09 April 2020

Report by Linda Summerton, Head of Oncology, tranScrip and Dominic Bowers, Pharmaceutical Physician, tranScrip

Introduction
The UK, along with the rest of the world, is living in unprecedented times in all areas of personal and business life due to the COVID-19 pandemic, which is putting new and very significant pressures on individuals, families and organisations. These pressures are already being felt most acutely within the NHS itself, as it not only grapples to deal with the rising tide of new COVID-19 cases within a system that is already at capacity, but also to maintain established health care provision in other areas. Professor Martin Marshall, Chairman of the Royal College of General Practitioners and Britain’s most senior family doctor warns ‘patients are still living with long-term conditions and still have non COVID-related health needs and illnesses, that, if left unmanaged or untreated, could have serious consequences.’ (The Times, 29th March 2020).

In this reporte, we will outline the NHS strategy to deliver optimal cancer care during the COVID-19 pandemic, review the statistics on delivery of cancer care services in the NHS and how they may be negatively affected, and highlight the learning from other countries in maintaining cancer care during these challenging times.

NHS strategy to deliver optimal cancer care during the COVID 19 pandemic
The NHS has strict guidelines to deliver cancer care, according to diagnosis and urgency, but these are now under considerable strain with redeployment of clinicians to prepare to treat patients with COVID-19, and consequent cancellations of surgery, therapeutic treatment and outpatient clinics. Additionally, the impact of social distancing to prevent the spread of the virus has seen the cancellation of regular cancer screening and closure of GP surgeries, which are so important in identifying the first signs and symptoms of cancer.

It is encouraging to see a positive and pragmatic response to the crisis from NHS England and NICE, outlining how to deliver cancer care in these unprecedented times [1]. In March 2020, NHS England published specialty guides for patient management during the COVID-19 pandemic for all specialties [2]. Specifically, for cancer care, the guidance recognises that the elective component of delivery may be curtailed, but that it is important to continue proper management of cancer patients while protecting resources to respond to COVID 19. 

The guidance considers all types of therapy, including surgery, systemic anti-cancer therapies, radiotherapy, and proton beam therapy. The guidance assigns patients to ‘priority levels’ according to the likely impact of the therapy on patient outcomes, and particularly survival. The guidance also identifies cancer patients most vulnerable to contracting COVID-19, including those who are severely immunocompromised through the nature of their disease or treatment. Professor Karol Sikora (Oncology) has commented that ‘they [the guidelines] are really quite sensible. I'm surprised to say that actually, I couldn't do better myself, and I think most of my colleagues feel the same.’ However, he also comments, ‘In terms of other issues with cancer, there's a lot of borderline here and that's going to be the problem ─ explaining to people why we're delaying or cancelling treatment is not easy. Dropping them an email is really not good enough.’ (Medscape, March 2020). Another challenge is that while the guidance is national, decisions are taken locally with regional variations a natural consequence. For example, on 23 March 2020 and under the pressure of mounting cases of COVID 19, a London hospital announced that it had postponed outpatient chemotherapy appointments and cancer surgery for 2 weeks to protect people with cancer who may be at high risk of developing severe illness from coronavirus; urgent operations will go ahead [3]. Additionally, BBC London News has made similar reports in recent broadcasts, with Professor Karol Sikora stating, ‘Delay is dangerous’ [4]. While this might be the only decision at the time given the local NHS pressures, it is not the best decision for these cancer patients if there were other ways of mobilising resources and protecting them from infection.

Can the guidance from NHS England be followed in practice?
The guidance recognises that cancer care may well be compromised due to several factors, including the risk of COVID-19 infection and staff sickness, redeployment, and shortages in medicine, and that difficult decisions are already being made. The challenge to deliver optimal cancer care is also being experienced by a system already under strain as identified by Carl Baker in the latest report from the Office for National Statistics (ONS) on cancer care delivery (February 2020):

  • Cancer waiting times are the worst on record. On all 8 measures that were recorded, annual performance in 2019 was lower than during previous years.
  • The waiting time target is that 93% of patients should have their first consultant appointment within 2 weeks of referral. This target was almost always met until 2018. Since then performance has fallen, and as of December 2019, the target has not been met for 10 months. August 2019 saw record low performance on this measure at 89.4% [5].

