Several posters have criticized the title of the news article "In gold-standard trial, colonoscopy fails to reduce rate of cancer deaths".
The actual study is titled
"Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death" [1]
The authors conclude that "In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. "
I find it generally more useful link to the (abstract) of the original article, rather than second hand news reports. The abstracts are usually pretty accessible for a somewhat technical audience, they're not written for domain experts only. As we see in the discussions here, it's questionable whether the rephrasing from journalists really adds anything.
There is nothing wrong with the title. The study failed to find a reduction in death rate despite lowering the incidence of cancer, and that is the center of the piece. It goes into detail of why this is surprising. The study authors were interviewed and agreed. The reporting actually adds a lot of context that you would never get from a link to a random study.
Like, for example, how it is called the “gold standard” because it’s a 10-year large scale randomized trial, and the doctors running the study are the ones who promoted colonoscopy as a tool to reduce cancer mortality in the first place.
The problem with the title is that it might lead individuals to believe they shouldn't bother with getting a colonoscopy. You can't conclude that from this study at all. If your doctor recommends you to get one, you probably should.
The study answers a question pertaining public health policy (should we invite everyone in some age group for a colonoscopy?). It does not answer any individual health/treatment/screening question. The article's headline and content is problematic because it's easy to confuse the two, and the vast majority of readers will never get involved in public health policy (but will certainly have to make lots of individual health decisions).
I’m so confused though, because based on my reading of it, it seems like the prostate screening thing where yes it might find cancer but no it won’t prevent deaths, so it might be better to just not know/do invasive procedures and treatment for it.
Is that the wrong conclusion to reach from the data?
In the case of colon cancer detected in a colonoscopy they can snip it out right there without a lot of effort, risk or lost function. Surgery on the prostate is likely to cause all sorts of problems for men.
> The problem with the title is that it might lead individuals to believe they shouldn't bother with getting a colonoscopy. You can't conclude that from this study at all. If your doctor recommends you to get one, you probably should.
The problem with your doctor's recommendation is that doctors recommend colonoscopy based on age, not whether you have any factors that might indicate colon cancer. I have no cancer of any kind anywhere in my family tree and they are always on me to get one.
From the article, a doctor who still believes in colonoscopy for everyone: “The first message is that screening saves lives [Ed: against this study's data] and prevents cancer. If we could have a chance to start everyone at age 45, I’d like that."
>The problem with your doctor's recommendation is that doctors recommend colonoscopy based on age, not whether you have any factors that might indicate colon cancer.
This study is meant to inform the public health policy of asymptomatic screening. They tried to see if there was a benefit in offering screenings to random patients, regardless of medical history. The currently recommended screenings for asymptomatic people were adopted because meta-analyses showed they reduced cancer mortality. In the US, the US Preventive Services Task Force keeps up with new studies and revises their recommendations: https://uspreventiveservicestaskforce.org/uspstf/home.
For people with family history or other risk factors, doctors will follow different screening guidelines or just order tests whenever they think it useful.
The study does not say that coloscopies don't help. The study measures a difference in the study's population. The study does indicate they don't affect outcomes as much as expected. However, their affect is positive.
The study's measured affect has wide errors bars indicating a larger sample size is needed. Subsequent studies could show the affect is more inline with expectations but are unlikely to show less affect.
The question as to whether this will be used to reinforce hesitancy for this procedure; we can already see it in the comment. Logic and reason are not naturally occurring traits. I predict this will be used to move more people into the control group. Going against medical advice is anecdotally meaningful.
No one in my family history going back several generations had colo/rectal cancer. Yet I developed it at age 41. Diet is increasingly viewed as a factor.
I had it at 26, go figure. My petvtheory is that in orser to get the average age back to 50, you need someone like me for every 80 year old, statistics are a bitch. That also means my children will have screening coloscopies starting age 16.
Have you got your genes tested? People can have Lynch syndrome and not develop cancer. Colon cancer is also a silent danger in that it can grow for years without any noticeable symptoms.
I got colon cancer at age 35 (despite being a vegetarian, BTW), and it was first then that suspicion was raised that there could be a hereditary component - which was later confirmed by a gene test.
I have never had cancer of any kind in my family tree, and I had a precancerous polyp found at 38yo.
You should get a colonoscopy. If you are at low risk and look totally healthy after, they'll tell you that you don't need another for a good while and you'll get the benefit of not (often) getting something that you don't think you need and, as a bonus, not die of treatable cancer.
You'll die of something else then. That's the part that so many people seem to overlook.
There is a money-making industry around colonoscopies and mamograms. I'm not saying to disregard medical advice in this regard as for any individual there may be good reasons to have these procedures. However you can't completely discount the financial incentives for the providers.
doctors recommend colonoscopy based on age, not whether you have any factors that might indicate colon cancer.
That's not completely true. As a Crohn's Disease sufferer, by doctor has been making me get them since I was a teenager. The indications are high for me. For "normal" people, the general wisdom (apparently based on intuition more than any quantitative analysis) has been that the risks catch up with the general population around 50.
> The problem with your doctor's recommendation is that doctors recommend colonoscopy based on age, not whether you have any factors that might indicate colon cancer. I have no cancer of any kind anywhere in my family tree and they are always on me to get one.
Wrong. They recommend on both. I had no cancer in my family history but then I got colon cancer (no, I hadn't gotten a colonoscopy before--yes, I was an idiot). As a result, all my siblings' (some of whom are still in their 30s) doctors had them get colonoscopies right away. All negative, thank goodness.
> The problem with the title is that it might lead individuals to believe they shouldn't bother with getting a colonoscopy.
That is exactly what I thought it was saying at a glance. If I skimmed the headline and moved on, instead of digging in, it might have contributed to an unconscious bias against the procedure.
