Speaking of Science - Bowel cancer prevention: from discovery and innovation to impact on survival in Australia

With one of the highest rates of bowel cancer in the world, Australia was the first country in the world to implement and sustain a national screening program using faecal immunochemical tests – more commonly referred to as the poo or stool test. This test gets mailed to eligible people aged over 50 every 2 years to conduct the free testing in the privacy of their own homes.

Beginning in 1936, NHMRC funded researchers made key contributions to the program’s initial development and ongoing conduct. NHMRC provided a succession of grants related to bowel cancer screening, including to our June Speaking of Science guest speaker, Professor Graeme Young AM of Flinders University.

Watch and listen as Professor Young discusses bowel cancer prevention from discovery and innovation to impact on survival in Australia.

Recorded on Thursday 25 June 2026 at 11:00AM-12:00PM AEST.

Video transcript

Professor Steve Wesselingh 0:02 
I think we might start and I know a few people are still joining, but we do want to give our speaker plenty of time to tell us everything he needs to. So thank you all for joining me. This cold morning. I think it's cold everywhere across Australia. So for our June webinar under the Speaking of Science series. I'd like to start by acknowledging the Traditional custodians of the lands that we're all meeting on across Australia and would like to acknowledge Aboriginal and Torres Strait Islanders who are meeting with us today. I acknowledge and respect their continuing culture and the contributions they make to the life of this nation. I pay my respects to Elders past, present, and emerging. Before we start formally get started today, I'd like to remind everyone that part of these webinars, and I think one of the best parts is the questions at the end. So really encourage people to think of some questions and you can put your questions into the team's Q&A function. Also, if you want to rewatch the webinar, a little bit like watching the Socceroos again or you want to actually encourage someone else to watch it, these are all recorded and are available on our website.

Professor Steve Wesselingh 1:25
Some of you may be aware that June is Bowel Cancer Awareness Month and this event raises awareness of Australia's second most common cause of cancer related death. It aims to champion what matters most to people impacted by bowel cancer and empowers everyone affected to live their best lives. With one of the highest rates of bowel cancer in the world, Australia was the first country in the world to implement and sustain a national population based organised screening programme using faecal immunochemical tests. Commonly referred to as the stool test, this gets mailed to people over the age of 50 every two years and they can conduct that test, that free test, in the privacy of their own homes and post it back in.

Professor Steve Wesselingh 2:17
Importantly though, there has been a relatively recent change and people aged between 45 and 49 can also now request that initial free test as we know that early onset bowel cancer numbers are rising. What people might not know is that beginning in 1936, and remember NHMRC is now 90 years old, NHMRC funded its first grant in this area in 1936 and we've provided ongoing grant funding related to bowel screening since then. And one of the people who has received some of that funding is today's guest speaker, Professor Graeme Young. Graeme, I'll call him Graeme because I know Graeme quite well, so calling him Professor Young seems a bit odd. So Graeme is the Matthew Flinders Distinguished Emeritus Professor at Flinders University. After training as a gastroenterologist, Graeme studied on a Fogarty International Fellowship at Washington University and then gained his MD by thesis at Melbourne University.

Professor Steve Wesselingh 3:31
Graeme has an international reputation in the field of colorectal cancer and colorectal health with an emphasis on prevention through lifestyle and screening strategies. As we will soon know more about, he was a key contributor to the establishment of bowel cancer screening in Australia and for eight years chaired the World Endoscopy Organisation Colorectal Cancer Screening Committee, which has driven the establishment of global screening programmes. His impact has been far reaching and represented across many awards and accolades and publications. And I'm not going to tell you how old Graeme is. He told me earlier but I'm not going to repeat that. But he did tell me that his group is still publishing at least one paper a month. So his research is clearly still ongoing. But he has been a principal investigator on 27 grants from NHMRC and MRFF. So an amazing career and a great person to talk to us about bowel cancer prevention. So I'm really looking forward to this. Graeme, over to you.

Professor Graeme Young 4:44
Thanks very much, Steve for that kind introduction. It's great to be here and for the opportunity to speak to this topic of bowel cancer prevention through screening, from discovery and innovation to impact on survival in Australia and also to acknowledge and recognise Bowel Cancer Awareness Month and NHMRC support. So today, following the brief from NHMRC, I wanted to share with you how science and careful attention to how it's been applied in the real world has contributed to establishing colorectal cancer screening in Australia and indeed globally.

Professor Graeme Young 5:20
Colorectal cancer screening, as you've already pointed out, is now an established major health strategy in most developed countries, supported by evidence that it's achieving its goal of reducing the community burden of disease. Einstein is credited with saying that “everything should be made as simple as possible, but not simpler”. This has been a long journey and it's a complex one, and I don't want to run the risk of oversimplifying it for the audience. But before I expand on that, I want to further acknowledge the traditional custodians of the lands on which we live today. And later you will hear from me that we must move beyond these words to support our First Nations people.

Professor Graeme Young 6:05
So the presentation that I'm going to give is developed from the impact case study that NHMRC released in 2024. And if you haven't seen it, you can access it on the website.There's 3 dimensions to this presentation. Firstly, the essential background where I'll talk about epidemiology, oncogenesis and early evidence related to screening.Then I'll present a historical framework, although you will see that these are actually overlapping with each other.Second, from how we did it and where we're going to go next, with I think some hopefully provocative comments on where we might go next. And then finally to explain the cyclic process that is fundamental to effective colorectal cancer screening.

