Bladder cancer remains a major clinical challenge as it is one of the most common and deadliest urological cancers with a high recurrence rate. Yet its diagnosis still relies heavily on invasive and costly procedures like cystoscopy (inserting a thin, tube-like instrument through the urethra) or cytology, a noninvasive test that can identify tumor cells shed in urine but has limited sensitivity.

Investigators of the current study were motivated to find a simpler, more comfortable way to detect and monitor bladder cancer. They analyzed urine samples from 156 patients with bladder cancer and 79 matched controls and using real-time PCR, measured the concentration and integrity (long-short size distribution) of cfDNA fragments from five genes (ACTB, AR, MYC, BCAS1, and STOX1).

“Our most significant finding was that the small fragment of the MYC gene may represent a valuable tool to diagnose bladder cancer, as it exhibited excellent specificity (97%) and predictive value (88%) for identifying muscle-invasive bladder cancer,“ explains lead investigator Pilar Medina, PhD, Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain.

MYC produces a transcription factor crucial for regulating cell growth, proliferation, and metabolism.

Additionally, researchers found that the ratio of large to small fragments of the housekeeping gene ACTB and the small fragment of the AR gene increased with disease severity, suggesting these could be reliable staging biomarkers. The integrity of these genes may be useful to identify bladder cancer relapse.

Lead author Raquel Herranz, MS, Haemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Health Research Institute Hospital La Fe (IIS La Fe), Valencia, Spain, notes, “With growing interest in liquid biopsies and personalized medicine, our study offers a timely and practical alternative to invasive diagnostics. This study is one of the first to comprehensively evaluate urine cfDNA fragmentation and integrity across most bladder cancer stages, bringing us closer to a future in which bladder cancer can be diagnosed and monitored through a simple urine test, improving patient comfort and care.”

Dr. Medina concludes, “Our findings show that urine can tell us much more than we thought; it holds the potential to transform how we detect and manage bladder cancer.”

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Most patients encountered the misinformation — defined as unproven or disproven cancer treatments and myths or misconceptions — even when they weren’t looking for it.

The findings have major implications for cancer treatment decision-making. Specifically, doctors should assume the patient has seen or heard misinformation.

“Clinicians should assume when their patients are coming to them for a treatment discussion that they have been exposed to different types of information about cancer treatment, whether or not they went online and looked it up themselves,” said senior author Carma Bylund, Ph.D., a professor and associate chair of education in the UF Department of Health Outcomes and Biomedical Informatics. “One way or another, people are being exposed to a lot of misinformation.”

Working with oncologists, Bylund and study first author Naomi Parker, Ph.D., an assistant scientist in the UF Department of Health Outcomes and Biomedical Informatics, are piloting an “information prescription” to steer patients to sources of evidence-based information like the American Cancer Society. The study paves the way for other similar strategies.

Most notably, the study found the most common way patients were exposed to misinformation was second hand.

“Your algorithms pick up on your diagnosis, your friends and family pick up on it, and then you’re on Facebook and you become exposed to this media,” Parker said. “You’re not necessarily seeking out if vitamin C may be a cure for cancer, but you start being fed that content.”

And no, vitamin C does not cure cancer.

Health misinformation can prevent people from getting treatment that has evidence behind it, negatively affect relationships between patients and physicians, and increase the risk of death, research has shown. People with cancer are particularly vulnerable to misinformation because of the anxiety and fear that comes with a serious diagnosis, not to mention the overwhelming amount of new information they have to suddenly absorb.

While past research has studied misinformation by going directly to the source — for instance, studying what percentage of content on a platform like TikTok is nonsense — little research has looked at its prevalence or how it affects people.

The team first developed a way to identify the percentage of cancer patients exposed to misinformation. UF researchers collaborated with Skyler Johnson, M.D., at Huntsman Cancer Institute, an internationally known researcher in the field.