Uh... I think it is what it's saying though? I mean, you should probably still get a colonoscopy if recommended by your doctor which it probably will be right now... but the effects of this study may be to change those recommendations down the line, that is what it suggests. (I think it's not the first, but I'm not sure).
> In this study, about 12,000 people in Sweden, Poland and Norway got colonoscopies. They saw a 31% reduction in their risk of colon cancer and a 50% reduction in their risk of dying from colon cancer compared with people who were not invited to get a colonoscopy.
Do people really ignore their doctor's advice because they saw a headline? I'm sure there are some examples, but that can't be the norm. Obviously a colonscopy can still be indicated for an individual even if it doesn't help by doing it en masse for everyone. Specific symptoms could indicate a colonoscopy would provide more information and there are a number of other conditions where it would be used besides colon cancer.
I can't realistically see anyone saying "No thanks, doc, I'm not going to get that colonoscopy you recommended, because I saw a headline"
This trend of saying a thing is bad because you can imagine some unbelievably stupid person misinterpreting it and misusing it is getting out of hand. At some point people are responsible for their own decisions.
"Study failed to find a reduction" _does not equal_ "There wasn't a reduction".
From the abstract: "The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16)"
Look at the confidence interval. This study was both consistent with a 36% reduction in deaths or a 16% increase in deaths. It's just a really wide range. All we can say about this study is that it didn't gather enough data to identify the size of the effect, not that there wasn't an effect.
This is likely because there wasn't that many people who died of colon cancer in any of the groups. This study just didn't track enough people to provide an answer.
> That is incorrect. The title is completely wrong....Look at the confidence interval. This study was both consistent with a 36% reduction in deaths or a 16% increase in deaths. It's just a really wide range. All we can say about this study is that it didn't gather enough data to identify the size of the effect, not that there wasn't an effect.
In a randomized controlled trial you either find a significant difference in your metrics, or you don't. There's no other option. In all cases where you don't find a significant difference, the problem is that the confidence interval is too wide for whatever difference seems to exist. Your argument here is a fallacy (i.e. "you just didn't do a big enough sample!") which is a variant of my personal favorite: "it would have worked if you'd done X, Y or Z!"
There's always another X, Y, or Z. The negative study is always too small for the people who believe in the thing it's testing. As a supporter of some intervention, the onus is therefore on you to prove your claim in a demonstrated scenario, not on everyone else to disprove it in all scenarios. Could it be true that colonoscopies have some significant benefit to mortality smaller than detectable by a 80,000-person RCT? Sure. But that doesn't make the headline wrong.
This study didn't find a mortality benefit. Arguing that there's some theoretical other study that might find a benefit isn't relevant.
> In a randomized controlled trial you either find a significant difference in your metrics, or you don't. There's no other option.
This is a poor way of thinking about statistics. Whether you reject or not a sharp null hypothesis doesn't give you much information (See for example: https://www.gwern.net/Everything). Failing to reject in particular, can be compatible with a wide range of effects.
>In all cases where you don't find a significant difference, the problem is that the confidence interval is too wide for whatever difference seems to exist.
With enough data, there could totally have been a tight range around no effect or a small effect. This is not what we got here though.
Also note that other variables such as cancer risk came out significant, so while this study doesn't provide much inductive evidence around cancer death, we do get some deductive evidence based on the known link between cancer and death. Not to mention that cancer and cancer treatments are not fun even when they don't kill you.
> With enough data, there could totally have been a tight range around no effect or a small effect. This is not what we got here though.
What the trial showed was a small effect with a wide uncertainty on a big sample. We cannot distinguish this from zero.
Again, could the observed effect be significant with a larger trial? Sure. But that's always true for a negative result. The objection carries no information.
I'm also confused about the "invited" group. Not all of them had the procedure and there is a part talking about lower cancer rates among the subset that actually accepted the invite. It sounds like there is still confusion about how to interpret it.
There's not confusion. The study did an intention-to-treat analysis, which failed to find a significant result.
"Intention to treat" here means that you count everyone in the group that got an invitation to get a colonoscopy, regardless of whether or not they actually did it. Though this sounds counterintuitive, it's the "gold standard" because, if you don't do this, you leave yourself open to bias -- maybe the people who seek out colonoscopy have some symptom, family history or other reason that leads them to seek out treatment. Maybe the people who get a test get more treatment, and that treatment is harmful in the marginal case. Or just as importantly: maybe the people who don't have the time/inclination to do one would be better served by an alternative test.
Everyone (including GP) is fixating on the magnitude of the primary outcome and squabbling about whether or not colonoscopies help people. But I think the more interesting aspect of this study is that it shows that the genetic tests probably aren't inferior to the invasive, painful, time-consuming rectal exam. If that's true, it's great news!
> Though this sounds counterintuitive, it’s the “gold standard” because, if you don’t do this, you leave yourself open to bias
Isn’t there just as much chance for bias if the treatment is voluntary? Maybe the people who are more likely to have health issues are less likely to treat them.
I think there is a valid question about how effective a colonoscopy is given that you get one, and a separate valid question about how effective telling people to get colonoscopies is. According to the article, this paper answer the second question strongly via “gold standard”, and the first question less strongly via secondary analysis.
Part of the reason it’s counterintuitive here is the title of the article is “effect of colonoscopy screening”, not “effect of a doctor’s invitation to have a colonoscopy screening”. The title more than suggests that we’re comparing the outcomes of actually having the screening to not having one.
> maybe the people who don’t have the time/inclination to do one would be better served by an alternative test.
I see what you’re saying - the overall effectiveness of our current system may be low because of a low rate of voluntary adoption of the colonoscopy is low, and even a lower accuracy screen could be more effective if more people opt in.