Additionally, new diagnoses of cancer through screening and GP visits will not be made during the pandemic. While this will decrease referrals to cancer specialists and alleviate resource shortages, the negative impact on the outcomes for these patients, and particularly survival prospects, is likely to be profound. Carl Baker notes that:

  • The number of urgent GP referrals for suspected cancer has risen substantially in recent years. In 2019, there were 2.38 million referrals ─ an average of 6135 per day.
  • In 2019, 163,614 patients were treated for cancer after urgent referral by their GP.

Hence, both a negative impact on delivery of routine cancer care and delays to identifying new cases of cancer, will lead to a sharp rise in mortality and morbidity over the coming 12−18 months.

What can we learn from other countries' experience of cancer care during the COVID-19 pandemic? 
The picture may seem bleak for cancer patients either waiting for diagnoses or receiving treatment as services are rationed, delayed and the risks of infectious complications weighs heavily on uptake of much needed innovative cancer treatments that will save lives. However, while there have been challenges in maintaining optimal treatment of cancer in countries which were first to suffer the COVID-19 outbreak [6], some positive stories have since emerged from both China and Italy that show, despite a rapidly spreading serious pandemic in both countries, their cancer services continued to deliver as expected. In Wuhan, the epicentre of the Chinese COVID-19 infection, delivery of radiotherapy was continued without interruption as infectious control measures were undertaken to halt transmission among cancer patients and staff [7]. The early result of a 0.48% infection rate in the hospital setting in Wuhan demonstrates the effectiveness of a robust and strictly performed infection control protocol within the radiotherapy unit. The Wuhan infection control protocol was comprehensive, covering a stepwise clinical pathway to manage suspected cases that included questionnaires, computed tomography (CT) scans,  reverse transcriptase polymerase chain reaction (RT-PCR) assays, on-site screening, a restructuring of the radiotherapy unit, and protection of healthcare workers in the facility. An article that reviewed a secondary care cancer centre near Turin in Italy showed that, operationally, it is possible to continue delivering cancer care to vulnerable cancer patients whilst still ensuring appropriate tight infection control measures [8].

Guidance from the European Society of Medical Oncology (ESMO) states, ‘Essential cancer services should be delivered but all steps should be taken to protect patients from infection with COVID-19. Individual risk from exposure to COVID-19 varies from patient to patient, and all risks should be balanced against the need for tumor control and discussed on a case-by-case basis with the patient' [9]. While ESMO also notes that, ‘In some oncology departments, cancer services have been prioritised according to urgency, giving high priority to patients receiving treatment for active disease while postponing follow-up visits,’ there is a clear statement that, ‘In the majority of patients, the benefit of following a well-planned and well-controlled anti-cancer treatment plan will outweigh the risk of a coronavirus infection.’ 

The negative impact of COVID-19 on clinical trials for cancer patients
The COVID-19 impact is also being seen within cancer clinical trials as biopharma consider cancellation of further recruitment into ongoing trials and starting new clinical trials. EMA and FDA guidance advise that patients can continue treatment depending on the trial and indication, but continuation will be subject to what is practically possible depending on healthcare resources. NHS guidance has been published regarding amendment to existing studies impacted by the wider COVID-19 response, and the UK National Institute for Health Research (NIHR UK) announced in March 2020 that it will be suspending all non-COVID-19 funded studies [10]. A Bioindustry Association (BIA) UK webinar on running a life science business during the COVID-19 pandemic recognised that many laboratory research studies will be delayed and that further recruitment to clinical trials may be suspended [11]. Impact on the collection of clinical trial data will be significant and, hence, there will be delays to completion of data sets for advanced novel therapies. Medium to long term effects on the approval and delivery of new cancer therapies will be a consequence. Learning from other countries who are further along in coping with the COVID-19 pandemic will be important in ensuring that ongoing clinical trials of new anti-cancer medicines suffer minimal impact [12]. 

