It is really never a good sign when a miraculous new breakthrough in veterinary medicine is announced on the internet. That isn’t where true scientific breakthroughs show up. Legitimate science is a slow, detailed process where even brilliant, revolutionary ideas have to go through a long, rigorous process of critique and exploration before they are accepted. Public relations press announcements are about making money and generating hype, not about exploring good science.
It is even less inspiring of confidence when the supposed breakthrough is offered by a person or institution with a track record of promoting pseudoscience.
In the case of OncoK9 Liquid Biopsy, such red flags abound. Press announcements with hyperbolic language like “pioneering,” “revolution,” and “breakthrough innovation” are not only meaningless but outright misleading when the only evidence offered to support them is a company study that supposedly “will be submitted for publication in a leading peer-reviewed journal” someday. Legitimate science does not start with press releases and then move to possiblepublication in the scientific literature.
It is also not inspiring of confidence that the product is being initially offered for sale by Petco, a company which has a sketchy history when it comes to pet health topics. Selling raw diets, grain-free foods and bogus nutritional supplements while running a vapid and unscientific public relations campaign lauding its ban on “artificial” ingredients in the foods sold at PetCo stores does not establish the chain as a reliable source of information on pet health.
So what is OncoK9? According to the company that developed the product, it is “a multi-cancer early detection (MCED) test for the detection and characterization of cancer-associated genomic alterations in DNA isolated from canine whole blood samples, using next-generation sequencing (NGS) technology.” Sounds fancy, eh? The idea is plausible. Cancer cells may, depending on the type of cancer and many other factors, circulate in the blood. If such cells are present, it is potentially possible to detect them by identifying genetic markers associated with such abnormal cells. If there are then other tests available to identify and locate the cancer, and if there are therapies that might be more effective in treating the disease when caught at an earlier stage, such a test could improve health and lifespan in dogs.
Notice all the “ifs” and caveats here? The idea is sound, but the devil is in the details, and this company has not even come close to proving that all the steps in this process will work in a way that actually benefits dogs. The test was developed by mixing DNA from cancer cells and healthy canine cells and showing that the test could detect the abnormal DNA. Apparently, the test was then applied to samples from dogs know to have and thought not to have cancer (this is the study that has not yet been submitted for publication but from which the company is reporting results in its marketing materials). That’s a good start, but a long way from proving that regular clinical use of this test will benefit canine patients.
The company recommends using the test as a screening tool, “as an annual screening test for dogs that are 8 years and older and/or belong to breeds that are highly predisposed to cancer.” Screening is a particularly tricky kind of testing because you are looking at dogs without any signs or symptoms of disease. Most apparently healthy dogs are actually healthy, so the risk of false positive results, finding disease that isn’t actually there, is higher than when testing sick patients.
The risk of overdiagnosis is also high. This is where a test finds a disease that is truly there but isn’t likely to ever cause any symptoms. Many kinds of screening tests in humans, based on the same idea that early detection of asymptomatic disease is better, have been scaled back because it turns out they do more harm than good. Finding a type of cancer that isn’t ever going to progress or make someone sick isn’t in their best interests if subsequent testing and treatment cause harm without any benefit in terms of health or increased lifespan.
Assuming the methods and controls for error and bias were appropriate and the data is accurate (all of which we have to blindly assume in the absence of any scientific publication), the company study suggests an overall sensitivity of 48% for the test. This means that 48%, less than half, of dogs with cancer will correctly test positive. This is not, on the face of it, a very sensitive test. However, if we are looking for cancer in dogs without any clinical symptoms, that might actually be a good thing. We would rather miss a case in a dog with cancer that is not causing any problems than mistakenly identify a dog as having cancer who doesn’t.
The specificity, that is the proportion of dogs without cancer who correctly test negative, is reported to be 97%. This is the more important value in this case since we don’t want to falsely diagnose cancer and send a lot of dogs into unnecessary, costly, and potentially dangerous further testing or treatment they don’t need.