One problem with drawing a conclusion this way is it ignores the possibility for dramatic changes in either opinion or in procedure of colonoscopies. What if we had the tech to do the colonoscopy at home in private? Would that change the voluntary rate of testing dramatically?
I had a friend that just underwent seven months of chemo for colorectal cancer. Looks like he'll be fine, but it was Stage IV, when it was discovered. Had a couple of surgeries, and radiation. The chemo was the worst, though. He channeled Uncle Fester, and this was a fairly robust, somewhat overweight chap.
So he would not go in the "death" column, but I guarantee that he would not be one to dismiss the seriousness of the disease (or its treatment).
I guess the question is if the scan makes a difference in intensity of treatment, if people who got a colonoscopy had fewer surgeries or fewer/less radiation. It doesn't say, I think? It's not at all obvious it would.
(In general, one would think people who got the colonoscopy got more treatment -- in this case despite having no lower a death rate -- but perhaps it does not include as much intense treatment).
For the chemo your friend likely experienced, this is especially true.
Colorectal cancer is often treated with the chemo cocktail, FOLFOX. The "OX" stands for oxaliplatin which causes nerve damage-- hearing loss (less than cisplatin, though), peripheral neuropathy, etc. The second half-life, in the body, of oxaliplatin is 535 months (44 years). And, the platinum remains in a reactive form.
I'd love to hear a professional chime in on if there are ways to speed the elimination. E.g., something like extended/extreme fasting (to free oxaliplatin from tissues) + sodium thiosulfate + blood plasma donation, or something?
"The first elimination half-life (t1/2) for cisplatin was 5.02 months and the second 37.0 months. For oxaliplatin, these half-lifes were 1.37 and 535 months."
"...it was shown that Pt species in pUF were still present in a reactive form."
IMHO it is chemo and the fact you very seriously face the prospect of an ugly, and lengthy, death that changes you. You and your loved ones, it affects everyone, I know it does.
Good for your friend to be on the way of recovering!
I'm not that surprised death rates were similar. Colonoscopies will catch pre-cancerous masses like polyps, so I can see the cancer rate being lower.
But if diagnosed with cancer, treatments are quite good for colorectal cancer, so you may not see that much of a difference in death rate on a 10 year horizon.
Well then the title is indeed misleading. It's not the colonoscopy that's failing to reduce cancer death rates, treatments are. Indeed the title should have been: with colon cancer deaths unchanged, screening and pre-malignant treatments are ever more important.
This is nonsensical. Any number of things are failing to reduce cancer death rates, including professional football and jelly donuts. This study is about colonoscopies also failing to reduce cancer death rates.
Changing the title to Don't Worry About Colon Cancer Death Rates, Just Continue To Do What You're Told would not have been better or more accurate.
What would be more accurate is to say the title is incomplete. Te details matter.
If the claim was "Voluntary colonoscopy screening does not reduce the risk of death over a 10 year period" it would likely be more accurate and at least calls out the "voluntary" nature of the patients examines and the limited time span of the analysis.
No study is ever perfect and everyone has limitations. You usually learn more by investigating the limitations than poking holes in the conclusions.
> The study failed to find a reduction in death rate despite lowering the incidence of cancer
This isn’t true. The secondary analysis shows a reduced death rate.
The problem with the title is that it says “Effect of Colonoscopy Screening”, not “Effect of telling people to get a colonoscopy screening”, where the primary analysis is making conclusions based on the latter.
Maybe this style of title is standard for medical journals, but the argument in this thread is based on the title priming us for what the paper is talking about, and directly leading to confusion.
"The study failed to find a reduction in death rate despite lowering the incidence of cancer, and that is the center of the piece"
Maybe you didn't read the article all the way through?
What it found was it merely inviting people to a colonoscopy did not result in less deaths from colon cancer, although it did result in fewer people being treated for it.
However, if you look at the people who actually took a colonoscopy, there was a 50% reduction in deaths from colon cancer.
Well, to be fair, the overall risk of death did not seem to be lower for the invited group. The risk was 11.04 vs 11.03 for those with invited colonoscopy, with fairly large confidence interval on the control group.
But the risk of colon cancer did decrease, with a risk reduction of 18%.
Maybe they just didn't track long enough to tease out a bigger risk reduction in overall mortality, or maybe colon cancer is associated with other risk factors for mortality (like age).
Why someone would latch onto one result and not the other is probably just "blow the lid off" style reporting.
Invited or not, if you don't show up to a colonoscopy you don't get one. Which means the study's data on invitations alone cannot be used to evaluate the effect of colonoscopies. Seems the study does provide data that allows this so, and shows clear differences in cancer rates and survival rates for those that did get colonoscopies.
Argueing about the randomization of these numbers, and the meta-statistical aspects of that, would be funny if the subject wasn't so serious. It is also the same level of discussion you get from people like JBP, meaning it at least misses the point by a mile.
You have to look at it from the perspective of medical practice.
The hypothesis is that inviting people for a regular check up reduces mortality. If a lot of people don’t take up the offer because the procedure is too invasive, carries some risk, etc. then that is a very relevant variable to take into account. Vs, for example, fecal testing as mentioned in the article. It could have a lower precision, but if uptake is 100% instead of the ~40% for colonoscopy the outcomes could be much better.
American health insurance really screws the pooch here. If you go for a colonoscopy without a previous fecal testing, it is a diagnostic procedure that is fully covered by your insurance without triggering deductible and copay. However, if you go for fecal testing first and then they find something suspicious that warrants a colonoscopy, it is no linger considered diagnostic (you have a legitimate problem now) and deductible/copays apply.
So in practice, doctors will tell you to just get the colonoscopy to save (your own) money.
For asymptomatic people without abnormal stool, colon cancer tests are called "screening," never "diagnostic." "Screening" is covered without cost sharing. Colonoscopy, fecal tests, etc.
