It’s important to understand your initial cancer diagnosis, and the ongoing monitoring.
This module covers:
Blood tests and tumour markers
Scans (MRI, CT, PET, ultrasound)
Genetic testing and liquid biopsies
Cutting-edge testing (N-NOSE and miRNA)
In this 2nd module, the topic is all about understanding cancer diagnosis, and all the kind of monitoring that goes along with this thoroughly unpleasant journey. I’m going to talk a little bit about cancer staging, cancer grading, blood tests, the various kind of scans, and then some of the advanced testing that is just becoming available, or that’s been available for a while but is just becoming affordable, or has been available for a while and isn’t particularly affordable, but it’s just becoming more reliable.
Cancer staging and cancer grading – these are often confused. Cancer staging – we usually think of four stages, often subdivided. Different cancers have different types of staging, especially different sub-stages. Cancer staging is really about where the cancer has got to. Unfortunately, cancer spreads and grows in other places of the body, and this is a unique point of cancer. Bits of your body can’t move to other bits of your body and start growing. There are mechanisms to stop that happening. When cells are floating around in your blood, they can’t just stop and stick somewhere. There are mechanisms to kill them, there are mechanisms to stop them sticking onto places. But cancer is able to subvert and get around a lot of this. So the staging depends on the point of origin of the cancer.
I am most familiar with colorectal cancer because that’s the cancer that I have. I think the staging for colorectal cancer is relatively simple, but other cancers follow the same kind of pattern.
Stage 1 is where there’s a tumor or tumors in one place, and particularly with hard tumors they’re going to be in an organ.
In stage 2, it has spread or maybe spreading within the organ, or maybe just getting to the edge of the organ coming through. With cancer in the intestine, it’s trying to get out of the wall of the intestine.
Stage 3, it has spread locally – often it’s going to be spreading to lymph nodes.
Stage 4 it can spread to distant organs.
Depending on which type of cancer, usually stages 1, 2 and 3, there’s at least some chance of a cure. Traditionally we’ve thought of stage 4 as being incurable, but there are some very strong exceptions to that. Colorectal cancer that’s just spread to maybe a couple of lymph nodes some distance away, or that’s just spread to the liver – some of those patients are able to be treated with curative intent, such as liver surgery, removing the primary tumor, followed up with some chemotherapy. Hopefully at some point in the future, the cancer hasn’t come back and it’s been long enough that the patient can be considered cured – whatever cured means.
In most contexts, I guess we’d say someone’s cured if their chance of having cancer again, is just the same as someone who wasn’t diagnosed with cancer. That’s a practical definition of cure that many of us are looking for, where our oncologist says there’s been no evidence of cancer for a certain number of years, and your chance of it recurring is as low as the general population.
So there’s staging and then there’s also grading. Grading is really what does the cancer look like under a microscope. This is in a pathology report – so maybe a biopsy has been taken or maybe a tumor has been removed, then it’s sliced up and examined under a microscope. Its grading is really about how different do the cells look, compared to normal healthy cells. There’s a Grade X which means they couldn’t do the grading, and grades 1-4. In Grade 1 they look like healthy normal cells, and in Grade 4 they look very mutated. It seems to be that as the grade gets higher, the cancer becomes more aggressive, so more chance of spreading, with more chance of becoming stage 4.
Now, cancer grading and cancer staging is useful for teaching how cancer works. It’s useful for making economic decisions about how our government should spend money on health care, what drugs should be approved and what drugs should not be approved. In my 6 years of dealing with cancer, and talking to hundreds of cancer patients around the world, I found no benefit at all in talking about cancer staging and cancer grading- none whatsoever. It seems completely irrelevant to patients. In theory, grading is to do with prognosis, as is staging, but I haven’t seen any use in it, from a patient’s point of view at all, in 6 years of talking to a huge number of patients around the world, in various cancer Facebook groups that I’m in.
So as I said, the grading comes from the pathology report and it’s physically cut up tissue, stuck under a microscope, and that’s called histology. So it might say “histology report”, or “pathology report”. The relevant bit for us, is that you basically need to take out cancer to do biopsies, to be able to say with any kind of degree of certainty, what is going on.
That’s why when the cancer is just found straight away, specialists are quite wary of talking about any kind of certain terms. So in my case for example, primary tumors were found during endoscopy/colonoscopy and there was a massive tumor in my intestine. As a patient, I’d say well it’s quite obvious it’s at least stage3, because if the cancer is that big, it can spread to other places. But of course the endoscopist was saying, “I have to wait for the biopsy results and then the scans.”