The likely legacy
Despite the NHS guidance, actions being taken now to delay potentially life-saving cancer diagnoses and treatment are likely to increase cancer deaths in the UK and worldwide over the next 12−18 months. Maintaining screening, diagnoses and interventions for cancer during the COVID-19 pandemic is critical to ensure the outcomes for cancer patients do not suffer. However, experience to date suggests that screening deferrals, and delays in referrals, diagnosis and timely treatment will affect survival outcomes in the medium term.

COVID-19 testing on a broader scale (both antigen PCR and antibody testing), will help to manage the risk of becoming infected with COVID-19 infection and allow for a return to the beginnings of normality in cancer screening, diagnosis and treatment. However, a backlog in diagnoses and treatment will be evident and will increase pressure further on cancer healthcare resources. 

Many biopharma organisations too will have clinical trials delayed and potentially compromised based on the impact of COVID-19 such that some clinical studies may be completely confounded due to missing data. Ultimately, it will be patients who suffer, as new treatments do not reach clinical practice and biopharma organisations have to account for financial losses in the price of new medicines.

On a positive note, if there can be one, innovation of implementing long espoused industry approaches to healthcare is happening rapidly. Professor Martin Marshall (Economist 4 April 2020) estimates that 9 in 10 GP appointments happened face-to-face before the crisis. Now, as GPs seek to keep patients away from pathogen-filled surgeries, he speculates that potentially as many as 9 in 10 are happening remotely. This measure saves both doctors’ and patients’ time and allows much greater flexibility for appointments. The COVID 19 pandemic will also hopefully drive tighter relationships between biopharma, academia, and healthcare delivery organisations such as the NHS not seen since the beginning of the HIV epidemic, to bring diagnostics, vaccines and treatments to the market with maximum speed and efficiency. Sadly, between pandemics infection research tends to return to the back burner, even though outbreaks of high mortality viral disease and rises in hospital antimicrobial resistance continue to occur. The hope is that this ‘Black Swan’ period of COVID-19 will lead to a full re-evaluation of health care priorities for future investment and distribution of vital health care services.

References:

  1. NICE Rapid Guidelines and Evidence Summaries. COVID-19 rapid guideline: delivery of systemic anticancer treatments. 2020; NG161
  2. NHS England & NHS Improvement. Coronavirus Secondary Care Speciality Guides. 2020
  3. Barking Havering & Redbridge University Hospitals. New measures to keep our patients safe. 2020; 23 March
  4. BBC. Terminal cancer patient's treatment delayed. 2020
  5. Baker C. NHS Key Statistics: England, February 2020. House of Commons Library Briefing Paper no 7281
  6. Yan S. Cancer patients in China denied treatment as healthcare resources are diverted to coronavirus cases. In The Telegraph. 2020
  7. Xie C, et al. Infection Control of 2019 Novel Corona Virus Disease (COVID-19) in Cancer Patients undergoing Radiotherapy in Wuhan. medRxiv 2020
  8. Krengli M, et al. Running a Radiation Oncology Department at the time of coronavirus: an Italian experience. Advances in Radiation Oncol 2020
  9. ESMO. COVID-19: supporting oncology professionals. 2020
  10. National Institute for Health Research. Q&A on the impact of COVID-19 on research funded or supported by NIHR. 2020
  11. BIA. Running a UK life science business in the COVID 19 pandemic. 2020
  12. DIA. COVID-19: Experts from China Speak on Conducting Clinical Trials During the Pandemic. 2020
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