However, given that the company actively recommends the test as a screening tool, it is likely most of the dogs tested will be healthy. A rule for screening tests is that the less likely the patients you test are to actually have the disease you are looking for, the more wrong answers your test will give you. One way of looking at this is with the Positive Predictive Value (PPV) of a test.
The company advertising materials calculate the PPV for OncoK9 based on guessing that 10%-20% of dogs tested will have cancer. This seems high (which would make the test look better than guessing a lower rate of hidden cancers), and there aren’t good research data to tell us what the actually prevalence of asymptomatic cancer is in dogs of a specific age or breed. The best data we have are variable and not consistent between studies, so I will give the company the benefit of the doubt on these guesses for the time being.
Using these numbers, then, the PPV for OncoK9 would be between 64% and 80%. At the low end, that means that 64% of the dogs with a positive test actually have cancer and 36% do not. It seems a bit concerning that we are going to tell over a third of the dogs we test that they might have cancer when they don’t. Presumably, this would be followed by x-rays, ultrasound, other tests, and potentially months to years of anxiety about this supposed hidden cancer, none of which would improve the health or longevity of these dogs. Even at the more optimistic figure of 80% PPV, 20% or 1/5 dogs testing positive would actually be healthy. This raises the potential for significant costs and harms from unnecessary testing and treatment for a lot of dogs.
And remember all of the other caveats about screening tests for cancer? What if the OncoK9 test is correct but we can’t find the cancer anywhere until it progresses? What if it is a type of cancer for which there is no effective treatment? What if it is a type of cancer that is non-progressive and is never going to make the dog sick or lead to death? What if treating the cancer earlier, and for a longer time, doesn’t actually work better than treating it when it causes symptoms that we can detect without this test? All of these are likely scenarios, and in none of these cases would the cost of the test or the cost, anxiety, and risks of further testing and treatment offer any benefits for the dogs. This test has significant potential to cause harm not only when it gets the wrong answer but even when it is correct!
Of course, having a test that reliably detects cancer at a stage where the dog is still healthy and can be effectively treated in a way that preserves health and prolongs life would be a great thing. I would welcome such a test once it was proven to work as intended. Unfortunately, there is no way to know if OncoK9 will lead to net benefit or harm to dogs based on the evidence currently available. Despite the undoubtedly good intentions of the people developing and promoting this test, it is disappointing, even irresponsible to market it without having first done the necessary work to show it will actually make life better for our canine companions.
I will keep an eye out for the promised publications. I will even hold out a little bit of hope that eventually studies will be done to determine if the test as actually used in practice reduces disease and saves lives or not. Unfortunately, my fear is that once the test is on the market, the research will stop and continued use will be supported by heartwarming anecdotes about dogs “saved” by an early cancer diagnosis. We will likely never know how much misdiagnosis and overdiagnosis comes from this test since there will be no financial incentive to do the necessary research to figure this out. For now, I would urge dog owners to think very carefully about spending $400 for a test that involves big promises, little evidence, and a lot of uncertainty.
Thank you. I just received an ad in my feed and knew it was nonsense. But, now everyone will come in asking about it. This is an even more in-depth explanation of all the reasons to be skeptical.
I can appreciate some of the skepticism expressed here based on your explanation of how the test works. My understanding is that the test doesn’t operate on a cellular level, but on a molecular one. Cancer cells need not be circulating in the blood. Wouldn’t genomic sequencing be useless if the markers it was utilizing were protected within live cells? It looks to me like it’s actually ctDNA and cfDNA that is being collected from the blood, not cancer cells.
This test is being used successfully in the human medical space (not just for cancer in an individual patient, but for fetal DNA released into the maternal bloodstream which signal genetic disorders & other birth defects.)
I don’t know any of the people behind OncoK9 and you could be right: it’s possible that this might just be a marketing scheme. I have some experience with successfully bringing nano-particle photothermal treatment from human oncology to animal health, so I do know that it’s also at least equally possible that this human breakthrough will have a beneficial impact in the veterinary space as well. Just a cheer for innovation here, and best wishes for the OncoK9 team. This looks big!
