The big read on cancer screening: The good, the bad and the shades of grey
The big read: In the past year we have all learned a lot about the limitations of cancer screening. So do the benefits of these programmes still outweigh the downsides? Emily Hourican, who was herself treated successfully for cancer, considers the evidence
It was going to be the thing that saved us all. Screening. A process aimed at detecting disease in infancy, before it has a chance to become full-blown and dangerous. In this country we have screening for breast cancer, cervical cancer, bowel cancer, and diabetic retinopathy (a common complication of diabetes that can lead to deterioration in vision).
The point of screening is that it is carried out on people who are well, not sick. They don't have symptoms - or none that have sent them to their GP anyway. The idea is that, by detecting early, before there are actual symptoms, their chances of survival are greatly enhanced, and their treatment will, hopefully, be less invasive and less toxic.
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It's a perfect theory - playing into a growing trend to treat the well population; to pre-empt and prevent, rather than waiting for alarm signals (although it has also been called 'coercive healthism', a demonstration of the power of the State over individuals, and, as one medical professional noted, "the normal code of medical ethics doesn't apply to screening. It is a different endeavour to the rest of medicine. Usually, a person with symptoms comes to you, the doctor. Screening is the opposite of that. It works the other way around. We doctors are going to people without symptoms.")
The Irish National Screening Service was established in 2007 with BreastCheck set up in 2000, CervicalCheck in 2008 and BowelScreen in 2012. And until very recently, all these were seen predominantly as something good, vital tools in the fight against cancer. And given that the latest figures are that one in two of us will develop cancer at some stage in our lives, we clearly need every bit of help we can get.
Also, given that the rate of breast cancer in this country is 2,890 new cases diagnosed every year, with over 2,700 new cases of bowel cancer per year, and around 300 new cases of cervical cancer, not to mention the emotional and psychological ripple effect of these diagnoses, these are cancers worth targeting
Recently however, many of us have fallen out of love with screening. The disaffection began with the cervical cancer controversy and moved outwards to include BreastCheck. It morphed from being primarily focused on the human errors involved, to a consideration of the concept and capabilities of the programmes per se.
We trusted those tests. In hindsight, it's obvious that we trusted them far too much. And this isn't entirely our fault - despite the availability of information, there was a general shyness in emphasising it. How many of us left the GP's surgery after a smear test for example, and were told: 'this is not failsafe. This is not a guarantee. You need to watch for the following symptoms…'? Certainly I never was. 'There you go, that's you done for the next two/three/five years…' was far more the attitude.
No wonder we felt cheated when the reality became obvious - not only was the test not failsafe, but it never could have been.
More and more, we are hearing from women who have decided not to avail of screening. "I don't see the point," one woman in her late 60s tells me. "The scandals have lowered my confidence in it, and I'm not sure how much difference screening makes. I'd rather go to my doctor if I have a concern."
First, it's important to understand that comparing screening programmes isn't possible, there is no like-for-like basis on which to do so. Cervical screening, although crude, inelegant and based on an old technology, is widely accepted to be a very effective way of mass screening of a population. Controversy notwithstanding, if you mass screen a population for cervical cancer, you will greatly reduce the number of women who will die of cervical cancer in that population.
Breast screening is a trickier issue, because mammography is, in the words of one health professional I spoke to, "nowhere near as good as cervical screening".
Also, and important to point out, is that screening programmes are not considered to be good tests for individual patients with symptoms. That is not their purpose. The purpose of a screening programme is to reduce the number of deaths from the cancer in question in the screened population; it is the crucial difference between screening and diagnostic testing that is often misunderstood.
Let's look primarily at the case for and against breast cancer screening. The aim of BreastCheck is "to reduce deaths from breast cancer in Ireland by finding and treating the disease at the earliest possible stage, when it is generally easier to treat and greater treatment options are available." Its own figures are that between the year 2000, when it was established, to the end of February 2019, "BreastCheck has provided 1.9 million mammograms to over 570,000 women and detected over 12,200 breast cancers; more than half of which were diagnosed at an early stage." It has been accredited three times by international experts, most recently in February 2018, "when BreastCheck achieved the highest level of certification, Level 4, from the European Reference Organisation for Quality Assured Breast Screening and Diagnostic Services (EUREF)."