>But if you have a screening test other than colonoscopy and the result is positive (abnormal), you will need to have a colonoscopy. Some insurers consider this to be a diagnostic (not screening) colonoscopy, so you may have to pay the usual deductible and co-pay.
You are complaining about the rare situation where someone gets fecal scanning first (and I agree this leads to perverse incentives)... But here's what the real racket is... American healthcare considers the colonoscopy preventative so the exam is covered... but if they see even a single polyp and decide to cut it off to get checked whether it is benign or not, that is not preventative but is diagnostic and thus is not covered and costs you $$$ in copays.
The question in this context is whether it’s an effective public health measure to recommend the procedure to a population: specifically, does it reduce the number of deaths over a given period?
Whether it’s effective on an individual basis is a related, but different, different question.
> cannot be used to evaluate the effect of colonoscopies. Seems the study does provide data that allows this so, and shows clear differences in cancer rates and survival rates for those that did get colonoscopies.
Really?
You cannot simple compare the outcomes for the people who got an invitation AND got the procedure done with the outcomes for the people who didn’t get an invitation.
You need the compare them with the people who didn’t get an invitation BUT would have got the procedure done if they had been invited.
> Invited or not, if you don't show up to a colonoscopy you don't get one. Which means the study's data on invitations alone cannot be used to evaluate the effect of colonoscopies. Seems the study does provide data that allows this so, and shows clear differences in cancer rates and survival rates for those that did get colonoscopies.
This is not an oversight on the part of the study designers. It's called "intention to treat", and studies are done this way to get past the problem that, when you invite a bunch of people to get colonoscopies (or tell them to comply with any medical procedure), the people who go through with it are statistically very different, in all kinds of ways, from the people who don't. This makes the direct comparison of "received treatment" vs "didn't receive treatment" mostly meaningless.
You're here advocating for everyone to ignore the study and do a direct comparison of "received treatment" vs "didn't receive treatment".
It cannot be used to say that the help either, but you wrote “Seems the study does provide data that allows this so, and shows clear differences in cancer rates and survival rates for those that did get colonoscopies.”
> I find it generally more useful link to the (abstract) of the original article, rather than second hand news reports. The abstracts are usually pretty accessible for a somewhat technical audience, they're not written for domain experts only.
If the second-hand news report is well done, it should give you more context on the matter, and so be more useful than the "raw" abstract.
I think it's more important to look at all-cause mortality, because treatment can also harm you. In this case it's a fairly tight confidence interval: "The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group (risk ratio, 0.99; 95% CI, 0.96 to 1.04)."
A lot of the comments here seem to come from the perspective that a colonoscopy is the only way to screen for colorectal cancer. There are also fecal sample tests such as FIT and FIT-DNA. Both involve home collection of fecal samples for testing. In the case of FIT yearly and FIT-DNA every 3 years. In the case of both if there is a positive result a colonoscopy is then performed. Outside the US annual FIT testing seems to be the standard of care versus a screening colonoscopy. A similar study with yearly FIT tests would be interesting to see. I suspect you might have a better compliance rate than the 42% seen in this study.
> When the investigators compared just the 42% of participants in the invited group who actually showed up for a colonoscopy to the control group, they saw about a 30% reduction in colon cancer risk and a 50% reduction in colon cancer death.
I’m really confused by this data. First of all, are they testing the efficacy of colonoscopy or the efficacy of inviting people to colonoscopy?
And then how is the former group’s reduction in deaths 50% and the latter group’s is about 0%?
The gold standard is the invitation. Imagine a study where you try to get one group of people to exercise, and you leave the other alone as a control group. Imagine you find that everyone who actually does the exercise lives much longer. This might be due to the exercise, or it could be that exercise doesn't work but healthier more responsible people followed through with the exercise. And the being healthier and more responsible causes you to live longer not the exercise.
This could also be true for the colonoscopy, that the more responsible/healthier people in the treatment group are more likely to get the colonoscopy and it's very possible responsibility/healthiness are driving the difference in health outcomes instead of the colonoscopy.
In this case they are examining colon cancer and deaths from it, and the colonoscopy is a diagnostic test for colon cancer. I feel that the results are being presented to the public in a very misleading way. People will read this headline and conclude that they don’t need to get a colonoscopy which I don’t think follows from this study at all.
> People will read this headline and conclude that they don’t need to get a colonoscopy which I don’t think follows from this study at all.
What this appears to show is that you need to get a colonoscopy to avoid colon cancer; but that you don't need to get a colonoscopy to avoid death. I'd much rather avoid colon cancer entirely than have colon cancer and survive.
But as GP pointed out, maybe you need something else to avoid death: something that is correlated with responding to the invitation to get a colonoscopy. Maybe if you're willing and able to get a colonoscopy when invited, you're willing and able to more pro-actively go to the doctor when you notice other issues that are indicative of colon cancer, allowing you to get early treatment. And conversely, maybe if you're not willing or able to get a colonoscopy when invited, you're more likely to ignore symptoms until it's too late.
Again, avoiding colon cancer in the first place is better than successfully treating it; but it does point to the fact that other interventions might be more helpful in actually preventing deaths.
> And conversely, maybe if you're not willing or able to get a colonoscopy when invited, you're more likely to ignore symptoms until it's too late.
Yes. This is the argument against relying on the secondary analysis in this study. Although the invited and standard care groups were randomized such that differences in putative confounders were adjusted for, the rejection of the intervention itself may have reintroduced systematic differences that reduce the reliability of the hypothesis that intention to screen for colon cancer reduces mortality. Possibly those who accepted screening colonoscopy are more attentive to other health and lifestyle practices that reduce colon cancer mortality.
