In just
a few short weeks, the coronavirus disease 2019 (COVID-19) pandemic has
transformed health care delivery around the globe. The crisis has dismantled
how care is delivered and forced clinicians to make difficult triage decisions
about what types and components of care have limited immediate value and which
are essential for optimal outcomes. Because some malignancies could pose an
immediate threat to survival, cancer provides a lens into the major shifts
currently underway in clinical care. Cancer and cancer-related treatments
frequently cause immunosuppression, and patients with cancer have excess
mortality risk from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
The magnitude of this risk is not yet known but early reports suggest a
substantial increased risk of death associated with COVID-19 infection among
patients with cancer, perhaps highest among those older than 60 years and those
with pulmonary compromise.1,2
The prevailing
clinical approach in medicine, the in-person visit between patient and
physician, has been upended. To flatten the growth curve of the COVID-19
pandemic, physicians have postponed or canceled nonacute procedures and
transitioned millions of visits to telehealth. The technology used to effect
this transformation is not new, but COVID-19 has forced widespread adoption of
remote encounters by video applications, patient portals, or phone calls.
Patients and oncologists have rapidly adapted to this new way of communicating
and many have found this approach satisfactory and sometimes preferred.
Barriers to remote care previously precluded by entrenched culture or billing
hurdles have quickly been surmounted.
In this
unprecedented context, what frameworks should be used to inform decisions about
how to modify cancer treatment based on patient and cancer-specific factors?
Oncology care generally falls into 4 categories: First is care that is not time
sensitive, can be delivered remotely, or both. This includes survivorship and
surveillance visits for patients who have completed cancer treatment and have
no acute symptoms to suggest recurrence. Low-risk patients receiving hormonal
or oral chemotherapy also can usually be evaluated remotely, and, in most cases,
blood work and imaging studies could be deferred until health system capacity
has recovered.
Second
is care that cannot be delivered remotely but for which treatment omission or
delay has a marginal effect on quality or quantity of life. A sizeable proportion
of oncology care involves systemic chemotherapy for patients with advanced
cancer. When clinical trial data demonstrate that the incremental survival
benefit of this therapy is limited, then omission or delay is appropriate given
the balance of potential benefit of treatment vs the risk if the patient
becomes infected with SARS-CoV-2. For example, for most metastatic solid
tumors, chemotherapy beyond the third regimen does not improve survival for
more than a few weeks; therefore, oncologists are advising supportive care
instead. For patients receiving adjuvant therapy for curable cancers, delaying
initiation or abbreviating the number of cycles is appropriate. Oncologists are
postponing initiation of adjuvant chemotherapy for some estrogen receptor–negative
stage II breast cancers by 8 weeks and administering 6 rather than 12 cycles of
adjuvant chemotherapy for stage III colorectal cancers. Because screening for
breast, colorectal, lung, and prostate cancer has been halted, the proportion
of screen-detected early-stage cancer is expected to decline over the next
several months. Although some patients are willing to undergo treatments for
small benefits, the pendulum of risk related to immunosuppression and exposure
at a health care facility tip the risk-benefit ratio away from treatment.
Low-grade tumors include many prostate cancers, carcinoid and neuroendocrine
tumors, some thyroid cancers, some central nervous system tumors, and some
lymphomas, for which treatment usually can be safely postponed by 8 to 12 weeks
or longer. The COVID-19 crisis is forcing elimination of low-value treatments
that were identified by the Choosing Wisely campaign, even though uptake of
recommendations to eliminate these treatments has previously been adopted
slowly.3
During
the pandemic, triage decisions require even more interspecialist coordination
and communication than usual. Postponing surgery and administering neoadjuvant
therapy as a bridge can decrease risk to the patient and preserve health care
resources. Similarly, radiation oncologists may omit, delay, or use shorter
courses to reduce the number of visits.
Third,
and most challenging, are situations for which delay has a moderate clinically
important adverse influence on quality of life or survival. For example,
randomized trial evidence demonstrates that 3 years of maintenance rituximab
after autologous transplant for mantle cell lymphoma improves overall survival
by 9%.4 Although treatment omission
increases the chance of relapse, some oncologists are omitting or delaying this
treatment. The incremental benefits of treatments with higher risk of infection
become deprioritized, and for many cancer types, oncologists are reasonably
prescribing marginally less effective regimens that have lower risk of
precipitating hospitalization. Oncologists are also using white cell growth
factor, more stringent neutrophil counts for proceeding with a next cycle of
therapy, and omitting use of steroids to manage nausea. When possible,
oncologists are substituting oral for intravenous agents and myriad other
modifications to minimize visits and hospitalizations.
