Cancer screening

In this episode of PodMD, seasoned medical oncologist Professor David Stewart will be discussing the topic of cancer screening, including a brief overview about cancer screening, who should undergo screening, the limitations of screening, how screening might look different in the future, debunking some oncology myths and legends and much more.


  • Transcript
    Please note this is a machine generated transcription and may contain some errors.
    *As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.

    Today I’d like to welcome to the PodMD studio Professor David Stewart

    Dr. David Stewart trained in medical oncology in the Department of Developmental Therapeutics at MD Anderson Cancer Center in Houston Texas, 1976-1978. He was on staff at MD Anderson from 1978 to 1980 and from 2003 to 2011, and at the University of Ottawa in Ottawa Canada from 1980 to 2003 and from 2011 to the present.

    His research has focused on various oncology themes, including the negative impact of dysfunctional regulation and clinical trial designs on the rate of clinical research progress, and the huge costs of this clinical research dysfunction in terms of increased health care costs and lives prematurely lost.

    He has more than 340 peer-reviewed publications. In April 2022 he published a book intended for patients entitled “A Short Primer on Why Cancer Still Sucks”, available through Amazon books or his website This book covers several topics, including why cancer is so common, limitations of screening, how cancer causes symptoms, different therapies, the future of cancer care, and more.

    Today, we’ll be discussing the topic of cancer screening

    *We do hope you enjoy this podcast but please remember that the advice here is of a general nature and is not intended as specific advice about a given patient. The views and opinions expressed in this podcast are those of the doctor, not PodMD.
    If you do have a patient on whom you require specific advice, then please seek advice from a colleague with appropriate expertise in that area.

    David, thanks for talking with us on PodMD today.

    David: Thank you for having me.

    Question 1
    The topic of today’s discussion is cancer screening. David, can you give us a brief overview about cancer screening?

    David: Well, I mean there being different ways of doing cancer screening for many years now and the whole idea is that the smaller cancer is when it’s discovered, the higher the probability of cure. Or to put it another way, from the time that cancer is still is initially formed, it can spew off metastatic cells, so to other parts of the body and the bigger it is, the higher the probability that that it will have, let out cancer cells that are going to establish themselves in other parts of the body.

    So a tumour as small as one millimetre already has about a billion cells in it that could, and every time it divides some of the cells that are produced as they divide could go off into other parts of the body. By the time a caster reaches a about a centimetre across, if you if you look carefully in the in the bloodstream, you can find up to 1,000,000 cash cells from that one centimetre to cancer, and so if you find cancers when they’re small, it increases the probability of cure, but it does not guarantee it because some of the cancer cells could have already established.

    But the reason that cancers can be curable at all is many of the cancer cells leave the cancer are sick cells and they are not capable of establishing metastases in other parts of the body. But the bigger they are, they higher the probability that at least some of the tumour cells leaving the primary tumour will become capable of establishing metastatic disease. But some very large cancers can nevertheless be cured by surgery. Some very small ones are incurable at because it depends on the size of the cancer as well as the characteristics of the cancer cells.

    Question 2
    Who should undergo screening?

    David: Especially the higher the risk of the person the more that they gain from it. If people are very low risk, they may not derive much benefit but high risk people should. So for example at people that have had prior colon polyps should undergo screening, or people that have a very strong family history of colorectal cancer should undergo screening. Patients with a very strong family history of breast cancer should undergo screening. Patients that that have been heavy smokers in the past should undergo screening for lung cancer, so the essentially the higher the risk of the person the the more that they could gain.

    And part of the risk is also age ,so that the older somebody gets, then the higher the risk of cancer, and the reason for that is that every day you’re alive, about 100 billion cells in your body are dividing and they’ve got an average of three mutations per every cell dividing, so each one of us has about 300 billion new mutations in our body every day. And the good news is that most of them are not important or they can be repaired, but some aren’t and so that but so the longer you’re alive, the higher the probability that some mutations will occur that can lead to the establishment of a cancer, so the and the number one risk factor for developing cancer is just getting one day older.

    Question 3
    What are the limitations of screening?