Or: If you compare a group of people who never get colonoscopies with a group of people containing many who do get colonoscopies, the same number of people die.
Imagine two cages filled with identical mice. One you drop some food into, and the other you don't. They starve to death at the same rate. Surprised?
The study results are "colonoscopies do not lead to a reduction in colon cancer mortality". Reporting that isn't misleading that's what the study says.
Basically in the treated group of 1103 of every 10,000 people died. And in the control group 1104 of every 10,000 people died.
So to summarize the study. Inviting someone to a colonoscopy reduces their risk of getting colon cancer by 22 basis points.
Their risk of dying from colon cancer by 3 basis points, and their risk of dying of any cause by 1 basis point.
With the actual risk reduction being up to 5x this assuming it's a 20% difference in the rate of getting colonoscopies which is driving the difference.
But this makes metformin look good because it drives a much larger overall reduction in risk.
> The study results are "colonoscopies do not lead to a reduction in colon cancer mortality". Reporting that isn't misleading that's what the study says.
The measured intervention was not the colonoscopy, it was the invitation to screen. Only 42% of invited patients actually got a colonoscopy. This is far more persuasive to me:
> "When the investigators compared just the 42% of participants in the invited group who actually showed up for a colonoscopy to the control group, they saw about a 30% reduction in colon cancer risk and a 50% reduction in colon cancer death. “That adds to a bunch of observational study data that suggests exposing people to colonoscopy can reduce risk of developing and dying of colon cancer,” Gupta said."
As a member of the public, I don't really care about invitation to screen, but do care about the efficacy of colonoscopy. I can see invitation to screen being an important concern from a public health standpoint.
The problem is whether or not they chose to get a colonoscopy is a confounding variable which inflates the value of the colonoscopy when some of the results are driven by other attributes.
Thank you for pointing out that insightful detail!
The control group was 50% of the population who didn't get an invitation.
The experimental group was 50% of the population who got an invitation for colonoscopy, but turned out to be subdivided into ~40% "health conscious" who actually followed up on the procedure, and ~60% who ignored it.
Presumably there's a corresponding ~40% "health conscious" component of the control group, but this experiment had no method for identifying them.
If the study only looked at that ~40% subset of the experimental group, as opposed to the entire group who received invitations, then they could no longer compare them to the control group.
Or it could be that the people that are not necessarily healthier, but have a history of cancer in their family, may be more likely to respond to a colonoscopy invitation? One way or the other, this is all just guesswork...
I feel this is a really reasonable take. This study doesn’t say anything bad about colonoscopy, it says that it is possible the effects are not only due to the colonoscopy so it is probably between 0 and claimed effect effective. Can’t really say where in the range from the study.
The study answers a question from health policy makers: Should we invite everyone (in some age group) for a colonoscopy? Based on this study, probably not.
It does not answer questions from individuals: Should I get a colonoscopy? If you have some good reason (symptoms, doctor advice, family history), probably yes (based on other studies, not this one).
To the extent that there’s a spread in those answers, a third possibility emerges: how can we, as health policy makers, find a way to make the invitations more effective at converting to administered colonoscopies?
Double blind studies require there to be data. An invitation doesn't speak to the effects of Colonoscopy screening at all, while simultaneously adding a confounding variable about participation. The data is about the effects of offering screenings, not the effect of those screenings, per se.
Lifelong data is the gold standard for questions about mortality and most Colonoscopy randomized trials started around 2010 (hence this very early 10-year study, which I would say is premature).
They used intention to treat in the analysis so it included everyone invited to get a colonoscopy but only 42% got the exam. So 58% did not even get the colonoscopy. It is impossible to say what colonoscopy does or does not prevent when the majority of people in the intervention arm of the study did not get the intervention.
Participation is a confounding variable if you compare the subset of invitation group that participated with the control group instead of the invitation to the control group. That's the whole reason they use intent to treat.
Lifelong correlational data is not the gold standard for questions about mortality. It's intent to treat RCTs.
> Participation is a confounding variable if you compare the subset of invitation group that participated with the control group instead of the invitation to the control group.
I believe that's what I said. That's certainly what was used. You can't compare the group subset that didn't participate, so it's a confounding variable.
> Lifelong correlational data is not the gold standard for questions about mortality.
AFAIK it is and has been over the last century. If you aren't tracking lifelong data, your mortality data is always skewed against hidden results because you didn't want to wait. When making a paper that isn't qualified (decade long effects vs effects), it's not expected to have short time-boxed data.
Seems the only way to prove the test itself reduces deaths is to force unhealthy/irrresponsible people to get colonoscopies. Is there another approach?
They're doing an intention to treat analysis, which can be a bit confusing, but statistically makes sense and is the gold standard for clinical trials.
You're basicall saying "our randomization at the beginning of the trial is key to avoid biases, so we can't reassign people from the treatment group to the other group, even if they practically don't get the treatment". The reason is if you allow people to switch, your assignment is no longer random. People who avoid the treatment may have different health properties than the ones who don't.
In essence, you need your trial to be robust and large enough that a few people not getting the treatment don't matter.
Then the title is wrong, since colonoscopies actually do increase survival rates (everything would have surprised me a lot as someone who was saved by one), but rather that invitations for colonoscopies don't work. No idea why, but maybe people willing to do one go anyway while those unwilling are very unlikely to follow an invitation. Either way, the title is wrong, misleading and very clickbaity.
What you're saying is not totally correct. If you look only at patients that did get a colonoscopy, you cannot be sure that it is the colonoscopy that helps, or another variable (those people might monitor their health closer). Your assignment is not random any more so you cannot make any causal statement.
Thanks. That explanation on avoiding selection bias makes sense, but it seems like the study is saying those who choose to get a colonoscopy (whether invited or not) are 50% less likely to die of colon cancer.