Thanks for this helpful article. I do hope this research gets done, but also doubt it will. I’ve included a link below to an article by a physician/researcher who fears the same financial incentives will be in play with liquid biopsies with humans. He’s also concerned they may well do more harm than good, not to mention bankrupting our already broken health care system.
https://www.statnews.com/2021/08/31/liquid-biopsy-misplaced-faith-in-early-cancer-detection/
Let me give you a view as a pet parent that’s just lost his Chesapeake Bay Retriever to hermangiosarcoma.
Gisele was 9 years old and very fit. She did a 5 mile hike with me 2 days before being diagnosed.
Gisele had a tumor on her spleen that ruptured and she had a splenectomy (total cost $12,000). After the meds wore off we got a short but incredible 11 days with her when she was like a puppy. On the 12th day she told us she was ready, and died surround by her family at home the next day.
Right now, other than hoping to get lucky with an ultrasound to detect this disease before it spreads, there’s nothing else available.
If there’s even a 30% chance this would help detect a tumor before it metastasizes or ruptures and can be removed in advance this is the best $400 a pet parent could ever spend.
While that makes sense, I can also tell you stories of dogs who had such screening done for the very same reasons and then had unnecessary surgeries, chemotherapy, and other tests and treatments that resulted not only in financial costs but in suffering for the pet. We always think of the potential benefits, but the potential harms are very real also, and the challenge is getting enough information to be able to balance the two appropriately.
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I’m hoping you could do a similar analysis on a competing test called NuQ. Are you familiar with it?
I’ve read through the studies they’ve conducted, and there are a few aspects that give me pause, but I have zero scientific background so I’m not sure if my skepticism is warranted.
Here’s a link to the company’s website, if you’re interested
https://veterinary.volition.com/vet-resources/scientific-resources
Love your website!
Yes, I’ve seen this, but haven’t had a chance to dig into whatever data there is yet. I’ll definitely add it to my list!
I’m curious if you’ve had a chance yet to research the Nu.Q Vet Cancer Test? I’d love to hear your take on that one too. I read that Texas A&M led in the research and development of it. https://vetmed.tamu.edu/gilab/service/assays/nu-q-vet-cancer-screening-test/
In general, the risks and benefits seem similar to OncoK9, but I don’t think the published evidence is as extensive. I have reservations about the general strategy of screening for cancer in this way, and the test itself cannot justify making any important decisions (e.g. chemotherapy, euthanasia). It might help convince some owners to pursue further testing if there is suspicion of cancer, but the testing needed would be the same as would be done without the test, so overall, I think the usefulness is pretty limited at this point.
If data emerge showing that use as a screening test actually leads to improved treatment outcomes and survival, I will be on board, but there is nothing yet to support that.
My dog recently had the Nu.Q test done and it came back High. The test results come back Low, Moderate and High. He is an almost 6 year old Bernese Mountain Dog that has no clinical signs. Today we did an ultrasound sound and found a small nodule on his spleen which we did a fine needle aspirate on. We also re-ran the Nu.Q test to see if we get another High result or the first one was a False/Positive. As an owner of a high risk cancer breed it is reassuring to know this test is out there but it is also maddening because we don’t know what we’re looking for.
Yes, and this is exactly the challenge with these tests. They can detect cancer at an earlier, treatable stage, or they can detect benign lesions that don’t matter and create lots of unnecessary anxiety, expense, and risk from additional procedures. Most incidental splenic masses (70%) are benign and do not require treatment. Also, fine-needles aspirate cytology is often nondiagnostic or inaccurate, so that adds a layer of uncertainty. It’s impossible to predict whether the test will benefit or harm an individual patient, but we need to at least be aware that sometime we’re better off not running it.
Good luck!
make sure these abdomen needle biopsies are with needles that are no larger than 22 gage or make sure your vet has blood available for transfusion on premise and can do exploratory lap on premise if needed. Biopsy guns with larger needles shot into the abdomen carry bigger risk.
