Cancer Diagnosis: Why don’t we scan and test everyone to detect cancer?

by Dr. Chang Yang Yew

It is well known that the survival rate of cancer patients is much higher if the cancer is diagnosed at an early stage. As medical technology evolves, there are now an abundance of scans and blood tests available to help doctors detect cancers and other diseases. Putting these two facts together, a natural question is: “Why don’t we scan and test everyone regularly so that we could pick up and cure more cancers?”

To answer the question above, it helps to first establish some yardsticks of how we measure the usefulness of a medical test:

• A test needs to reliably display positive result when a disease is present (in medical jargon it needs to be sensitive) – just imagine the futility of a “cancer test” which misses half of the cancer patients.
• A test should be reasonably specific, which means that amongst healthy people, it should not give a falsely positive result. False positive results contribute to anxiety and complications from subsequent invasive medical tests and procedures.
• Lastly, the most meaningful measure of a test’s usefulness is its effect on mortality. The important question is, “Does this test save lives?”

It is clear that ideal tests should be 100% sensitive (all cancer patients are detected) and 100% specific (all healthy individuals are negative for cancer). However, due to limitations of many tests, testing everyone indiscriminately is a futile exercise for most diseases.

One of the biggest cancer news which hit the mainstream media in recent time was about Jack Andraka, a 15-year-old boy from US who invented a test to detect pancreatic cancer in its early stages, promising a dramatically improved cure rate [1]. 

A common misconception regarding modern medicine is that diagnosing a disease is as easy as ‘doing the appropriate blood test’, like matching a fingerprint with a criminal

Pancreatic cancer is one of the most fatal cancers in the modern era. As the pancreas is seated deep inside abdomen, patients do not usually suffer obvious symptoms in early stages, hence it is typically only diagnosed at an advanced stage, and about 75% of patients die within one year of diagnosis [2].

The simple, fast and cheap blood test Jack Andraka invented promises an unprecedented revolution in the detection of pancreatic cancer. This test costs 3 cents to produce, is nearly 100% accurate, and won him the grand prize in the prestigious Intel International Science and Engineering Fair. It employs nanotechnology to detect mesothelin, a type of protein which is present when one has pancreatic cancer. He hopes that this test will one day become available on supermarket shelves, and everyone could just pick it up and do this test during their free time, and no one will die from late stage pancreatic cancer any more.

It’s a nice little idea, but unfortunately one that will never work.

First and foremost, congratulations are due for this bright young man for his dedication and progress in scientific research at such a young age. Having his name on a “cancer sensor inventor” as a 15-year-old boy is an amazing feat. Unfortunately that’s where his achievement ends. This invention will not save lives; in fact if it were to be introduced unregulated in local supermarkets, it will do more harm than good to public health.

A common misconception regarding modern medicine is that diagnosing a disease is as easy as ‘doing the appropriate blood test’, like matching a fingerprint with a criminal. However, the majority of medical diagnoses are simply not made this way.

Let’s look at the pregnancy test as an example. The standard urine or blood pregnancy tests today are extremely accurate, and it works by detecting the βHCG hormone which is secreted during pregnancy. So, if someone tests positive for βHCG, then she is pregnant, right? WRONG.

While the vast majority of positive βHCG is due to pregnancy, sometimes it could also be due to sinister causes called gestational trophoblastic diseases which are a type of tumour in the reproductive organs. However, in practice, if a lady has missed her period and is tested positive, she would be told “you are pregnant” unless something is amiss with the story.

This is due to:

• There are far more pregnant people than people with this tumour.
• The fact that she has missed her period makes pregnancy the more likely an explanation.

βHCG is useful because:

• In pregnancy βHCG level is always elevated*. (It is sensitive)
• When it is elevated, the vast majority of the cases are due to pregnancy, the rare exception being the gestational trophoblastic disease.  (It is highly specific)
• Its usage enables good outcome (you know you are pregnant hence you commence antenatal care etc.)

While these three conditions, especially the last, may seem trivial, they are the criteria that any diagnostic test have to meet prior to being practical. If someone comes along and develop a new 5-cent pregnancy test, they will either have to meet these criteria, or be disregarded despite costing only 5 cents.

Another famous example is PSA (Prostate-Specific Antigen), a protein elevated in prostate cancer. PSA screening is in common use to screen for prostate cancer (it’s no longer recommended for everyone but that’s a long story on its own). As prostate cancer is such a slow growing tumour, it’s been found that even after using PSA and detecting some earlier cases, the mortality is almost the same whether or not we screen everyone with PSA [3].

