Latest news with #FredHutchinsonCancerCenter
Yahoo
3 days ago
- Health
- Yahoo
HIV's Most Promising Breakthrough Has Taken a Hit
Solving HIV vaccination—a puzzle that scientists have been tackling for decades without success—could be like cracking the code to a safe. The key, they now think, may be delivering a series of different shots in a specific sequence, iteratively training the body to produce a strong, broad immune response that will endure against the fast-mutating virus, ideally for a lifetime. Figuring out which ingredients to include in those shots, and in which order, is one of the trickiest immunological conundrums that researchers have ever faced. But mRNA, the fast, flexible technology that delivered two of the world's first COVID-19 vaccines in record time, is ideal for that kind of brute-force tinkering, and may be the most important tool for getting an effective HIV vaccine, Julie McElrath, the head of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, in Seattle, told me. Multiple mRNA-based HIV vaccines are now in clinical trials, and early data suggest that they're prompting the type of immune responses that researchers think are essential to keeping HIV at bay—and that other vaccine candidates have struggled to elicit at all. But recently, several promising mRNA HIV-vaccine candidates have slammed up against a technical roadblock. In two small clinical trials, 7 to 18 percent of participants developed rashes and other skin reactions after getting the shots—including multiple cases of chronic hives that troubled volunteers for months after they were immunized. All of the vaccines were manufactured by Moderna. The rashes aren't life-threatening; they're also readily treatable. Still, they can be debilitating and distressing. 'I've had patients who literally can't go to work,' Kimberly Blumenthal, an allergist and immunologist at Massachusetts General Hospital, who has treated people with chronic hives, told me. The rate at which they're occurring in the trials is also out of the norm, and no one has an explanation yet for the root cause. To prioritize patient safety, mRNA HIV-vaccine research in people has slowed as researchers try to suss out the cause of the hives, William Schief, the Scripps Research Institute biophysicist who helped design one of the vaccines, told me. (Schief also holds titles at Moderna and at IAVI, the nonprofit that sponsored some of the HIV-vaccine work.) At any time, a side effect this uncomfortable and prolonged would give researchers pause. But in 2025, a setback for a high-profile mRNA vaccine trial—focused on HIV, no less—could more fundamentally upend potentially lifesaving research. Secretary of Health and Human Services Robert F. Kennedy Jr., a longtime and prominent anti-vaccine activist, has repeatedly questioned the safety of mRNA COVID vaccines. He and agency leaders are already recommending that fewer Americans take vaccines and creating new hurdles to vaccine approval. Since January, the National Institutes of Health, under HHS's direction, has also terminated funding for hundreds of research projects related to HIV and vaccines. This week, the department canceled Moderna's nearly $600 million contract to develop mRNA-based flu vaccines. The HIV-vaccine studies that detected the skin reactions were also supported by NIH funding, and the researchers involved collaborated directly with NIH scientists. But those partnerships have since been terminated, and the NIH is now telling several agency-supported researchers working on HIV vaccines that the government is not planning to continue funding their work, according to several researchers I talked with. When reached for comment, Emily Hilliard, HHS's press secretary, wrote in an email, 'The reality is that mRNA technology remains under-tested, and we are not going to spend taxpayer dollars repeating the mistakes of the last administration, which concealed legitimate safety concerns from the public'—referencing the mRNA-based COVID-19 vaccines, which were rigorously tested in clinical trials, and billions of doses of which have been safely administered people around the world. Under normal circumstances, detecting rashes in a small vaccine-safety study would represent a routine scientific setback, and prove that the trials served their intended purpose. But the administration's anti-vaccine stances have created a culture of fear among scientists: Several of the researchers I contacted for this story declined to comment, for fear of publicly tying their name or institution to reporting on mRNA vaccines and losing funding for their research. Science requires resources and open discussion—in torpedoing both, the Trump administration is rapidly undoing decades of progress toward ending the HIV pandemic. Researchers running the mRNA HIV-vaccine trials first took note of the rashes in 2022, shortly after studies began. After Science magazine reported about the side effect connected with the IAVI-sponsored vaccine, many scientists in the field weren't sure what to make of the finding. The trial in which it had been reported had enrolled only 60 people, and it wasn't set up to rigorously look at a mysterious side effect. 