Poor clinical outcomes for patients with cancer during the COVID-19 pandemic.

According to global cancer statistics, there were an estimated 18·1 million new cancer cases and 9·6 million cancer deaths worldwide in 2018. In the ongoing COVID-19 pandemic, these millions of patients with cancer seem to be more susceptible to the viral disease than the general population. Indeed, they could be more likely to develop severe complications of COVID-19, owing to their immunosuppressed status caused by both the cancer and anticancer therapies, such as radiotherapy, chemotherapy, and surgery. In this urgent situation, it is crucial to characterise the clinical features, risk factors, and outcomes of patients with cancer and COVID-19.

In The Lancet Oncology, results from two independent, multicentre studies on patients with cancer and COVID-19 have been published—both done in Hubei, China, the initial epicentre of the pandemic. Kunyu Yang and colleagues investigated the clinical characteristics, outcomes, and risk factors for mortality in 205 patients with cancer and COVID-19. 30 (15%) patients were transferred to an intensive care unit and 40 (20%) died while in hospital. Receipt of chemotherapy within 4 weeks of symptom onset was a risk factor for in-hospital death (odds ratio [OR] 3·51 [95% CI 1·16–10·59]; p=0·026). Yang and colleagues also highlighted that compared with patients with solid tumours, those with haematological malignancies had a higher case-fatality rate (nine [41%] of 22 patients vs 31 [17%] of 183 patients) and had more severe events such as acute respiratory distress syndrome (six [27%] of 22 vs 17 [10%] of 177) and acute renal failure (four [18%] of 22 vs nine [5%] of 177). Faster disease progression, more frequent hospital admissions for chemotherapy, increased susceptibility to bacterial coinfection, and greater myelosuppression and immunosuppression could explain the poorer prognosis in patients with haematological malignancies compared with those with solid tumours. In the second study in The Lancet Oncology, Jianbo Tian and colleagues included 232 patients with cancer and COVID-19 during the same period, who were statistically matched to patients with COVID-19 without cancer. Tian and colleagues found that patients with cancer had increased risk of developing severe or critical COVID-19 than patients without cancer (OR 3·61 [2·59–5·04]; p<0·0001). They also identified several novel predictors for poor prognosis, such as advanced tumour stage (OR 2·60 [95% CI 1·05–6·43]; p=0·039), elevated tumour necrosis factor α (1·22 [1·01–1·47]; p=0·037) and N-terminal pro-B-type natriuretic peptide (1·65 [1·03–2·78]; p=0·032), and reduced CD4+ T cells (0·84 [0·71–0·98]; p=0·031).

It should be noted that the two studies have inherent limitations. Because both studies enrolled patients from hospitals designated for COVID-19 treatment, there is overlap in the hospitals involved and thus possibly in the patients enrolled. Both studies were retrospectively designed, with incomplete documentation, recall bias, and a lack of dynamic clinical and laboratory data. The sample sizes were not large enough to support the results with high confidence. Neither study was able to analyse the relationship between clinical outcomes and treatment strategies. Moreover, the authors did not analyse the frequent thrombophilic complications in cancer as well as in COVID-19: deep vein thrombosis and pulmonary embolism. Despite these limitations, the two groups have provided information that can help to provide more appropriate care for patients with cancer and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and monitor reliable markers during the infection course.

A few other short reports with small sample sizes have also focused on patients with cancer, describing clinical characteristics of patients with cancer and investigating their prognosis.5, 6, 7 The studies found higher risk of SARS-CoV-2 infection in patients with cancer compared with the general population in Wuhan, and higher risk of severe events in patients with cancer and COVID-19, particularly those who had received antitumour treatment recently. When taking all studies into consideration, patients with cancer and COVID-19 in China have a case fatality rate of up to 20%, which is much higher than that of the community (1·8–7·2%), as reported in various countries (figure ). Moreover, patients with cancer who had received chemotherapy, targeted therapy, or immunotherapy, or had undergone surgery 2–4 weeks before presenting with COVID-19 were found to have an approximately 4-times higher risk for in-hospital death than patients who had not been recently treated with anticancer therapies (figure). Targeted therapy and immunotherapy are of particular concern during the pandemic. In multivariable logistic regression analysis in the study by Tian and colleagues, these therapies were found to confer a 3·29 times (95% CI 1·26–8·61; p=0·015) increased risk of developing severe COVID-19. Therefore, oncology teams should pay close attention to immunotherapy-related adverse effects, such as severe neurotoxicity, myocarditis, and pneumonitis, which might negatively affect survival of patients with COVID-19.

Figure

Pooled analysis from the current published evidence

(A) Case-fatality rate of patients with cancer and COVID-19. (B) Odds ratio for in-hospital death for patients receiving anticancer therapies within 2–4 weeks before onset of COVID-19 versus those who did not receive such anticancer therapies. *Weights are from random-effects analysis.

The data described above raise an important issue: should anticancer treatment be postponed during the COVID-19 pandemic? We should keep in mind that the primary risk for patients with cancer during the pandemic is reduced access to hospitals and inability to receive necessary medications in a timely fashion. This pandemic is putting unprecedented pressure on health-care services worldwide, which have become increasingly focused on caring for patients with COVID-19. All aspects of cancer treatment have been affected: not only screening, referral, and clinical testing in symptomatic cancer diagnosis, but also treatment and follow-up of patients with cancer. A report from the Netherlands has shown a decrease in cancer diagnoses during the COVID-19 pandemic, with the overall rate of cancer diagnosis decreasing by 27% from Jan 6 to March 2, 2020. Patients might be anxious about being exposed to SARS-CoV-2 in a health-care setting, and might struggle to consult with a general practitioner in the midst of strict social distancing and lockdown policies. In this context, treatments for people living with and beyond cancer are being delayed. Some patients with cancer—especially those with haematological malignancies—are at increased risk of disease progression, tumour relapse, and death while waiting for treatment. Therefore, it is likely that postponing cancer care without consideration of its implications could cost more lives among patients with cancer than COVID-19 itself. Extreme caution is required in delaying life-saving cancer therapies.

Some preliminary recommendations have been proposed to guide decisions on delaying or continuing cancer treatment during the COVID-19 pandemic. They are based mainly on categorising patients into low, moderate, or high risk of disease progression without anticancer treatment. For some types of tumour including lung and pancreatic cancer, acute leukaemia, and highly aggressive lymphoma, timely diagnosis and management are warranted. For others such as breast and thyroid cancer, delaying therapeutic interventions might be considered. Such a modification might not affect long-term outcomes, whereas their potential exposure to COVID-19 could be risky or even fatal. These recommendations can be cautiously applied in current clinical practice until evidence-based guidelines are available.

In conclusion, patients with cancer have worse clinical outcomes of COVID-19 than those without cancer. Further studies regarding comprehensive management of patients with cancer and COVID-19 are urgently needed to provide better health care to this patient population.