There is no suggestion that BreastCheck is anything other than an excellently managed screening service. The question is around screening per se, not the individual service.
So the fundamental questions that need answers are these: What good does breast screening do? And what harm does it do? And does the good outweigh the harm?
It all sounds easy enough. Except that the evidence is based on statistics culled from various different studies, some very old by now, other s dubious in quality, and therefore, like all statistics, can vary considerably: statistics, like puppets, can be made to do many dances. There are complicated concepts such as absolute risk and relative risk, and percentages that look like one thing but turn out to be rather different when drilled down into.
First, let's talk about the good. BreastCheck offers routine breast screening to women aged 50 to 67 every two years. So how many cancers has the programme caught: "At the end of February 2019, BreastCheck had detected over 12,200 breast cancers; all in women aged over 50," says a spokesperson.
How many deaths from breast cancer has the screening service prevented? "This has not been established, however the National Cancer Registry of Ireland (NRCI) calculated that between 2000 and 2007 in the east of Ireland that there was a 9pc reduction in breast cancer mortality. These early findings are likely to increase with further follow-up and the authors conclude that BreastCheck is on track to achieve 20pc mortality reduction and if all women participated it could be up to 30pc."
Let's take 20pc as the figure; 20pc of deaths from breast cancer prevented. That would be in line with international findings. And that sounds great. Except that, for anyone who knows anything about statistics, that isn't an absolute percentage, it's a percentage of a percentage; a reduction from something fairly small, to something even smaller, in this case that the likelihood that you will die of breast cancer while in the screened age-group drops from 2.1 pc to 1.7 pc.
And it doesn't take into account the significant advances made in treating all breast cancers, but particularly late-stage breast cancers that would previously have resulted in death.
Asked his opinion of breast cancer screening, Professor John Crown, consultant oncologist, founder of the Clinical Trials Unit at St Vincent's Hospital and the Irish Clinical Oncology Research Group, and former senator, says: "The impact that mammography makes on a screened population, while important, is relatively modest. The general feeling is that if you screen over the age of 50 with annual or two-yearly mammograms, you will reduce the death from breast cancer in that population of patients by about 20pc. There are studies that suggest you reduce it by less."
He also makes the point that, "the mortality for breast cancer in America, which leads the world in breast cancer treatment as it does in most things in oncology, thankfully began to drop in the 1990s and has been dropping ever since. Is this because of screening or is it because of better treatment? The original feeling was that this was all screening, but it is now thought that much/most of it is due to better drug treatment, which has improved dramatically, out of all recognition. Screening probably makes a difference, but not by as much as we thought."
BreastCheck also say that "out of every 1,000 women screened for breast cancer, seven women will be diagnosed with cancer." Again, that sounds good. But critics of screening programmes will say that a more accurate barometer of the benefit of such a programme is to calculate the number screened to the number of deaths prevented. This is what's known as Number Needed To Screen (NNS), in general, considered a more meaningful analysis. And there, the landscape looks a little different.
Michael Baum, a professor emeritus of surgery at University College London, publishing in the British Medical Journal in 2013, estimated that 10,000 women would need to be screened to prevent three to four deaths.
An infographic commissioned by the NHS and quoted in an excellent 2014 London Review of Books piece by Paul Taylor, Professor of Health Informatics at University College London, gives a roughly similar picture: If 200 women are screened every three years between the ages of 50 and 70, then by the time they are 80, 15 will have been diagnosed with breast cancer. Of that 15, 8 will be diagnosed and survive; they would have survived anyway without screening. One has her life saved by screening; she would have died without it. Three die of breast cancer even though they were screened. Three are diagnosed with a cancer that would never have become life-threatening.
This would suggest that around 3,500 women have to be screened to prevent one death.
