The [false]positive side of screening

Screening for Disease: Is earlier always better?

That title sounds a little wrong, you are thinking 'well, yes of course it is'. But bare with me. We have all heard of screening tests and are likely to have been through them. What is the harm in this? There is a lot of misinformation that is congregated around screening tests, leading to a lot of misunderstanding. Superficially, it appears to be good advice to give to ‘get something or other checked’. If there is something wrong in your body, you’d want to get it checked, yes? So, logically, we should be tested for everything regularly, yes? Well, no. We have an unfortunate thing in science called false positive. Meaning we would get a lot of anomalous results leading to a diagnosis and further tests to analyse something that isn’t actually there. 

Screening healthy people is a task that should be approached with caution. If you decline a screening, you will always have a little nagging voice in your head saying “what if?’ – you will, it is the nature of the human mind. So, should you have been offered the screening in the first place? I am going to focus on one type of screening in this blog; PSA. This is due to me researching into it naturally, and was not all too shocked at the information found. It was something I always somewhat knew, but not quite to this extent.

Prostate Screening

Prostate cancer is a very common cancer in men, occurring worldwide. There are two categories within prostate cancer, we have the aggressive and high death rate form and the slow growing, less likely to even have any symptoms. The latter of the two is most prominent and never really progresses to cause any health dangers during a patients’ lifetime, it is thought that 50% of men actually have the cancerous cells present - which will not develop. The screening test for prostate cancer is blood test in which they are looking for prostate specific antigen (PSA). A PSA test is looking at the levels of antigen in the blood, the test isn’t a ‘yes it is there’ or ‘no it is not there’, it requires interpretation. In an ideal world, we would like to have the rapid growing, life threatening cancers detected rather than the slow growing cancers as these don’t normally threaten a patients’ life. The side effects of prostate surgery to remove the cancer are invasive, scarring and leads to impotence, incontinence and cardiac problems.

PSA

PSA is an enzyme that is produced by prostate cells. Small amounts of PSA are observed in the blood at around 0.1-2.5ng/ml. Although, this appears to be very convoluted in the literature, many report the level is around 4-10ng/ml. So, if we don’t really have a consensus of the level that should be present normally, why would we look at it to detect cancers? These levels are said to be “normally” raised when prostate cancer is present. However, there are many other things that will effect PSA levels, including: ejaculation, weight, aspirin, infections and non-cancerous tumours. Evermore and more shockingly there is no clear cut-off level in which medical professionals use to differentiate those who have cancer and those who do not based on PSA levels. It is reported that 1 in 5 with clinically significant cancer will have a PSA level that is within the ‘normal’ reported range. If a doctor is using the 2.5nm/ml as the cut off, he could report cancer in a case with a PSA level <4.0 but higher than 2.5ng/ml. Even this report published by harvard have a different view of the levels that vary with age. Despite these limitations and high ability for misinterpretation, PSA routine testing is advised by medical professionals and companies that are selling these tests.  

 

Is there any harm in this?

Two questions that are required with any screening technique:

• Is there evidence to prove that early detection equates to a better overall outcome?
• Is there any harm from the testing?

In 2010, a systematic review was published in Biomedical Journal concluded that, as expected, PSA screening increased the likelihood prostate cancer diagnosis. However, it was found that there was no evidence of any impact on the death rate from the cancer itself (or the death rate overall for that matter). Risk factors, age and disease all need to be taken into consideration. Double blind randomized trials give very conflicting results with regards to the effectiveness and the test concentrates on disease specific mortality as opposed to the mortality overall. Richard Ablin, the discoverer of PSA recently wrote that the PSA test is being misused and is highly unreliable. Talking to New Scientist, Dr Ablin was reported stating:

“So, first is that PSA is not cancer-specific. Second, the level of PSA deemed worrying is arbitrary – 4 nanograms per millilitre or higher. As PSA is not cancer-specific, no level is diagnostic. Third, prostate cancer can be aggressive or, more often, very slow-growing. We can’t tell which is which.

Last, many men will develop prostate cancer by age 70. If an older man has a PSA level that prompts a biopsy, it is likely you will find cancer. Since you can’t tell if it’s aggressive, many men get treated unnecessarily – and risk life-altering side effects including impotence and incontinence”

 Source

This is all backed up by surmountable clinical trials. A study published in The New England Medical Journal screened over 1000 subjects before they saved one life. This lead, on average, to around 50 false positive patients, many of which unnecessarily undertook radiation therapy or even surgery. To put that into a simpler visual, this was taken from the Australian public health: 

“you have to screen 1408 men and treat an additional 48 men to prevent one prostate cancer death over 9 years. In other words, only 1 of those 48 men is going to benefit over the next 9 years; the other 47 … have undergone treatment for no benefit within this period.”

As stated prior, the treatment isn’t exactly nice and the side effects do change your life. We aren't seeing any better overall outcomes if we are including the unnecessary diagnoses (which we are) and we have a lot of harm from the testing, the over diagnosis. Thus, the two points that give the screening processes validation do not actually work.

Conclusion

Prostate cancer screening is easy, its just a blood test. But the results and the fallout are unaccountable. If 50% of men have the cancerous cells that wont progress into anything, then is it rational to have them undertake surgery? This screening method, like many others, is shadowed with over-diagnosis and the side effects from the treatment measures are significantly debilitating and life changing. So, should this still be being used? The decision is yours, the evidence is conflicting and mostly non-existent in the case for this particular screening technique. Don’t be fooled, this isn’t the only screening that actually has little success rate, there are many others - just as there are many others that are very effective. I am not discouraging (or trying to discourage) people from being screened from cancers, I just think there are many cases where it causes more harm and panic than good. At the bare minimum, the limitations of this and other screening processes should be clarified and communicated to a patient before the screening is carried out. 

There are plenty of books with sections on screening and the consensus amongst scientists with mass reviews of the evidence. I implore you to read them.