Our pups father just died of a ruptured spleen at age 7. As I understand that’s a young age to die of cancer. They say it’s genetic. The breeder now urged everyone who purchased a puppy from the same litter to get our dogs screened. Ours are 4 which some say is the perfect age to start screening at it there’s a predisposition. Is that a viable option? Would yearly catch it early? If not, what can be done to catch it early? There’s something that doesn’t add up to me. How can we not detect this cancer? I’m so hopeless and scared because I don’t want them to die earlier than they have to.
I’m sorry that you are in this position.
The idea that cancer ‘is genetic,” is way too simplistic. The risk of getting in can be increased by genes, but also by environment and the interaction between them and by random chance events. So being related to a dog whoo had this is a concern, until it’s not destiny.
Given that the risk may be higher of your dog (though we don’t really know by how much) a screening test like this is reasonable. However, you have to be aware that
1. no test is perfect, so you could get positive results when he doesn’t have cancer or negative results when he actually does. The test does a pretty good job of minimizing these risks, but they are still there.
2. It isn’t clear how acting on a positive test would help. Presumably, if the test is positive you might do an ultrasound and chest x-rays to look for masses. If there is one in the spleen, you could take the spleen out. this would prevent a rupture, but it usually isn’t curative, so he could very well still develop spread elsewhere. If there are masses in the chest, there really won’t be anything useful you can do. So you have to ask yourself how you would react to the test results and will you be OK knowing that you might find a cancer you can’t do anything about.
There is no perfect answer in this situation. The idea that finding it early leads to a better outcome is appealing, but we don’t yet know for sure this is true with this test or this kind of cancer.
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I am an MD using this sort of technology with my patients. (the GALLERI TEST and the SHIELD TEST). With 40 years of experience, I am elated to have such precision based technology available. While I still perform standard cancer screening tests, such as colonoscopy, mammography, pap smear, PSA, a thorough history and physical exam, I welcome adjunctive testing as part of my offerings. I caught an early colorectal cancer with the Shield Test. The patient had a normal colonoscopy just two years prior (and she was not at high risk of colorectal cancer). Bear in mind that the sensitivity of these types of tests is much higher in the fast growing, aggressive cancers, that are often far too advanced, when finally diagnosed. I have great hope that these types of tests will provide earlier diagnosis and cure. As a canine owner, I am seeking out currently available offerings, as an adjunct to the superb care offered by our veterinarian.
As you know, all screening tests have risks as well as benefits, and their performance is a function not only of the tests themselves but of thee prevalence of the condition in the population being tested. Positive and negative predictive value need to be considered, which is especially difficult in veterinary medicine as we lac k the basic epidemiologic data needed, such as disease prevalence estimates.And over diagnosis is an important concern, which can only be identified in patient population data, not in individual patients. Changes in PSA and mammography practices have reflected this issue, but again in vet med we often have no data to tell us the number needed to test for each case detected and no way to know how many patients are being harmed. Anecdotes such as the one you mention are very compelling, but they are also subject to recall bias, confirmation bias, and many other cognitive errors, so they don’t tell the whole story.
I suspect these tests will be a useful part of preventative medicine, but without appropriate use they can cause harm to patients, unnecessary anxiety for owners, and they can raise treatment costs, which is particularly concerning since, unlike human medicine, there is no financial support for veterinary care for many people, and many animals go without care or are euthanized due to financial constraints even when they have treatable problems. we need to make use of such new technologies thoughtfully, rationally, and with a clear-eyed, eviidence-based approach to maximize their benefits and minimize their harms.
Oncotect is another competitor that claims they produce “The World’s Only At-Home Cancer Screening Test for Dogs:” https://oncotect.co/
It’s much less expensive and uses urine, instead of blood, is clinically tested on over 500 dogs and has 83% Sensitivity and 96% Specificity. Plus, of course, it can be used at home and doesn’t require a trip to the vet. Plusses and minuses there…