Earlier this year, as the COVID-19 pandemic was spreading across the United States, federal health officials and cancer societies urged Americans to delay routine cancer screenings and other elective procedures to keep them out of clinics to avoid potential exposure to the coronavirus and to preserve hospital capacity during the pandemic response. And Americans heeded the advice.

Data from the electronic medical records vendor Epic and Komodo Health, a San Francisco–based company that collects and analyzes health-care data, show that during the months of March and April, the percentage of cancer screenings plummeted from previous years.

“We are seeing a fairly dramatic decrease in new cancer diagnoses at major cancer centers…. These decreases in diagnoses are related to the disruptions in screening and evaluating these patients.”

— Norman E. ‘Ned’ Sharpless, MD

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According to Epic, screening appointments for breast, cervical, and colon cancers in March 2020 decreased between 86% and 94% compared with average volumes in the prior 3 years.¹ A review of the billing records of 320 million patients released by Komodo Health found that the total number of colonoscopies and biopsies performed dropped nearly 90% by mid-April compared with the same period in 2019. The company’s analysis also found that new colorectal cancer diagnoses were down more than 32% by mid-April, and the number of colorectal cancer surgeries fell by 53% compared with the previous year.²

Although postponing cancer screenings and other delays in cancer care may have protected people from contracting COVID-19, these measures may have inadvertently traded one serious illness for another. “We are worried about swapping one public health emergency for another public health emergency, and we don’t want to let that happen,” said Norman E. “Ned” Sharpless, MD, Director of the National Cancer Institute (NCI).

In addition to the toll this pandemic is taking on American lives—by the middle of this year, the coronavirus has killed more than 150,000 people in the United States³—it may also negatively impact cancer mortality, which has been declining steadily in the country since 1990.⁴ The first early indication of how cancer mortality may be shaped by the COVID-19 pandemic will come in the 2021 Annual Report to the Nation, which is jointly issued by the NCI, the Centers for Disease Control and Prevention, the North American Association of Central Cancer Registries, and the American Cancer Society.

“Typically, we see declines in cancer mortality of between 1% and 2% each year. But now, we are starting to see the pandemic’s effects on cancer mortality, which could be to that degree in the other direction, an increase of between 1% and 2% in cancer mortality in 2021, 2022, and 2023,” said Dr. Sharpless. “Right now, I think that is unlikely to happen if we can minimize the impact of the pandemic on our patients and take collective action.”

In a wide-ranging interview with The ASCO Post, Dr. Sharpless discussed the COVID-19 pandemic’s long-term impact on patients with cancer; the disruption on cancer research, clinical trials, and new drug approvals; and how the country can be better prepared to meet the challenges of the next health crisis.

Overcoming Health Consequences From COVID-19 and Cancer

Please talk about how the COVID-19 pandemic might result in increased cases of advanced cancers diagnosed over the next few years and the impact that might have on patient outcomes.

This is an important topic, one that is subtle and nuanced. We are dealing with the convening risk of two major health issues: a viral pandemic that has significant mortality and morbidity associated with it, and deaths from cancer, which represent an even greater problem from a mortality perspective. Cancer is a disease in which early diagnosis and treatment are beneficial; thus, if the response to the pandemic leads to a delay in early cancer diagnosis and decreased care, that may cause an increased burden of cancer suffering and cancer death. We are worried about swapping one public health emergency for another public health emergency, and we don’t want to let that happen.

It is a tricky problem because, in some instances, it is prudent to reduce hospital usage and to limit patient exposure to hospitals. There is a need to preserve hospital capacity in certain areas where we are seeing significant viral outbreaks. But, on the other hand, there is a need to continue providing cancer care.

The NCI decided a few months ago to look at this issue, and we asked our Cancer Intervention and Surveillance Network (CISNET) to model predictions on cancer mortality increases. At the time, we didn’t have great data on how significant the decreases and delays in screening from the pandemic were going to be, and so we made some assumptions to try to model this. In retrospect, I believe our assumptions were quite conservative, because the pandemic has disrupted cancer care to a greater degree than we expected.