'The sort of feeling was, Yeah, that's a bit weird, God knows what happened,' John Moore, an HIV researcher and vaccinologist at Cornell, told me. This April and May, though, researchers independently published two papers describing the rashes, for four separate vaccines, in two separate trials: one for the IAVI-backed vaccine and another run by the HIV Vaccine Trials Network. Now, the side effect is 'real, confirmed, generalizable,' Moore said. 'And we don't know why it's happening.' The vaccines in question target slightly different parts of the virus. But all of them rely on a Moderna-manufactured mRNA backbone, and all of them triggered, in up to about 10 percent of participants, chronic hives that emerged a few days or weeks after vaccination and in many cases lasted for months. That's a long time to be battling itching and discomfort—and it threatens to be a major deterrent to completing the series of vaccines, or potentially starting at all, Genevieve Fouda, an immunologist and HIV researcher at Cornell, told me. Delayed, chronic hives have long been known as a rare side effect of vaccines, including mRNA-based COVID vaccines. But the rates are generally very low—usually well under 1 percent, and often detectable only in massive studies of thousands of people. To see these rashes crop up in two small safety studies—one of 60 people, the other of 108—is a significant departure from precedent, scientists told me. And working out why they're appearing at such high rates will take time. Although researchers understand that the reactions are a kind of autoimmunity—in which the body inadvertently learns to attack itself—they don't know exactly why rashes occur after certain immunizations or infections, Blumenthal told me. In this case, the data so far do point to the specific combination of mRNA and HIV as a root cause. Other mRNA vaccines, including Moderna's, haven't had this issue to anywhere near this degree; neither have other HIV vaccines that have made it into people. And several researchers pointed out to me that, so far, the only trials that they're aware of in which these hives have turned up at this frequency have involved a Moderna-manufactured product. None of the other vaccines being tested by the HIV Vaccine Trials Network, for instance, has seen rashes at that rate—including other, non-Moderna mRNA HIV vaccines, Jim Kublin, the director of HVTN, told me. (Barton Haynes, the Duke immunologist leading work on one of the non-Moderna vaccines, told me he and his colleagues have not encountered the same skin-reaction problem.) Hives also appear to have been a more common side effect of the Moderna COVID vaccines than of the Pfizer ones, though still overall rare. 'This is truly an outlier in terms of what we've seen,' Robert Paris, a vice president at Moderna, told me. A persistent mRNA problem would be a major blow to HIV-vaccine development. When the technology emerged, it sped progress like nothing else: 'Things that originally took us about three years, we could do them in maybe three and a half months or so,' Mark Feinberg, the head of IAVI, told me. The early results for these vaccines have also been very promising, and before the hives were detected, researchers were well on their way to testing even more iterations of mRNA-based HIV vaccines, to crack the final immunization code. But for the moment, 'there's no appetite to say, 'Let's try all these different immunogens and see what happens,'' Schief, the Scripps researcher who helped design one of the vaccines, told me. Still, most of the researchers I spoke with insisted that they'll find a solution soon. The mRNA vaccines for HIV 'are not at all dead in the water,' Kublin told me. If needed, scientists could tweak the vaccine recipe, or combine the mRNA approach with another technology. The fix may be as simple as lowering the vaccine dose, a strategy that Schief and Feinberg are working to test in a new trial based in South Africa. (Moderna's COVID vaccine also contained more than three times as much mRNA as Pfizer's—and one study found that lowering the Moderna dose seemed to reduce the rate of certain skin reactions.) Successful HIV vaccination may require a balancing act—minimizing hives, while still delivering enough mRNA to rile up the immune system. But researchers may not be able to drive the rates of skin reactions down to zero: HIV is especially adept at cloaking itself from the immune system, and there may be few ways to force the body to attack the virus without producing collateral damage. And Schief and others couldn't say what rate of hives would be acceptably low. The virus is so infectious