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Findings of a phase III clinical study funded by UK government grants and presented at the June 2018 meeting of the American Society of Clinical Oncology (ASCO) suggest that the time a patient needs to spend on Herceptin, (chemical name trastuzumab), a drug widely used to treat an aggressive form of breast cancer, could be halved from 12 to 6 months. This would save insurers, governments, healthcare providers and patients significant sums of money and possibly reduce the incidence of side effects, which can include heart problems.
 

In this Commentary
 

This Commentary: (i) summarizes the findings of the clinical study and some expert reactions to it and (ii) describes the different subtypes of breast cancer and the drug trastuzumab.  The Commentary also broaches a broader concern about the escalating costs of life-saving or life-extending cancer therapies, which show no sign of either slowing or reversing. According to ASCO, in the US, newly approved cancer drugs cost on average US$10,000 per month, with some costing as much as US$30,000 per month. This causes financial hardship for many American patients and their families. In the UK, which has a large devolved public healthcare system, cancer therapies are a postcode lottery because medicines that patients receive depend on whether their local healthcare provider can afford them. In emerging economies, where the prevalence of breast cancer is rising, only a privileged few breast cancer patients have access to trastuzumab. Notwithstanding, patients should gain some comfort from Herceptin’s patents expiring and biosimilar versions of trastuzumab entering the market, which is expected to make the drug cheaper and more accessible.  
 

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Breast cancer is a heterogenic disease and biomolecular changes in breast cancer involve the expression of genes. The disease is classified according to the 4 subtypes of genes expressed: (i) luminal A, which accounts for 51 to 61% of all breast cancer patients, (ii) luminal B, which accounts for 14 to 16%, (iii) basal-like, which accounts for 11-20% and (iv) the HER2 subtype, which accounts for 15 to 20% of all breast cancer patients and is the focus of this Commentary. Each subtype has different clinical features, different prognoses and different responses to therapies. HER2 protein overexpression is the result of amplification of the HER2 gene and is associated with aggressive tumour growth and consequent high rates of recurrence and mortality in patients. HER2-positive breast cancer is not inherited but is a somatic genetic mutation, which occurs after conception and therefore the new DNA does not enter the eggs or sperm.

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• International study shows that while British cancer survival has improved over the past 20 years the UK’s cancer survival rates lag behind the European average in 9 out of 10 cancers
• 10,000 cancer deaths could be prevented each year if the UK hit the European average
• Analysis shows that some British cancer survival rates trail that of developing nations such as Jordan, Puerto Rico, Algeria and Ecuador
• Since the inception of the NHS in 1948 policy makers and clinicians have viewed the problem as the NHS being under staffed and underfunded
• But the answers to the cancer care challenge in the UK are not that straight forward
• The world has changed and is changing while policy responses to challenges have remained static

 

Part 1 of this Commentary  described the CONCORD-3 study reported in the January 2018 edition of The Lancet, which suggested that although 5-year cancer survival rates (the internationally accepted indicator of cancer care) have improved in Britain over the past 2 decades, the UK lags behind most large European countries in cancer care.
 
This is part 2 of the Commentary, which begins by describing some of the UK’s initiatives over the past 20 years to improve cancer mortality rates, speed up diagnoses and enhance the quality of cancer care for people living with the disease. All arrive at similar conclusions: that UK cancer care strategies have reduced cancer mortality rates over time, but there is still more that can be done. They do not compare Britain’s cancer mortality rates with other European nations. Notwithstanding, there appears to be some consensus among leading clinicians and policy makers that the UK’s failure to close the cancer care gap with other European nations is because NHS England is underfunded and understaffed. While this explanation might provide part of the answer it does not tell the whole story. The answer might be less to do with extra funds and extra staff, and more to do with the fact that the global healthcare ecosystem has changed quicker than the thinking of UK policy makers and quicker than structural changes to NHS England. To the extent that this is the case, improving cancer care in Britain may not require more money and more staff, but more innovation and more focus on actual patients’ needs rather than on what policy makers can provide politically.
 

 
Over the past 20 years the UK government has commissioned a number of strategies, taskforces and reports all aimed at improving cancer diagnoses, treatments, and management, and enhancing the quality of life of people living with the disease and reducing premature deaths. In 2000, NHS England launched a National Cancer Plan, which was, “committed to addressing health inequalities through setting new national and local targets for the reduction of smoking rates, the setting of new targets for the reduction of waiting times, the establishment of national standards for cancer services, and investment in specialist palliative care, the expansion and development of the cancer workforce, cancer facilities, and cancer research.” This was followed in 2007 by the Cancer Reform Strategy, which was designed to build, “on the progress made since the publication of the NHS Cancer Plan in 2000, and sets a clear direction for cancer services for the next five years. It shows how by 2012 our cancer services can and should become among the best in the world.”
 

Independent cancer taskforce
 

In January 2015, an Independent Cancer Taskforce was launched by NHS England, “to develop a five-year action plan for cancer services that will improve survival rates and save thousands of lives.” The NHS established the taskforce on behalf of the Care Quality Commission, Health Education England, Monitor,  Public Health England and theTrust Development Authority. The taskforce was chaired by Harpal Kumar, then, CEO of Cancer Research UK, and was comprised of representatives from a cross section of the cancer and healthcare communities.