Typically in cancer patients, cancer is found in some cases through some kind of screening, or often we’re at the hospital for some other reason, maybe some maybe some kind of cancer-related symptom. But in the case of colon cancer for example, 50% of patients present with no symptoms. In my case, it was a bad reaction to antibiotics. Fortunately, the doctor was a bit suspicious and sent me in for testing, and it was found before I had a fatal intestinal obstruction and dropped down dead.
So I wanted to go over blood tests and tumor markers. Typically after someone has had surgery, the cancer has been staged, you’ll be having ongoing blood testing and ongoing scans. Of course scans and blood testing can also be a big part of diagnosis, scans in particular. Blood testing is something that we get very used to quite quickly. Typically you’re going to be having monthly blood tests for a long time, hopefully if you stay nice and healthy for a long time.
We’re concerned with various aspects of blood testing. For example, tumor markers which are potentially related to the cancer in our bodies. Tumor markers are often called “biomarkers”, (especially in the US). These are things you can measure, that hopefully relate to the amount of cancer, the activity of the cancer, and maybe its potential to spread. It’s a very inexact thing.
One of the reasons it’s inexact, is of course typically we wouldn’t know our normal tumor marker levels before being diagnosed with cancer, and maybe that’s going to change in the future. Maybe whenever you go for a health check, they’ll measure a whole panel of tumor markers and keep that on record for you. But that doesn’t happen at the moment, so that’s one reason, is that we don’t know the baseline.
Tumor markers can be elevated for various reasons. A very common tumor marker – CEA, which is used for a whole range of cancers, can go up in response to treatment. So you can get a bit of a shock when you start some chemo and CEA rises, or start radiotherapy and CEA suddenly rises. It can be scary. Often with tumor markers, the oncologist will say “Don’t worry so much about the absolute number, but look for is it rising or falling over time” – that kind of thing.
Tumor markers are not accurate, they may be a good predictor for some patients, they may be a poor predictor for others. They may work well for you for a while, and then not work well for you later, which happened to me.
For colon cancer, we typically measure CEA and CA 19-9. For different cancers there are different tumor markers. Some tumor markers are used for a whole range of cancers. CEA seemed to be a good measure of what was happening, because it was rising for a couple of months and I had my 3-monthly full body scan, maybe I would see tumor growth. When CEA was falling, I could see tumor shrinkage or tumor disappearing. Then at some point it became at least temporarily useless, because CEA was nice and stable, but then the scan revealed a 75 mm tumor covering my liver, which came as quite a surprise.
So trends are important. Having 2 markers that are good indicators for you, is obviously really good. If the tumor markers seemed to be a poor indicator, it’s really worth pushing the oncologist for what other tumor markers may be available. There are tumor markers that seem to be useful, but only a bit, and thus aren’t standard. But those might be a good option for you.
There’s more research coming up, actually markers all the time. I think that my oncologist for a while was measuring a different marker CA125, which is usually associated with gynecological cancers like ovarian cancer, but for colorectal cancer, it does seem to be useful for cancer that have spread to the abdominal membrane as well.
So that might be worth doing if your tumor markers don’t seem to be reflecting your situation as seen in scans. If your oncologist is cooperative, they may be able to order a whole bunch of new markers for you, and if they see some that are elevated, then those might be worth monitoring after a while. New tumor markers are being invented all the time so it’s worth asking about those as well.
When we have our blood tests, a whole range of stuff is measured. We will typically have what’s called a Full Blood Count in the UK (in the US it’s called Complete Blood Count). This is looking at the red blood cells, white blood cells and platelets. Red blood cells are very important for us, because they carry oxygen to cells and they carry carbon dioxide away from cells, which allows us to live. They’re very relevant for us as cancer patients, because unfortunately some chemotherapies cause a lot of problems with the manufacturing of red blood cells which happens in your bone marrow, and in some cases actually, these counts can be used to see if certain kinds of cancer have spread to the bone marrow.
Then we also look at the white blood cells which help fight infection. Of course and unfortunately, various cancer treatments cause white blood cell suppression or immunosuppression. Chemo tends to reduce the number of white blood cells, and that often gets to a point where you have to have a chemo break or a chemo- holiday.