Professor Graeme Young 6:50
So to start with the background and the epidemiology, colorectal cancer is ranked 7th in the top 20 leading causes of death in Australia. It ranks second as a second leading cause of cancer death in Australia of all ages, second only to lung cancer and considerably higher than prostate and breast cancers. It was also the fifth most commonly diagnosed cancer in 2025.The next part of background is that not all Australian residents are the same. The average lifetime population risk of colorectal cancer is about 5% in Australia and we'll dissect that out a little bit more later. But importantly, 90% of colorectal cancer occurs in those in the upper half of population according to risk, based on risk assessments, according to all the lifestyle things that you can see in the diagram.

Professor Graeme Young 7:52
This graph shows the age specific incidence for 2017 in Australia and I've marked in red the ages from now 45 through to 75 where the screening programme applies. So you can see that colorectal cancer starts to get more frequent around age 40 and just keeps climbing. Age-specific incidence also varies by sex, with it being significantly more common in males.But the difference is not great - about a 5 or 6% lifetime risk for men and about 4% for females.On the global scene, Oceania, and Australia is most of the population of Oceania, contributes the highest incidence as a region globally. But you'll see that proportionally the mortality is relatively low and it's only North America that has a comparably low mortality, although its incidence is not quite as high as in the Oceania region.

Professor Graeme Young 8:57
In this graph on the right, you will see, not that clearly I admit, but relative incidences in developing countries and Australia is very close to being the top there. It depends a bit on the year that you use, but we have been at the top on occasions. But importantly, you'll see that the countries with red or orange bars had by 2018 organised colorectal cancer screening and all of those red and orange bar countries were screening in the way we do with faecal occult blood tests. The next part of the colorectal cancer story really is to provide a brief understanding of colorectal oncogenesis. So this is a stepwise process which highlights why screening has been considered as a control measure. It starts with a few molecular genetic changes in a few cells in the lining of the bowel, which multiply and then it can progress to what we call a pre-invasive lesion, often referred to as a polyp, but they're not always a polypoid shape. Adenoma is the word that commonly people will hear of.

Professor Graeme Young 10:10
Plenty of evidence around the world now shows that if you remove these lesions, you'll stop cancer forming. However, it's rare to get symptoms from these preinvasive lesions. Similarly, if it progresses to bowel cancer, which is when these cells become invasive into the tissues, the early stages of bowel cancer, that is the first three of four stages are highly curable, ranging from 60 to 95% in Australia. But again, especially for stages 1 and 2, people uncommonly have symptoms and this is where screening becomes an important consideration if we are to control it.

Professor Graeme Young 10:49
So screening would appear to be the answer, but we need to consider firstly what is screening and WHO decreed on what screening should be probably about 50 years ago now.What WHO said is that screening is the testing for the presence of disease in apparently healthy people where they have no recognised increased in risk for that disease, in particular, no symptoms.The public health goal is to reduce the community burden of colorectal cancer and inherent in that is acceptability, feasibility, quality of care, equity and monitoring all of which are quite crucial to success.

Professor Graeme Young 11:30
So achieving a reduction in colorectal cancer-specific mortality requires early detection of curable cancers, and achieving a reduction in incidence when it comes to screening requires detection and removal of the precursor lesions. Now the implication of this WHO model is that this is a cyclic process.It's not just a test. So it starts with firstly inviting the subject, that's a behavioural issue.

Professor Graeme Young 12:01
Then the performance of this non-invasive screening test in the Australian and most countries’ models, that's a biotechnology issue.Then if the test is positive, one goes to diagnostic verification which is colonoscopy. This is a clinical procedure. If there's a lesion that needs treatment, it's treated, also clinical. And then it doesn't matter how you get around to this point in the cycle, Everybody goes back into this revolving cycle, which is an organisational process for the healthcare system.

Professor Graeme Young 12:33
The point is that it's much more than just doing a test, because if any step in this cyclic process fails, then the entire process itself will fail. So the NHMRC investment has been really quite substantial. And this is a diagram taken from the impact study published in 2024.I'm not going to go through that in detail, but we'll focus on some aspects as we go forward. Australian researchers were involved on the ground floor back in 1970 and throughout that time, NHMRC has made major contributions, going beyond when that diagram was made. It is still making major contributions going forward into the future.

Professor Graeme Young 13:19
The major contributors to that impact study was myself along with Jim St John, Finlay Macrae, Symonds, Salkeld, Cole, Turnbull, Wilson, Irwig, Glaziou and Solomon. I'm embarrassed to say that because of the time issues, it's not going to be possible to really give due recognition to these people and those that have followed since with advancing the area. So you can see from that timeline that it's really taken us 5 decades to get to where we are. In 1971, the guaiac faecal occult blood test was developed by an American inventor. From 1980 on, Jim St John, who mentored myself and Finlay Macrae, set up a basic and clinical research network at Royal Melbourne Hospital, Melbourne University.

Professor Graeme Young 14:06
And the goal of that was to better understand the nature of bleeding from colorectal cancer and its precursors relative to the natural background bleeding that does occur in the bowel. And then to better understand the chemical fate of haemoglobin in the gut. We were fortunate because by 1993 and to 1996 there were three population-based randomised controlled trials using the very early prototype faecal occult blood test which was the guaiac test. And they showed that even with this early, relatively insensitive test, there were significant reductions in colorectal cancer mortality. And an important meta-analysis that was conducted a few years later in Australia put together the results of all of these studies.

Professor Graeme Young 14:54
And what they showed was a 16% reduction in mortality on an intention-to-screen basis and about a 25 to 40% reduction in participants.

