INNOVATIONS IN 26 November 2021
Illustration by Harry Campbell
As the novel coronavirus swept through Boston last March, Toni Choueiri was worried. He was concerned not only about the rapid rise in COVID infections but about the swift shutdown in cancer screenings.In Boston—and around the nation—colonoscopy suites stood empty as patients refused to come in, terrified of setting foot in any hospital or clinic. Screening center schedules, once full of mammography appointments, cleared dramatically. Hospital corridors quieted; screening center workers were sent home. Hospital administrators struggled to find enough PPE to take care of urgent surgeries, and elective procedures fell to the wayside. As COVID cases surged frighteningly across the country, cancer detection seemed to be the last thing on anyone’s mind.Choueiri, who directs the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute, saw a steep drop in new consultations in the pandemic’s early months. The veteran oncologist feared that the lack of screenings, which aim to detect cancer at its earliest stages, would lead to a tidal wave of missed diagnoses. He worried about tumors seeding, taking hold, growing and metastasizing without being detected. He envisioned a future with streams of patients who had cancers so advanced he could no longer cure them. Part of Innovations In Early Cancer Detection Driven by these concerns and a desire to know exactly how bad the problem was, Choueiri and his colleagues turned to the data. Their study, published in JAMA Oncology in January 2021, showed a steep drop in screening from March to June of 2020 in his health system, Massachusetts General Brigham. More than 60,000 patients are typically screened there for cancer in a three-month period; in the first three months of the pandemic, he says, fewer than 16,000 came in for tests. In those early days National Cancer Institute officials estimated the pandemic would result in 10,000 excess cancer deaths in breast and colon cancer alone over the coming decade.Screenings for some cancers fell by 90 percent when COVID struck, making a postpandemic surge of cancer deaths seem a foregone conclusion. As the pandemic wore on, some cancer centers began to report a worrisome increase in advanced cancer diagnoses. But as more time passed and screenings resumed, the outlook grew less dire. COVID may prove to be a grand experiment assessing the import of cancer screening, and results are beginning to trickle in. But because both the disease and its epidemiology are so complex, those results may take years, or even decades, to become clear.Skipped ScreeningsOne patient whose pandemic screening turned up early-stage breast cancer was Senator Amy Klobuchar of Minnesota. After delaying the procedure, she had a routine mammogram in February 2021. With surgery and radiation completed and a good prognosis in hand, Klobuchar is urging others not to put off their screenings. ‘I hope my experience is a reminder for everyone of the value of routine health checkups, exams and follow-through,’ she wrote in a recent blog post.Cancer kills some 600,000 people in the U.S. every year. Screening tests such as Pap smears, mammograms, colonoscopies, lung scans and prostate-specific antigen tests clearly save lives: although rates vary by cancer type, five-year survival is consistently higher when the disease is caught in its early stages. Yet as the pandemic spread throughout the U.S. and the world, rates of those routine screenings fell precipitously. This was especially true for colonoscopies, the most invasive screening and an exam that many avoided even before the pandemic. Choueiri’s health system usually performs more than 9,000 colonoscopies in any three-month period; in March, April and May of last year, there were just over 1,700 in total. Similar drop-offs were seen across the country, where in some cases up to 95 percent of colonoscopies were missed in the first months of the pandemic.Screening rates synchronized with pandemic waves, bouncing back in the summer of 2020 before falling during subsequent surges. Those who never rescheduled may be up to two years behind. ‘Between the peaks, what we didn’t see was sufficient recovery,’ says Karen E. Knudsen, chief executive officer of the American Cancer Society. ‘We’ve made progress getting people back in the door, but there’s a large population that is underscreened. We don’t know the impact of this yet, but it’s definitely a problem.’One major issue, Knudsen says, is that people who miss screenings aren’t always flagged for follow-up. And some tests, such as those for prostate cancer, are harder to track using medical records because of how they are coded. In fact, she says, determining how many people are overdue for screening is virtually impossible because of the diverse settings in which patients receive screenings