bookmark18 15 Since peaking in the early 1990s (at 215 per 100,000 population),U.S. cancer death rates have declined by 27 percent. HYPERLINK l _bookmark19 16 This decline translated into more than2.9 million fewer cancer deaths from 1991 to 2017. HYPERLINK l _book

27、mark20 17 And breakthrough therapies such as Avastin and Herceptin for breast cancer, Keytruda for lung cancer, and Yervoy for melanoma help explain why American citizens enjoy the highest cancer survival rates in the world. For instance, over 99 percent of U.S. women suffering from localized breast

28、 cancer are still living five years later. HYPERLINK l _bookmark21 18 One study estimates that approximately 73 percent of survival gains in cancer are attributable to new treatments, including medicines. HYPERLINK l _bookmark22 19 Moreover, as Lichtenberg explains, “During the period 20002011, the

29、premature (before age 75) cancer mortality rate declined by about 9 percent. In the absence of pharmaceutical innovation during the period 19851996, the premature cancer mortality rate would have increased about 12 percent during the period 20002011.” HYPERLINK l _bookmark23 20Yet, as Azra Raza, a p

30、rofessor of medicine and director of the MDS Center at Columbia University, writes, “Cancer is still beating us I have been studying and treating cancer for 35 years, and heres what I know about the progress made in that time: There has been far less than it appears.” HYPERLINK l _bookmark24 21 She

31、points out that, for all this progress, overall cancer death rates are not dramatically different from what they were in the 1930s, before they began increasing alongside the rise in smoking. Indeed, while the age-adjusted death rate per 100,000 U.S. population from heart disease fell by roughly two

32、-thirds from 1950 to 2010, the similar rate for cancer just barely decreased. (See HYPERLINK l _bookmark2 figure 3.) As. Dr. Bert Vogelstein, a professor of oncology at Johns Hopkins University, explains, part of this disparity can be attributed to the fact that the heart disease research community

33、has largely focused on early detection and prevention, “whereas the oncology community has been more focused on curing advanced disease.” HYPERLINK l _bookmark25 22 Or, as Raza puts it,“We now invest a lot of effort into finding minimal residual disease. Why not apply the same rigor and focus to fin

34、ding minimal initial disease?” HYPERLINK l _bookmark26 23Figure 3: Age-adjusted rate of death per 100,000 population HYPERLINK l _bookmark27 24Thus, despite some progress, cancer still afflicts millions annually and imposes tremendous costs on the U.S. health care system, as well as the broader econ

35、omy. Cancer is the second-most-costly disease in the United States. HYPERLINK l _bookmark28 25 Cancer accounts for an estimated 5 to 11 percent ofthe annual total U.S. health care budget. HYPERLINK l _bookmark29 26 In 2017, cancer care cost the United States an estimated $177 billion (an increase of

36、 approximately 39 percent since 2010), equivalent to 1 percent of U.S. gross domestic product (GDP). HYPERLINK l _bookmark30 27 Medicarethe federally administered health care program that covers more than 60 million seniors and persons with disabilitiesshoulders roughly one-third of this cost annual

37、ly. HYPERLINK l _bookmark31 28 The United States invests about $27 billion annually on cancer screening tests. HYPERLINK l _bookmark32 29Cancer is the second-most common cause of death in the United Statesexceeded only by heart diseasealthough it is expected to become the leading cause of American f

38、atalities by 2030.More than $94 billion in earnings were lost in the United States in 2015 due to cancer deaths. HYPERLINK l _bookmark33 30 A 2008 study estimated that the value of life lost from all cancer deaths in the year 2000 totaled $960.6 billion and predicted that the total value of life los

39、t in 2020 from cancer deaths in the United States would reach $1.5 trillion. HYPERLINK l _bookmark34 31 The tremendous costs cancer imposes conversely suggest tremendous benefits if cancers could be detected earlier when treatments are more likely to succeed and as more-effective treatments and ther

40、apeutics for cancer are invented. In fact, Murphy and Topel, considering the benefits of increased longevity and improved quality of life, find that a 1 percent reduction in mortality from cancer could deliver roughly $500 billion in net present benefits, while a cure (if one could be achieved) coul

41、d deliver$50 trillion in present and future benefits. HYPERLINK l _bookmark35 32 Similarly, Lakdawalla et al. examined trends in survival after cancer diagnosis from 1988 through 2000 and argued that improvements intreatments led to approximately 24 million more life years for patients, at an econom

42、ic value of$1.9 trillion. HYPERLINK l _bookmark36 33 Their research finds that the overwhelming amount of economic value produced from investments in cancer research and development (R&D) made by the public and private sector have flowed to patients, with health care providers and pharmaceutical com