Professor Graeme Young 15:04
So you'll see that with this early technology, the effect was definite and worthwhile, but nonetheless quite modest. The concern that Jim St John, myself and Fin Macrae had was that the guaiac test that was being used was a crude, qualitative and insensitive test.So let's step through some of the steps in this cyclic screening process to see what's gone on in the past and where it's heading in the future.First let's start with the non-invasive facael occult blood test.

Professor Graeme Young 15:37
The question that we wanted to answer, we being Fin and Jim and myself, was to really understand what was happening to haemoglobin in the gastrointestinal lumen.And what was evident from the bit of literature was that bacteria in the gut split haemoglobin into the iron protoporphyrin molecule and the globin peptide.It's the early occult blood tests, which we now abbreviate the guaiac FOBT chemical tests that detect haem.They're qualitative, they're interfered with by diet, meat and vegetables included, and they can detect bleeding from anywhere in the gastrointestinal tract.And they're very simple old-fashioned tests.And you can probably see from this development card, there's a faint bit of blue here.

Professor Graeme Young 16:24
You had to be skilled in reading this, you couldn't automate any of this.And this to us seemed to be a problematic test. It was during the 1980s that we realised that there was potential for immunochemical detection of the globin peptide from a few papers that had been published by other people.And as we thought about this, we thought, well, OK, this is an immunochemical test.There's probably not going to be any interference from the dietary factors.And because globin may be digested, it won't detect bleeding from the large intestine.In fact, three of us ingested our own blood in tomato juice to actually show quite directly that while the guaiac test was detecting blood that travelled through the entire gut the faecal immunochemical test didn't detect even 100 ml of blood because globin was very readily digested.

Professor Graeme Young 17:21
So this was going to be a colon-selective test, and of course the technology has become much more sophisticated now so that we now have very good latex agglutination technologies that can quantitatively measure the faecal haemoglobin concentration.And I'll come back to the advantages of that later on.The first question that we thought about was, well, this is potentially a new test.There is a commercial availability of a qualitative FIT test. We need to compare it to the early guaiac tests. And what we did was we compared the accuracy of one of the early qualitative FIT tests to a guaiac test in patients of known neoplastic status.

Professor Graeme Young 18:09
And what you can see in the graph is that it was significantly more sensitive in this cohort.
Not that much more sensitive for cancer, but more sensitive nonetheless.It was quite a bit more sensitive for adenomas, which is important if we're going to detect preinvasive lesions.And this increased sensitivity was not achieved at the cost of specificity. When we published this paper this really led to the world taking notice of the potential for FIT tests to be useful in the screening context. But then we had to consider how would we move forward to the WHO model? So I want to take you through a few of the steps that related to government and policy and so on that addressed this.

Professor Graeme Young 18:58
In 1989 myself and Jim St John with Fin Macrae, through the Gastroenterological Society of Australia, provocatively wrote some guidelines on colorectal cancer screening without the evidence of the randomised control trials.The Americans did the same thing at the same time. But by 1993 and '96 the three randomised trials came through to prove the benefit of gFOBT.Then in 1996, I was approached by Glenn Salkeld to join him on a modelling of cost effectiveness of colorectal cancer screening.

Professor Graeme Young 19:34
And what we went and did was to model cost-effectiveness using the Australian cost data, the performance and impact measures from the Minnesota randomised controlled trial, (which was a high sensitivity, low specificity test).And here's what we found, that in fact colorectal cancer cost per life year saved was about $25,000.This was of the same order of magnitude as breast cancer screening and cervical cancer screening.So, screening would be cost effective. There is a considerable number of publications that have gone forward now since those years, looking at current Australian data to reaffirm that it really is cost effective.

Professor Graeme Young 20:19
But this paper was crucial because we're able to feed this through to the political processes and to NHMRC and so on, to get their attention.So, in 1997 the Australian Health Technology Advisory Committee, AHTAC, was established to advise on the cost-effectiveness of the new and existing medical technologies and several of us were on that committee.By 1999, the NHMRC-endorsed Australian Council Cancer Council guidelines for prevention and early detection and management of colorectal cancer screening recommended that we proceed to population screening.These guidelines were crucial because they achieved consensus among key organisations, professionals.There were clinicians who only wanted to do colonoscopies.

Professor Graeme Young 21:15
There was a wide range of skilled people with particular interests and we felt that we had to get their ownership of the guidelines if we were to achieve a fully organised colorectal cancer screening programme according to The WHO model. That was achieved through these consensus guidelines.So it didn't matter how good the science was, unless we got to the point of getting agreement of the parties, it wasn't going to proceed.There was a federal budget in 2000 that provided several years' of funding for a pilot programme to establish and test a simple model, and I'll come to the results of that in a second.

Professor Graeme Young 21:53
And that included funding for a cancer screening pilot register where the data was all held federally and confidentially.So soon after that the Department of Health established a Bowel Cancer Screening Implementation Committee and then, decided soon after 2001 and based on the some of the research that had already been provided, to use the faecal immunochemical test in a pilot as the screening test rather than a guaiac test.And Australia was the first country to make the decision to do that.

Professor Graeme Young 22:35 
Now because of the WHO model and the fact that it's cyclic, the issue is that nothing is going to be detected if invitation of people is not successful, if people do not participate.While all of these political decisions were being made, we needed to actually prove that the removal of dietary restrictions was going to make it easier for people to participate.