In July 2015, the Independent Cancer Taskforce published a report entitled: Achieving world-class cancer outcomes: a strategy for England 2015-2020. The report identified key elements of a world class cancer care system and suggested that this is what British cancer patients should expect and what NHS England should aim to provide by 2020. The strategy included, “effective prevention (so that people do not get cancer at all if possible); prompt and accurate diagnosis; informed choice and convenient care; access to the best effective treatments with minimal side effects; always knowing what is going on and why; holistic support; and the best possible quality of life, including at the end of life.” According to the report such a strategy would achieve world-class cancer outcomes and save 30,000 lives a year by 2020.
 

Two months before the publication of the Taskforce’s report, in May 2015, the UK government launched a National Cancer Strategy. This was its second 5-year program to implement a world-class cancer strategy designed to increase the prevention of cancer, speed up its diagnosis, and improve the experience of people with the condition. It suggested that rapid progress had been made in a number of key and high-impact areas, and stated that, “if someone is diagnosed with cancer, they should be able to live for as long and as well as is possible, regardless of their background or where they live. They should be diagnosed early, so that the most effective treatments are available to them, and they should get the highest quality care and support from the moment cancer is suspected.”

 

In October 2017, NHS England published an interim report of its 2015 National Cancer Strategy, which suggested that, “Survival rates for cancer have never been higher, and overall patients report a very good experience of care. However, we know there is more we can do to ensure patients are diagnosed early and quickly and that early diagnosis has a major impact on survival. We also know that patients continue to experience variation in their access to care, and this needs to be addressed. Early diagnosis, fast diagnosis and equity of access to treatment and care are central to the ‘National Cancer Programme’ and the transformation of services we want to achieve by 2020-21.” According to an NHS spokesperson, “Figures show that cancer survival is now at an all-time high in England, as a result of better access to screening, funding for effective new treatments and diagnostics and continued action to reduce smoking.”
 

The OECD’s November 2016 Health at a Glance report suggests that in 2013 (the latest year for which data have been published) the UK spent 8.5% of its GDP on public and private healthcare. And, a 2016 report from the King’s Fund, a charity, suggests that projected spending on NHS England as a proportion of the UK’s GDP in 2020-21 is 6.6%, just 0.3% above what it was in 2000.
 

Notwithstanding, linking cancer mortality rates to the proportion of GDP nations spend on healthcare is not straightforward. This is partly because of, (i) different nations have different sources of healthcare funding, and (ii) a person’s purchasing power is different in different countries. Fluctuations in relative national economic growth make such comparisons over time and between nations challenging. According to The Health Foundation, a higher percentage of UKhealthcare spending is publicly funded compared to other European countries. For example, “In 2012, publicly funded spending accounted for 84.0% of UK healthcare spending. This is the third highest level in the EU-15 (average: 76.5%).  In 2012, UK public spending on healthcare was slightly higher than the EU-15 average of 7.6% of GDP”. Between 2008 and 2012 the average annual change in healthcare spending per person was lower for the UK than most EU-15 countries, which was largely the result of Greece, Ireland and Portugal making significant cuts to their healthcare spending. The rising prevalence of cancer and other chronic long-term diseases, is a significant driver of increased healthcare costs. According to OEDC data, UK spend on chronic lifetime conditions is similar to the European average. However, the UK spends less than other European countries on pharmaceuticals and out-of-pocket payments. Further, on average, UK patients spend less time in hospital and generally use fewer resources (measured in terms of staff and beds).
 
A 2017 paper published by the Nuffield Trust suggests that, when taking into consideration different sources of healthcare funding and purchasing power parity, the UK’s healthcare spend actually might be keeping up with that of other European nations.
 

Let us now consider staffing. In 2017, The Royal College of Emergency Medicine reported that primary and emergency care doctors, which are crucial for the early diagnosis of cancer, were experiencing significant recruitment and retention challenges. According to 2018 figures, NHS England has nearly 100,000 jobs unfilled, which include 35,000 nursing posts and 10,000 doctor vacancies.  The total vacancies represent 1 in 12 of all NHS posts, which is enough to staff about 10 large hospitals. Further, the high number of unfilled NHS posts coincides with 0.25m more people visiting A&E in the first quarter of 2018 than in the equivalent period in 2016. According to Saffron Cordery, the director of policy and strategy for NHS Providers, “These figures show how the NHS has been pushed to the limit. Despite working at full stretch with around 100,000 vacancies and a real risk of staff burnout, and despite treating 6% more emergency patients, year on year in December (2017), trusts cannot close the gap between what they are being asked to deliver and the funding available”. A February 2018 finance report suggests that NHS England is heading for a £931m deficit in 2018 and is "dangerously" understaffed. This year-on-year deficit was revised to a projected £1.3bn shortfall, which is 88% worse than planned.
 