Prostate cancer is so slow-growing that a lot of patients die with prostate cancer rather than from prostate cancer. On the other hand, screening gives rise to a lot of anxiety and risk over the need of doing further biopsy tests. Hence, PSA is only recommended for particular high risk groups, and/or after an informed discussion is conducted [4].

Now back to the story of mesothelin and pancreatic cancer.

Mesothelin is a protein which is present in cells lining the heart, chest cavity and abdominal cavity, and its level is increased in multiple cancers including pancreatic cancer, ovarian cancer and mesothelioma (cancer of chest cavity lining). This makes it a potential “cancer marker” for blood test. However, a major difference exists between mesothelin and established useful tests such as ßHCG.

For ßHCG, with the rare exception of the gestational trophoblastic disease, the range of ßHCG level in non-pregnant and pregnant women are so distinctly different, making it both sensitive and specific. However, for mesothelin, the range of level is not similarly distinct. In a study looking at mesothelin levels in healthy people and pancreatic cancer patients, it is found that these two ranges overlap so much that it is impossible to differentiate the two groups with enough sensitivity and specificity [5].

Even though Jack claims this test to be 100% sensitive, it only means that it will detect a particular level of mesothelin 100% of the time. It is not known what the specificity is i.e., how often a healthy patient is falsely tested positive. Given the overlap above, the logical conclusion is the specificity is low.

Let’s put this in practical terms. If a person tests positive for mesothelin, he could either have pancreatic cancer, other pancreatic conditions, ovarian cancer, mesothelioma, or have nothing at all. Not that useful isn’t it?

At this juncture, one might refute that even if some healthy people are mistakenly tested positive, they could always just do more tests and find out that they don’t have disease – isn’t that better than the alternative, having pancreatic cancer and not knowing it? The answer is a resounding NO.

As pancreatic cancer is such a rare disease, if everyone is tested with mesothelin, there will be fewer disease detection (true positives) than false positives. The thousands of people who have false positive results will now go through more tests (CT scans, biopsies etc.), and all these tests actually have inherent risks (CT increases the risk of cancer, biopsies are invasive procedures and may cause severe infection and bleeding).

At the end of the day, despite costing only 3 cents, such a test will end up harming more healthy people due to over-investigation, than saving the few lives from actual disease detections (refer to the rule 3 of the “usefulness yardstick” above).

To sum it up: This young man has a promising future but is no cancer saviour. He has not discovered something that millions of scientists in thousands of labs have overlooked in decades of research. Unfortunately there has been a huge media circus surrounding his invention, most of which have focused on perpetuating the “prodigy cancer saviour” feel-good story without commentary from established scientists to put things into  context.

This may distort the public perception on cancer research, and could end up instilling distrust amongst public in proper scientists and researchers. In the comment section of the aforementioned news article [1], the top comment is about how such an invention (like the many dozens of “cancer cures” invented each month) will never see the light of the day because pharmaceutical companies need to keep making money from cancer treatment drugs rather than saving people’s life with cheap, easy and effective inventions like this. Such popular misconceptions insult the efforts of millions of scientists in labs worldwide, who toil away in their often frustrating and mundane efforts day in day out, without the benefit of being glorified in the media as a cancer saviour.

When something sounds too good to be true, it is often because it is. Medicine is hard, and that is why there is no easy solution such as “let’s test everyone for cancer everyday”.

Footnote:

* In early pregnancy of less than 1 week, βHCG may be negative. If clinical suspicion is high, a repeat test in 2-3 days time will give a definitive answer. 

References

[1] Did this 15-year-old just change the course of medicine? Schoolboy invents early test for pancreatic cancer that killed Steve Jobs: http://goo.gl/IYA6p

[2] American Cancer Society. Cancer Facts & Figures 2010. Atlanta: American Cancer Society; 2010: http://www.cancer.org/acs/groups/content/@nho/documents/document/acspc-024113.pdf

[3] U.S. Preventive Services Task Force. Screening for Prostate Cancer; 2012: http://goo.gl/J5Eqb

[4] American Urological Association. Early detection of prostate cancer: AUA Guideline: http://www.auanet.org/education/guidelines/prostate-cancer-detection.cfm

[5] Sharon, E, Zhang, J., Hollevoet, K., et al. (2012). Serum mesothelin and megakaryocyte potentiating factor in pancreatic and biliary cancers. Clinical Chemistry and Laboratory Medicine, 50:721-725.

About the Author

Dr. Chang Yang Yew is a Malaysian medical doctor who is currently training as an anaesthetist in Australia, and is passionate about debunking harmful misconceptions inside and outside medicine. Find out more about Chang Yang by visiting his Scientific Malaysian profile at http://www.scientificmalaysian.com/members/changyang