Using the conservative assumptions we made for colon and breast cancers, in which the data from our models are most significant, we found that a 75% decrease in screening for those cancers over a 6-month period resulted in deferred or delayed care that alone would be enough to produce a 1% increase in excess deaths for those two tumor types over the next decade. Those cancers combined to kill about a million people over that period, so that means 10,000 additional deaths just from those two tumor types over the next 10 years. Obviously, if delayed screenings and deferred cancer care related to the pandemic are greater than we expect them to be, the number of deaths would be greater.

“Virology research related to coronavirus serology will be valuable for understanding the basic biology of the immune response, which underpins cancer immunology.”

— Norman E. “Ned” Sharpless, MD

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We didn’t model for forecasts in mortality increases for lung, prostate, and pancreatic cancers or other important cancers because our models are not as accurate at predicting mortality for those diseases. However, there is no reason to believe these disruptions in screening and care won’t affect those diseases as well.

Anecdotally, we are seeing a fairly dramatic decrease in new cancer diagnoses at major cancer centers that treat a lot of patients. Again, there is no reason to believe the incidence of cancer has declined over this period. Therefore, these decreases in diagnoses are related to the disruptions in screening and evaluating these patients.

Taking Collective Action to Mitigate COVID-19’s Impact on Cancer

What should oncologists do to encourage patients to maintain screenings and treatment schedules during this time?

Our overarching message to oncologists is that we have to take collective action to minimize the impact of the pandemic on our patients. We have to appreciate that cancer is still the same problem it has always been. A lot of cancer care comes under the rubric of “elective” care, which can be postponed for 1 or 2 weeks, but that word can be confusing. Unfortunately, much of the care we provide in oncology may be considered “elective,” but it is still medically necessary and cannot be postponed indefinitely or for months.

We have to all agree this is a problem. We have to do what is right for our patients while also protecting them from exposure to the coronavirus. We also have to protect caregivers from patients who may have the coronavirus, so we have to realize that cancer care during the pandemic will be challenging. However, I believe that by working together, we can address this problem successfully. Although there is no one simple solution, there are a number of things we can do.

For example, we can take advantage of innovations such as telemedicine. We can now do things by phone that we once thought could only be done in person, including clinical trial enrollment and some clinical trial visits. The NCI, working with the U.S. Food and Drug Administration (FDA) early in the pandemic, provided a lot of flexibility for the continuation of clinical trials in cancer research, so patients would not have to come into the hospital for routine clinical visits. Patients with cancer are finding they can get a lot done over the phone, which is really valuable, and they are going to want to continue telemedicine services once the pandemic is over.

In July, the NCI issued a request for information related to telemedicine’s new era in oncology. The goal is to identify scientific gaps and research needs related to the delivery of cancer-related care via telehealth to learn more about the effectiveness of telehealth and its potential for continued use in cancer care even after the pandemic.

Also, hospitals and clinics are going to have to use a level one, two, and three risk-stratification approach to identify patients who are most at risk for a worse cancer outcome if a procedure or clinic visit is postponed. Oncologists will figure out a way to ensure these patients are evaluated and treated, which may require innovative point-of-care testing. As a result, there are many things we are already learning about that will allow the continuation of cancer care in this environment.

Preventing a Rise in Cancer Deaths

What are your greatest concerns about the potential long-term impact of the COVID-19 pandemic on cancer care?

The longer the pandemic goes on and the more disruptions we have to cancer care, the more upstaging in cancer we will see. In other words, patients will not be diagnosed early through screening, when they first become symptomatic. In our CISNET forecast modeling, we had a couple of different scenarios—one centered on screening alone being affected, and one centered on usual care for symptomatic evaluation of patients alone that was impacted. What we published is the combined analysis of what we think will happen in the real world, but we also found there is an interaction between those two things. There is synergy; if you stop screening, those patients with aggressive cancer will present with a symptomatic cancer later and will not be evaluated because of the pandemic, and care will be further postponed.

So, there is a dramatic combination side effect on upstaging, and that is why I don’t expect the bad news to be linear. For example, if you double the amount of time that we can’t take care of patients, you double the poor outcomes. I think it can be worse than that. If the pandemic were to go on longer, at some point we might have an even more dramatic interaction to create upstaging and worse diagnoses.

