The development and introduction of new pharmaceuticals has played a pivotal role in reducing US cancer deaths. While pharmaceuticals have played a significant role in reducing cancer mortality, winning the war on cancer is a multifaceted battle. To prevent delayed diagnoses and suboptimal treatment and allow patients to “catch up” on delayed screenings and treatments (to the extent possible), adjustments need to be made swiftly. In this column, we explore what factors are the primary causes of the reduction in cancer mortality in the United States and how COVID-19 is impacting our progress in the treatment of cancer.
Cancer mortality rates have fallen significantly over the last 20 years. Between 2000 and 2010, overall age-adjusted cancer mortality rates decreased by about 1% per year globally.1 In the United States, the trend has been equally pronounced. Overall, the US cancer mortality rate declined by 29% between 1991 and 2017, translating into an estimated 2.9 million fewer cancer deaths.2 Notably, cancer mortality rates fell by 2.2% between 2016 and 2017, the sharpest single-year drop on record.2
This leaves us with 2 key questions: what factors are the primary causes of the reduction in cancer mortality, and does COVID-19 threaten to stall this progress?3
The Role of Pharmaceuticals in Averting Cancer Deaths
The development and introduction of new pharmaceuticals has played a pivotal role in reducing US cancer deaths. In our own research using Surveillance, Epidemiology, and End Results (SEER) data, we estimated that the introduction of new cancer drugs was associated with 1.3 million deaths averted in the United States between 2000 and 2016. Cancer drug approvals were associated with significant decreases in deaths from the 15 most common tumor types combined, and specifically from lung, renal, non-Hodgkin’s lymphoma, leukemia, melanoma, colorectal, and breast cancers, even after accounting for better detection through the incidence rate. Given that many of these cancers had prognoses of less than 1 year prior to recent new drug approvals, our results suggest that new treatments play an especially important role in reducing mortality in certain cancers.2,4 Furthermore, our estimate may be conservative. New oncology indication approvals occurred more frequently in recent years; therefore, the majority of the improvement in mortality from these approvals will likely be achieved after the end of our study period (ie, 2016). A number of other studies using data from different countries have also found that the number of new drug approvals was significantly associated with large reductions in premature mortality.5-10
These findings should not be surprising as there has been significant momentum in cancer drug development. Specifically, between 2000 and 2016, 106 new drugs were approved across 173 different indications (ie, tumor types). The majority—more than 70%—of the approvals (124 new indications) came after 2008. Novel immunotherapies as well as cell and gene therapies have resulted in major advances in the treatment paradigm for certain tumor types.
While pharmaceuticals have played a pivotal role in reducing cancer mortality, winning the war on cancer is a multifaceted battle. Other factors that explain the recent decline in cancer mortality include changes in risky lifestyle behaviors, increased screening, earlier diagnosis, and the introduction of innovative therapies. Smoking—which accounts for roughly 20% of cancer deaths globally11—decreased from 20.9% to 13.7% in the United States between 2005 and 2018,12 contributing significantly to the decline in lung cancer incidence and mortality. Screening programs have also been linked to mortality declines in breast,13,14 cervical,15-17 and colorectal cancer,18,19 all of which had uptake rates of >50% in 2015.20 The incidence of distant stage disease in these tumor types also decreased from 1980 to 2015,21 suggesting earlier diagnosis has contributed to the decline in mortality. While positive developments in cancer treatment, screening and lifestyle are all good news, the emergence of a global pandemic threatens this progress.
Will Covid-19 Reverse Our Progress?