43、panies appropriating 5 to 19 percent of the total economic value created, with the rest accruingto patients. HYPERLINK l _bookmark37 34THE IMPORTANCE OF EARLY CANCER DETECTIONEarlier cancer detection generates significant health and economic benefits, as the two following sections attest.Health Bene

44、fitsCancer is most effectively and efficiently treated when it is caught early, when it is localized, and before it has metastasized to distant parts of the body. As one report explains, “Survival rates improve dramatically when cancer is diagnosed early and the disease is confined to the organ of o

45、rigin before it has had a chance to spread, and the cancer is more likely to be treated successfully.” HYPERLINK l _bookmark38 35 Early detection, especially resulting from effective cancer screening protocols, is paramount to reducing mortality from cancer. As the American Cancer Society explains,

46、“Screening is known to reduce mortality for cancers of the breast, colon, rectum, cervix, lung (among current or former heavy smokers), and probably prostate.” HYPERLINK l _bookmark39 36 Overall, patients survival rates are 5 to 10 times greater when cancer is detected at an early stage rather than

47、at a late stage. HYPERLINK l _bookmark40 37 When cancer is diagnosed after it has spread, the five-year cancer-specific survival rate is 21 percent, compared with 89 percent when the cancer is diagnosed early and still localized. HYPERLINK l _bookmark41 38 According to a study by Clarke et al., “Pro

48、jected Reductions in Absolute Cancer Related Deaths from Diagnosing Cancers Before Metastasis, 20062015,” detecting cancers with distant metastases at earlier stages could potentially reduce cancer-related five-year mortality by at least 15 to 24 percent. HYPERLINK l _bookmark42 39 The study found t

49、hat detection of multiple cancer types earlier than stage IV could reduce at least 15 percent of cancer-related deaths within five years, affecting not only cancer-specific but all-cause mortality. Stage IV cancers represented 18 percent of all estimated diagnoses but 48 percent of all estimated can

50、cer-related deaths within five years. Assuming all stage IV cancers were diagnosed at stage III, 51 fewer cancer-related deaths would be expected per 100,000, a reduction of 15 percent of all cancer-related deaths. Assuming one-third of metastatic cancers were diagnosed at stage III, one-third diagn

51、osed at stage II, and one-third diagnosed at stage I, 81 fewer cancer-related deaths would be expected per 100,000, a reduction of 24 percent of all cancer-related deaths. HYPERLINK l _bookmark43 40Earlier detection of cancers saves both lives and costs for health care systems and economies more bro

52、adly.The importance of early detection becomes even clearer when examining its impact on survival rates for certain forms of cancer. Well more than 90 percent of women diagnosed with breast cancer at the earliest stage survive their disease for at least five years, compared with about 15 percent for

53、 women diagnosed with the most-advanced stage of disease. More than 80 percent of lung cancer patients will survive for at least one year if diagnosed at the earliest stage, compared with around 15 percent for those diagnosed with the most-advanced stages of the disease.Unfortunately, only about 15

54、percent of lung cancers are diagnosed at the localized stage, when clinical intervention can markedly improve patient outcomes. HYPERLINK l _bookmark44 41 Ninety percent of women diagnosed with earliest-stage ovarian cancer survive their disease for at least five years, compared with around 5 percen

55、t for women diagnosed with the most-advanced stage of disease. And more than nine in ten bowel cancer patients will survive the disease for more than five years if diagnosed at the earliest stage. HYPERLINK l _bookmark45 42Earlier detection makes all forms of cancer intervention more effective than

56、when cancers are diagnosed at later stages. As Dr. Vogelstein notes, patients with stage III colorectal cancer, if they have micrometastases (i.e., a very small micro-metastatic disease, even if already spread to other organs), given chemotherapy, can recover almost 50 percent of the time; whereas i

57、f the cancer becomes visible and bulky (visible metastases), the recovery rate is close to nil. This also holds true for the newest, most cutting-edge interventions, such as targeted immunotherapies (i.e., immune checkpoint inhibitors) and CAR-T-based (chimeric-antigen receptor T cell) therapies: Re

58、covery rates are far higher in patients with low tumor burdens than with high. HYPERLINK l _bookmark46 43 Indeed, in quite many cases, these technologies mean that patients with localized (i.e., Stage I-II) solid tumors are potentially curable. As Raza writes (about what this evidence makes clear):W

59、hat we need now is a paradigm shift. Today, the newest methods generating the most research and expense tend to be focused on treating the worst caseschasing after the last cancer cells in end-stage patients whose prognoses are the worst.We need instead to commit to anticipating, finding, and destro

60、ying the first cancer cells. HYPERLINK l _bookmark47 44Unfortunately, only five types of cancerbreast, cervical, colorectal, prostate, and “high-risk” lunghave guideline-recommended screening options available today, whereas the vast majority of cancers, including blood, head and neck, pancreatic, o