It is important to note the historical background here. We’ve seen a decline in cancer and cancer mortality every year since the early 1990s. This trend reflects a number of successful interventions, including early screening and detection, prevention approaches, tobacco control, as well as better treatment, better surgery, better radiation techniques, better combination chemotherapy regimens, and the advent of chimeric antigen receptor T-cell therapies. All of these factors have contributed to this remarkable decline in cancer mortality.

Typically, that decline is about 1% to 2% per year. But now, we are starting to see the pandemic’s effects on cancer mortality, which could be to that degree in the other direction—a 1% to 2% excess in mortality in 2021, 2022, and 2023. Right now, I think that is unlikely.

Overcoming the Slowdown in Drug Development

What will be the impact on cancer research as clinical trials are disrupted during the pandemic? Will there be delays in discovery and FDA approvals of new treatments of cancer during this time?

The NCI can regrant, disperse grants, and conduct research during this time. We are open for business. We are able to do what we need to do, and the FDA is able to do its work. Even while we are all teleworking, the FDA can review new drug applications and approve new drugs. It is surprising that much of the federal process can go on just fine during a prolonged period of telework, so that is the good news.

However, the bad news is that accrual to clinical trials has really suffered. At the NCI Community Oncology Research Program, our National Clinical Trials Network, and the Experimental Therapeutic Clinical Trials Network, we’ve seen an almost 50% decrease from peak accrual. It is beginning to tick back up, but it’s where it was. Accrual in pharma-sponsored clinical trials has been affected to an even greater degree, on the order of 70%. Nontherapeutic trials, for example screening trials, have also been severely affected by the pandemic despite our efforts at maximal flexibility, including allowing telemedicine and simplifying the clinical trials process.

This is bad news because clinical trials lead to progress for new therapies and new approaches in cancer care. The expense of conducting a clinical trial and the duration of the trial are directly related to the patient accrual rate. If you cut that rate in half, clinical studies take twice as long and cost twice as much to complete, and that will lead to a downturn in drug approval.

If the pandemic had not occurred, we would be looking at one of the best years ever—possibly the best year—for new drug approvals in oncology. So, 2020 was looking like a great year for cancer progress until March. Now, we are getting trials restarted, and, hopefully, we can return to that very high–performance rate quickly. However, it is impossible to think these disruptions to clinical trial accrual will not slow meaningful drug discovery for a year or two.

Expanding Research Resources to COVID-19

Have funding and human resources been diverted from cancer research to investigate therapies and vaccines for COVID-19?

We have been asked by Congress and the National Institutes of Health to help with the COVID-19 research efforts, and we are complying. For example, our Frederick National Laboratory for Cancer Research is doing serology testing on human papillomavirus and other viruses, so we repurposed some of that lab’s capacity to work on coronavirus research. I believe these research efforts are also good for cancer; getting patients back to the hospitals and clinics as quickly as possible will be very good for patient outcomes, so we all want to see an end to the pandemic as soon as possible. I think virology research related to coronavirus serology will be valuable to understanding the basic biology of the immune response, which underpins cancer immunology. So, I am excited about those studies scientifically and believe they will be very important to the cancer effort as well.

This modest use of some of our capabilities has been necessary and has not hurt the agency. Our main job of trying to end cancer suffering has proceeded unabated despite the need to work on other diseases and given the fact that our employees are teleworking.

The bigger impact of the pandemic has been the inability of scientists to return to the laboratories to do basic research and, as I mentioned, to resume clinical trial accrual. We are concerned about these issues and are trying to figure out how we can get the scientific engine restarted quickly.

To ensure the continuation of NCI research, we have allowed flexibility for NCI grant recipients, so they can conserve their funds during the pandemic and carry over those funds into 2021 as their laboratories restart. That should be reassuring to scientists who may be concerned about their NCI funding expiring in 2020.

We also understand that philanthropic donations to foundations have declined because of the tough funding environment right now, and many of those donations fund training grants. To help address this challenge, the NCI put out a notice to postdocs stating that if their funding from a foundation has been interrupted because of the pandemic, and they work in a lab that already has an NCI grant, they can ask for a supplement to that grant to fund their work until their fellowship is restarted.