and deadly that some minor side effects may be worth the risk, if the vaccine is effective at generating the right immune response. But even a perfect, immunity-inducing shot won't do the world any good if people are afraid to take it. Still, if a rash can dissuade someone from vaccination, so, too, can misinformation, or an official's decision to stop recommending a shot. No vaccine progress will be made if the federal government doesn't want it to happen: Paris, of Moderna, told me that earlier this spring, the NIH terminated its partnership with the researchers developing these mRNA HIV vaccines, forcing the scientists to seek alternate sources of support. And yesterday, Schief and Haynes were told that their groups at Scripps and Duke would not have the opportunity to renew funding for the two HIV-vaccine-focused research consortia that their institutions lead—millions of dollars that the researchers had been told to expect they would receive, and that have been powering the development of their mRNA shots. The rationale, Haynes told me, as it was described to him, was 'due to the desire to go with currently available approaches to eliminate HIV.' Currently available approaches include community education and preventive drugs, but notably, no vaccine. (HHS did not respond to questions about these funding shifts.) 'Unless we can find a substitute source of support, this work won't go forward,' Haynes told me. If the project of HIV vaccination looks less promising right now than it has in years, that's not about science or technology, or about any single side effect: It's about politics. Article originally published at The Atlantic
Atlantic
3 days ago
- Health
- Atlantic
HIV's Most Promising Breakthrough Has Taken a Hit
Solving HIV vaccination—a puzzle that scientists have been tackling for decades without success—could be like cracking the code to a safe. The key, they now think, may be delivering a series of different shots in a specific sequence, iteratively training the body to produce a strong, broad immune response that will endure against the fast-mutating virus, ideally for a lifetime. Figuring out which ingredients to include in those shots, and in which order, is one of the trickiest immunological conundrums that researchers have ever faced. But mRNA, the fast, flexible technology that delivered two of the world's first COVID-19 vaccines in record time, is ideal for that kind of brute-force tinkering, and may be the most important tool for getting an effective HIV vaccine, Julie McElrath, the head of the Vaccine and Infectious Disease Division at Fred Hutchinson Cancer Center, in Seattle, told me. Multiple mRNA-based HIV vaccines are now in clinical trials, and early data suggest that they're prompting the type of immune responses that researchers think are essential to keeping HIV at bay—and that other vaccine candidates have struggled to elicit at all. But recently, several promising mRNA HIV-vaccine candidates have slammed up against a technical roadblock. In two small clinical trials, 7 to 18 percent of participants developed rashes and other skin reactions after getting the shots—including multiple cases of chronic hives that troubled volunteers for months after they were immunized. All of the vaccines were manufactured by Moderna. The rashes aren't life threatening; they're also readily treatable. Still, they can be debilitating and distressing. 'I've had patients who literally can't go to work,' Kimberly Blumenthal, an allergist and immunologist at Massachusetts General Hospital, who has treated people with chronic hives, told me. The rate at which they're occurring in the trials is also out of the norm, and no one has an explanation yet for the root cause. To prioritize patient safety, mRNA HIV-vaccine research in people has slowed as researchers try to suss out the cause of the hives, William Schief, the Scripps Research Institute biophysicist who helped design one of the vaccines, told me. (Schief also holds titles at Moderna and at IAVI, the nonprofit that sponsored some of the HIV-vaccine work.) At any time, a side effect this uncomfortable and prolonged would give researchers pause. But in 2025, a setback for a high-profile mRNA vaccine trial—focused on HIV, no less—could more fundamentally upend potentially lifesaving research. Secretary of Health and Human Services Robert F. Kennedy Jr., a longtime and prominent anti-vaccine activist, has repeatedly questioned the safety of mRNA COVID vaccines. He and agency leaders are already recommending that fewer Americans take vaccines and creating new hurdles to vaccine approval. Since January, the National Institutes of Health, under HHS's direction, has also terminated funding for hundreds of research projects related to HIV and vaccines. This week, the department canceled Moderna's nearly $600 million contract to develop mRNA-based flu vaccines. The HIV-vaccine studies that detected