How is the current COVID-19 situation affecting patients with neuroendocrine cancer, and what will be the long term impact?

The past few months has been an incredibly difficult time for healthcare professionals, patients and carers. The NHS has made huge changes at local levels to focus on the pandemic, with many uncertainties at every stage. Many patients are confused as to whether they are at increased risk of poor outcomes from Coronavirus Disease 2019 (COVID-19) caused by the SARS-CoV-2 Virus. Some patients are concerned about visiting hospital for treatment because of the risk of infection with COVID-19. Patients are also concerned about delays in scans and treatments due to the current crisis (in a recent survey by Neuroendocrine Cancer UK, over 50% of patients asked said that COVID-19 had in some way affected them or their care).

The general cancer advice is that anyone with stage 4 cancer is at least at medium risk from COVID-19. This was derived from an early publication from China that cancer patients with COVID-19 had a higher mortality that non-cancer patients (controls). However, this study has been criticised in a subsequent letter as the ages were very different in the two groups (https://doi.org/10.1016/S1470-2045(20)30149-2). A recent study from France has shown no excess risk from COVID-19 in breast cancer patients compared to controls, and that other comorbidities (medical conditions) and ethnicity were more important than the presence (previous or current) of cancer (Vuagnat, P., Frelaut, M., Ramtohui, T. et al. COVID-19 in breast cancer patients: a cohort at the Institut Curie hospitals in the Paris area. Breast Cancer REs 22, 55 (2020). (https://doi.org/10.1186/s13058-020-01293-8).

An increase in mortality in COVID-19 for cancer patients has been quoted as 6% (compared with 11% cardiovascular disease and 2% for no comorbidity) so the increase is moderate.

Not all cancers have the same risk. NHS England warned that certain groups are particularly vulnerable to serious illness if they become infected with COVID-19. These groups include individuals who are undergoing active chemotherapy or radical radiotherapy for lung cancer, and patients with cancers of the blood or bone marrow (Lancet Oncology 2020).

The question of the risk of therapies is very difficult to quantify. A pragmatic diagram assessing risk/benefit is published in Nature Reviews (https://www.nature.com/articles/s41571-020-03626/figures/1). Clearly, patients with Neuroendocrine Neoplasms (NENs) are not mentioned, but most therapies using everolimus/sunitinib/chemotherapy and Peptide Receptor Radionuclide Therapy (PRRT) would seem to fit in the middle risk group alongside, for instance, chemotherapy for metastatic colorectal cancer. However, in spite of logic dictating that chemotherapy, radiotherapy and targeted therapies in common cancers would cause excess mortality in COVID-19 infection, this appears not to be the case in a recent large cohort collected in the UK (https://doi.org/10.1016/S0140-6736(20)31173-9). A clear discussion should take place with patients if considering commencing these treatments or opting for a short postponement. AS the incidence of COVID-19 in hospitals and the community reduces as time goes on, the risk of COVID-19 on these treatments decreases. These can be complex decisions, adding to the anxiety and patients should be supported as much as possible alongside local arrangements.

A few therapies would seem to be much higher priority, for instance radiotherapy for spinal cord compression, surgery for small bowel obstruction, heart valve surgery for severe carcinoid heart disease. These may go ahead in spite of any risks. However, results of surgery with COVID-19 infection are poor with high mortality and post-operative pulmonary complications. Therefore, if possible, some surgery for cancer should be delayed unless urgent and likely to lead to an emergency admission. Certainly, non-urgent surgery should be postponed. (https:/www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31182-X/fulltext). The Lancet paper suggests post-operative pulmonary complications and that mortality is high after surgery so non-urgent surgery should be postponed. Again, as the pandemic resolves, these risks may change and patients should be supported as much as possible alongside local arrangements.

Most patients can wait some time for therapies but the difficulty for them has been not knowing how long a delay to expect. Most therapies have only had a short delay (about 6 weeks at most). However, many patients remain nervous about travelling to appointments for scans and therapies and many are reluctant to come in for surgery to a place where there may be a risk of COVID-19 infection. In addition, travelling on public transport to large centres which tend to be in large cities has been a very major concern for some patients. There is now a backlog in some centres  related to imaging and endoscopy services which may impact diagnosis and ongoing management.

Fortunately, most consultations can be done remotely, and as already occurs in some centres, we will see an increase in scans and other tests being done in smaller hospitals; many people will not travel to large cities for scans and blood tests that can be done locally. Much chemotherapy can be administered and monitored locally, with advice from a specialist MDT. Currently, PRRT is centralised in a few centres, but this may also change in the future. Somatostatin analogue therapy has been continued in most patients and this is now frequently given at home, in GP surgeries or in local hospitals and there should be very few patients travelling to the NET centres or other hospitals for it. The provision of somatostatin analogue therapy homecare services reflects the ‘amazingly well-developed’ infrastructures – local and national – for delivering services to patients with neuroendocrine tumours. Although most remote reviews are appropriate and adequate in the current situation, the lack of face-to-face interactions may have detrimental effects in terms of quality of assessment, patient satisfaction, and lost opportunities for learning and teaching.

Anxiety has been a feature in the current pandemic and coping with uncertainty can have negative consequences for mental health. This has affected many of our patients and also health care workers, but fortunately we have a good network of specialist nurses and patient support groups that can help reassure everyone. We must also acknowledge that the patient support groups and charities have suffered financially during the crisis and finances in the NHS will be uncertain.

The whole pandemic has been an uncertain time. It is important to emphasise that although now the risk of COVID-19 infection is reducing and things should revert towards normal over time, some things may never go back to the way they were. Although this could be seen as negative, positive consequences could include: less distance to travel for some reviews and simple scans; a choice of oral therapies where available (rather than intravenous)/ and local or home delivered somatostatin analogues. However, meetings of patients in large groups and meetings with and between health care workers are going to be a challenge for a long time to come.

We are in a changing world, and every week there is new information. The COVID-19 crisis may have created an impetus for change for the better, and it is vital that we use this as an opportunity to develop services in partnership with patients and all stakeholders.