Achieving the Goals of the Cancer Moonshot Requires Progress against All Cancers

President Joseph R. Biden and First Lady Dr. Jill Biden have long championed the goal of dramatically improving the lives of people and their loved ones facing cancer, including the launch of a Cancer Moonshot in 2016 and reaffirming this commitment in 2022 by calling for a national, whole-of-government commitment to “end cancer as we know it today” as part of a reignited Cancer Moonshot (1). An end to cancer as we know it today means that all people with cancer live full and active lives free from cancer's harmful effects and that cancer is prevented so that far fewer people face a cancer diagnosis. It means that we make meaningful improvements to address the shortcomings of how we experience cancer today. For example, we must address the fact that we often diagnose cancer too late, we experience inequities in access to care and outcomes, there are cancers for which we do not have answers, and we do not yet know how to optimally target treatments to individual patients. Overcoming these challenges is the ultimate goal for so many individuals who have devoted their careers to ending cancer. We are building on significant progress; during the last 30 years, the cancer death rate has fallen by a third, and millions are living longer and healthier lives after a cancer diagnosis.

To provide a measurable focus for the Moonshot, President Biden also challenged us to reduce age-adjusted cancer mortality by at least 50% over the next 25 years. This is a goal that all of us can understand and embrace. The achievements of the initial phase of the Cancer Moonshot laid important groundwork for the accelerated progress that will be needed to reach this goal. It is essential to remember that ending cancer as we know it is much more than the numbers. The numbers represent individuals, families, and larger communities looking for more time together. In addition to achieving the mortality reduction goal, therefore, we must also improve the experience of people living with and surviving cancer.

Reducing age-adjusted cancer mortality by 50% over the next 25 years is a goal worthy of being called a national moonshot. It will take innovation to deliver new ways to prevent, detect, treat, and survive cancer. We also must ensure that the tools we have today and those we develop along the way reach all Americans. As described in detail below, the goals of the Cancer Moonshot were set as a commitment to make urgent progress for all individuals and families facing cancer. This will require each of us to do our part to maintain and accelerate the aggressive progress in reducing cancer mortality that has occurred in recent years, and to address any factors threatening that progress.

In their article, “Opportunities for Achieving the Cancer Moonshot Goal of a 50% Reduction in Cancer Mortality by 2047,” Shiels and colleagues address the feasibility of achieving such a significant mortality improvement (2). Using data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Disease Control and Prevention's National Center for Health Statistics, these researchers assessed current trends in age-adjusted cancer mortality for the six top causes of cancer death (which together account for more than half of cancer deaths) and for all other cancers. They then calculated the mortality reduction over the next 25 years should the current mortality trends in these cancers continue. This analysis found that overall cancer mortality declined by 1.4% per year from 2000 to 2015 and by 2.3% per year from 2016 to 2019. They showed that, even if the most recent trend continues at its current aggressive rate, age-adjusted cancer mortality will drop by 44% by 2047, short of the Cancer Moonshot goal. Achieving the 50% reduction President Biden set as our goal requires cancer mortality to decline by an average of 2.7% per year over the next 25 years. Given the accelerated mortality reduction we have seen from 2000 to 2019, attaining this goal might seem relatively straightforward. It most definitely is not.

Figure 1A illustrates projections made by Shiels and colleagues, assuming that the 2016 to 2019 rate of cancer mortality reduction continues unchanged until 2047. This shows that only for lung cancer will we achieve the desired 50% mortality decrease over this time if we at least maintain recent gains. It is clear from this figure that we must accelerate progress for all cancers. Figure 1B provides a view of the different disease categories contributing to cancer deaths in 2019. The category of “Other” collectively accounted for 14.2% of cancer deaths and includes malignancies that each represent less than 2% of cancer deaths. Examples include cancers of the skin (melanoma and nonmelanoma skin cancer), stomach, thyroid, oral cavity and pharynx, larynx, cervix, soft tissues, bones and joints, and gallbladder. This is a very heterogeneous group with respect to incidence and lethality, with some of these cancers (e.g., nonmelanoma skin and thyroid cancer) having a relatively high incidence and only rare subtypes with high mortality and others (e.g., gallbladder cancer) that are quite rare but demonstrate high overall death rates. Because these cancers or their lethal subtypes are relatively uncommon, they are difficult to study and progress has generally been slow.

To illustrate the importance of making significant progress for all cancers, not just those that are the most common contributors to cancer deaths, it is useful to consider what would be required if we made little or no progress for the combined category of uncommon cancers (the pie wedge labeled “Other” in Fig. 1B) that contributed 14.2% of the total age-adjusted cancer mortality in 2019. If the mortality rate for these cancers remains unchanged over the next 25 years, then meeting the mortality reduction goal requires an average yearly decrease of 3.44% per year for all of the other more common causes of cancer death. This level of yearly reduction presents a far greater challenge.

As outlined in the article by Shiels and colleagues, recent decreases in cancer mortality can be attributed to three main factors: primary prevention, early detection, and better cancer treatment. To achieve the 2047 goal, we must aggressively pursue all proven and developing strategies in these areas. For prevention, this includes eliminating tobacco use; counteracting infectious causes of cancer with vaccination against human papillomavirus and hepatitis B virus; screening for and treating chronic hepatitis B and C; accelerating a whole-of-society effort to decrease exposure to cancer-causing toxins; and promoting risk-reducing behaviors that include a healthy diet, exercise, minimal alcohol use, and limited sun exposure. Although there has been recent progress in cancer primary prevention, we expect to see a future increase in cancer deaths related to the obesity epidemic, creating new headwinds opposing progress toward the 50% goal. In early detection, there is much to be gained by improving the uptake of breast, cervical, colorectal, and lung cancer screening according to current guidelines from the U.S. Preventive Services Task Force. We must also pursue new early detection tools, especially for those cancers like pancreatic and ovarian that are often diagnosed in advanced stages with poor outcomes (Table 1). Finally, our cancer care delivery system must be incentivized at a national level to ensure that every person with cancer or at risk for cancer receives the diagnostic and therapeutic measures that they need.