the skin reactions were also supported by NIH funding, and the researchers involved collaborated directly with NIH scientists. But those partnerships have since been terminated, and the NIH is now telling several agency-supported researchers working on HIV vaccines that the government is not planning to continue funding their work, according to several researchers I talked to. When reached for comment, Emily Hilliard, HHS's press secretary, wrote in an email, 'The reality is that mRNA technology remains under-tested, and we are not going to spend taxpayer dollars repeating the mistakes of the last administration, which concealed legitimate safety concerns from the public'—referencing the mRNA-based COVID-19 vaccines, which were rigorously tested in clinical trials, and billions of doses of which have been safely administered people around the world. Under normal circumstances, detecting rashes in a small vaccine safety study would represent a routine scientific setback, and prove that the trials served their intended purpose. But the administration's anti-vaccine stances have created a culture of fear among scientists: Several of the researchers I contacted for this story declined to comment, for fear of publicly tying their name or institution to reporting on mRNA vaccines and losing funding for their research. Science requires resources and open discussion—in torpedoing both, the Trump administration is rapidly undoing decades of progress toward ending the HIV pandemic. Researchers running the mRNA HIV-vaccine trials first took note of the rashes in 2022, shortly after studies began. After Science magazine reported about the side effect connected with the IAVI-sponsored vaccine, many scientists in the field weren't sure what to make of the finding. The trial in which it had been reported had enrolled only 60 people, and wasn't set up to rigorously look at a mysterious side effect. 'The sort of feeling was, Yeah, that's a bit weird, god knows what happened,' John Moore, an HIV researcher and vaccinologist at Cornell, told me. This April and May, though, researchers independently published two papers describing the rashes, for four separate vaccines, in two separate trials: one for the IAVI-backed vaccine and another run by the HIV Vaccine Trials Network. Now, the side effect is 'real, confirmed, generalizable,' Moore said. 'And we don't know why it's happening.' The vaccines in question target slightly different parts of the virus. But all of them rely on a Moderna-manufactured mRNA backbone, and all of them triggered, in up to about 10 percent of participants, chronic hives that emerged a few days or weeks after vaccination and in many cases lasted for months. That's a long time to be battling itching and discomfort—and it threatens to be a major deterrent to completing the series of vaccines, or potentially starting at all, Genevieve Fouda, an immunologist and HIV researcher at Cornell, told me. Delayed, chronic hives have long been known as a rare side effect of vaccines, including mRNA-based COVID vaccines. But the rates are generally very low —usually well under 1 percent, and often detectable only in massive studies of thousands of people. To see these rashes crop up in two small safety studies—one of 60 people, the other of 108—is a significant departure from precedent, scientists told me. And working out why they're appearing at such high rates will take time. Although researchers understand that the reactions are a kind of autoimmunity—in which the body inadvertently learns to attack itself—they don't know exactly why rashes occur after certain immunizations or infections, Blumenthal told me. In this case, the data so far do point to the specific combination of mRNA and HIV as a root cause. Other mRNA vaccines, including Moderna's, haven't had this issue, to anywhere near this degree; neither have other HIV vaccines that have made it into people. And several researchers pointed out to me that, so far, the only trials that they're aware of in which these hives have turned up at this frequency have involved a Moderna-manufactured product. None of the other vaccines being tested by the HIV Vaccine Trials Network, for instance, has seen rashes at that rate—including other, non-Moderna mRNA HIV vaccines, Jim Kublin, the director of HVTN, told me. (Barton Haynes, the Duke immunologist leading work on one of the non-Moderna vaccines, told me he and his colleagues have not encountered the same skin-reaction problem.) Hives also appear to have been a more common side effect of the Moderna COVID vaccines than of the Pfizer ones, though still overall rare. 