It’s a simple fact that the most effective thing we can do to cure more cancers is to catch them earlier. If we find bladder cancer at an early stage, the five year survival is 88%; if we catch it at a late stage, when it has started spreading around the body, it drops below 15%. This is why we screen for certain diseases, including breast, bowel and cervical cancer. These large-scale screening programs are the best hope we have for majorly reducing the toll cancer takes on our lives.Screening, however, is hard. The main problem we face is accuracy. An ideal test would flag up 100% of sick people and 0% of healthy people. However, these tests are never perfect. There is always a percentage of sick people who are not flagged up (false negatives) and a percentage of healthy people who are incorrectly labelled as sick (false positives). And these problems can get pretty bad pretty quickly.The following diagram illustrates this issue. It shows the results of a test that is quite accurate (one that has 90% accuracy) applied to a common disease that is present in 1% of the population.
As you can see above, what sounds like a good screening test results in 10 times more false positives than true positives, while it also tests one person as negative while they are actually positive.In a large population, even a small percentage of error translates into a large number of misidentified patients. This can result in a crippling financial burden on the health system, as well as unnecessary worry, stress and pointless treatment for perfectly healthy people.As a result, only extremely accurate tests can be used in the clinic, which is the reason we screen for so few diseases. So how do we get around this? Well, obviously we have to develop more accurate tests, and a lot of effort is currently being invested in this field.Additionally, we can also improve things by being more selective about the people we screen. If a disease is present in 1% of the general population, but present in 5% of people over 65, then we can screen just the over 65s.So using the above the example of a test with 90% accuracy, if the prevalence is 5% instead of 1%, then rather than 10-times more false positives than true positives, there is just over 2-times. If the test were 98% accurate, then we would have far more true positives than false positives. This increased accuracy in a specific population is what we are working towards.
However, while significant research is being carried out in the development of new tests, it is disappointing to note that this is still a small percentage of cancer research funding. According to the National Cancer Research Institute, in 2011 (the most recent year I could find numbers for), research into early detection, diagnosis and prognosis received just 12.6% of cancer research funding.While it is understandable that research into a “cure” is more attractive than research into early diagnosis, the potential benefits of early diagnosis far outstrip that of drug development. Encouragingly, this level of funding is increasing steadily, and rose from 8.1% in 2002 to 12.6% in 2011. If this research can result in more viable screening programs, this will provide a significant clinical benefit to cancer patients.For more information about screening, I’d recommend having a look at the sense about science website, which does a great job of describing not just this problem, but also many others that arise in screening populations for diseases.
Can dogs smell cancer?
This week the Guardian reported on the ability of dogs to detect prostate cancer.
Dogs trained to detect prostate cancer with more than 90% accuracy The Guardian - 11/04/2015
Italian scientists published a study this week that showed that two dogs they tested were able to detect prostate cancer with remarkable accuracy. One of the dogs correctly detected all cases of prostate cancer and the other detected 98.6% of cancers. On the other hand, the dogs falsely detected cancer in 1.3% and 2.4% of the negative samples too. Both dogs are German Shepherds that had previously been trained for bomb detection, and while their success as bomb sniffers was not addressed, the paper shows that as prostate cancer sniffers they are pretty amazing.How does this compare?In real terms, what do these numbers mean?Consider the UK male population of roughly 30 million, with 0.15% of them being diagnosed with prostate cancer every year. That is 45,000 men.If we test all 30 million men every year, the more accurate dog will detect almost all of the 45,000 cancers each year. However, as it also detects 1.3% false positives, it will also falsely identify the disease in 390,000 perfectly healthy men (1.3% of 30,000,000).This number of false positives may not sound very impressive, but let’s put it in perspective: the standard lab-test for prostate cancer (PSA test) would detect around 27,000 of the 45,000 cancers, but crucially would detect a whopping 3,900,000 false positives! (The exact numbers for this depends on various variables, but I have used the estimates from here, using 3.0 ng/ml testing). So not only does it falsely detect many more prostate cancers than there really are, but importantly almost half of men that do have the disease walk away undiagnosed.This is still a hypothetical situation as PSA is not used routinely to screen for prostate cancer in the general population, but it does emphasise just how effective these dogs are at detecting this disease. I have included a little explanation of cancer screening below for anyone who is interested.Practicalities of using dogs in the clinicThis isn’t the first time dogs have been suggested as good cancer detectors. There have previously been reports of them detecting lung cancer, breast cancer and bladder cancer (albeit with far less impressive results than this). However, at the moment it is just not viable to introduce dogs to the clinic. A test used for cancer detection has to be reliable, and other studies haven’t proven as successful as this one. Add to that the practicalities of using live animals in the clinic (training, housing, feeding and handlers), and you can begin to see why this is not currently planned.However, if scientists can figure out what it is the dogs are actually detecting (at the moment they have no idea), it may be possible to design a much better lab-test for it which will be far easier to get into the clinic. These “electronic noses” are already in clinical trials for lung cancer, and are showing promising results. Whether these will prove to be cheaper and more effective than dogs remains to be seen, but for the time being it is a very active and interesting area of research. And, let’s be honest, most people are likely to prefer having their urine sniffed by a dog than have a rectal examination, the current standard test for prostate problems… Screening for cancerScreening for a disease means testing an entire group of people for the disease, regardless of whether they show symptoms or not. The NHS in the UK provides a screening service for breast, cervical and bowel cancer. These are tests that people undergo as part of a normal health check-up, once they reach a certain age. These screens aim to flag up any potential problems, so the patients can go for further tests.While we have tests for many other cancers, these are the only three that it is deemed cost effective to screen for. Take the PSA test for prostate cancer, mentioned above. The cost to the NHS to further test the high number of false positives would be immense. On top of that there is the worry and stress experienced by people who test positive wrongly. There has been debate in the medical field as to whether breast cancer screen is worth doing, for the same reason.Obviously it would be very desirable to screen the population for every cancer. The earlier a tumour is caught, the better. However, the tests we have for the large majority of cancers are either not reliable enough, or are too expensive, for screening purposes.