Just on that point, I have looked a lot for research about chemo breaks, and there doesn’t seem to be any good research about how long it’s safe to stop chemo for, and what the effects of that are on your long-term survival. I just haven’t found good data. I talked to lots of oncologists about it , and it’s basically just their feeling of how many cycles of chemo they think it’s safer to miss. In some cases, you may better switch to a different chemo that doesn’t cause bone marrow suppression, or that causes less white blood cell suppression.
In the notes that I’m in the process of producing for you, I go into all the various points of the blood tests, e.g. what the different numbers mean, what the different things stand for etc. But typically with red blood cells, you’re measuring the hemoglobin, which is the ability to carry oxygen; you’re measuring what % of the blood is actually red blood cells, because there’s loads of water in there, and various nutrients and loads of platelets and white blood cells in this whole mixture, but it’s useful to know the % of blood cells.
Platelets are the things that make blood sticky, and they’re very important in wound healing. For cancer patients, they’re very relevant because if platelets are very low, you may not be able to have surgery.
This happened to me- I waited months and months hoping for surgery, wishing that the platelet count would creep up. It seems that my spleen is big; an enlarged spleen probably from liver surgery, maybe scarring inside the liver, causing local hypertension which could cause a large spleen. One of the jobs of the spleen is to break down old platelets. If the spleen is too big, it’s too enthusiastic and it destroys healthy new platelets as well.
So platelet count is important. Also another reason platelet count is very relevant for surgery, is that if the platelet count is low and you’re doing abdominal surgery, you may be told you can’t have an epidural because it’s too dangerous.
These kinds of things are actually not decided by the surgeon.Usually I think it’s the anesthesiologist, who is the person that is in charge of your anesthesia, but they’re really also in charge of vital signs during the surgery, and your fitness to have the surgery in the first place. So they make decisions about whether you can have an epidural or not, or can you even have the surgery or not.
Some surgeons will agree that you can have a platelet infusion, but some don’t and it depends a lot on the surgery.
In my case, the platelet count was just about enough to do the surgery and it was all fine.But the surgeon didn’t really want to do a platelet infusion, because he felt that maybe the platelets would just get all destroyed very quickly anyway, and he wasn’t sure about the quality of my platelets that could be tested. So platelet count is very important for us for various reasons.
We’re also, as cancer patients, very concerned with liver function. This affects your fitness for surgery for example, but also affects your ability to have chemo. Chemo is broken down in the liver, and in some cases we’re taking drugs that turn into chemo drugs in the liver – things like zeloda or TS1 you might have heard of. They get metabolized into chemo drugs in the liver. So liver function is very important, and unfortunately various cancer treatments cause trouble with our liver.
Radiotherapy to the liver causes damage to the liver function. Surgery to the liver obviously reduces liver function for quite a while, but it should return to normal. Chemo reduces liver function. Those liver function parts of the tests, things like gamma GTP, they’re really important. You can read about that in the guide I’m putting together for you.
There’s also what’s called the chemistry panel or the metabolic part of the blood test. That’s looking at nutrients in the blood, but also things like enzymes and the electrolytes. There’s things like your potassium level, sodium level, that kind of thing. Some of those are very relevant to whether you can safely have certain drugs or not.
All the details will be in the guide as some of it’s quite technical, but it’s worth always keeping copies of the blood tests. I’ve just found it’s really worth pushing the specialists and the oncologists as well, if there are issues, what can be done to fix them. Is it just a case of a chemo-break, or are there alternatives. I don’t enjoy chemo, I did it for five years, but it’s very important and I felt very uneasy having chemotherapy breaks.
On to scans- I know that obviously most of us have had all the different types of scans possible, but just very briefly I will explain what the scans involve as well, just in case maybe some of you haven’t had a PET scan, or you’ve had maybe CT but not MRI.
As patients, we often wonder what’s the best scan to have. But that’s not really a relevant question, because the scans have different uses and they’re used in different situations.
So to just go over like the 3 common scans: the CT scan – that is essentially just X-rays. CT stands for Computed Tomography. It just means a picture made of slices. Essentially you’ve got an x-ray machine that has a moving table. You lie down and it takes an extra view, and it moves you a little bit, takes another one, moves you a little bit and does this for 10 to 20 minutes, maybe up to 30 minutes depending on the scan and the resolution.If they’re smaller slices, you’re going to get a more accurate picture, but the scan is going to take longer.
Often we’re going to be doing a CT scan that is called an enhanced CT scan or a CT scan with contrast. This is where a contrast agent is put into you by an IV drip or intravenous injection. That could be done by a nurse or it could be done by machine. You might have a nurse who will come and place the needle in you and attach it to a drip but it’s got a pneumatic syringe, and that contrast agent, as the name suggests, gives more contrast to the scans. It spreads throughout your body and then on the scan, the differences between tissues and things will show up more with more contrast.