'This is truly an outlier in terms of what we've seen,' Robert Paris, a vice president at Moderna, told me. A persistent mRNA problem would be a major blow to HIV-vaccine development. When the technology emerged, it sped progress like nothing else: 'Things that originally took us about three years, we could do them in maybe three and a half months or so,' Mark Feinberg, the head of IAVI, told me. The early results for these vaccines have also been very promising, and before the hives were detected, researchers were well on their way to testing even more iterations of mRNA-based HIV vaccines, to crack the final immunization code. But for the moment, 'there's no appetite to say, 'Let's try all these different immunogens and see what happens,'' Schief, the Scripps researcher who helped design one of the vaccines, told me. Still, most of the researchers I spoke with insisted that they'll find a solution soon. mRNA vaccines for HIV 'are not at all dead in the water,' Kublin told me. If needed, scientists could tweak the vaccine recipe, or combine the mRNA approach with another technology. The fix may be as simple as lowering the vaccine dose, a strategy that Schief and Feinberg are working to test a new trial based in South Africa. (Moderna's COVID vaccine also contained more than three times as much mRNA as Pfizer's—and one study found that lowering the Moderna dose seemed to reduce the rate of certain skin reactions.) Successful HIV vaccination may require a balancing act—minimizing hives, while still delivering enough mRNA to rile up the immune system. But researchers may not be able to drive the rates of skin reactions down to zero: HIV is especially adept at cloaking itself from the immune system, and there may be few ways to force the body to attack the virus without producing collateral damage. And Schief and others couldn't say what rate of hives would be acceptably low. The virus is so infectious and deadly that some minor side effects may be worth the risk, if the vaccine is effective at generating the right immune response. But even a perfect, immunity-inducing shot won't do the world any good if people are afraid to take it. Still, if a rash can dissuade someone from vaccination, so, too, can misinformation, or an official's decision to stop recommending a shot. No vaccine progress will be made if the federal government doesn't want it to happen: Paris, of Moderna, told me that earlier this spring, the NIH terminated its partnership with the researchers developing these mRNA HIV vaccines, forcing the scientists to seek alternate sources of support. And yesterday, Schief and Haynes were told that their groups at Scripps and Duke would not have the opportunity to renew funding for the two HIV-vaccine-focused research consortia that their institutions lead—millions of dollars that the researchers had been told to expect they would receive, and that have been powering the development of their mRNA shots. The rationale, Haynes told me, as it was described to him, was 'due to the desire to go with currently available approaches to eliminate HIV.' Currently available approaches include community education and preventive drugs, but notably, no vaccine. (HHS did not respond to questions about these funding shifts.) 'Unless we can find a substitute source of support, this work won't go forward,' Haynes told me. If the project of HIV vaccination looks less promising right now than it has in years, that's not about science or technology, or about any single side effect: It's about politics.
LeMonde
21-05-2025
- Health
- LeMonde
Age at first menstruation influenced by dietary quality
On average, girls experience their first menstruation between the ages of 12 and 13 – a figure that has steadily declined over the past two centuries. A study published on May 6 in the journal Human Reproduction found that the eating habits of pre-adolescent girls could influence this biological milestone, independent of body mass index (BMI) or height, which are already known to affect the age at first menstruation. "We observed [...] that a healthier diet was linked to menstrual periods starting at an older age," said Holly Harris, associate professor at Fred Hutchinson Cancer Center in Seattle who coordinated the study. "As earlier age at menarche is associated with multiple later life outcomes, including higher risk of diabetes, obesity, cardiovascular disease and breast cancer, this may be an important period for trying to reduce the risk of these chronic diseases." To conduct this research, scientists examined the eating habits of approximately 7,000 American girls aged 9 to 14 who had not yet gone through puberty when they were recruited for the prospective Growing Up Today Study (GUTS) cohort. On average, they had their first period at age 13.1, consistent with data from the general population. At enrollment and then at regular intervals during the follow-up, participants completed a questionnaire on how often they consumed 132 types of foods and drinks – ranging from never or less than once a month to once or several times a week.
Scientific American
19-05-2025
- Health
- Scientific American
How Do Doctors Treat ‘Aggressive' Prostate Cancer like Joe Biden's?