And so with funding, what we did was we tested two general population cohorts of people in Adelaide where we offered them all the faecal immunochemical test.But we asked one of the cohorts to actually follow the guaiac based diet.And what we found was that in those who didn't have to follow the diet, there was a 12.6% higher participation rate.

Professor Graeme Young 23:27
So we started to address some of the behavioural barriers.The next behavioural barrier was, and for those of you who have done a faecal occult blood test,especially if you've done an early one, you'll know with the old guaiac tests that you had to sample three stools and you had to dive deep down into the toilet bowl to scoop up bits of faeces and spread it on a card. Whereas the inventors of the new faecal immunochemical tests for commercial reasons were coming up with novel sampling from a paper saddle and only needed one or two samples to achieve what was required.

Professor Graeme Young 24:05
So again in Adelaide we conducted a participation study where we offered, I think it was about 400 or 500 people per group either the guaiac test, and over a 12-week periodat that time the participation rate with the guaiac test was only about 23%, or the faecal immunochemical test, an early qualitative one, just two sample rather than three,and what we saw there was that there was a 16% increase in the participation rates. But participation rates were still relatively low.And so I was fortunate to have a few great behavioural scientists in Adelaide, Carlene Wilson and Deborah Turnbull. And so what I asked them was what can we do? How can we increase people's awareness?

Professor Graeme Young 24:55
And so they suggested that what we do is test the trans theoretic model of a willingness to act.And in the initial study done on quite a few thousand people, we showed that 53% of Australians at that time, and we were talking about the mid 2000s, were not even ready to act.So we had a problem and then the question was what can we do about it? And so we used a technique that's been used in public health and other strategies such as tobacco usage, etc. What we decided to do was conduct yet another randomised population trial where we offered people the FIT screening test out of the blue, shown in the pink columns.

Professor Graeme Young 25:43
And to the other group we gave them an advanced notification letter that described the importance of screening and what it can do for you. And just that advanced notification letter increased screening by 9%, which may not sound much, but at a population level is really quite a lot.This became incorporated at that time into the screening program in Australia and at least half a dozen countries around the world have also used this strategy.We also wanted to test advocacy and we did a number of advocacy studies, but the one that I want to refer to is that of general practitioner advocacy.And what this graph shows is over three rounds of screening, whether people participated at least once in the black columns or whether they participated on all three occasions in the green columns.

Professor Graeme Young 26:38
The columns on the left refers to a letter that was effectively signed by me.The columns on the right were for a letter that was signed by the GP. And what you can obviously see is that the benefit of people believing that the letter came from their GP was substantial, and particularly important to maintain sustained participation over at least three years.And it's very important to recognise that screening for colorectal is never a once-off thing. It does need to be repeated at appropriate intervals.This is now being further studied by a number of groups in Australia with much more innovative approaches that can be applied in practice using tools like SMSs to inform people.

Professor Graeme Young 27:27
So by 2002 it was decided that Australia should conduct three pilot studies to actually see what might be achieved in the Australian context using a two-sample FIT test.I won't go into the detail of the pilot studies, but one of them was conducted in Adelaide and what we wanted to do was to ask the question “of those whose colorectal cancer was diagnosed in the National Bowel Cancer Screening Program pilot in SA where they diagnosed at an earlier stage than everyone else was” because this was going to be crucial to achieving mortality benefit.

Professor Graeme Young 28:10
So we compared stage distribution of colorectal cancer cases detected by the National Bowel Cancer Screening Program to those detected by any other means.There were more than 3000 colorectal cancer cases in South Australia diagnosed in this period 2003 to 2008 during which the South Australian pilot was conducted.And in essence here's what we found. On the left, you'll see the FIT positive stage distribution and the right that for those in anyone diagnosed by any other means. The proportion of stage 1 highly curable cancers almost doubled from 19 to 38% and the stage of very difficult to cure cancers (four) fell from 12% to 3%.

Professor Graeme Young 29:02
In addition to that, about 40% of people were willing to participate and this was very early on without any publicity.These were invitation letters out of the blue without publicity. So the program worked and the government committed to expanding the roll out across Australia.So to continue with the National Bowel Cancer Screening Program, there were key things that needed to be decided. In the period of 2004 to 2006, it was formally decided by the program advisory committee that Australians would be offered a 2-day faecal immunochemical test. If it was positive, they would be advised by letter with a recommendation to attend their GP for diagnostic confirmation and the results were then monitored centrally in a register.

Professor Graeme Young 29:54
Now it's taken from then until now to involve everyone in the final target age group. In 2006 it started just with people aged 55 to 65, and by 2024 it finally extended to include 45 to 49 year-olds.I have to say that for a lot of us this was a frustratingly slow process, but it was understandable in the context of working out how best to implement this in Australia. I wanted to spend just a couple of slides to give you an idea of what's happened to the burden of colorectal cancer in Australia during the period 2003 to 2024.This graph is taken directly from the AIHW report, and what it shows is the change in fatal burden in years of life lost.

Professor Graeme Young 30:50
And if we look at the ages where the National Bowel Cancer Screening Program has steadily rolled out, you can see that according to this AIHW modelling of community burden, between 2003 and 2024, the total burden has fallen significantly.It's fallen 27%.I'd like to say that it's all due to screening, but of course we can't necessarily say that.If we look at the annual age standardised incidence counts over the years, starting from 1982, you'll see here that it was pretty level up until about when the roll out of the national program started.But since then there's been a steady downward trend over the time that the National Bowel Cancer Screening Program has been in place.