Also I’m not sure if the article mentioned this, but the data seems to imply that the % of people who opted to get a colonoscopy was similar in the invited and control group.
That suggests something strange though – that those who were invited but non-tested were more likely to die of colon cancer than non-invitie non-testers.
I suppose that by refusing to get a colonoscopy even when specifically prompted to do so, you're maybe sorting yourself into a more "unhealthy" group than the general population of non-colonoscopy-havers.
It would be unethical to refuse to invite someone with a family history of colon cancer. Thus I think it is perfectly reasonable to assume there is something different.
Sensationalist title to a good news story: there was no intent-to-treat effect, but a low conversion rate. The ETT is a pretty impressive 50% mortality reduction. Also study is limited by a short 10 year follow-up period but there will be a 15 year follow up.
When everyone invited for a colonoscopy is compared to the control group
42% showed up and got a colonoscopy
18% fewer people got colon cancer
same number of people died of colon cancer
When everyone who got a colonoscopy is compared to the control group
30% fewer got colon cancer
50% fewer people died of colon cancer
This data makes me think the mortality reduction benefit is bogus, but the cancer prevention benefit is real, and probably greater than 18%, maybe closer to 36-40%. If the colon cancer mortality benefit was real you'd see some reduction in the intention to treat group, and it'd be smaller than the cancer prevention effect. (The most aggressive cancers tend to be harder cancers to catch in time because they most so quickly, so most cancer screening tests will prevent more cancers than deaths)
Where are you getting "50% mortality reduction" from? The article says the reduction was zero:
> After 10 years, the researchers found that the participants who were invited to colonoscopy had an 18% reduction in colon cancer risk but were no less likely to die from colon cancer than those who were never invited to screening.
> When the investigators compared just the 42% of participants in the invited group who actually showed up for a colonoscopy to the control group, they saw about a 30% reduction in colon cancer risk and a 50% reduction in colon cancer death
I don’t see how that says much about the usefulness of colonoscopy.
The people in the treatment group who didn’t show up must have had a 36% increase in colon cancer death (not explicitly stated in the article, but can be derived from the numbers. You need 42% × 50% + 58% × ? = 1), and (solving 42% × 70% + 58% × ? = 1) a 21% increase in colon cancer risk.
Something must have made them different from the control group. Maybe, they didn’t show up because they already were being treated for colon cancer?
Right, so to properly isolate the effect of the colonoscopy on mortality, we need to do a randomized trial with just people like you -- people who would definitely get a colonoscopy if invited -- to see what the effect is. Because you're also more likely to act on early warning signs and get a cancer diagnosis in time to treat the cancer rather than die.
> Because you're also more likely to act on early warning signs and get a cancer diagnosis in time to treat the cancer rather than die.
This seems to imply we should discount all treatments because people who choose to get treatment are more likely to get better, coincidentally by the same amount as the treatment's efficacy.
The question here is a question that the medical establishment is trying to answer: namely, "What can we, as the medical establishment do, to reduce deaths from colon cancer?" For a long time, the answer has been, "Invite people to take colonscopies". What the data here appears to show is that the action, "Invite people to take colonoscopies" doesn't actually reduce deaths from colon cancer. If the medical establishment wants to actually reduce deaths from colon cancer, they'll need to figure out something else.
I guess I do agree that the headline is likely to be counterproductive. What the data might show is that the most effective thing you as an individual can do is to be the kind of person who takes colonoscopies when invited. The unfortunate effect it might have is to make more people into the kind of people who don't take colonoscopies when invited.
> I guess I do agree that the headline is likely to be counterproductive. What the data might show is that the most effective thing you as an individual can do is to be the kind of person who takes colonoscopies when invited. The unfortunate effect it might have is to make more people into the kind of people who don't take colonoscopies when invited.
Agreed. Except the most effective thing you can do as an individual is have a colonoscopy, not be the sort of person who would have one :-)
> Except the most effective thing you can do as an individual is have a colonoscopy, not be the sort of person who would have one :-)
So we have two hypotheses here:
1. Having the colonoscopy is the thing that reduces deaths from colon cancer
2. Having the colonoscopy correlates to some other factor, X; and it's actually X which reduces the deaths from colon cancer.
X, for instance, could be a high willingness / ability to see the doctor when you experience early symptoms of colon cancer. That is, the more willing you are to go to the doctor when you start to have early symptoms of colon cancer, the more likely you are to survive it; and the more willing/able you are to go to the doctor when you have early symptoms of colon cancer, the more willing/able you are to have a colonoscopy.
What evidence do you have to believe that #1 is true, rather than #2?
Because if #1 is the case, the medical system should push hard on colonoscopies. But if #2 is the case, pushing colonoscopies might be a red herring. In fact, it might be counterproductive -- I've heard that colonoscopies are unpleasant; if you pressure people who don't like doctors into having a colonoscopy, and they have a terrible experience, then when they experience early symptoms of colon cancer, they may be more likely to procrastinate to avoid having another one. Rather, if #2 is the case, the medical system should try find out what can be done to make people more willing / able to get early medical care.
No, but you need to account for it when considering efficacy, because people who choose to follow through on treatments may also be taking other steps that may also improve their outcomes, and it can be hard to tease out because the mere act of telling them they should have a screening might change other behaviours even without being prompted by doctors in a way that's recorded.
E.g. it's a reasonable hypothesis that patients who are more motivated to show up might also be more motivated to look up possible causes and what other steps they can take to improve their chances.
In other words, it's reasonable to expect people who comply to potentially get better at a higher rate than the efficacy of a single treatment, and teasing out how much of this effect is due to the intervention itself and how much is due to changed behaviour due to the referral is hard.