COVID-19 has affected virtually every aspect of cancer care, from the research and development of new therapies, to diagnosis and treatment. The pandemic has shut down research labs,22 cancelled academic conferences, and put many non-COVID-related clinical trials on hold,23 all of which will likely delay drug development timelines. Already the National Cancer Institute (NCI) has implemented more flexible clinical trial enrollment allowances and initiated the NCI COVID-19 in Cancer Patients Study.24
Cancer diagnoses have declined sharply25 since the start of the pandemic in the United States and United Kingdom,26 but unfortunately not because cancer is suddenly less common. Rather, cancer diagnoses are being delayed due to less frequent screenings; less timely screenings results in disease detection at later stages and poorer patient prognoses.24 Cancer surgeries17 as well as critical cancer treatment, tests, and procedures have also been delayed since the beginning of the pandemic.18-20 Screenings for breast, colorectal, and cervical cancers were down more than 60% between March and June 2020.27 Oncologists are increasingly replacing intravenous therapy prescriptions with oral drugs to avoid office visits and prescribing treatments that in some cases may be less effective but that have fewer adverse events and lower risks of hospitalization. In addition, unemployment rates have soared,21 leaving many uninsured or underinsured,22 potentially further limiting patient access to new cancer treatments. Prolonged quarantine may also reduce physical activity and increase smoking/alcohol consumption, all of which are related to cancer risks.24-26
To address these issues, cancer screening and treatment pathways can be modified to minimize patients’ risk of exposure to and severe complications of COVID-19 so that patients can safely seek screenings and medical attention for cancer symptoms. Minimizing cancer patients’ exposure to COVID-19 is critical; they are particularly vulnerable to COVID-19 as a result of immunosuppression, poor performance status, advanced age, and/or comorbid conditions.28 Cancer patients who test positive for COVID-19 have a two- to six-fold greater risk of death than individuals without cancer who are COVID-19 positive.29 There is a significantly greater risk for use of a ventilator, admission to the intensive care unit, and death among patients with cancer and COVID-19 compared to those with COVID-19 and without cancer, and a relatively higher risk of these events among those with metastatic disease and/or lung metastases. In that study, individuals with hematologic and lung cancer were at the highest risk, however, other studies found no significant difference for those with hematologic cancers.30,31 Cancer care delivery could be rearranged to insulate cancer patients from COVID-19 in “cancer hubs,”3 permitting cancer patients to receive infusions with less fear of COVID-19 exposure and allowing critical cancer surgeries to resume. Appropriate use of telehealth for monitoring patients and clinical trial participants will also reduce COVID exposure risk.32 The development of a COVID vaccine and widespread COVID vaccination will also help reduce the risk of transmission to vulnerable populations such as cancer patients.
Combined, these interruptions and challenges are likely to affect patient outcomes,23 but the full extent of their impact will not be known for years to come. NCI estimates24 that avoidable deaths from delayed screening for breast and colorectal cancers alone will reach 10,000 by 2030, but this is surely an underestimate of the full impact of the COVID-19 pandemic on cancer outcomes.
Innovative cancer treatments prevented 1.3 million deaths between 2000 and 2016, by our estimation. COVID-19 is presenting serious challenges and threatening the progress made to date. However, by resuming cancer clinical trials, screenings, and treatment safely, we can fight COVID-19 and continue the great progress we have made in reducing cancer mortality. Policymakers and health care organizations will need to work together and employ creative approaches to protect cancer patients and ensure that the COVID-19 pandemic does not reverse this progress. Through decisive and collective action, policymakers, health care systems, providers, and patients can prevent losing any additional ground in the war on cancer.
1. Hashim D, Boffetta P, La Vecchia C, et al. The global decrease in cancer mortality: trends and disparities. Ann Oncol. 2016;27(5):926-933. doi:10.1093/annonc/mdw027
2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi:10.3322/caac.21590
3. Richards M, Anderson M, Carter P, Ebert BL, Mossialos E. The impact of the COVID-19 pandemic on cancer care. Nat Cancer. 2020;1(6):565-567.
4. Welch HG, Kramer BS, Black WC. Epidemiologic signatures in cancer. N Engl J Med. 2019;381(14):1378-1386. doi:10.1056/NEJMsr1905447
5. Lichtenberg FR. The impact of pharmaceutical innovation on premature cancer mortality in Canada, 2000-2011. Int J Health Econ Manag. 2015;15(3):339-359. doi:10.1007/s10754-015-9172-2
6. Lichtenberg FR. The impact of pharmaceutical innovation on cancer mortality in Belgium, 2004-2012. Forum Health Econ Policy. 2016;20(1). doi:10.1515/fhep-2015-0042
7. Lichtenberg FR. The impact of pharmaceutical innovation on premature cancer mortality in Switzerland, 1995-2012. Eur J Health Econ. 2016;17(7):833-854. doi:10.1007/s10198-015-0725-6
8. Lichtenberg FR. The impact of pharmaceutical innovation on cancer mortality in Mexico, 2003-2013. Latin Am Econ Rev. 2017;26(1):8.
9. Lichtenberg FR. The impact of pharmaceutical innovation on cancer mortality in Russia, 2001-2011. J Pharm Health Serv Res. 2018;9(2):79-89. doi:10.1111/jphs.12219
10. Lichtenberg FR. The impact of new drug launches on life-years lost in 2015 from 19 types of cancer in 36 countries. J Demogr Economics. 2018;84(3):309-354. doi:10.1017/dem.2018.11
11. American Cancer Society. Global Cancer Facts& Figures 4th Edition. Atlanta: American Cancer Society; 2018. Accessed November 29, 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/global-cancer-facts-and-figures/global-cancer-facts-and-figures-4th-edition.pdf
12. Creamer M, Wang T, Babb S, et al. Tobacco product use and cessation indicators among adults—United States, 2018. MMWR Morb Mortal Wkly Rep. 2019;68(45):1013-1019.