Professor Graeme Young 31:45
Again, it's clearly not going to be just due to that. And if we look at the mortality, you'll see that the mortality drop commenced a bit before then, which is clearly a reflection of improving treatment as well as earlier stage detection of colorectal cancers. So in short, these few graphs quite clearly show that there is a benefit to the colorectal cancer screening programme and that across the board, for whatever reason, we're seeing reductions in the problem in Australia.

Professor Graeme Young 32:16
So what's next? Well, I ended up with quite a long list of what's next and I want to take you through some of these points and then I'll return to this later on.The list includes issues such as managing colorectal colonoscopy resources, increasing participation, personalising what has been a one-size-fits-all program.Because everyone, no matter what your age, no matter what your gender, or other risk factors, you are given a faecal immunochemical test. And the threshold that we use for positivity is standardised.So we're going to look at some of these issues to see what might we consider to do next. The first question was about the positivity threshold that's used to report a positive faecal occult blood test, a FIT test, as being important.

Professor Graeme Young 33:13
So quite some years ago, and plenty of others have also demonstrated the same here, if you measure the faecal haemoglobin concentration using the quantitative FIT tests, the concentrations of blood are much higher in patients with cancer, significantly higher than those with high-risk adenomas, which are also significantly higher than the other groups that you might expect.Thus, with the quantitative tests, one can then choose the faecal haemoglobin concentration that becomes the positivity threshold for the test.This is really important because the total positivity rate determines the colonoscopy workload.Can we cope with the workload?

Professor Graeme Young 33:58
It also determines how many of the cancers and especially the precursors that you detect. And of course, if you want to get higher sensitivity, you have to be prepared to do more colonoscopies, and that depends on health programme capabilities. A very big issue here and around the world.So being able to adjust the threshold is crucial for meeting goals.
Recently we modelled all the Australian data to work out what this really meant in practice. And a number of things emerge from this.

Professor Graeme Young 34:30
This is a complex slide and I'll just speak to a couple of the key points.If we look at the threshold that's used in Australia, the haemoglobin concentration of 20, in the Adelaide data that we looked at, it meant the sensitivity for colorectal cancer was about 60%.In practice it's actually a bit higher than that, it's about 65%. But in this data that was the level. The population positivity rate is shown by the finely dotted line, the sensitivity is shown by the black columns.The population positivity rate, at 7%, was about that of the Australian programme.

Professor Graeme Young 35:11
Now quite a number of countries around the world, and it's shown in this table, are choosing a faecal haemoglobin test threshold that suits their population capability and goals.You'll see that Switzerland uses the most sensitive cut-off, but Australia is quite close to that at 20, whereas countries such as Scotland and England are down at the insensitive level.I'd also point out that Sweden has already implemented a different cut-off for women and for men.The other point I want to make from the graph that I showed you previously is that we showed that in Australia it's very important to do a two-sample test.

Professor Graeme Young 35:55
Many countries have been moving to a one-sample test, but a two-sample test is actually better and more efficient and Australia is now continuing to adopt that in the national programme.If Sweden's personalising the FIT test positivity threshold, then can we consider further personalization of the program? This is now becoming a very hot topic in Australia and overseas. So there are a number of risk variables that need to be considered. There's firstly, the risk variables for colorectal cancer that are unchangeable.I'm sorry, the automation has stopped working on this slide.These include sex, personal history, dietary, lifestyle, obesity, physical activity, if you have diabetes mellitus and so on. And it's these lifetime risk factors that tell us who to screen and when to start screening.And you can immediately see if we start modelling these on an individual basis, we may be able to change our screening paradigms.

Professor Graeme Young 37:05
Then there are the risk predictors for the point in time risk for colorectal cancer and this is where the non-invasive tests such as FIT or improvements on that, and I'll touch on that, as well as symptoms are important because they tell us when to actually perform the colonoscopy. So could we consider personalisation of individual risk. One of the options is to consider the starting age for screening. This graph shows you the age distribution for colorectal cancer in Australia. And the dotted line corresponds to the risk level that applies when you are the average person aged 45 in Australia.

Professor Graeme Young 37:51
So in Australia, we now start screening when you've reached the risk of a 45 year old.However, this Korean study on the left showed you that the starting age could be varied by 5 to 10 years between men and women if you're going to start them at the same level of risk rather than the same age.

Professor Graeme Young 38:15
And if you throw in family history, it also shows that there's a 10-year difference between whether or not you've got family history. So the point here is that using risk factors that have been shown in the previous slide, and there's multiple studies now underway looking at combining all the risk factors to aid the personalization of screening, might better tell us when to start screening. So if you have a higher risk, it means that the precedent risk level is reached earlier. So you start younger. And if your risk is lower, you could potentially start older. So there's a number of major risk score studies going on in Australia now by other groups, particularly from Mark Jenkins and

Professor Graeme Young 39:01
John Emery's groups, such as the Colorectal Cancer Risk Prediction (CRISP) study and the SCRIPT trial, which is a study protocol for a randomised controlled trial of polygenic risk scores.The marginal benefit of these is yet to be proven, but they're going to be very important if we're really going to seriously consider personalization. The next issue that I wanted to touch on is that of the biomarker options and the nature of the bio sample for colorectal cancer screening. Remembering that the world is generally screening with a faecal immunochemical test, but we have options now. Chemical nature of biomarkers includes not just the peptide haemoglobin but also DNA, RNA, proteins, metabolome and microbiome I might say, and bio sample options don't necessarily need to be restricted to stool.