That contrast agent feels very odd. It’s like a strange warm feeling spreading throughout your body – not particularly pleasant, particularly the first time you have it. It’s a bit of a weird feeling in your mouth, as well. Many patients say they feel like they’re going to wet themselves, but contrast agent is important because it makes the scan more useful.
MRI can also be done with a contrast agent and I’ll talk about MRI scans in a second. But one of the key points of the contrast agent (and let’s go back to blood testing), is that it can cause kidney damage- which means if you’re having kidney issues, you’ll often have to do the scan without the contrast agent. I have talked to various radiographers and oncologists and stuff about this damage, and I’ve read some papers on it. As far as I could see, I’m not a doctor, but the chance of it causing damage if you got completely normal kidneys is kind of close to zero. It just seems that in every case, that the danger is if you have impaired kidney function.
MRI scans used a different contrast agent, an iodine-based one, and there doesn’t seem to be any risk at all. The reason it’s just a bit of concern, is that you don’t really want to be doing damage to your kidneys because it’s irreversible. So that’s just something to bear in mind, if you’re having kidney issues. Just remind everyone, “Look, it says poor kidney function on high blood tests, do we really want to be doing this with contrast?”. But generally, they’ll be far more aware of that than we are, so it should be fine.
CT scans are good for showing skeletal features. They’re good for showing structures between organs. They’re good for showing changes of sizes in organs. So you might see for example, lymph nodes that are swollen and therefore could be cancerous. That’s what CT scans are useful for. The images aren’t super clear. MRI scans are much clearer images, but MRI scans are good for seeing the difference between healthy and diseased tissue. They are good for when you need a very accurate picture, so for planning surgery for example. If you are going to have liver surgery for example, then you’d have a liver MRI shortly before the surgery.
One issue with them is that it can be very difficult to tell the difference between cancer and excess liquids in the body, so that’s one thing against MRIs. An MRI is a magnetic scan – it stands for magnetic resonance imaging. They used to be called NMRI, (N stands for nuclear and that freaked too many people out so they dropped the N) but it’s still the same scan. The key point is that despite the “n” in NMRIs, MRIs are magnetic scans, there is no radiation – not like a CT where it’s using X-rays.
In CT scans, the radiation dose is very very low. As far as I can tell, it shouldn’t have any consequences for adults. With kids, it’s a very different thing, just the same way a normal X-ray. Modern X-rays are digital, with very low radiation. When I was a kid, X-rays used quite a bit of radiation. It was said that you should only have one a year.
MRIs are the very noisy scan. I don’t know why but the machine is ridiculously noisy. That can be quite unpleasant, especially the first time. I’ve had lots of MRI scans, lots and lots of CT scans, and quite a few PET scans as well. The MRI machine is less claustrophobic. For MRI, you can ask for an open machine. Some hospitals have an open machine, which is not enclosed. I don’t believe there are such things as open CT machines. There maybe, but if you are the kind of person that panics when you’re told to lie in a tunnel with a big noisy machine around you, it can be worth asking if there’s any alternative.
Potentially the one alternative, if you’re looking at a specific part of the body, would be an ultrasound. For example, you can have an ultrasound liver and with that, you’re lying on a bed, and a medical technician does an ultrasound scan with a handheld device. So that may be an option. So if there’s an issue for you, it’s worth asking. Don’t just think nothing can be done.
PET scans are positron emission tomography scans. That’s the one where you’re injected with a radioactive sugar called FDG, and it goes around your body, which takes about an hour. When you do a PET scan, you have to lie in a darkened room for an hour beforehand. Generally here in Japan you’re not allowed to read, or listen to anything. You just just lie down. The reason they don’t want you reading, is because your eyes are moving around and then the FDG would start to pull up in your eyes. PET scan shows the activity of tissue and organs. If there’s cancer, the FDG should build up in that area while you’re lying down for an hour waiting for your scan. If certain organs are working too much, they will glow on their PET scan.
Typically a PET scan is PET/ CT which means the machine has a CT scanner built in. When you have a PET/CT, you can’t have the contrast agent and that’s just because there would be too much contrast when the images are fused together. With PET/CT you get 3 images. You get the PET image (which is the one with the colors on glowing for tumors and things), the CT image, and then you get the fused image. They don’t put any contrast in, because the image would be like an overexposed photo.