13. Plevritis SK, Munoz D, Kurian AW, et al. Association of screening and treatment with breast cancer mortality by molecular subtype in US women, 2000-2012. JAMA. 2018;319(2):154-164. doi:10.1001/jama.2017.19130
14. Massat NJ, Dibden A, Parmar D, Cuzick J, Sasieni PD, Duffy SW. Impact of screening on breast cancer mortality: The UK program 20 years on. Cancer Epidemiol Biomarkers Prev. 2016;25(3):455-462. doi:10.1158/1055-9965.EPI-15-0803
15. Landy R, Pesola F, Castañón A, Sasieni P. Impact of cervical screening on cervical cancer mortality: estimation using stage-specific results from a nested case-control study. Br J Cancer. 2016;115(9):1140-1146. doi:10.1038/bjc.2016.290
16. Sasieni P, Castanon A, Cuzick J. Effectiveness of cervical screening with age: population based case-control study of prospectively recorded data. BMJ. 2009;339:b2968. doi:10.1136/bmj.b3115
17. Rustagi AS, Kamineni A, Weinmann S, Reed SD, Newcomb P, Weiss NS. Cervical screening and cervical cancer death among older women: a population-based, case-control study. Am J Epidemiol. 2014;179(9):1107-1114. doi:10.1093/aje/kwu035
18. Levin TR, Corley DA, Jensen CD, et al. Effects of organized colorectal cancer screening on cancer incidence and mortality in a large community-based population. Gastroenterology. 2018;155(5):1383-1391.e1385. doi:10.1053/j.gastro.2018.07.017
19. Zauber AG. The impact of screening on colorectal cancer mortality and incidence: has it really made a difference? Dig Dis Sci. 2015;60(3):681-691. doi:10.1007/s10620-015-3600-5
20. Hall IJ, Tangka FKL, Sabatino SA, Thompson TD, Graubard BI, Breen N. Patterns and trends in cancer screening in the United States. Prev Chronic Dis. 2018;15:e97. doi:10.5888/pcd15.170465
21. National Cancer Institute. Stage at diagnosis. Cancer Trends Progress Report 2019. November 2020. Accessed November 29, 2020. https://progressreport.cancer.gov/diagnosis/stage
22. COVID-19 hits cancer research funding. Cancer Discov. 2020;10(6):756-756. doi:10.1158/2159-8290.CD-ND2020-007
23. van Dorn A. COVID-19 and readjusting clinical trials. Lancet. 2020;396(10250):523-524. doi:10.1016/S0140-6736(20)31787-6
24. Sharpless NE. COVID-19 and cancer. Science. 2020;368(6497):1290-1290. doi:10.1126/science.abd3377
25. Kaufman HW, Chen Z, Niles J, Fesko Y. Changes in the Number of US patients with newly identified cancer before and during the coronavirus disease 2019 (COVID-19) pandemic. JAMA Netw Open. 2020;3(8):e2017267-e2017267. doi:10.1001/jamanetworkopen.2020.17267
26. IJzerman M, Emery J. Is a delayed cancer diagnosis a consequence of COVID-19? Pursuit. April 30, 2020. Accessed November 29, 2020. https://pursuit.unimelb.edu.au/articles/is-a-delayed-cancer-diagnosis-a-consequence-of-covid-19
27. Mast C, Menoz del Rio A. Delayed cancer screenings – a second look. July 17, 2020. Accessed November 29, 2020. https://ehrn.org/articles/delayed-cancer-screenings-a-second-look/
28. Zhang L, Zhu F, Xie L, et al. Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China. Ann Oncol. 2020;31(7):894-901. doi:10.1016/j.annonc.2020.03.296
29. Mehta V, Goel S, Kabarriti R, et al. Case fatality rate of cancer patients with COVID-19 in a New York hospital system. Cancer Discov. 2020;10(7):935-941. doi:10.1158/2159-8290.CD-20-0516
30. Dai M, Liu D, Liu M, et al. Patients with cancer appear more vulnerable to SARS-CoV-2: a multicenter study during the COVID-19 outbreak. Cancer Discov. 2020;10(6):783-791. doi:10.1158/2159-8290.CD-20-0422
31. Li Q, Chen L, Li Q, et al. Cancer increases risk of in-hospital death from COVID-19 in persons <65 years and those not in complete remission. Leukemia. 2020;34(9):2384-2391. doi:10.1038/s41375-020-0986-7
32. Will COVID-19 permanently change cancer care? National Academies of Sciences, Engineering, and Medicine. July 20, 2020. Accessed November 29, 2020. https://www.nationalacademies.org/news/2020/07/will-covid-19-permanently-change-cancer-care