In this study of patients with cancer who developed COVID-19, we identified advanced age, history of smoking, palliative intent of treatment and presence of more than 2 comorbidities to be risk factors for severe COVID or death within 30 days. Advanced age and palliative intent of treatment remained independently associated with 30-day mortality. Recent systemic anti-cancer therapy, gender and cancer type were not significantly associated with adverse outcomes.
Since the onset of the COVID-19 pandemic, there have been concerns about the outcomes of COVID-19 in patients with cancer. A meta-analysis of 26 studies including 23736 patients with cancer found a pooled all-cause in-hospital mortality rate of 19%, with nearly three times higher odds of dying than those without cancer.4 Early data from China suggested that patients with cancer and COVID had a considerably poorer survival than the general population with mortality estimates between 20 and 29%.14–17 These studies were limited by their small sample sizes and largely retrospective nature. Subsequent studies from other parts of the world reported short-term mortality rates between 10% and 29% in patients with cancer and COVID, with the UK and some countries in Europe reporting much higher fatality rates than other parts of the world.5–7,18−21 The results from our study are at the lower end of the published range of fatality data on COVID-19 outcomes in patients with cancer.
The dissimilarity in results between these quoted studies need to be interpreted keeping in mind that they were done at various time periods corresponding to different phases of the pandemic. Studies at the beginning of the pandemic typically reported higher case fatality rates as very little was known about the disease and its management. Also, differences in testing strategies between countries may imply that in some studies, patients with cancer who were symptomatic with mild disease and potentially favourable outcomes may not have been identified as opposed to those with moderate and severe disease, resulting in higher estimated fatality rates. Another factor which needs to be considered is the indication for hospital admission. Our study and other studies from India10,11 reported only 4 to 11% of severe COVID cases among those admitted, compared to 20 to 45% in other studies.5,6,18,21 Inadequate facilities for home isolation, possibly led to a number of hospital admissions for social reasons in patients with mild disease, leading to a reduction in the proportion of those with severe disease and a decrease in hospital mortality. In addition, the outcomes of patients with cancer and COVID-19 need to be compared to the outcomes in the general population for that same country. Countries such as Italy and the UK have reported population case fatality rates of 3 to 5% compared to 1.1% in India .1 These differences could be partly related to population characteristics, with developed countries having a high proportion of elderly individuals with comorbidities.22 For example, many African countries where the life expectancy is low and the population is predominantly young have reported very low COVID fatality rates.23 Other associated factors include time trends in the spread of the pandemic, capacity and strategy for testing, and the accuracy of reporting deaths.22 The low COVID fatality rate in India could also be because of the decreased severity of infection, possibly due to cross-immunity from exposure to other coronaviruses which are endemic in the population.9
The focus of research on COVID outcomes in patients with cancer has been to identify prognostic factors to aid risk stratification and early recognition of patients likely to have adverse outcomes. In keeping with the published literature, we found that advanced age was an independent risk factor for poor outcomes after COVID, and within this group, elderly patients who had received recent systemic anti-cancer therapy had worse outcomes than those who did not.6,17,18 Similar to other studies, we found that the presence of comorbidities and smoking adversely affected COVID severity and outcomes.6,21 Our study also showed no impact of gender, type of cancer or recent SACT on COVID-19 outcomes. These findings strongly support the continuation of cancer care in most patients during future surges of the pandemic.
Our results showed that treatment with palliative intent was a significant adverse prognostic factor for COVID outcomes, regardless of whether active anti-cancer treatment had been recently administered. This can be attributed to the debilitation caused by the cancer itself, compounded by the effects of COVID. Paradoxically, Di Cosimo showed that patients with metastatic disease receiving anti-cancer therapy had better COVID outcomes than their untreated counterparts;24 however, this is possibly confounded by selection bias as patients with better general health and performance status are more likely to receive active treatment. Our study suggests that the treatment of patients with advanced, metastatic cancers should be guided by the magnitude of benefit based on the de-novo or progressive nature of cancer, expected toxicities with treatment and potential risks of COVID-19 related complications. This highlights that emphasis should be given to shared-decision making in this scenario. This is particularly true when healthcare systems are overwhelmed by COVID-19, and the resources diverted to palliative chemotherapy would be at the expense of delivery of care to those with other disease conditions, including patients with cancer who are on treatment with curative intent.
Initial data from China suggested that recent SACT was a risk factor for COVID severity and mortality.14 Based on this, several international organizations issued guidelines for the management of cancer during the pandemic, which included risk minimization by care prioritization, de-intensification of therapies, and postponing therapy where possible.25 Subsequent studies from other parts of the world have shown differing results – while some studies showed that recent SACT, especially chemotherapy and immunotherapy were risk factors for severity of infection or mortality, other data showed no evidence of an association.5,6,7,18,19 A systematic review found that chemotherapy within 30 days prior to diagnosis of COVID increased the risk of death but not of severe COVID while other therapies (including radiation and immunotherapy) had no such effect.26 While this may be explained on the basis of the intense immunosuppression caused by chemotherapy, it needs to be interpreted cautiously. First, many studies have not been able to capture reliable data on the nature and timing of systemic therapy in relation to COVID and the available data is quite limited. Second, studies may have grouped all forms of anti-cancer therapy which would dilute the effect of individual treatments. Third, changes in practice during the pandemic may have resulted in only fitter patients receiving intense chemotherapy, thus confounding the results.
Our study has several strengths. First, to the best of our knowledge, it is one of the largest single-centre studies examining the outcomes of COVID-19 in patients with cancer, and is possibly the most robust prospective data available from this part of the world. Second, this was a pragmatic study which included all patients regardless of age, cancer type or severity of COVID-19. Finally, being a referral centre in the state for patients with cancer who developed COVID-19, it is likely to be fairly representative of the real-world situation. One possible limitation is that a small proportion of patients who were relatively less symptomatic, but did not have facilities for home isolation were admitted in hospital for social rather than medical reasons, thus potentially skewing the severity scoring of the illness; however, these numbers were few; moreover, since we used categories of disease (mild, moderate and severe) rather than actual scores, this is unlikely to have influenced the results.
The results of our study have important policy-level implications. We have demonstrated that in our setting, most patients with cancer who developed COVID-19 had mild disease and favourable outcomes. Considering that India has a huge burden of COVID cases and has had multiple surges in the number of active infections, this finding is important to assuage fear in patients and treatment-providers. With increasing realization of the adverse outcomes that are likely by deferring active cancer treatment, our results support the continuation of cancer care even during pandemics. Treatment of cancer during the pandemic has been severely hampered due to multiple reasons: inability of patients to access care due to fear of contracting COVID or travel restrictions, reduction in existing cancer care facilities either because of conversion to COVID care centres or due to staffing issues (illness, quarantine or travel restrictions) and recommendations to downscale or delay cancer therapies. A study across 41 cancer centres in India found substantial reductions in volumes of patients treated at these centres during the peak of the pandemic.27 Even in the pre-pandemic period, several low and middle income countries faced challenges with cancer care related to lack of access, delayed stage presentation and poor outcomes.28 In such settings, further reductions in cancer care are likely to have disastrous consequences. Many of these countries are now seeing new waves of COVID infections and the findings of this study reinforce that cancer care should not be deprioritized even during a pandemic.