Years ago I learned that this is the reason why they don't do colonoscopies without good reason in Finland.
I asked from a doctor who is a friend why you have regular colonoscopies in the US but not in the Finland and he said "no evidence and colonoscopy has a small risk factor".
If you do medicine for profit and are allowed to advertise and market, doing more is always better.
I haven't read the article - only the abstract, but it does report: "No perforations or screening-related deaths occurred within 30 days after colonoscopy." I guess something could have happened later than 30 days but we'd need the full article for that.
Vinay Prasad, MD (Heme/Onc) gives a very good rundown on why this trial is so important. He also points out why having accurate data for screening recommendations is so crucial. USPTF has been making recommendations recently without data to back up them up and get appropriately taken to task for that.
"He prefers iconoclastic approaches, whether by directly funding asteroid detection or advocating for nuclear power to combat global warming."
Ooh, scary dude. /s
Kids nowadays. I remember when nuclear power was a futuristic clean energy sort of ideal and when the way we figured out who was right and who was wrong on a complex topic was to let both sides openly debate and then pick who is more credible by how each is able to rally the facts in defense of their position.
Beware your society, which is doing the same thing to people like Kirsch that it did to Socrates two thousand years ago. The masses never change, apparently. All that changes is whether they're held in check or whether they're exploited by demagogues.
This is about colonoscopy screening. If you give a fecal sample and it comes up as suspicious, the next step will be a colonoscopy anyway.
A colonoscopy is quite unpleasant; you starve for a day, and take an enema. They may sedate you before the procedure. If they don't, then the procedure is quite uncomfortable; not exactly painful, but unpleasant.
Incidentally, if they find and remove a polyp, they will plant a tattoo inside your gut to mark the spot, for the benefit of future spelunking visitors.
The enema is replaced with a laxative often. That is still really hard, I barely got half of mine down and was in a rough state the morning of the procedure.
I was sedated, so laxative was the hardest part of the ordeal, not the fasting or actual procedure.
Wow, colonoscopy with no sedation must be extremely awful. Isn't sedation the default anywhere? I remember the papers I had to sign were really serious about advicing sedation.
I couldn't be sedated, because I had no companion to take me home, and a taxi doesn't cut it.
I wouldn't describe it as "extremely awful". It was very uncomfortable; I'd compare it to 40 minutes of dental hygiening.
I think it's nuts that they use this procedure for screening. I'm screened for bowel cancer annually, using a fecal sample pack they send me through the post, and that I post back. No hospital visit, no treatment room, no expensive equipment, no nurses and doctors. The only reason I can think of for using colonoscopy as a screening technique is that it's costly.
Thanks for these corrections. Yes, I should have said "fast". And indeed for my recent colonoscopy, I was given laxative, not an enema, it's a sachet of powder that you dissolve in a litre of water; you then have to gulp that down as well as drinking lots of water. Years ago I had a sigmoidoscopy, and then they did give me an enema. That's the only time I've had an enema, and I didn't know what to expect. It was very rapid, and rather dramatic.
Every person will have some amount of cancer as they get older. Some of the cancer will not be aggressive or disruptive enough to cause a problem before the person dies of another old-age related infirmary.
Treating cancer is not free. Treatment reduces the quality of life of the person treated. Elderly people are slower to heal, and more at risk for complications. To treat a cancer that would not cause problems in the natural lifespan of its host is an expensive mistake.
Screening technology can expand our ability to detect cancer without giving us the insight to know dangerous cancer from inconsequential cancer. When we go on to treat inconsequential cancer we've actually reduced the years of healthy life of the patient.
This. My father had a faecal test which showed he possibly had cancer - the colonoscopy confirmed this.
Sadly my oldest brother didn't catch his so quickly and the colonoscopy he had showed he was pretty far along, and ultimately the cancer spread and killed him.
I now have one every 5 years until I hit 50 then I'll move to every 2 years. The test is pretty pain and issue free, the only 'bad' part if the laxatives first, but after seeing my brother die, it is well worth the couple of hours of discomfort.
My older brothers had continued with faecal testing, but after some pushing moved to colonoscopies too, as we'd rather catch it early, than once it has taken hold.
Please be aware that the procedure is not risk-free and there is general concern in the medical community that it does more harm than good in healthy adults.
5/1000 colonoscopy patients have complications (some fatal) which is way higher than the base rate for colon cancer.
This is a very complex subject because the sensitivity of tests for colorectal cancer has improved over time and more testing is being done. This makes it appear as if there is a great increase in colorectal cancer when there really isn't.
A very interesting related study has become known as "The Norwegian Colorectal Study" found that early testing was a waste of money since only those with a family history of colorectal cancer or IBS symptoms or both actually got colorectal cancer before 55. For most people the polyps which are precursors to colorectal cancer do not appear before age 55. That means that the current push for aggressive testing starting at 50 is a distracting waste of time, money, and effort that should be eased back.
There have been some really interesting studies which showed that in order to get colorectal cancer you have to accumulate 4-6 deletrious mutations in the same cells. People with genetic predispositions are born with 2-3 of those mutations. That's why we see this age association. (Just remember being fascinated and thought I would add some context.)
“They’re doing a 15-year follow, and I would expect to see a significant reduction in cancer mortality in the long term,” Dominitz said. “Time will tell.”
After all the debate here in HN about the interpretation of the data and the statistics, I'm really looking forward to see a post in 15 years with the new study.