and because there is no national infrastructure that tracks them in real time. ‘We don’t know who didn’t come back,’ Knudsen says.According to a study published in JAMA Oncology in April, nearly 10 million people missed screenings for breast, colon and prostate cancer between March and May of 2020, but no one knows how many of those tests remain unscheduled. Those who missed screenings, Knudsen says, are likely to be people who haven’t been screened before, because they either just became eligible during the pandemic or were already hesitant. ‘We can infer that hesitancy is only enhanced with COVID,’ Knudsen says.Tracking Missing PatientsCoaxing overdue patients into a clinic is one of Rachel Issaka’s primary concerns. Issaka, a gastroenterologist and assistant professor at the Fred Hutchinson Cancer Research Center and University of Washington, says it is critical that health systems track down these missing patients. A study she published in June found that hundreds of colonoscopies were canceled between March and May 2020, and more than half of those people had not yet returned. Of those who did, more than 5 percent had new cancers. That implies that around 5 percent of the people who haven’t returned may also have cancer, she says, but won’t know it. Similar scenarios are likely playing out at health systems across the country; a study that surveyed gastroenterology practices last year found that two thirds did not yet have a plan in place to follow up on missed appointments, although some have now begun this work in earnest.Issaka is working diligently to contact and shepherd in her more skittish patients. One powerful tool is at-home detection tests for colon cancer. A low-cost fecal immunochemical test, or FIT, can detect blood or tumor DNA in stools and catch 70 percent of colon cancer cases. But a positive FIT result requires a follow-up colonoscopy, and scheduling that, Issaka says, remains challenging. Credit: Jen Christiansen; Source: ‘Trends in Breast Cancer Screening in a Safety-Net Hospital during the COVID-19 Pandemic,’ by Hana I. Velazquez et al., in JAMA Network Open; August 6, 2021 (data)
Telehealth has proved a surprisingly effective way to persuade overdue patients to visit the clinic. A study published in JAMA Oncology last spring examined the precipitous drop in breast, colon and prostate cancer screenings and found that telehealth patients were more likely to come in for exams. Patients who are concerned about in-person screenings can use telehealth appointments to talk with their primary care physicians about setting up a plan based on personal and familial risk factors, says the American Cancer Society’s Knudsen. ‘Screening is knowledge. It’s power,’ she says.Although much communication in oncology, particularly of bad news, is best done in person, the pandemic has shown that telemedicine can play an important role in cancer care and should remain in place, says Choueiri, who is also a professor of medicine at Harvard Medical School. ‘It’s helped a lot,’ he says. ‘We can stay in touch with patients, maybe even better than before.’The pandemic-imposed challenges to screening prompted the American Cancer Society to create tool kits explaining current screening guidelines in clear and simple language. It is also spreading the word that patient access to screening must be made easier. One way is to move screenings out of hospitals and into clinics and, when possible, even mobile vans. Another is to open up scheduling in off-hours. ‘Can you do screenings on Saturdays or in the evenings?’ Knudsen asks. ‘Those turned out to be really popular times for mammography.’Uncertain Mortality ModelsThere is little doubt that the chaos ushered in by the pandemic will lead to more cancer deaths. But determining how many has been difficult: many cancers are slow-growing, their development can be complex, and factors such as treatment decisions play a big role in outcomes. To assess how missed screenings might affect cancer mortality rates, the National Cancer Institute turned to Oguzhan Alagoz, a professor of industrial and systems engineering at the University of Wisconsin–Madison whose research involves modeling both cancer epidemiology and infectious diseases.’The question is really interesting because it’s a combination of the two areas I work in,’ Alagoz says. His first estimates, unveiled in a widely read editorial published in Science in June by NCI director Normal E. Sharpless, showed that missed screenings might result in 5,000 additional deaths in breast cancer alone over the next decade. A separate group, looking at missed colon cancer screenings, predicted another 5,000 deaths.When Alagoz produced his breast cancer estimates early in the pandemic, he thought the numbers might not be truly representative. So he worked to refine them, using better data with three powerful