    David: So that again, the limitations are that some very small cancers may nevertheless metastasize so that so that’s an issue, so that even though people undergo screening by the time the cancer is found, it may already be too big to cure. o that’s one thing, and so that like if a 1-millimetre tumour can metastasize, usually you cannot detect that in any scan or any radiological procedure so that so it’s OK for bigger tumours that are found early enough so that that works, but some may be just too small so when they when they first start developing metastases.

    The other big thing is false positives, so that many people will undergo a screening that they have a false positive and essentially the lower the risk you are, the higher the probability that any positive is found would be a false positive. And for example, if only one in 10,000 people will have malignancy about 100 people will have a false positive and so that there will be many, many times as many false positives as there will be true positives. And so, and the false positives can lead to anxiety, can lead to a lot of additional testing, including some risks associated with it. So the radiation associated with repeated scans or the risk of serious or fatal complications from biopsies that maybe on a false positive. So this is this is an issue with screening, just the fact that the false positives may lead to problems and but also that it may miss things.

    Also a patient may undergo 1 screening exam and have nothing then a year later undergo another one and find if we found that they’ve got metastatic cancer just because the cancer may develop in that period in between the screening episodes, so that’s another issue with screening as well. But typically though, for most screenings you have to screen hundreds of people to prevent one cancer death, and so that’s a lot of people undergoing a lot of testing to just prevent one death.

    The other issue is that when the when people present on screening, they’ll often talk about relative risk reduction. So they may say that with low dose cat scanning for heavy for heavy smokers that the relative reduction and risk of death from lung cancer is 16% but the absolute reduction is only about one in 250 so that the relative risk reduction sound good, but in fact the absolute reduction is actually quite small, and even that with lung cancer that having to screen 250 people to prevent one death. That’s far better than, for example, as a breast cancer where you have to screen many times more people than that to prevent one death. Both of them prevent a lot of deaths, but you have to screen a lot of people to prevent one death.

    Question 4
    Why are many cancers not detected until they are advanced and incurable?

    David: So the biggest problem there is that they produce no symptoms until they’re quite large. So I often told my patient with lung cancer that we’d be much better off of the cancer. Being people sick when it was very small and drew attention to itself, but it just does not do that. And part of the problem is that the organs, likely the lung and the pancreas and liver etc, have very very few few nerve fibres. So people do not have pain until the cancer is large enough that it reaches the outside surface of the organ and starts to invading into adjacent structures. And at that point, people start to developing pain, or if there’s a very large cancer there, maybe what’s referred to as visceral pain, but visceral pain is very poorly localised. People cannot tell really where it is, and so this is a major reason that cancers can become very large before they found.

    So some cancers like breast cancer patient may be may feel that term and as so that draws attention to it and that’s one of the reasons that only 15% of people who develop breast cancers die from it because it may be found when it’s fairly small or a bowel cancer may bleed into the bowel and so a person may see blood and maybe detected that way, but for something like lung cancer that may produce no symptoms at all until It’s quite far advanced. And then often when it does start producing symptoms, it may just be weight loss. The patient may still have an excellent appetite, and they’ll just think that their diet they’ve been trying sold for so many years to lose weight for the all these new diets and finally they found a diet to that that works. And so I’ve told my friends would be where the diet that finally works because it may be actually, an indication of advanced malignancy. But eventually the it does also start producing loss of appetite and accelerating weight loss, so that could draw attention to itself. But it’s just that the fact that that the cancers will produce very few symptoms until they are far advanced.

    Question 5
    How might screening look different in the future?

    David: So in the future, it may be a blood test. So right now screening is mammography for breast cancer, or pap smears for cervical cancer or colonoscopy or [inaudible] blood screening for colon cancer etc. In the future it’s very highly probable that’ll be a blood test. So that in the past I was hoping that we would just have to look for evidence of a mutation that causes lung cancer or that caused another kind of cancer, but then it was with great surprise when I read articles that those mutations may also occur in benign and diseases as well. For example, about 50% of malignant Melanoma may have it be BRAF mutation but to up to 80% of some benign moles may have that same mutation and there’s a whole bunch of other instances where benign conditions may have cancer mutations, so just grading for the mutation would not be enough to do it.