Professor Graeme Young 39:57
Obviously neoplasm shed or leak markers into the gut lumen, but. They clearly leak markers into the blood as well. In a separate study, we were particularly interested in what people would think about a blood test compared to a stool test. And this goes back about 15 years now since we did this study. We went to a randomly selected group of people that we knew were familiar with stool testing and blood testing. And we asked them would you be prepared to do a blood test even if you had to go to see a doctor, relative to doing a stool test, which you could do at home.Perhaps not surprisingly, 78% said they'd rather do the blood test.

Professor Graeme Young 40:44
Although the of the 22% who said they'd rather do the stool test, they said it's a more logical sample to be using for bowel cancer. So some people think about doing what they're doing rather than just do what they're told. There's huge interest around the world in blood tests. Many investigators are exploring the potential for new non-invasive tests to improve upon the quantitative FIT. And what I'm showing you here very briefly are the results of a collaborative study between our own team, and we have university interest in a patent here, CSIRO and various industry partners, seeking to find circulating tumour DNA markers in blood. The panel on the left shows two markers with good discriminatory prospect, BCAT1 and IKZF1.

Professor Graeme Young 41:36
We were looking for epigenetic markers which showed good separation between normal and the neoplastic tissues. We then went on to do a series of clinical trials once colleagues had developed an appropriate blood test where we wanted to compare a once-off FIT test with a blood test based on these two markers. And what we found across three or four studies is that the sensitivity for cancer was just about as good as it was with FIT. However, when it came to adenomas, these two ctDNA biomarkers were less useful compared to the FIT test. The specificity at the level that we'd set was not too bad. But again, perhaps potentially a little bit problematic.

Professor Graeme Young 42:29
A lot of investigators are now exploring not just larger panels of circulating tumour DNA markers, but also other omics.But unfortunately with the blood tests, what's really happening is they they're turning out to be very good for detecting cancer, but they're not good at detecting the precursors that we're really interested in, in the colon and which we'd like to be able to find more of these if we are to have a major impact on incidence as well as mortality through screening. The second last topic that I wanted to address was moving forward with the issues of equity.

Professor Graeme Young 43:11
Remember, this is a cyclic process.There's many steps along the way and there's plenty of opportunity for inequity.I don't have the time to take you through the National Bowel Cancer Screening Performance Indicators, which were being published for 2023, but I want to focus on just a couple of them.So firstly, the participation rate overall was 42% for the Australian public, 40% for men and 44% in women.Not high enough. But if we looked at the variables associated with this, age, region, that's where you lived, socioeconomic status, remoteness were all important variables in the participation rate. The other outcome that varied was the diagnostic assessment rate. So overall, if you had a positive FIT test, 86% of people went forward to colonoscopy.

Professor Graeme Young 44:10
Actually on the global scene, Australia does exceptionally well.There's very few countries that do better than that and the wait for colonoscopy on average is 62 days. However, for people in the lower socioeconomic groups, disability and remoteness, the diagnostic assessment rate fell significantly and the wait time was also longer. There's various demographic variables associated with the other key performance indicators of the national programme as well.

Professor Graeme Young 44:47
So I've had the opportunity to look at the equity of some of the National Bowel Cancer Screening Program outcome measures for 2025.And what we show here are data from the National Bowel Cancer Screening Program reporting equity across certain demographic categories for key program indicators.You'll see the participation rate in First Nations people, Indigenous people, is lower than in non-Indigenous people.The screening positivity rate was 8%, which is higher than in non-Indigenous people. The diagnostic assessment rate colonoscopy was lower, at 78% versus 86%, and the time between positive screening and getting the diagnostic assessment was longer at 78 days versus 62.

Professor Graeme Young 45:42
Now quite importantly, the incidence of bowel cancer in our Indigenous peoples was significantly higher than the other groups, and the mortality was substantially higher. We are now in the process of publishing this report. But just to summarise these, what we're now finding in Indigenous Australians is the age-specific incidence of colorectal cancer is higher, 30% higher. One-fifth of Indigenous Australian populations are diagnosed before the age of 50, which is twice as high roughly as that of other Australians. Rectal cancer is proportionately more common and there's a paucity of contemporary data explaining these differences.For example, once they start treatment, do they complete it and what's the treatment response like? We don't know.

Professor Graeme Young 46:44
Fortunately from Karen Canfell's group, they've recently published on the screening of Indigenous Australians, including those aged 45 to 50 years. And the economic modelling showed that it was going to be cost effective.This work has led now to the implementation of lowering the screening rate, and that was supported, unanimously supported, by an Indigenous Council. Now the last point that I really wanted to touch on was the prevalence of colorectal cancer by. So if we look at this graph, the prevalence of colorectal cancer is shown here at all ages, 54% are men, 46% are women.But if we look at the prevalence in what by 2022 was the National Bowel Cancer Screening Program spread of 50 to 74 years, only 50% of colorectal cancers were occurring in the national program relevant age group.And actually by 2025 that's fallen to 47%.

Professor Graeme Young 48:05
What's happened is that the change has been due to an increase in colorectal cancer incidence in people under 50 years of age.So there's now a great interest in the young-onset colorectal cancer.The media is saying a lot about it. And just quickly to summarise it, the incidence in Australia is now about 12 per 100,000 versus 7 per 100,000. That's rising at a rate of 2 to 4% in people under 50. It's now the deadliest cancer in men in that age group in the second-deadliest cancer in women. Fortunately, a targeted call for research into early onset cancer was set up in 2025 as a collaboration between Cancer Australia and NHMRC, and four projects were awarded which are looking at temporal molecular signatures as the etiological drivers, identifying risk factors, looking at care for survivors and modelling cost-effectiveness. And the lead investigators include Erin Symons, Dan Buchanan, Alexander McCarthy and Jie-Bin Lew.