The survey questions were based on five categories of unproven or disproven cancer treatments — vitamins and minerals, herbs and supplements, special diets, mind-body interventions and miscellaneous treatments — and treatment misconceptions. The myths and misconceptions were adapted from National Cancer Institute materials and included statements like “Will eating sugar make my cancer worse?”

The team surveyed 110 UF Health patients diagnosed with prostate, breast, colorectal or lung cancer within the past six months, a time when patients typically make initial treatment decisions.

Most had heard of a potential cancer treatment beyond the standard of care, and most reported they had heard of at least one myth or misconception. The most common sources were close friends or family and websites, distant friends/associates or relatives, social media and news media.

The findings mark a shift in misinformation research, with major implications for the doctor-patient relationship, said Bylund, a member of the Cancer Control and Population Sciences research program at the UF Health Cancer Center.

“I still think media and the internet are the source and why misinformation can spread so rapidly, but it might come to a cancer patient interpersonally, from family or friends,” she said.

Most patients rarely discussed the potential cancer treatments they had heard about with an oncologist, the study also found.

Next, the researchers plan to survey a wider pool of patients, then study the outcomes of interventions designed to decrease misinformation exposure, like the information prescription.

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The authors of the new JAMA Network Open paper say their findings show how vital early detection of cancer can be, while also highlighting the importance of considering unintended side effects in any future pandemic planning.

Co-lead author Dr Kaustubh Adhikari (UCL Genetics, Evolution & Environment and The Open University) said: “When lockdowns were introduced as a much-needed measure to stop the spread of Covid-19, there were extensive unintended consequences. Many screenings were cancelled and medical treatments were delayed.

“As many people missed appointments to detect or treat skin cancer, their cancer progressed to a later stage, which resulted in more expensive care and a greater risk that the treatment would not be successful.

“It’s alarming that for just one disease, there were many years of life lost, a lower quality of life for many thousands of people, and billions of pounds of economic impact – this may be just the tip of the iceberg of the consequences of delayed diagnosis and treatment due to lockdowns. While the lockdowns did save many lives by mitigating the toll of Covid-19 itself, it is important that we learn from the experience to ensure that if another pandemic arises, we can effectively balance different healthcare priorities.”

The team of researchers, from the UK, Switzerland, Germany, US, Italy, Australia and Hungary, were investigating the health economic consequences of delays in diagnosing melanoma, a common type of skin cancer and one of the 10 most common cancers in Europe. The analysis was based on information from 50,072 patients of two cancer treatment centres in Switzerland and Italy, supported by further data from the UK and Belgium.

The researchers estimated how many people’s cancer would have progressed from one stage to the next due to delays in beginning or continuing treatment, as both screening services and treatments were disrupted in 2020 and 2021 due to lockdown restrictions, staff shortages, and fear of infection. They estimated that for roughly 17% of people with melanoma, their cancer would have progressed to a higher stage in 2020-2021, due to delays in diagnosis or treatment of two to three months or longer.

The research team then estimated the additional medical costs, as treating later-stage cancer is more expensive and comes with a lower chance of success. These cost estimates included both the direct costs to healthcare providers (such as the NHS), as well as the broader impacts such as the loss of productivity (indirect costs) due to disability and years of life lost.

The researchers estimated that delays to melanoma diagnoses contributed to 111,464 years of life lost across 31 countries in Europe, with a total economic cost of £6.1bn (€7.1bn or $7.7bn USD). Most of the costs (94.5%) were indirect costs such as loss of productivity.

Co-lead author Dr Elisabeth Roider (University Hospital of Basel) said: “Our findings show that preventative healthcare always needs to be a top priority, both in normal times and in times of crisis; any plans for potential future pandemics need to consider unintended side effects on a wide range of health conditions and plan holistically.

“Delays to diagnosis and treatment can be devastating to people affected by cancer, so getting prompt evaluation and treatment is vital for people concerned about their health, while screening programmes need to be treated as a priority by healthcare system leaders.”

The research was supported by the Research Foundation of the University of Basel, the ProPatient Foundation, University Basel, the Goldschmidt Jacobson Foundation, and the Swiss National Science Foundation.

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