The NHS staffing challenges are aggravated by the fact that British trainee primary care doctors are dwindling, newly qualified doctors are moving abroad, and experienced doctors are retiring early. Over the lifetime of NHS England, the UK has trained significantly fewer healthcare professionals than it needed, and the supply of qualified young British people has consistently outstripped the number of places in medical schools and nurse training. According to data from the General Medical Council (GMC), between 2008 and 2014 an average of 2,852 certificates were issued annually to enable British doctors to work abroad. A 2015 British Medical Association (BMA) poll of 15,560 primary care doctors, found that 34% of respondents plan to retire early because of high stress levels, increasing workloads, and too little time with patients.  Further, it is estimated that 10% of doctors and 7% of nurses employed by NHS England are nationals of other European countries. The uncertainties of Brexit (a term for the potential departure of the UK from the EU) add to NHS’s recruitment and retention challenges of healthcare professionals. According to a 2017 Health Foundation Report, in 2016, more than 2,700 nurses left the NHS; an increase of 68% since 2014.
 

Notwithstanding, NHS staff shortages are not new. In the 1960s, NHS hospitals in Britain introduced mass recruitment from Commonwealth countries, and this has influenced staffing policies ever since. Being able to recruit doctors and nurses from foreign countries provided NHS England with an “easy” solution to staff shortages. However, over the past 2 decades the global healthcare ecosystem has changed significantly, while UK healthcare staffing policies have not kept pace with the changes. Today, there is a substantial gap globally in the supply and demand of healthcare professionals. Countries such as India, which traditionally could be relied upon to provide healthcare professionals for NHS England, have changed and the pool of potential Indian recruits have shrunk. Over the past 2 decades, the Indian economy has improved and the nation has developed a number of world-class hospital groups such as Apollo, Fortis and Narayana Health, which offer internationally competitive terms and conditions to Indian doctors and nurses. Increasingly Indian hospitals retain more of the nation’s healthcare professionals, and indeed attract doctors working in the UK and the US to return. Further, NHS England has tended to be staffed on the basis of what successive governments can afford rather than what NHS patients’ actually need.
 

Although there is a significant shortage of healthcare professionals in NHS England, it is not altogether clear that, (i) significantly increasing the number of NHS health professionals in the short to medium term will be possible, and (ii) simply increasing staff numbers will improve cancer care. Over the past 2 decades, as technologies and demographics have changed, so the demands on cancer professionals have changed. It is not necessarily the case that the NHS has the right mix of staff with the right mix of skills to deal effectively with changing conditions.  Changing traditional roles rather than simply boosting numbers might contribute more to reducing cancer mortality rates and improving the quality of cancer care. Further, it seems reasonable to suggest that, with the aforementioned challenges, a greater proportion of the UK’s annual healthcare spend might be more effective were it directed at cancer prevention rather than “diagnosis and treatment”.
 

Preventing cancer
 

Cancer screening
 

Reconciling bureaucracy with innovation
 

Cancer is a vexed and profoundly challenging disorder. As soon as you read about a breakthrough you have news that the cancer has outwitted the scientists, hence the name, “the emperor of all maladies”. Cancer care in the UK has improved, but still the majority of British cancer patients would faire significantly better in other European countries. When reflecting on the myriad of cancer strategies, reports, and taskforces over the past 2 decade you cannot help but think that NHS England suffers from an element of bureaucratic inertia: the inevitable tendency of the NHS to perpetuate its established procedures and modus operandi, even if they do not reduce cancer mortality rates to those experienced by other European nations. The UK policy debate to resolve this problem tends to be dominated by “more”: more money, more doctors, more nurses. Historically this has provided successive governments with a “get-out-of-jail-card” because circumstances meant that the NHS could always provide more. This is not the case today. The global healthcare ecosystem has changed quicker than UK cancer strategies and quicker than structural changes in the nation’s healthcare system. Improving cancer care in the UK will require more than inertia projects. It will require more innovation, more long-term planning, more courage from policy makers, more attention to actual patients’ needs rather than providing what is politically available. The UK healthcare establishment should be minded of Darwin who suggested that, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”

An approach to combat this is to treat a cancer with one target drug, and if the cancer returns with newly developed resistance, identify how that resistance occurred and target that with another drug, and so on, until the cancer and its resistances are beaten.  This is similar to accepting that a local traffic jam may be bypassed, and finding and blocking all the ways around the jam.
 
Another approach is to target and block something critical for the survival of a specific cancer. This is similar to blocking a strategic point that controls all the traffic coming in and leaving a city. For example, taxi drivers clogging up Trafalgar Square and bringing London to a standstill. But scientists are a long way from achieving this because researchers don't know whether such targets in relations to cancers exists, and even if they did, they don't know whether they can be blocked effectively. And, even if such targets were discovered and were blocked, scientists still don't know what would be the side effects of doing so. 
 
Takeaways
For personalised medicine to be successful, clinicians and scientists need to track the evolutionary trajectories of cancers in patients through sequential episodes of treatment and relapse. Besides being a major clinical and scientific challenge, this is also a significant informational and communication challenge, which networks such as EUTROC are addressing.