Professor Graeme Young 49:22
Fortunately, those groups are now getting together to form a consortium. And Dan has just forwarded me this slide to show you how we can bring to bear the modern technologies that were not available to us 20 and 30 years ago, when we were playing around with FIT, to bring benefit to Australia and improve the personalisation issue. So to sum up in terms of the future directions where might we be heading, personalisation of the management of colonoscopy resources is really important. This can be done in various ways with the FIT tests.We can personalise risk-based decision-making using Bayesian likelihood, flexibility of test configuration, risk-based genomic screening and maybe even microbiome screening. These are possibilities. We need to be looking at achieving equitable participation and implementation of screening and cross-culturally safe approaches, which in fact is a really very big challenge for us and this is very much a behaviour and health information approach as well as coordination of health services.

Professor Graeme Young 50:31
We'd like to increase the participation rate from about 42% to 70%. About 30% of people are otherwise up to date or not eligible for screening. We'd like to find new non-invasive tests. There's a huge amount of work going on around the world, but at the moment quantitative FIT remains the standard. There's also challenges for increasing awareness. We need to be considering widening the age group of eligibility, and not just for under 50 year olds but also for the significant proportion of people who are over 75 years.To do any of this, we're going to need better quality of data and accessibility.And there are other issues such as understanding why cancers are missed. We need to be able to manage cases along the cycle-of-care pathway, which some countries do very well.

Professor Graeme Young 51:28
And finally, a topic that I haven't even had any chance to discuss has been the integration of lifestyle and chemotherapeutic approaches with screening. So in summary, I'd like to thank you for the opportunity to provide you with this.I did intimate at the beginning it wasn't going to be an easy subject. It was quite vast.I want to thank the thousands of study volunteers that have helped us and other investigators over the years to get to where we are now. Many hundreds of colleagues have been co-authors on papers that I've participated in and I'm embarrassed to not be able to show them. The photos here show some of the Flinders teams that are now capably led by Erin Symons since I stood down. The principal investigators on the impact study have been quite vital in taking this forward.

Professor Graeme Young 52:31
I'm grateful to the many funding institutions that are supporters for the universities who've given us a free rein and to Finlay Macrae who's worked along-side and in parallel with me over the years. But especially to Jim St John who's photograph I can't show you now but who sadly passed away just late last year. It was in 1982 when he said to me, can you help me understand the fate of haemoglobin in the gut? Because this is going to influence our testing for screening for colorectal cancer. And that's what really started us off. So thank you very much for listening to this long saga of what I think is truly an Australian success project. And with thanks to all the funders and supporters.Thank you.

Professor Steve Wesselingh 53:18
Thanks, Graeme.What a fantastic talk and a fantastic story of translation really. Fifty years of translation from when you first started to the impact that we're seeing now. And interestingly, just highlighting that it was biomedical discoveries, but then it was writing guidelines and then it was developing a registry and then it was understanding public health promotion and how the public responds.So it was all parts of the sort of scientific process from discovery to public health. So such a great, great story. So thank you very much. And Fin Macrae, I think, was listening. He did say he had to leave early, so he might not have caught the whole talk, but he did send us a little message. So I just wanted to point that out to you. We've got one question already, but maybe I'll start. You've talked a lot about colorectal cancer control and screening as the sort of fundamental underpinning of that. But is screening the only answer to colorectal cancer control?

Professor Graeme Young 54:30
Well, no. No, clearly it's not Steve. Some of our NHMRC grants were directed at understanding the dietary factors that influence risk and how they change colorectal cancer biology. So there's a lot of evidence now both directly scientific and epidemiological associations, that show that diet and lifestyle are quite fundamental to your risk. And we believe that the increase in early-onset colorectal cancer is now because of the changing of diet that people commenced in their teens and 20s, is now having a cohort effect and starting to become important when they're 40. So I think there's a lot to be gained by dietary prevention and lifestyle, but how practical it will be is unclear. The thing is screening works if you don't look after yourself. I think that's always going to be the challenge.

Professor Graeme Young 55:24
And there's also chemotherapeutic options, and Fin Macrae's led some very important work with the preventive benefit of very low dose aspirin on colorectal cancer as well. So there may be some even simpler and other pill options that will emerge in the future. 

Professor Steve Wesselingh 55:50
So Ellie Mccall's asking a question and she thought you've actually given a great talk and you'd answered all her questions. But she wondered about the Lung Cancer Screening Program which was started last year and did they look at your success and barriers that you had looked at through the bowel cancer screening? So do you know whether they learnt from you when they set up the lung cancer screening?

Professor Graeme Young 56:12
Look, I do not know the answer to that. I would be very surprised if they hadn't looked at a broad lot of evidence across both the world and Australia and other screening programs before they went ahead. Because I know they're very conscious of the WHO model of screening and the whole importance of making everything work. So I would think so, but I don't know the facts. 

Professor Steve Wesselingh 56:32
One of the sort of worrying bits of information you provided was about Aboriginal and Torres Strait Islanders. Do we know whether that's an equity remoteness issue or do you think there is other biological issues there as well?