So those are the main scans. Then there’s also ultrasound, which can be really helpful if you get an ultrasound done by a surgeon, because they’re really good at it. I should say that for whole body scans, as a cancer patient, you’ll often be having a CT scan every three months.
Hopefully after some treatment, your oncologist says good news and is going to do the next scan in four months, and then later six months and then hopefully once a year. But in those whole body scans, the radiographers are very good at finding cancers and changes in whole body scans. But it does seem that for a scan of an organ or analyzing the bit of a whole body, scanning an organ by a surgeon who specializes in the area, can sometimes see things that a radiographer might miss, because they have better knowledge of local anatomy.
I should say that scans don’t really show cancer. Scans show things or possibilities of things, and are very open to interpretation, and the probability of something being a tumor or not, or being tumor growth or not, is very open to interpretation.
In my case for example, because I have stage 4 cancer, the burden of evidence, the threshold for evidence, is quite a bit lower. If something appears, you can say “ it’s probably cancer”. But just as an example, 50% of scans of lungs have some kind of nodules, and the majority of those wouldn’t be cancer. You can get things called granulomas in your lung, where a little bit of grit has gotten into the lung, and some tissues built up around that.
So scans are very open to interpretation. Maybe that will change soon, because of course now we’re just on the verge of getting scans looked at by artificial intelligence systems instead of radiographers, or artificial intelligence systems plus radiographers. So maybe it’s changing, but it’s not an exact science at all.
One thing to bear in mind is, you hear people saying things like “I can’t believe the radiographer missed this new tumor” or something like that. It’s very understandable to feel like that, but that’s not the reality of how scanning works. Scans may or may not show changes and things. When I had a 75 mm tumor appear over my liver, it was found in a PET/CT scan, but it didn’t show up on the PET part of it. PET scans can usually show things of around 8mm and this is 75 millimeters, but the density was lower than the glowing bit of the PET Scan would see. But because it was a PET/CT scan, it showed up on the CT scan part of it.
Briefly, genetic testing and liquid biopsies. Liquid biopsies are very advanced blood tests, looking at things like circulating tumor cells. There are cells from the tumors that are swimming around in our blood, so looking at “free DNA”, ie DNA material. For some liquid biopsies, the analysis includes the full genome of the cancer, which means they’re doing a full genetic analysis of the cancer, looking hopefully for mutations that are actionable, which means that there’s some drug that is good for targeting that mutation. It may be a drug commonly used for another cancer type that may be worth trying .
The circulating tumor cell tests or “free DNA tests, are potentially useful for warning you if you have no visible tumors and the tumor markers are stable, but if you find circulating tumor cells, that may be a good indication that you should have another scan soon or something like that.
These advanced tests- the most famous liquid biopsies are the Impact liquid biopsy which is from Memorial Sloan Kettering the US, and also Foundation 1 is another famous good biopsy.
You can generally have them in many countries – you might find a local place that does testing. For example, when I had a liquid biopsy a few years ago in Japan, it was sent to the US for analysis. I had the MSK Impact one and it found three mutations, one of which had no drug associated, one of which had a clinical trial that was recommended against because it was too toxic, and the third one, there was a clinical trial but I couldn’t join because I’d had one of the drugs of the combination of drugs that was in the trial.
The new tests that are just becoming available now are things like Micro-RNA testing and the N-Nose test. These are, at least at the moment, very sensitive tests for cancer screening.
Micro-RNA is looking for little bits of non-functioning RNA. As we remember from school, RNA does the work of DNA. One of its roles is it goes out and does things like DNA, but instead of two strands, it’s one strand. This really developed as a screening test, and it’s screening from a drop of blood . So it’s a pin prick and then it can screen for hundreds of cancers. But potentially of use if you’ve got to the stage of No Evidence of Disease, and you’re wondering what you should do – should you continue chemo for a while, obviously to keep an eye on things, so it might be useful in that case.
The N-Nose test is one that uses a worm or a bunch of worms. It uses nematode worms which are the type that you often have as parasites in your intestines, and they’re very averse to cancer – they will move away from cancer. You have a sample taken and put on a slide, and a bunch of worms put in there, and a specialist will look and decide if the worms are slithering away from the sample enough to suggest that it’s cancerous. But those are maybe 100 times more accurate than tumor markers- that is the figure that I’ve heard.
So that’s really been an overview of staging and grading, and blood tests and the different scans and some of the advanced testing.