Fourth,
and more clear, is cancer treatment that has the potential to cure and cannot
safely be delayed. This includes most patients with new diagnoses of acute
leukemia, high-grade lymphoma, and those with chemotherapy-responsive tumors
such as testicular, ovarian, and small cell lung cancer. Despite the risks,
oncologists are not modifying such treatments because these cancers are likely
more lethal than COVID-19. For example, most allogeneic transplants cannot be
safely postponed. Both donors and recipients are undergoing SARS-CoV-2 testing
before induction starts.
Once a
patient’s cancer and perceived risk of contracting SARS-CoV-2 infection are
determined, the next step is to consider the capacity of the local health care
system to meet existing and projected needs. This requires knowledge about
whether the system is in the preparatory, acute, or crisis phase of the
pandemic. In the preparatory phase, the health care workforce is intact and
hospital beds and equipment including ventilators are available. In the acute
phase, the workforce has limited capacity but is functional and through
strategic reorganization, there is some ability to deliver routine cancer care.
In the crisis phase, the health care system is overwhelmed with COVID-19 cases
and has no surplus capacity with respect to hospital beds, equipment, or staff.
In the
first weeks of April 2020, oncologists in epicenters like New York City and
Detroit are often opting for regimens with lower efficacy but lower risk of
hospitalization, whereas oncologists in Denver and Raleigh have confidence—at
least for the moment—that beds will be available and therefore have not yet had
to make as many modifications. Although accrual to therapeutic trials has
slowed dramatically and acquisition of biospecimens for correlative studies has
largely stopped, oncologists remain focused on ensuring that clinical trial
participants can continue to receive their protocol-directed therapy and
evaluations where it is safe to do so. The twin goals are to minimize harms to
research participants and to ensure that disruptions from the COVID-19 pandemic
do not prevent the ability to test study hypotheses. Ensuring that the pandemic
does not exacerbate existing disparities for cancer patients based on race,
ethnicity, and class and access to specialty care is also a priority.
Oncologists
report unprecedented levels of cooperation and collegiality across borders.
Clinicians in Milan and Barcelona are sharing their experiences with those in
Boston and San Francisco. The oncology community has united to share
strategies, formulate guidance, collect data, and design and execute treatment
protocols. Clinicians report deriving comfort and professional solidarity from
these interactions. Consortia to identify which patients are most at risk of
infection, determine how antineoplastic therapies influence the course of
COVID-19 illness, and understand when it may be safe to resume treatment have
proliferated with remarkable speed and receptivity.
Many
patients with cancer are concerned that their needs will be overlooked or
marginalized during the COVID-19 crisis. Attending to these legitimate concerns
has become, and should be, a focus. Balancing the value of cancer treatments
with competing risks during a time of declining resources will increasingly
present ethical and logistical challenges to clinical standards and humanism.
Because most hospitals and outpatient infusion centers now prohibit visitors
from accompanying patients, there is intense attention on clarifying advance
directives, health care proxies, and end-of-life care preferences. Oncologists
and patients must prioritize these conversations.5 However, the essential empathy of
oncology practice will continue to transcend the new physical barriers
presented by masks and telehealth.
In the
space of a month, approaches and accepted norms of cancer care delivery have
been transformed of necessity. Most of these changes would not have occurred
without the pandemic. Although the immediate priority is to save lives, in the
aftermath and recovery phase, evaluating the effects of COVID-19 on cancer
mortality will be a priority. Planning for resuming cancer treatment and
screening to mitigate harms is already underway. It is also likely that some
changes provoked by the crisis will permanently transform how to treat cancer,
in some cases perhaps for the benefit of both patients and their physicians.
Article
Information
Corresponding
Author: Deborah Schrag, MD, MPH, Dana Farber Cancer Institute, 450
Brookline Ave, Boston, MA 02115 (deb_schrag@dfci.harvard.edu).
Published
Online: April 13, 2020. doi:10.1001/jama.2020.6236
Conflict
of Interest Disclosures: Dr Schrag reported receiving grants from
the National Cancer Institute, the Patient-Centered Outcomes Research
Institute, and the American Association for Cancer Research; receiving personal
fees from Pfizer; and receiving nonfinancial support from Grail. Dr Basch
reported receiving grants from the National Cancer Institute and the
Patient-Centered Outcomes Research Institute; and receiving personal fees from
Memorial Sloan Kettering Cancer Center, the Research Triangle Institute,
CareVive Systems, Sivan Healthcare, Navigating Cancer, and Self Care Catalysts.
No other disclosures were reported.
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