I would suggest reading the editorial also. Study has major limitations. From the doctor who wrote the editorial on Facebook Dr Jason Dominitz:
"I'm honored to have been invited to write an editorial for the NEJM about the landmark NordICC study comparing screening colonoscopy to usual care (no screening) in Norway, Poland and Sweden. The NordICC results were somewhat disappointing in that colonoscopy only reduced colorectal cancer incidence by 18% at 10 years, with no significant mortality benefit. But only 42% of individuals who were invited to have a colonoscopy followed through. For those that did have colonoscopy, mortality was reduced by 50%. This study highlights the importance of adherence with screening. Also, we know that colonoscopy quality is variable and 29% of the endoscopists were not meeting quality benchmarks for polyp detection. So if you are getting a colonoscopy, ask your doctor what their "ADR" (adenoma detection rate) is. If they don't know, find another doctor to do your colonoscopy. The ADR should be well over 25% and, ideally, over 40%. "
https://www.nejm.org/doi/full/10.1056/NEJMe2211595https://www.nejm.org/doi/full/10.1056/NEJMoa2208375...
Shouldn't this study properly be called "Effect of Offering Colonoscopy Screening on Risks..."? The headline result is based on the 18% decrease in CR cancer among people who were offered a colonoscopy. Of the people offered, only 42% actually got a colonoscopy. That means in the "colonoscopy group" 58% never even had one. Among those who did get one, there was a 31% decrease in CR cancer, and a 50% reduction in deaths from CR cancer.
All the study really proves is that offering someone a colonoscopy isn't the same thing as giving them one.
The problem with this study is that the analysis is based upon intention to treat. Only 42% of those who were randomized to get a colonoscopy actually got one. The cancer incidence was 18% lower among all people who were invited to get a colonoscopy. If we assume rate among people who were invited to get a colonoscopy but did not go through with it is the same as the rate of people who did not get a colonoscopy then the cancer rate would be more like -2/3 among those who got a colonoscopy.
Irresponsible click bait title. If you are over 40,take a colonoscopy. I lost my brother (44) from colon cancer which could have been totally prevented. It was a very painful and depressing experience, multiple rounds of chemotherapy and surgeries that lasted over four years and sent his family into bankruptcy. He stopped eating solid foods weighing only 47 kilos and died from suffocation, pretty much liquid accumulating and pressing against his lungs until he could no longer breath. It's a slow and horrible dead that can be prevented with a simple one hour procedure done once every 5-10 years and in many cases 100% covered by insurance.
> please use the original title, unless it is misleading or linkbait; don't editorialize
I'm finding myself disappointed with the application of guidelines here. The title has been changed to a completely made up headline, differing from the original, which is editorializing. It's the second time this happens in the past 24 hours - yesterday the ".. you idiot" part was removed from a blog post completely numbing the post's intention. Neither was misleading or clickbait.
EDIT: while typing this comment, the title has been changed yet again to reflect the paper's title "Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death".
This post was submitted with the following title from the original article per the guidelines:
"In gold-standard trial, colonoscopy fails to reduce rate of cancer deaths"
I’m quite surprised in 2022 that news coverage is not mentioning the now well-known risks associated with colonoscopies. AIUI they are no longer recommended in the EU for routine screening because of the very high rate of dangerous side effects, on net increasing all cause mortality in the general population.
The article here just looks at cancer mortality, which is not what anyone should care about.
I believe what he discovered is important. Not that I believe his advice to drink ionized water (Kangen water) is scientifically sound. But that does not matter for the discovery that switching to eat rice and veggies cleans your intestine.
I’m unique guess in the world. We’re all going to die. If you make it to 57, awesome. After that it’s all a bonus.
Take that attitude, and you really don’t put off much. You don’t turn down any invites. And do wake up with the Sun.
Life is awesome!
Don’t be so afraid of death. It’s not that bad. Really.
Source: survived an NDE. Was not my time was told, but did get a great tour of the afterlife.
Don’t worry so much.
And treat strangers with kindness, they were very insistent on that. They keep score. Heaven or Hell. It’s your decision.
Title and end conclusion of the article are contradicting. Last paragraph says, "If you cannot take 2 days off, then you have other options. If you want to take test once in 10 years, Colonoscopy is the king". This means Colonoscopy is still the king if you can take 2 days off from your work ( which I believe most workers should be able to as this is important for one's life ). Not sure how this is beneficial for the readers of this article.
When the polyp has been nipped, it is gone. If you have a colon with no polyps (left) in it, you should be safe from colon cancer for at least a decade (how long polyps take to develop from mutation into a tumour).
- what if the presence of polyps is not all bad? i.e. maybe they keep the immune system in a tumor-responsive state, or they locally deplete nutrients that would otherwise feed other pre-cancerous cells?
You might not die if you leave that cancer alone, but you might get part of your colon removed, or get a colostomy bag, or get your anus surgically sewn shut til death -all of which not necessarily changes your life expectancy.
Looking for death vs no-death alone as an outcome for medical diagnosis/treatment is short sighted.
Good discussion here, but I think the main message might get lost in the noise:
* Colonoscopies reduce incidence of colon cancer but apparently not death from colon cancer.
* This is probably because colon cancer therapies are good, so even if you get colon cancer your prognosis is good.
* The take-away is not that colonoscopies reduce your chances of death, but that they reduce your chances of having to suffer colon cancer and subsequent therapies. That might still be a good trade-off.
If you had a science background, the term "Gold-standard trial" would have meaning to you as a term for randomized double-blind studies with a large sample size. I don't know what textiles have to do with it.
The actual study is titled "Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death" [1]
The authors conclude that "In this randomized trial, the risk of colorectal cancer at 10 years was lower among participants who were invited to undergo screening colonoscopy than among those who were assigned to no screening. "
I find it generally more useful link to the (abstract) of the original article, rather than second hand news reports. The abstracts are usually pretty accessible for a somewhat technical audience, they're not written for domain experts only. As we see in the discussions here, it's questionable whether the rephrasing from journalists really adds anything.
[1] https://www.nejm.org/doi/full/10.1056/NEJMoa2208375