Former president Joe Biden has been diagnosed with prostate cancer, his office announced on Sunday. The 82-year-old has what is described as an 'aggressive form' of cancer that has already spread to his bones. Though his disease is serious, there are promising treatment options, and Biden could potentially live for years with the diagnosis. What is a Gleason score, and what does Biden's mean? Biden has a Gleason score—a benchmark ranking of prostate cancer severity —of 9 out of 10, his office revealed. This puts him in a category called Gleason Grade Group 5. The numbers represent the proportion of prostate cells that look malignant rather than normal under a microscope; a higher number represents a more serious, faster-spreading cancer. Biden's score suggests that a large portion of his cells look abnormal and that his cancer is relatively high-risk: 'He has the most aggressive Gleason pattern,' says oncologist Marc B. Garnick, a professor of medicine at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston. On supporting science journalism If you're enjoying this article, consider supporting our award-winning journalism by subscribing. By purchasing a subscription you are helping to ensure the future of impactful stories about the discoveries and ideas shaping our world today. In Biden's case, the cancer has already become metastatic, meaning it has moved beyond its origin point in the prostate and reached his bones. 'Unfortunately, I'd say it is a very serious condition when prostate cancer spreads outside of the prostate and goes to distant places like the bone,' says Peter Nelson, vice president of precision oncology at the Fred Hutchinson Cancer Center in Seattle and head of the prostate cancer research program at the Fred Hutch/University of Washington/Seattle Children's Cancer Consortium. 'Essentially it's not a curable cancer.' Just how serious the situation is depends on the details of the cancer's spread to the bones. 'The critical question is: How many bone metastases does he have, and what is the anatomic location of the metastases?' Garnick says. 'This is a situation where the devil is in the details.' What are Biden's treatment options? The treatment for Biden's form of cancer, called metastatic hormone sensitive prostate cancer, is likely to be what's known as doublet therapy—a combination of two drugs that target the production and activity of testosterone. This hormone is key to the situation because it fuels the growth of prostate cancer cells. Its active form, called dihydrotestosterone, interacts with a cell part called the androgen receptor. This receptor then tells the cell to proliferate and grow. Biden could possibly be prescribed a drug such as leuprolide (Lupron) or relugolix, both of which shut off the signal in the brain that tells the testicles to make testosterone. In addition, he'll probably take a second drug, such as apalutamide, enzalutamide, darolutamide or abiraterone. These agents inhibit the cells' androgen receptors to block the action of testosterone. The drugs, taken as a combination of injections and pills, can work together to shrink the prostate gland and bone lesions. If Biden responds well to the treatment, it's likely that he won't need chemotherapy. 'I would say he has a more than 90 percent chance of responding to the treatment and likely has at least several years of predicted response to that therapy,' Nelson says. 'The problem is: it's not a cure, and eventually the prostate cancer becomes resistant to that type of therapy.' This treatment can also lead to side effects such as loss of muscle mass and strength, deterioration of bone health and metabolic effects. 'Testosterone is a very important hormone for men, so when you suppress it, you can have these side effects,' Nelson adds. Still, Biden's prospects are much more promising than they would have been even a decade ago, thanks to advances in treatment research. 'In the past, the median duration of survival of someone presenting with bone metastases [from] prostate cancer was two and a half years,' Garnick says. 'We now have patients living five, 10 and 15 years because of the new modalities available.' What else can doctors do? In addition to prescribing hormone therapy, Biden's doctors will likely test the former president's tumor to see if he has any mutations in certain cancer genes that would suggest specialized treatments were called for. For instance, some prostate cancers end up being genetically linked to other cancers such as breast and ovarian cancer, through the presence of the genes BRCA1 or BRCA2. 'Those are genomic abnormalities that can exist that can increase the likelihood of prostate cancer,' Garnick says. If that's the case for Biden, he could receive specific drugs, such as poly (ADP-ribose) polymerase, or PARP, inhibitors, that target the type of prostate cancer he has. How bad is prostate cancer in general? Prostate cancer is among the most common forms of cancer in older men. The American Cancer Society estimates there will be about 313,780 new diagnoses of the condition and 35,770 deaths attributed to it in the U.S. in 2025. 'It's not surprising that a man in his 60s to 80s would have a diagnosis like this—[prostate cancer] affects one in eight men in the U.S.,' Nelson says. 'The ironic part is: Biden did so much to emphasize the importance of biomedical research in addressing our cancer burden. But he should benefit from that investment in making improvements in understanding cancer and how we can better develop therapies for it.' Biden's successor, President Donald Trump, has shifted course since beginning his second term. His administration has made significant cuts to funding for cancer research and has eliminated thousands of jobs in the Department of Health and Human Services, including hundreds of employees at the National Institutes of Health, the world's largest funder of cancer research. 'My plea is not to turn our back on the tremendous progress that's being made,' Nelson says. 'We still have a long way to go because we're not curing advanced prostate cancer, even though we're extending men's lives. We still need major investments in biomedical research to develop true cures.'