    But there are other things that look promising, including looking for DNA methylation patterns, because cancers have very distinct DNA methylation patterns that are different from normal cells. So if you can find those, you may be able to determine not only the malignancy is probably present. But also, you may give you a clue what organ to look. Also, if you look at gene copy number so cells with several amplifications, several extra copies of a gene might be an indication of a malignancy as well. And also there are other chemicals that can be produced by the cancer that may give an indication that cancer is present, so I think that there’s a very high possibility that within by 10 to 20 years from now, that screening will be with a blood test rather than their current methods that are used.

    Question 6
    How does cancer cause appetite loss, weight loss and fatigue?

    David: So that so that the weight loss is partly by causing appetite loss, but also other things as well. So that in your normal cells in your body, as glucose as a cell is converting sugar or glucose into energy it’s being converted into what’s called ATP. So ATP are molecules are energy molecules. So and when you breakdown 1 glucose molecule it will produce about 36 to 38 Atps using the process oxidative phosphorylation that is used in most normal cells. And that relies on a steady supply of both auction and glucose and sugar when you’re running, then not enough oxygen can get to yourselves rapidly enough in your muscles so the muscle cells convert to what’s called anaerobic glycolysis. So it’s a way of breaking down glucose that does not require oxygen. And when that happens, th cells can breakdown oxygen our glucose very rapidly, but each glucose molecule only produces 2 Atps rather than 36 to 38 Atps. And so it wastes energy, but the advantage is that can produce those Atps much faster then through oxidative phosphorylation so it’s very fast way of producing it.

    And in the in the process and the muscles produce lactic acid as they break it down, whereas the other normal cells produce instead carbon dioxide. Right now with cancer they do something that’s very unique, they rely on what’s called the Warburg phenomenon, which is aerobic glycolysis. So then, instead of using oxidative phosphorylation, they will break down the glucose using glycolysis and so just two Atps are produced per glucose molecule and so very inefficient, but they can produce those two glucose is much faster than they could by oxidative phosphorylation, so they can out compete their normal cells in their environment that are using oxidative phosphorylation, so because they’re producing those Atps much faster, and so as long as they’ve got a ready supply of glucose then they can burn them very rapidly to produce ATP’s.

    The other thing is, as it produce lactic acid that lactic acid is toxic to immune cells and also to the surrounding normal cells. So again, they can poison their surrounding normal cells and they can poison immune cells, so that gives the cancer cells a real growth advantage. And in the process of doing that they waste energy so that a cancer might use up as many as 1500 calories per day just through that process, so that causes weight loss even if you’ve got good appetite. But the other things that the cancer does as a as a cancer is growing, immune cells invade into the cancer and as immune cells invade and they produce cytokines.

    As a cancer grows the cytokines, the immune cells come in and produce cytokines like TNF or tumour necrosis factor alpha and interleukin 6, they will directly impair appetite by affecting the appetite centre and so that is what begins to lead to appetite loss in patients. The other thing also is that they will slow down stomach musculature and so the stomach does not empty as rapidly, so the patient will eat a Big Breakfast and then their stomach stays full so they cannot eat lunch or dinner because the stomach is still full. So that also happens as a result of these cytokines.

    Other thing the cytokines do as it will actually breakdown muscle so that they will that will lead to what’s called cachexia. So muscle breakdown to produce glucose for the for the tumour. And so if you’re on a desert island and you have no food, then your body will try to preserve muscle by breaking down fat. But instead what the cancer does, because through these cytokines produced by the immune system it actually breaks down, breaks down muscle to feed the cancer with glucose.

    The cytokines also impair lipid metabolism, so those fall the lipid metabolism, so you cannot form fat and this faulty utilisation of fat as a result of the of the cytokines as well and the cytokines at the same time that they’re doing this, they not only they’re not just the breaking down muscle. But also other organs like heart and lung and even brain, so that if you do careful cognitive testing and patient with cancer, you often find that they’re cognitively impaired because the effect of these cytokines on the brain. Also, there can be excess serotonin production and the serotonin will actually lead to a food wasting syndrome, so people will feel hungry and they’ll start to eat, but they’ll true and true and true and just cannot get it to go down. And this is similar to what’s called food wastage that’s seen in in in rodents with too much as serotonin, so that it’s the impact on both the energy wastage that and also on muscle breaking down muscle that leads to the to weakness and fatigue and patients with cancer.

    Question 7
    What is the best treatment for cancer-induced appetite loss, weight loss and fatigue?

