Despite widespread vaccination, patients with cancer still face a slew of pandemic-related challenges.
The COVID-19 pandemic has been hard on people living with cancer — and Maura Dowling, an oncology nursing specialist from the National University of Ireland Galway, wanted to know more about the patient experience. So, over the course of this past year, she and her colleagues periodically interviewed patients in Ireland, first as the country emerged from its January peak in COVID-19 cases and later as national vaccination campaigns got underway.
For many people battling cancer, the vaccine rollout brought a sense of relief and hope, says Dowling. “It’s almost the equivalent to winning the lotto, having this full vaccination,” one patient told her. “Now that I’ve had the second dose, I really feel way more, you know, just relaxed about everything,” said another.
But even with the widespread availability of highly safe and effective vaccines in many parts of the world, patients with cancer are by no means in the clear — and will not be for some time — when it comes to the burdens imposed by the COVID-19 pandemic.
High rates of ongoing viral transmission have forced vulnerable patients to remain largely isolated. Breakthrough infections, although typically less severe among the vaccinated, can still disrupt treatment. And not every patient with cancer retains the immune function to garner the full benefits of inoculation.
Moreover, many patients are still dealing with the enduring effects of long-haul coronavirus infections. Plus, cancer clinics, although ostensibly back in full operation, are still adapting to the new realities of post-pandemic medicine — which includes trying to address disruptions in the screening, diagnosis and treatment of many patients who slipped through cracks during the global health crisis.
“Back to normal doesn’t necessarily take into account the backlog,” says Larissa Nekhlyudov, a cancer survivorship specialist at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute, both in Boston, Massachusetts. “And we don’t know what the lingering effects will be of delayed screening and delayed cancer treatment.”
So far, the effects seem to be manageable. In the Netherlands, clinical epidemiologist Sabine Siesling and her colleagues have been following patient outcomes ever since the country’s national screening programs for breast, colorectal and cervical cancers were temporarily suspended at the beginning of the pandemic. Diagnoses of new cancers consequently plummeted through much of last year, as people missed their usual mammograms, colonoscopies and Pap smear tests. With those programs up and running again, the incidence of screen-detected tumors is back to pre-pandemic levels — but it is not noticeably elevated in a way that would indicate any sort of clinical catch-up.
Intuitively, one might then expect that as more early-stage cancers go undiagnosed, patients might be presenting to oncologists with more-advanced and aggressive disease — and, anecdotally, that does seem to be the case in some places. “We are certainly seeing people diagnosed at later stages,” says Deborah Doroshow, a lung cancer specialist at the Tisch Cancer Institute of the Icahn School of Medicine at Mount Sinai in New York City. But according to Siesling, her team has not yet observed any such ‘stage shift’ in their national cancer registry records.
Could it be that pandemic-related disruptions in screening efforts were not long enough to cause any major, population-scale changes in patient outcomes? “It’s a bit reassuring,” says Siesling, who holds dual appointments at the Netherlands Comprehensive Cancer Organisation in Utrecht and the University of Twente in Enschede. But longer-term follow-up is still needed to assess the full impact of COVID-19-related screening delays, she points out.
One potential upshot of fewer people getting screened for cancer is fewer people receiving invasive treatment for the earliest forms of disease. Take, for example, ductal carcinoma in situ (DCIS). Detected by mammography, these pre-invasive tumors occur when breast cancer cells take root inside the walls of the milk ducts, but have not spread to surrounding tissue. The standard treatment remains surgery, often followed by radiation and hormone therapy. But with fewer than half of DCIS cases progressing to invasive cancers, some oncologists have long advocated active surveillance instead.
Laura Esserman is a breast cancer surgeon at the University of California, San Francisco, and one of the most vocal proponents of this ‘watchful waiting’ strategy. “The pandemic has made this approach more acceptable,” she says. And together with new decision-making tools that Esserman is working on to personalize the treatment of DCIS, she hopes that more clinicians will embrace a less aggressive approach to managing pre-invasive cancer, even now that hospitals and screening programmes are back to business as well. COVID-19 “certainly has opened people’s minds to different approaches — and that is good,” she says. “What we need,” Esserman adds, “are more trials and more innovative approaches to learn how to better manage this condition.”
Pandemic-related healthcare campaigns have also provided clinicians with new opportunities to engage people in cancer-prevention efforts. In Philadelphia, for example, internist Carmen Guerra and her colleagues from the Perelman School of Medicine at the University of Pennsylvania have been offering fecal immunochemical testing kits, an at-home screening option for colorectal cancer, alongside vaccines and diagnostic tests for COVID-19 — plus flu shots — at pop-up clinics around the city.
By partnering with community groups and predominantly Black local churches, Guerra, the associate director of diversity and outreach for the University of Pennsylvania’s Abramson Cancer Center, hopes to address racial health disparities in the dual burdens of cancer and COVID-19.
People with certain forms of cancer do not always stand to gain from vaccination. Although studies show that patients with solid tumors generally develop robust immune responses after vaccination, regardless of whether they are receiving active treatment or not, those with hematological cancers often do not.
This is especially true for people with B cell malignancies, such as chronic lymphocytic leukemia, or those taking B cell–depleting therapies such as the CD20-directed agent rituximab — because without the immune cells needed to mount a humoral response against the vaccine antigen, these patients develop few if any protective antibodies. “It’s quite impressive to see just how vulnerable some of our patients still are,” says Matthias Preusser, an oncologist at the Medical University of Vienna in Austria who has studied the issue.