Professor Graeme Young 56:54
Yeah, the short answer is no. Because of time, I didn't have the chance to just go into the data. But the issue with one of the tables that I produced was that the outcomes according to remoteness, will include Aboriginal people, so the category of remoteness will include Indigenous First Nations people.The results were not the same in that category compared to the Indigenous people. Then of course people self-report as being Indigenous.So genetic and biological influences just haven't been dissected out yet. And that research really needs to be done. The data as it stands at the moment shows that it's not just about remoteness or lack of services.There's potentially some other biological effects.

Professor Steve Wesselingh 57:53
Yeah, thanks for that. And then we have a question. Do you think we will ever realise the rhetoric of making bowel cancer history? So can you speculate on prevention versus early detection as the dominant path?

Professor Graeme Young 58:09 
OK So, you know ageing is associated inherently with genetic instability and we will never escape that. So therefore will we get rid of bowel cancer? Unless we have a perfect simple test for bowel cancer precursors and everyone is willing to do them and get the colonoscopies and then healthcare providers are willing to spend all the money that it'll take to do that relative to anything else I don't think we will. But I think the bright side of this is that colorectal cancer is the only cancer where we have a multidisciplinary preventive strategy. We've got screening, but we've also got diet and lifestyle. So we can bring all of those things together to have a really good effect. So I'm not into the predictions yet, and I'm sure it's a provocative question. In the end, it's going to need to be a multidisciplinary approach to really totally control the issue. 

Professor Steve Wesselingh 59:19 
And that probably leads on to a question about personalization and precision medicine. Where do you think precision medicine is going to take us in colon cancer? 

Professor Graeme Young 59:35 
Yeah. So I've been involved in quite a few conferences in the last four or five years and there are some exceptionally clever people who are gathering all the data and running through the Bayesian analysis and so on that help us to look at the data. And the inferences in my talk was that they are probably going to tell us who to screen and when to start screening. It's a slightly different question from when you get to do the colonoscopies and things like that, but putting that aside.The biggest issue is how readily available and easily accessible are the data. Now we know that sex and we know that age are readily accessible as is socioeconomic status because we have people's post codes.

Professor Graeme Young 1:00:15
So we can tweak elements of the National Bowel Cancer Screening Program, particularly the threshold positivity that we use, according to those criteria, and get a sort of a subcategory of personalisation. To go into the further personalisations we don't yet know what are the key drivers in all the variables. And that's the sort of job the Australian studies are hopefully going to tell us – the ones that are going on now.And we if we can refine that to a small group of variables, we may well be able to put those into practice. We're then going to have to prove by modelling that the incremental benefit it worth it because it's going to cost more money to do that.So it's great to say let's personalise things, but the practical application of that is still a fair way from knowing where we're going to go.

Professor Steve Wesselingh 1:01:04
Yeah, yeah. And I think so. This might be the last question because we are past time, but it's looks like a terrific question. This question is Nord ICC, which I presume is the Nordic colon cancer screening programme, has not yet shown a reduction in colorectal cancer mortality. The investigators suggest that that may be because treatment has improved so much, but advanced CRC still has high mortality. Question one, do you think treatment is getting so good that mortality is rare? If that day comes, is screening to decrease incidence still justified?

Professor Graeme Young 1:01:43
Yeah.So, yeah. So firstly there's a huge international debate. I've had about 20 emails come in to me in the last couple of days about the conferences that are going to be held in Europe in about two or three months' time that's going to debate the results of the Nordic trials and what all the implications of of that are. So we do need to understand that the evidence that that faecal occult blood test-based screening really definitely does reduce mortality. That is clearly there. The Nordic trials, the impact is compromised a bit by the participation rates. And I think you need to be thinking about how you are measuring the benefit. The public health benefit of a screening program is what's the benefit when considering everybody, whether they did the test or not. The personal benefit is considering only those who did the test. There is clearly a benefit from colonoscopy screening for those who actually did the test. So we mustn't lose sight of that.

Professor Graeme Young 1:02:51
The treatment success rates in Australia for bowel cancer. The cure, which is really the five-year disease-free survival rate, is 95% for stage 1, about 80% for stage 2 and actually 60% now for stage 3, which is extraordinarily good and which follows on the intent of the question really. Our treatments getting really, really good. But for stage 4, it's way down, about 5%. So, we haven't seen yet some of the sort of controlling drugs that you have available for other cancers. For example, with breast cancer, there's some fabulous new drugs for breast cancer that really control things.They're starting to appear for colorectal cancer. But are we really going to be able to suppress the colorectal cancers in the same way? I don't know. It's not my field, but I do not think that treatment alone is going to be the success. However, we're doing very well in Australia and I think that despite me being rather critical at the end when raising all of these things that we could do, Australia is doing very, very well on the world scene.

Professor Steve Wesselingh 1:04:07
So I think we might stop there.There's obviously a quality of life issue there too. You'd prefer to get treated for stage 1 rather than to go through chemotherapy etc for stage 3, wouldn't you? I would have thought. But Graeme, that that's been a fantastic story, a fantastic presentation and you can see by the questions a lot of engagement from the audience as well. And we had a lot of people online. So fabulous interest and a really important area in Australian health. And as I said, when you'd finished, you know, for the NHMRC to see our funding working in discovery, but then also in public health, in the development of guidelines, in the development of databases, etc.I think it's just fantastic. And really that's because of your leadership and the work that you've done with your team.

Professor Steve Wesselingh 1:05:05
So I'd just like to congratulate you, all the people you worked with and your teams and thank you for a fabulous presentation. Thanks very much.

Professor Graeme Young 1:05:14
Thanks for the opportunity.

Professor Steve Wesselingh 1:05:15
Thanks everybody. Getting lots of claps there, Graeme.