cancer models that incorporated numerous factors related to breast cancer—such as delayed screening, treatment effectiveness and long-term survival rates—and the nuanced ways they intersect to affect mortality over time. ‘Everyone can tell you what will happen immediately, but it’s hard to say what’s going to happen in five or 10 years,’ Alagoz says. ‘If there’s a huge increase in smoking, you’re not going to see more lung cancer right away. You’re going to see that 10 or 15 years down the road.’After a more detailed analysis and after seeing screenings rebound from what he calls the ‘panic phase’ of March and April 2020, Alagoz now says those early mortality numbers were far too high. In revised estimates, published in the Journal of the National Cancer Estimate last April, Alagoz and his colleagues suggested the pandemic could lead to 2,500 excess breast cancer deaths in the coming decade, half as many as they had first predicted. ‘The entire estimate was too pessimistic,’ he says. ‘Any individual death is sad, but if there is any silver lining, it’s that this isn’t as bad as we feared.’One reason death rates may be curbed, Choueiri says, is that oncologists did aggressive triage work to screen and treat patients who needed care most. His hospital system reported fewer missed cancer diagnoses than he expected, and he thinks this was because people at highest risk of cancer and those with palpable symptoms were most likely to be screened even during the pandemic’s most dangerous peaks. ‘Screenings never stopped 100 percent,’ Choueiri says. ‘Who were the patients who continued to be screened? They were the highest, highest risk.’Some oncologists say this ‘risk stratification’—prioritizing screening, diagnosis and treatment for those most at risk or with obvious symptoms—should stay in place after the pandemic ends so treatment can be provided quickly to those who need it most.COVID’s Long ShadowUnderstanding the pandemic’s effects on cancer mortality is a complicated task because delayed screenings aren’t the only factor involved. Increased alcohol consumption and reduced physical activity—behaviors common during long pandemic lockdowns—can increase cancer risk as well. But postponing an exam can be a major danger. In November 2020 Vincent Valenti, a retired screenwriter in Brooklyn, noticed his voice was hoarse. He attributed it to all the screaming he did on election night. But it persisted for weeks, and his girlfriend encouraged him to get it checked. Valenti, 71, refused. He wasn’t going near a hospital or doctor until he was vaccinated. ‘You walked by hospitals, and there were all these morgue trucks parked outside,’ he says. ‘I knew something was wrong, but I wasn’t going to go near a hospital.’ In February of this year, once he had received two doses of vaccine, he scheduled an appointment with an E.N.T. ‘She scoped me and jumped back,’ he says.There was a tumor on his larynx, stage 3, that had almost reached his lymph nodes. It was a shock to both Valenti and his doctor. He wasn’t considered high risk for laryngeal cancer because he doesn’t drink heavily or smoke. After seven weeks of chemotherapy and radiation, Valenti says, there was no trace of the tumor, and a recent PET scan confirmed that the cancer did not metastasize. Valenti was told his cancer would likely have been caught at stage 2, or even stage 1, if he had gone in right away. Credit: Jen Christiansen; Source: ‘Changes in Newly Identified Cancer among U.S. Patients from before COVID-19 through the First Full Year of the Pandemic,’ by Harvey W. Kaufman et al., in JAMA Network Open; August 31, 2021 (data
Research published in JAMA Network Open in August shows that Valenti is far from alone. The study reports that diagnoses of eight cancer types dropped nearly 30 percent during the first pandemic wave of 2020, rebounded somewhat during the summer and early fall, then fell by 20 percent during the pandemic’s winter surges. Such consistently low numbers indicate that many cases will continue to be undiagnosed, the authors wrote.Some programs have already reported an increase in the detection of cancers. Lung cancer, the nation’s leading cause of cancer death, is of particular concern because it can be so aggressive. The University of Cincinnati’s lung cancer screening program was closed for three months. When screening resumed, patients remained scarce, and no-shows were frequent. But among those who did come in, ‘we noticed we were seeing many more suspicious lung nodules than usual,’ says Robert Van Haren, a thoracic surgeon and assistant professor of surgery at the University of Cincinnati Medical Center, who analyzed the effect of the pandemic on cancer screenings. ‘Even small changes in the size of a lung cancer can be important for overall survival,’ he says. ‘That’s th
https://www.nature.com/articles/d41586-021-03404-7