And that, for the vast majority of us, is probably an entirely acceptable number. If that was all the weighing-up involved, I doubt there would be any debate about this.
However, alongside the good, it is necessary to consider the harm of screening programmes. This falls into two categories: False negatives and false positives.
Let's deal with false negatives first. This is where screening occurs, abnormalities are missed and a woman is wrongly told there is no cause of concern. The NHS calculates that around one in five breast cancers will be missed at screening (false positives are more common in younger women, and those with dense breasts) over a 20-year period. This is a known and, I think, pretty well understood aspect of breast screening, one that is clearly communicated to women when they show up for screening. It is undesirable, but understandable.
Far less clear, and less well communicated, is the issue of false positives, and, linked to that, over-treatment. Again, figures vary, but BreastCheck say that "one in 20 women who receive a BreastCheck mammogram is called back for more tests." That's 5pc of women. The US and UK put their recall figures at closer to 10pc. 'More tests' in this scenario include further mammograms and possibly biopsies, and of the recalled percentage, only about 0.5pc will be found to have cancer.
Again, this might seem - and perhaps is - acceptable. After all, the end result is, mostly, good news: no cancer. But, there is unquestionably a great deal of stress associated with the recall process - research suggests that it takes a full year for women's anxiety levels around breast cancer to return to normal after a false positive. In fact, research conducted by BreastCheck shows that women who have been recalled for a false positive are significantly less likely to present for subsequent screening mammograms.
And then, allied to the false positives, but even less easy to analyse, is the idea of over-treatment. This is where a cancer that may be slow-growing and non-aggressive, is treated like any other tumour - with some or all of the anti-cancer arsenal. As Professor Paul Taylor says, "I think it's more difficult to evaluate the harm than the good. The key thing is over-diagnosis, and you can't measure that in an individual. You can't say 'this individual was over-diagnosed.' It's a population-level concept, and an artefact of the screening process - yes, you have uncovered this disease but the people you have uncovered it in don't benefit because there is no associated change in mortality."
The key example here is ductal carcinoma in situ (DCIS). This is where the cells that line the milk ducts of the breast have become cancerous, but they have not spread into surrounding breast tissue. DCIS is considered non-invasive or pre-invasive breast cancer, and is also known as 'stage zero' cancer.
Right now, the guidelines are that DCIS be considered as cancer and treated accordingly. Typically this will mean surgery and radiation, with all the attendant psychological and physical traumas they bring. However, it is well-known that not all DCIS progresses, which means that had it not been detected, for some women, this would never have presented as a problem. They, therefore, have been over-treated. The problem is that it isn't currently possible to tell which DCIS will progress and which won't. There are trials underway - Cancer Research UK are comparing surgery with monitoring by having yearly mammograms, but they are still recruiting, until July 2020 - so any results are very far off.
DCIS is the precise point where the success of the screening programme becomes especially problematic. As Professor John Crown says: "The victory for the screening programme is picking up DCIS before you get invasive cancer. Somebody with DCIS will have a far less intrusive treatment than somebody whose cancer is picked up by screening as an invasive cancer. That's what you do the whole thing for. That's where it really comes into its own."
But he also agrees that "yes, there is a more philosophical question, but this is controversial - does screening pick up cancers that would not kill the patient? And under those circumstances, should we be doing screening at all?"
This is indeed a philosophical question. One that is hard to quantify in absolute terms. As Dr Nora Pashayan, senior clinical lecturer in Applied Health Research in the Institute of Epidemiology and Healthcare at University College London, and with a clinical background in public health medicine, points out that, "you can evaluate how many false findings you have - these are measurable, easy, observable. You can evaluate how many interval cancers you have. That too is measurable, whereas the other aspects are more difficult." But, she says, the data suggests that, "for every one death from breast cancer prevented by the screening programme, you have two over-diagnosed cases. Is that too much? That is something that we as a society have to decide - what is an acceptable value?" And, she is quick to emphasise, this isn't something women should be left to struggle with alone. "We can involve them in the decision-making, but without throwing it back on them. We are not leaving the burden of decision on the patient."