Achieving a 50% reduction in cancer mortality in 25 years will be impossible without addressing cancer health equity. Many populations experience health inequities, including people from some racial and ethnic minority groups, people with disabilities, women, people who are LGBTQI+ (lesbian, gay, bisexual, transgender, queer, intersex, or other), people with limited English proficiency, and people living in rural locations. Cancer occurrence and mortality vary between racial and ethnic groups and by differences in wealth, educational attainment, employment, health insurance coverage, and local availability of health care providers. For example, in 2019, deaths from cancer occurred in 171/100,000 non-Hispanic Black people compared with 151/100,000 non-Hispanic white people (3).

Inequities are created by barriers that make it more difficult for health benefits to be achieved by people who struggle with access to tools for prevention, early detection, and quality care. One example is the difference in current tobacco use among populations defined by different social determinants of health. Although tobacco use has declined overall, it remains higher among residents of rural compared with urban locations (27.3% vs. 17.7%), among those without health insurance (27.3% of those who are uninsured vs. 12.5% of those with Medicare), and among those with different levels of educational attainment (24.2% of those with a high school diploma vs. 8.6% of those with a graduate degree) (4). Direct evidence suggests we can overcome inequities in cancer outcomes by addressing differences in risk factor exposures and access to health knowledge, as well as barriers to receiving health care for cancer prevention, early detection, and treatment (5, 6).

Finally, doing more of what already works is necessary, but not enough. We must develop new ways of preventing, detecting, and treating cancer. The bedrock of discovery is basic research, which seeks to understand the fundamental nature of cancer's biological characteristics and identify ways to counteract the forces that produce cancers and allow established cancers to harm an individual. How does a normal cell transition to a malignant state, and how do the components of the surrounding tissue support the growth and spread of a tumor? How do lifestyle and environmental influences impact this transition? How can we destroy or block the growth of tumor cells while maintaining the health of normal tissues? How can powerful forces within the body, such as the immune system, be marshaled to destroy cancer? How does treatment affect the quality of life of cancer survivors, and what can be done to minimize both short-term and long-term toxicity? Answers to these questions and many others provided by fundamental research are required to reduce cancer risk, create new drugs, develop new diagnostic procedures, and identify better combined-modality treatments.

Recent successes encourage us to work even harder to find treatments that will work for everyone who needs them. In 2014, only 15% of people with metastatic melanoma were alive 5 years after diagnosis, and available therapies were rarely effective. Immunotherapy has doubled 5-year survival to 30% for patients diagnosed during 2011 to 2017 (7). Lung cancer treatment has also improved considerably due to a better understanding of the factors driving tumor growth. Mortality from non–small cell lung cancer (NSCLC) has declined at a population level at rates faster than are attributable to decreased incidence, and this effect is mainly due to new treatments. Agents that effectively target oncogenic drivers of NSCLC, such as EGFR and ALK, have been introduced, beginning in 2003 when the EGFR inhibitor gefitinib was approved by the FDA. In 2015, the first immune checkpoint inhibitor therapy was approved for patients with advanced NSCLC, providing an important new option for those whose cancers do not contain targetable driver mutations. An analysis of mortality at a population level for the United States found that cancer-specific survival improved among men with NSCLC from 26% in 2001 to 35% in 2014, with a similar pattern among women (8). This improvement was found across all races and ethnic groups. Population-level data from the time following the introduction of immune checkpoint inhibitor therapy have yet to emerge, but based on survival increases seen in recent clinical trials, are expected to show significant additional improvement over the coming years.

Finally, another important consideration is that the 50% cancer mortality reduction goal by 2047 applies to age-adjusted mortality. The total number of people dying from cancer depends on the size and age distribution of the U.S. population. On the basis of current growth rate projections, the U.S. population is expected to increase to approximately 389 million in 2050. Cancer is much more frequent in older adults, and the number of people in the United States at or above age 65 is expected to increase from 56.1 million in 2020 to 84.7 million by 2050. In absolute numbers then, a 50% decrease in age-adjusted mortality translates to a reduction in the number of U.S. residents dying from cancer from 608,000 in 2022 to 573,000 in 2047; however, the number of cancer deaths in 2047 would be approximately 907,000 if death rates remained stable at the 2022 rate. This observation illustrates the importance of another Cancer Moonshot goal: ensuring that every person with cancer and every cancer survivor of any age has a high quality of life, free from cancer- or treatment-associated side effects.

Reducing age-adjusted cancer mortality by 50% over the next 25 years truly challenges us to eliminate health disparities; make societal changes that promote prevention and early detection; and develop and implement new, effective methods of preventing, diagnosing, treating, and surviving cancer. It requires a major commitment across all of society, with significant investment on all fronts: fundamental research, clinical and translational research, public health, and cancer care delivery, among others. It will mean that many more people with cancer will live full and active lives and that many more cancers will be prevented so that fewer people will face a cancer diagnosis. The impact on the nation's health outcomes overall and on the equity and productivity of our society will be tremendous. We can and must meet this challenge: People with cancer, our loved ones, friends, neighbors, and colleagues are counting on us.