Medscape
16-05-2025
- Health
- Medscape
Colorectal Cancer Screening Choices: Is Compliance Key?
SAN DIEGO — In the ever-expanding options for colorectal cancer (CRC) screening, blood tests using precision medicine are becoming more advanced and convenient than ever; however, caveats abound, and when it comes to potentially life-saving screening measures, picking the optimal screening tool is critical. Regarding tests, 'perfect is not possible,' said William M. Grady, MD, of the Fred Hutchinson Cancer Center, University of Washington School of Medicine, in Seattle, who took part in a debate on the pros and cons of key screening options at Digestive Disease Week (DDW) 2025. 'We have to remember that that's the reality of colorectal cancer screening, and we need to meet our patients where they live,' said Grady, who argued on behalf of blood-based tests, including cell-free (cf) DNA (Shield, Guardant Health) and cfDNA plus protein biomarkers (Freenome). A big point in their favor is their convenience and higher patient compliance — better tests that don't get done do not work, he stressed. He cited data that showed suboptimal compliance rates with standard colonoscopy: Rates range from about 70% among non-Hispanic White individuals to 67% among Black individuals, 51% among Hispanic individuals, and the low rate of just 26% among patients aged between 45 and 50 years. With troubling increases in CRC incidence among younger patients, 'that's a group we're particularly concerned about,' Grady said. Meanwhile, studies show compliance rates with blood-based tests are ≥ 80%, with similar rates seen among those racial and ethnic groups, with lower rates for conventional colonoscopy, he noted. Importantly, in terms of performance in detecting CRC, blood-based tests stand up to other modalities, as demonstrated in a real-world study conducted by Grady and his colleagues showing a sensitivity of 83% for the cfDNA test, 74% for the fecal immunochemical test (FIT) stool test, and 92% for a multitarget stool DNA test compared with 95% for colonoscopy. 'What we can see is that the sensitivity of blood-based tests looks favorable and comparable to other tests,' he said. Among the four options, cfDNA had a highest patient adherence rate (85%-86%) compared with colonoscopy (28%-42%), FIT (43%-65%), and multitarget stool DNA (48%-60%). 'The bottom line is that these tests decrease CRC mortality and incidence, and we know there's a potential to improve compliance with colorectal cancer screening if we offer blood-based tests for average-risk people who refuse colonoscopy,' Grady said. Blood-Based Tests: Caveats, Harms? Arguing against blood-based tests in the debate, Robert E. Schoen, MD, MPH, professor of medicine and epidemiology, Division of Gastroenterology, Hepatology and Nutrition, at the University of Pittsburgh, Pittsburgh, checked off some of the key caveats. While the overall sensitivity of blood-based tests may look favorable, these tests don't detect early CRC well,' said Schoen. The sensitivity rates for stage 1 CRC are 64.7% with Guardant Health and 57.1% with Freenome. Furthermore, their rates of detecting advanced adenomas are very low; the rate with Guardant Health is only about 13%, and with Freenome is even lower at 12.5%, he reported. These rates are 'similar to the false positive rate, with poor discrimination and accuracy for advanced adenomas,' Schoen said. 'Without substantial detection of advanced adenomas, blood-based testing is inferior [to other options].' Importantly, the low advanced adenoma rate translates to a lack of CRC prevention, which is key to reducing CRC mortality, he noted. Essential to success with blood-based biopsies, as well as with stool tests, is the need for a follow-up colonoscopy if results are positive, but Schoen pointed out that this may or may not happen. He cited research from FIT data showing that among 33,000 patients with abnormal stool tests, the rate of follow-up colonoscopy within a year, despite the concerning results, was a dismal 56%. 'We have a long way to go to make sure that people who get positive noninvasive tests get followed up,' he said. In terms of the argument that blood-based screening is better than no screening at all, Schoen cited recent research that projected reductions in the risk for CRC incidence and mortality among 100,000 patients with each of the screening modalities. Starting with standard colonoscopy performed every 10 years, the reductions in incidence and mortality would be 79% and 81%, respectively, followed by annual FIT, at 72% and 76%; multitarget DNA every 3 years, at 68% and 73%; and cfDNA (Shield), at 45% and 55%. Based on those rates, if patients originally opting for FIT were to shift to blood-based tests, 'the rate of CRC deaths would increase,' Schoen noted. The findings underscore that 'blood testing is unfavorable as a 'substitution test,'' he added. 