COVID-19 and systemic anticancer therapy: exploiting uncertainty

The COVID-19 pandemic has not only disrupted lives, but has put health-care systems under considerable strain. The resource demands for the acute treatment of patients with COVID-19 had to be balanced against resources needed for regular care of patients with cancer during the peaks in COVID-19 incidence. Initially, there were concerns that patients with COVID-19 who were undergoing cancer treatment would have considerably increased mortality rates. Subsequently, cancer screening programmes were temporarily paused and cancer treatments were scaled down according to rapidly published guidelines.1, 2 The effect of reductions in treatments prescriptions on the prognosis of patients with cancer is not yet known, but the impact on patient concerns about their treatment and follow-up has been substantial. A survey of more than 5000 patients in the Netherlands has shown that even among patients who had no alterations to their treatment since the pandemic began, one in four patients reported being concerned or very concerned about potential consequences for their treatment or follow-up, with higher proportions reported in regions with incidence considered high enough to overwhelm health-care systems (>200 cases per 100 000 people).³ The restrictions on face-to-face consultations will have added to this uncertainty. At present, a second wave of COVID-19 is being observed in many European countries, and thus uncertainty remains. Practical strategies for clinicians have been proposed, to employ in conversations with patients, caregivers, and family to address the uncertainty associated with their care.⁴

In The Lancet Oncology, James Clark and colleagues⁵ analysed the impact of COVID-19 on systemic anticancer treatment registrations in England, immediately after lockdown and after new treatments were implemented to reduce patient risk, using registration data for systemic anticancer treatment for various oncological indications. A decrease in total registrations was observed immediately after the onset of the COVID-19 pandemic in April, 2020, when compared with the control period (September, 2019 to February, 2020; relative reduction 32%, absolute difference 4·2 SDs, p<0·0001), which was likely due to the reluctance of clinicians to expose patients to harm from oncology treatments, the fear of patients contracting COVID-19 in the hospital, a reduction in referrals and subsequent diagnoses, and reduced capacity of hospitals. The total number of registrations increased in May, 2020, but remained 10% lower than in the control period (absolute difference 1·3 SDs, p<0·0001) and in June, 2020, the number of registrations had increased by 15% when compared with the control period (absolute difference 1·9 SDs, p<0·0001). It is impossible to infer causality from these registration data, but the analyses of registrations between April and June, 2020, provide a convincing case for the conclusion that the quick recovery of systemic anticancer treatment prescriptions was attributable to treatments given temporary approval by the UK National Health Service.

Innovative strategies to decrease the burden of treatment for health-care systems were welcomed after the onset of the pandemic. The rapid implementation of newer anticancer treatments, possibly with a better risk–benefit ratio, as described by Clark and colleagues, seems reassuring, but also highlights some issues that require discussion. Refraining from neoadjuvant treatment with little survival benefit or palliative treatment that only extends life by a few months, as proposed by Clark and colleagues, should always be an option in a process of shared decision making, not only during a pandemic. However, the default introduction of less toxic but more expensive regimens should be carefully considered and balanced against the sustainability of a health-care system that is already under pressure.

Generally, in Europe, the European Society for Medical Oncology magnitude of clinical benefit scale⁶ is adopted to guide the use of new anticancer drugs. Rapid availability for high priority indications based on this scale should not be delayed.⁶ Late introduction of new and active medication might lead to loss of life-years in general.⁷ Use of new expensive medications outside the registered indication (eg, for an earlier line of therapy), has the potential to cause harm. Nevertheless, the COVID-19 pandemic has lead to more thoughtful provision of toxic adjuvant and palliative regimens with only small benefits, and thus could provide a unique window of opportunity for assessing the effects of de-escalating systemic anticancer therapy, which might stimulate the development of more refined and less toxic treatments.⁸ The decision on whether the benefits are worthwhile, considering not only the toxicity but also the burden of treatment and the long term side-effects, should always be shared with the patient during treatment consultations.9, 10

The COVID-19 crisis has forced oncologists to make choices in unpredictable situations, and to limit treatments, especially in the non-curative setting.² This issue has lead to uncertainty among both clinicians and patients and their families, which should be recognised and discussed.⁴ This pandemic might result in more careful evaluation of indications for treatment, and after the crisis has ended, to involve patients in decisions about these treatments.

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