Studying the Effects of COVID-19 on Patients With Cancer

What are you learning about the effect of COVID-19 on patients with cancer?

We are supporting a few cancer and COVID-19 registries, including the COVID-19 and Cancer Consortium Registry (CCC19; https://ccc19.org). We have also opened our own clinical trial, the NCI COVID-19 in Cancer Patients Study (NCCAPS; https://clinicaltrials.gov/ct2/show/NCT04387656) to collect blood samples, medical information, and images from patients with cancer diagnosed with COVID-19. The study will allow us to analyze the severity of the coronavirus in these patients and the effects of the virus on cancer therapy and clinical outcomes. It will also give us the ability to perform biomarker studies to understand the prevalence of cytokine abnormalities, as well as perform germline sequencing to define genetic polymorphisms associated with severe COVID-19 disease and mortality.

So far, the registry efforts have taught us that some patients with cancer who contract COVID-19 seem to have a worse prognosis than those without cancer. For example, patients with lung cancer and those with hematologic malignancies seem to have worse outcomes, which is not surprising. We are also seeing that these patients are likely to gain access to some of the experimental medicines for COVID-19, including remdesivir, dexamethasone, and tocilizumab for COVID-19–induced cytokine-release syndrome. However, there is more to learn.

The most interesting question to me about COVID-19 clinical outcomes is why there is such a strong age disparity in outcome. I can’t think of another viral disease in which the illness is so much more lethal in an 80-year-old patient than a 20-year-old patient. There is a notion that certain types of cancer therapy, such as cytotoxic therapies like platinum-based chemotherapy and radiation therapy, cause a form of physiologic or accelerated aging, putting older patients with cancer at greater risk of death from COVID-19.

This is an interesting scientific question. The NCI and the National Institute on Aging have held joint meetings on the topic to see whether this notion is true and whether anything can be done to circumvent worse outcomes in these older patients. We have learned a lot about the clinical outcomes of this virus since March, but there are more key questions to address regarding clinical approaches to improve outcomes.

Preparing for the Next Health Disaster

What lessons can be taken from this pandemic to better prepare us for future catastrophic health events?

This is an interesting discussion we are going to have after life returns to normal. There are a lot of lessons to be derived from this pandemic that will affect how we approach clinical care going forward. The COVID-19 pandemic has exposed our challenges in collecting health-care data, and I think that process could be improved without overhauling the entire health-care system.

Even within the current health-care system, we can have a much stronger and more aggregated data collection system. Such a system would allow us to know in real time what is happening to patients with cancer, heart disease, Alzheimer’s disease, or a new health problem.

Having such a system in place would be a clear public health good, both for a pandemic response and for the implementation of general usual health care, and we are going to have to look at how to accomplish this goal. There are a lot of great capabilities regarding data collection, but we are not making full use of them to improve our knowledge about patient care. We must do better. 

DISCLOSURE: Dr. Sharpless reported no conflicts of interest.

REFERENCES

1. Epic Health Research Network: Preventive cancer screenings during COVID-19 pandemic. Available at www.ehrn.org/wp-content/uploads/Preventive-Cancer-Screenings-during-COVID-19-Pandemic.pdf. Accessed August 20, 2020.

2. Komodo Health: New colorectal cancer diagnoses fall by one-third as colonoscopy screenings and biopsies grind to a halt during height of COVID-19. Available at https://knowledge.komodohealth.com/hubfs/_RESEARCH_BRIEFS/COVID19_Impact_on_CRC_Patients_Research_Brief_Komodo_Health_Fight_CRC.pdf. Accessed August 20, 2020.

3. Johns Hopkins University & Medicine Coronavirus Resource Center: COVID-19 dashboard by the Center for Systems Science and Engineering at Johns Hopkins University. Available at https://coronavirus.jhu.edu/map.html. Accessed August 20, 2020.

4. Simon S: Fact & figures 2018: Rate of deaths from cancer continues decline. Available at www.cancer.org/latest-news/facts-and-figures-2018-rate-of-deaths-from-cancer-continues-decline.html. Accessed August 20, 2020.