'In fact, widespread adoption of blood testing could increase CRC morbidity.' 'Is it better than nothing?' he asked. 'Yes, but only if performance of a colonoscopy after a positive test is accomplished.' What About FIT? Arguing that stool-based testing, or FIT, is the ideal choice as a first-line CRC test Jill Tinmouth, MD, PhD, a professor at the University of Toronto, Ontario, Canada, pointed to its prominent role in organized screening programs, including regions where resources may limit the widespread utilization of routine first-line colonoscopy screening. In addition, it narrows colonoscopies to those that are already prescreened as being at risk. Data from one such program, reported by Kaiser Permanente of Northern California, showed that participation in CRC screening doubled from 40% to 80% over 10 years after initiating FIT screening. CRC mortality over the same period decreased by 50% from baseline, and incidence fell by as much as 75%. In follow-up colonoscopies, Tinmouth noted that collective research from studies reflecting real-world participation and adherence to FIT in populations in the United Kingdom, the Netherlands, Taiwan, and California show follow-up colonoscopy rates of 88%, 85%, 70%, and 78%, respectively. Meanwhile, a recent large comparison of biennial FIT (n = 26,719) vs one-time colonoscopy (n = 26,332) screening, the first study to directly compare the two, showed noninferiority, with nearly identical rates of CRC mortality at 10 years (0.22% colonoscopy vs 0.24% FIT) as well as CRC incidence (1.13% vs 1.22%, respectively). 'This study shows that in the context of organized screening, the benefits of FIT are the same as colonoscopy in the most important outcome of CRC — mortality,' Tinmouth said. Furthermore, as noted with blood-based screening, the higher participation with FIT shows a much more even racial/ethnic participation than that observed with colonoscopy. 'FIT has clear and compelling advantages over colonoscopy,' she said. As well as better compliance among all groups, 'it is less costly and also better for the environment [by using fewer resources],' she added. Colonoscopy: 'Best for First-Line Screening' Making the case that standard colonoscopy should in fact be the first-line test, Swati G. Patel, MD, director of the Gastrointestinal Cancer Risk and Prevention Center at the University of Colorado Anschutz Medical Center, Aurora, Colorado, emphasized the robust, large population studies showing its benefits. Among them is a landmark national policy study showing a significant reduction in CRC incidence and mortality associated with first-line colonoscopy and adenoma removal. A multitude of other studies in different settings have also shown similar benefits across large populations, Patel added. In terms of its key advantages over FIT, the once-a-decade screening requirement for average-risk patients is seen as highly favorable by many, as evidenced in clinical trial data showing that individuals highly value tests that are accurate and do not need to be completed frequently, she said. Research from various other trials of organized screening programs further showed patients crossing over from FIT to colonoscopy, including one study of more than 3500 patients comparing colonoscopy and FIT, which had approximately 40% adherence with FIT vs nearly 90% with colonoscopy. Notably, as many as 25% of the patients in the FIT arm in that study crossed over to colonoscopy, presumably due to preference for the once-a-decade regimen, Patel said. 'Colonoscopy had a substantial and impressive long-term protective benefit both in terms of developing colon cancer and dying from colon cancer,' she said. Regarding the head-to-head FIT and colonoscopy comparison that Tinmouth described, Patel noted that a supplemental table in the study's appendix of patients who completed screening does reveal increasing separation between the two approaches, favoring colonoscopy, in terms of longer-term CRC incidence and mortality. The collective findings underscore that 'colonoscopy as a standalone test is uniquely cost-effective,' in the face of costs related to colon cancer treatment. Instead of relying on biennial tests with FIT, colonoscopy allows clinicians to immediately risk-stratify those individuals who can benefit from closer surveillance and really relax surveillance for those who are determined to be low risk, she said.