Switzerland, after a recent analysis of the best available data around breast screening, is rowing back on screening, and recommending that "no new systematic mammography screening programmes be introduced, and that a time limit should be placed on existing programmes."
Elsewhere, for the moment, there is no appetite to get rid of screening programmes.
"I think it's politically impossible to get rid of it," says Professor Taylor, of the UK programme. "It's probably not the best use of the money. But," he cautions, "that is not certain. I wouldn't go to the barricades and say 'this is a shocking waste of money and should be got rid of,' because I don't think we really know. And I think in that situation, it's there, it would be difficult to get rid of it, and so the thing to do is think through - how can we make it better?"
He's correct that getting rid of the screening programme is "politically impossible" - no politician would touch the idea.
Because as much as breast cancer is a health and welfare issue, it is also a deeply emotional issue, one that the vast majority of us have lived out in our own lives or through the lives of those closest to us.
No cost-benefit analysis can adequately assess the impact of stories of women who have benefited; whose cancers have been caught, early, by screening.
So, what could be done to improve it? One possibility is to categorise women according to risk based on genetics. "We can come up with a polygenic risk score, so that instead of screening all women aged 50-69 every two years, we screen women with a risk level above a certain threshold. If we don't screen women in the lowest third of the risk group, then we can reduce over-diagnosis by a quarter," explains Dr Pashayan.
"To do this, you have to risk-assess everyone, so there is a cost, but if you are screening less often, you are reducing those costs. In a cost-effectiveness analysis, we find that the risk-based approach is more cost effective than the current age-based programme."
There are other possibilities - better imaging, automation of mammogram reading, a better understanding of the progression of DCIS, blood tests that will indicate the presence of cancerous cells - all of which are possible or soon-to-be possible.
The final, and in some ways most important, question is, what do patients - women - want? That, too, is complicated.
"That's one of the things that's striking about this debate," says Professor Taylor. "A lot of clinicians and academics are questioning the value of screening, but if you ask women what they want, they want screening."
He points out that even in focus groups where time is taken to explain carefully and clearly to women all the possible risks associated with screening, "they still come away and say 'on balance, I want it, because it could save my life.'"
And even though that is slightly at odds with the findings of BreastCheck - that women who have been recalled for a false positive are significantly less likely to present for subsequent screening mammograms - for the moment anyway, that is how it falls: Women want a screening programme.
And they want an accurate one.
Other screening programmes
This is a very good example of a case where the benefit-harm analysis, the fundamental controversy over whether you are helping or harming a patient, led to the non-recommendation of a screening programme in Ireland.
The expert opinion is that some men benefit from PSA screening, but many more are likely to be over-diagnosed and so overall, at a population level, the harms (incontinence and impotence as a result of treatment) outweigh the benefits. Also, the mostly slow-growing nature of prostate cancer influences the decision.
In America where prostate screening does exist, the Public Services Task Force on Screening recently gave a much more nuanced recommendation for PSA screening. That said, there are calls for a full prostate screening programme to be implemented in Ireland.
Introduced in Ireland in 2012, a review of the first round of BowelCheck, until 2015, showed 196,238 people took up the invitation, with 8,062 people invited to attend for a colonoscopy and 521 cancers detected (giving an overall detection rate of 2.65 per 1,000 people).
One medical expert who works within the field expressed concerns, not with the screening programme itself, but with the landscape in which it is being conducted.
"Bowel screening is working reasonably well," he says. "It is picking up cancers. The problem is that people with symptoms are waiting six months or a year for an endoscopy, and now we are diverting resources into screening those without symptoms. We need to fix the endoscopy waiting lists first, then worry about screening."
This ties into concerns around screening in general - the idea that governments are spending time and money on people who are well, even though, if you get sick then you will, certainly in this country, often find it hard to access healthcare.
There is a paradox there, a disconnect between the way we wish to be as a society - pro-active, preventative - and the way our health service actually functions - overburdened and often clumsily reactive.