Even without B cells, however, most patients do seem to generate vaccine-induced T cell responses, notes Samra Turajlic, a medical oncologist at the Francis Crick Institute in London. And studies of people with blood cancer who had impaired B cell function have linked elevated T cell counts with improved survival.
For these reasons, Turajlic advocates that all patients with cancer, regardless of disease or treatment course, be prioritized for full courses of vaccines, as well as booster shots as those become available in various countries. “The hope,” she says, “is that the boosters will bring these patients above the line as far as the neutralizing antibodies are concerned. And if not, they will further boost their T cell response.”
“The challenge clinically is when to give the COVID-19 vaccine to cancer patients,” notes Christopher Cogle, a hematologist and health-policy researcher at the University of Florida College of Medicine in Gainesville. For some patients, maximizing the immune benefits of vaccination may require pausing treatment with an immunomodulatory therapy. But, as Cogle points out, “you can’t give a treatment holiday without fear of the disease relapsing or progressing.”
Cogle would like to see more research into this issue that could inform best practices on how to immunize patients with cancer safely and effectively. “Not only would this be applicable to the current viral threat,” he says, “but it would be applicable to the next one that comes as well.”
There are, however, some patients who never produce cellular or humoral immune responses, even after a third dose of vaccine. Mount Sinai hematologist Samir Parekh thus advises routine screening of immune responses after vaccination for the most vulnerable patients with lymphoid malignancies. Extra safety measures and passive antibody treatments should then be considered for those who remain unprotected against the virus, he says.
With so much uncertainty about individual levels of vaccine-elicited protection, many patients with cancer have been erring on the side of caution when it comes to disease prevention. Cancer epidemiologist Shelley Tworoger and her colleagues at the Moffitt Cancer Center in Tampa, Florida, have been tracking the mood and behaviors of their patient population over the course of the pandemic. Despite the widespread availability of vaccines, Tworoger says, many people continue to engage in risk-mitigation practices such as social distancing, which fuels feelings of loneliness and takes a psychosocial toll on the patient community.
Those who have been immunized against COVID-19, along with vaccine-hesitant people who are unlikely to ever get the jab, are leaving the house and attending social gatherings somewhat more now than they did last year, Tworoger’s research shows. But “there’s still a lot of anxiety,” she says. “It doesn’t seem like vaccination is changing their risk mitigation behaviors as much as you’d expect. Cancer patients are still being very careful.”
That might help explain why many patients continue to see their medical staff remotely, even now that they have the choice of in-person visits. At the Seattle Cancer Care Alliance, for example, a steady 15% of all consultations continue to be done over computer screens, according to telehealth program manager Andy Peet. That number is down from a 40% high at the apex of the pandemic. But it is a major change from pre-COVID-19 times, when hardly anyone used the clinic’s telehealth services.
“That genie is out of the bottle,” Peet says. Tele-oncology “is becoming part of the new normal and just the way we offer cancer care.”
Many patients also simply enjoy the added flexibility in cancer care that the pandemic showed was possible. For Jill Feldman, a patient with lung cancer and advocate in Deerfield, Illinois, the initial coronavirus lockdown forced her to delay one of her regularly scheduled low-dose computed tomography scans. She ended up on a triannual schedule, instead of her usual four scans a year — a protocol she has stuck with close to two years later.
It might seem like only a small change, but “it makes a world of difference to me,” says Feldman, a co-founder of the EGFR Resisters, an advocacy and support group for patients with EGFR-positive lung cancer. It is only one less scan per year, yet to Feldman it means she can “forget about [the cancer] for a little while longer and live a more normal life.”
Long road ahead
Nothing is yet fully normal, however. And many patients with cancer who contracted COVID-19 are faced with reminders of their illness every day. According to one UK study, around 15% of all patients with cancer who have been infected with the coronavirus SARS-CoV-2 report lasting after-effects — and those persistent symptoms often lead to disruptions, discontinuations and adjustments to treatment that can negatively impact quality of life and survival outcomes.
Study author Alessio Cortellini, a medical oncologist at Imperial College London, presented these findings at the European Society for Medical Oncology’s (ESMO) annual congress in September. He is now looking for ways to minimize the impact of these ‘long COVID’ cases. By analyzing blood samples from patients with cancer who recovered from SARS-CoV-2 infection, he has identified a signature of inflammatory biomarkers that might help predict which people are most at risk for long-term complications. With this knowledge, Cortellini says, “we could then prioritize these people for proactive treatment.”
Among healthcare workers, surveys also show that many cancer specialists continue to feel professional burnout from the daily grind of COVID-19. Because of overwork and under-resourcing, one quarter of respondents to a global survey led by ESMO said they were considering a career change, including a departure from oncology practice entirely. “It is therefore urgent and vital for organizations and countries to monitor any changes in their workforce closely,” says Jonathan Lim, a medical oncologist at the Christie NHS Foundation Trust in Manchester, UK, who presented the study on behalf of the ESMO Resilience Task Force. That way, cancer clinics can plan their staffing needs accordingly.
Many cancer specialists are hopeful that with vaccines, precautions, time and experience, their patients’ care will look much like it did before the pandemic — perhaps with some improvements based on lessons learned over the last two years. “But I don’t think this will happen very soon,” Preusser says. “We just have to keep living with this for the time being.”
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Dolgin, E. Cancer’s new normal. Nat Cancer 2, 1248–1250 (2021). https://doi.org/10.1038/s43018-021-00304-7
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Nature Cancer (2021)