    David: By far the best treatment is just treating the cancer. If you make the cancer shrink then that will often improve all those things. So back in the old days, we thought that treating the cancer, we might get prolongation of life expectancy by a little bit, but there would be a lot worse quality of life because of the side effects of the treatment. But in fact, whether what the studies kept on showing was the quality of life was better with treatment of the cancer, because making the cancer shrink improved quality of life improve things like appetite and weight loss and fatigue and a whole bunch of other things so despite the side effects of the of it.

    Now, the other thing that helps with fatigue is just being more active again in the old days we used to tell people to rest a lot, but those are wrong advice because then the muscles just soften up and be more active a person can be the better, so exercise is very important and cancer patients to try to keep the muscles in shape. Other things that help for people that find that they fill up fast and are still full at lunch from breakfast is eating six small meals a day often works better than eating three large meals a day.

    Question 8
    What are a couple of “oncology myths and legends” that patients may ask their physicians about?

    David: OK, so that there are all sorts of oncology myths and legends that some that patients have, some that physicians have, some that oncologists have. But they probably the two that I hear most frequently from my from my patients. One is don’t eat sugar because of each sugar, it will just feed the cancer, but it doesn’t make any difference how much for you that you eat. The cancer will feed itself just by breaking down your muscle, so a diet is important in getting cancer. So if you eat lots of fresh fruits and vegetables, you’re less likely to get it. But once you have it, diet is does not have all that big an impact and eating avoiding sugar does not really help treat the cancer. So that’s one of them.

    Another big one that I’ve heard frequently is that that surgery will make the caster spread faster, exposing the cancer dare will make it feel spread fast. And that was based on the on the what used to happen before we had scans. So somebody would present with the cancer and they undergo exploratory surgery where they opened up. See that there was very extensive cancer, couldn’t remove it and just close them up again and the patient was would die rapidly. That was going to happen anyway, but to the patient and their family it appeared that the surgery had made the cancer spread faster, but it actually doesn’t do that. In simple terms or putting another way surgeries by the best by far the best way to cure a localised cancer and so much better to do it. Having said that, if you do remove a large cancer, then as a cancer grows, you get what’s called [inaudible] growth. So the growth rate does slow down and if you remove the large cancer, there’s less competition for nutrients and so you will get increased rapidity of cancer growth after that. But if it’s if it’s all small, and then the trick then is to get the patient under Advent treatment after that to so that if there is any residual cancer to kill off those tumour cells. But for patients that told me that they want to not undergo surgery because will make the cancer spread faster, that’s not usually the case.

    And among oncologists by far the most common oncology, myth and legend is that the blood brain barrier is important that it will protect tumours in the brain from chemotherapy. But that’s probably not that has minimal impact of any. The blood brain barrier does keep drugs out of the out of the normal brain, but the reason that brain metastases light up on scans is because of the fact that blood brain barrier is disrupted. So the the contrast medium gets out into into the tumour. That’s why it lights up. Also the reason that adima around the tumours because of blood brain barrier is disrupted, but we did many studies years ago that showed that high concentration of chemotherapy drugs are achieved in human brain tumours, even if only low concentrations are achieved in the normal central nervous system and also so people say well in patients with brain metastases, they don’t live as long as people with metastatic disease that don’t have brain metastasis. And that’s true, except for the fact that patients that they their life expectancy of patients with brain metastases is identical to the life expectancy of patients with liver metastases or bone metastases or adrenal metastasis or subcutaneous metastases.

    The trick is that if you’ve got metastatic disease but not in the brain, there’s a high probability that you’ll be stage M1A disease, which means metastases is just in the lungs, and the plural only, and those patients have much better prognosis, so that if you compare patients with brain metastasis to patients without brain metastases, the group you’re comparing to them as a lot of patients that our stage M1A disease that a better prognosis. So that’s why it looks like the brain metastases are doing so much worse. But it’s no worse, and liver or bone or adrenal metastasis. But it has some major negative consequences if we treat patients with brain metastases different from patients with other other places with metastatic disease.

    Question 9
    How will cancer treatment look different in the future?

    David: So we can’t say for sure. All I can say for sure is that it will look different and as long as we keep on doing research and the reason I can say that is because things look so much different now than they did 5 or 10 or 15 years ago. Things keep on changing rapidly, so as long as we do the research, things were going to keep on changing rapidly. Now there will be some areas that don’t change very much or they don’t change nearly enough ,other things that will change a lot. For example, currently we we use adjuvant chemotherapy, so people that have undergone surgical resection of the tumour will give them chemotherapy to try to eradicate any residual cancer. By about 10 years from now will we will no longer be doing that. Instead, we’ll be doing a blood test a couple of weeks or two or three weeks after the surgery, and if we can still find circulating tumour cells or circulating tumour DNA at that point, we will know that there’s residual cancer as well and so we will be treating for minimal residual disease rather than being a so-called adjuvant treatment.

    If we cannot find any residual cancer cells or tumour cells, then there will be high probability that patient will be cured, so that’s one very important, I think in the future. Also, like right now, immunotherapy has radically changed things over the past eight or ten years, and but and that’s just by tackling 2 of what’s called the immune checkpoints. So your body has many checkpoints to keep your immune system from attacking your normal cells. But they can also protect tumour cells from the immune system as well, and so right now the two that we can target are the ctla 4 system with [inaudible] and the PD1 PDL system with drugs like [inaduible] and pembrolizumab, but there’s a total of at least 13 immune checkpoints in the body and some of them are probably very important to have in situations where we cannot, that they’re not successfully treated with current immune checkpoints and and so over the next few years we’re going to be getting lots more information on the impact of of blocking some of those other immune checkpoints, and it’s highly probable that some of them at least will be very, very useful and treating cancers that are now not sensitive to immunotherapy.

    And the future also, that in the more distant future there’ll be far more personalization of therapy, so that, for example, there are some drugs that are being used now called bytes or bispecific T cell engagers where one arm of that antibiotic targets a tumour antigen and will stick to a Tumour cell and the other arm will stick to an immune cell, and so I’ll bring the immune T cell in close to the tumour cell. So the so that the tumour cell or the T cell can kill the tumour cell. But in the future, I envision that we’ll be looking for new antigens produced on the on the your individual tumour cells, and we’ll be able to write very rapidly build a warhead that will recognise that new antigen is unique to your tumour and attach it to that byte so it’ll be what. So the bytes will be off the shelf, that’ll have one arm too attached to T cell. The other arm will have a free end that we can then attach something that’s unique to you, so it will be able to attack your specific tumour ourselves. So I think the technology could already be there to do that, so it’s already there, but it’s going to take us 10 or 20 years to figure out how to do it.

    Concluding Question
    Thank you for your time here today in the PodMD studio. To sum up for us, could you please identify the three key take home messages from today’s podcast on cancer screening?

    David: So on cancer screening, high risk people it’s a very helpful very import. Low risk people is much more likely to be a false positive, so just have to bear that in mind in deciding whether or not to screen low risk people as well. The one of my colleagues here who’s ahead of our breast screening programme has pointed out to me that if they screen young patients who have low risk, they will nevertheless save a lot of lives, but they’ll have a large number of false positives, so it’s just something to discuss with patients, the pros and cons of screening. If particularly if they’re low risk, if they’re high risk, then no question they should be screened, and it will have a higher probability of saving their life. The other thing with screening is at in the future, in the not-too-distant future, maybe a blood test rather than the current ways that we’re doing it.

    Thanks for your time and the insights you’ve provided.

    David: Well, thank you very much for inviting me again. If anybody wants more information, they can find it in my book “A short primer on white cancer still sucks”. And that book is easily obtained through Amazon Books or throw from my website and in the book I actually cover a lot of different things, including why cancer is so common, screening different treatment methods and oncology myths and legends, but also systems issues, why it takes far too long to develop new anti-cancer drugs, and how that contributes to both an excess loss of life because there’s delay and and approving new drugs, but also has a key driving factor in the incredibly high cost of drugs. The cost of drug development has soared massively over the past few decades. And that’s that directly contributes to the very high cost of drugs. I also cover the differences in the Canadian and American health care systems. And some of it might be applicable also to the Australian system. But just to showing how the strengths and weaknesses in those two and that there is no one perfect health care system.

*As always, all in this PODMD podcast is intended for health professionals and the comments are of a general nature. Information given is not intended as specific medical advice pertaining to any given patient. If you have a clinical issue with one of your patients please seek appropriate advice from a colleague with expertise in the area.