Screening Foes Strike Back

Opponents of population-based cancer screening aren’t going away anytime soon. Just weeks after publication of a landmark study claiming that cancer screening has saved $7T over 25 years, screening foes published a counterattack in JAMA Internal Medicine casting doubt on whether screening has any value at all. 

Population-based cancer screening has been controversial since the first programs were launched decades ago. 

  • A vocal minority of skeptics continues to raise concerns about screening, despite the fact that mortality rates have dropped and survival rates have increased for the four cancers targeted by population screening.

This week’s JAMA Internal Medicine featured a series of articles that cast doubt on screening. In the main study, researchers performed a meta-analysis of 18 randomized clinical trials (RCTs) covering 2.1M people for six major screening tests, including mammography, CT lung cancer screening, and colon and PSA tests. 

  • The authors, led by Norwegian gastroenterologist Michael Bretthauer, MD, PhD, concluded that only flexible sigmoidoscopy for colon cancer produced a gain in lifetimes. They conclude that RCTs to date haven’t included enough patients who were followed over enough years to show screening has an effect on all-cause mortality.

But a deeper dive into the study produces interesting revelations. For CT lung cancer screening, Bretthauer et al didn’t include the landmark National Lung Screening Trial, an RCT that showed a 20% mortality reduction from screening.

  • With respect to breast imaging, the researchers only included three studies, even though there have been eight major mammography RCTs performed. And one of the three included was the controversial Canadian National Breast Screening Study, originally conducted in the 1980s.

When it comes to colon screening, Bretthauer included his own controversial 2022 NordICC study in his meta-analysis. 

  • The NordICC study found that if a person is invited to colon screening but doesn’t follow through, they don’t experience a mortality benefit. But those who actually got colon screening saw a 50% mortality reduction.  

Other articles in this week’s JAMA Internal Medicine series were penned by researchers well known for their opposition to population-based screening, including Gilbert Welch, MD, and Rita Redberg, MD.

The Takeaway

There’s an old saying in statistics: “If you torture the data long enough, it will confess to anything.” Among major academic journals, JAMA Internal Medicine – which Redberg guided for 14 years as editor until she stepped down in June – has consistently been the most hostile toward screening and new medical technology.

In the end, the arguments being made by screening’s foes would carry more weight if they were coming from researchers and journals that haven’t already demonstrated a longstanding, ingrained bias against population-based cancer screening.

Value of Cancer Screening

A new study claims that medical screening for diseases like breast and cervical cancer has saved lives and generated value of at least $7.5T (yes, trillion) over the last 25 years. The findings, published in BMC Health Services Research, are a stunning rebuke to critics of screening exams.

While the vast majority of doctors and public health officials support evidence-based screening, a vocal minority of skeptics continues to raise questions about screening’s efficacy. These critics emphasize the “harms” of screening, such as overdiagnosis and patient anxiety – an accusation often levied against breast screening. 

Screening’s critics also target the downstream costs of medical tests intended to confirm suspicious findings. They argue that a single screen-detected finding can lead to a cascade of additional healthcare spending that drives up medical costs.

But the new study offers a counter-argument, putting a dollar figure on how much screening exams have saved by detecting disease earlier, when it can be treated more effectively. 

The research focused on the four main cancer screening tests – breast, cervical, colon, and lung cancer – analyzing the impact of preventive screening on life-years saved and its economic impact from 1996 to 2020, finding …

  • Americans enjoyed at least 12M more years of life thanks to cancer screening
  • The economic value of these life-years added up to at least $7.5T
  • If everyone who qualified for screening exams got them, it would save at least another 3.3M life-years and $1.7T in economic impact
  • Cervical cancer screening had by far the biggest economic impact ($5.2T-$5.7T), followed by breast ($0.8T-$1.9T), colorectal ($0.4T-$1T), and finally lung ($40B). 

Lung cancer’s paltry value was due to a small eligible population and low screening adherence rates. This finding is underscored by a new article in STAT that ponders why CT lung cancer screening rates are so low, with one observer calling it the “redheaded stepchild” of screening tests.  

The Takeaway
Screening skeptics have been taking it on the chin lately (witness the USPSTF’s U-turn on mammography for younger women) and the new findings will be another blow. We may continue to see a dribble of papers on the “harms” of overdiagnosis, but the momentum is definitely shifting in screening’s favor – to the benefit of patients.

Radiation and Cancer Risk

New research on the cancer risk of low-dose ionizing radiation could have disturbing implications for those who are exposed to radiation on the job – including medical professionals. In a new study in BMJ, researchers found that nuclear workers exposed to occupational levels of radiation had a cancer mortality risk that was higher than previously estimated.

The link between low-dose radiation and cancer has long been controversial. Most studies on the radiation-cancer connection are based on Japanese atomic bomb survivors, many of whom were exposed to far higher levels of radiation than most people receive over their lifetimes – even those who work with ionizing radiation. 

The question is whether that data can be extrapolated to people exposed to much lower levels of radiation, such as nuclear workers, medical professionals, or even patients. To that end, researchers in the International Nuclear Workers Study (INWORKS) have been tracking low-dose radiation exposure and its connection to mortality in nearly 310k people in France, the UK, and the US who worked in the nuclear industry from 1944 to 2016.

INWORKS researchers previously published studies showing low-dose radiation exposure to be carcinogenic, but the new findings in BMJ offer an even stronger link. For the study, researchers tracked radiation exposure based on dosimetry badges worn by the workers and then rates of cancer mortality, and calculated rates of death from solid cancer based on their exposure levels, finding: 

  • Mortality risk was higher for solid cancers, at 52% per 1 Gy of exposure
  • Individuals who received the occupational radiation limit of 20 mSv per year would have a 5.2% increased solid cancer mortality rate over five years
  • There was a linear association between low-dose radiation exposure and cancer mortality, meaning that cancer mortality risk was also found at lower levels of exposure 
  • The dose-response association seen the study was even higher than in studies of atomic bomb survivors (52% vs. 32%)

The Takeaway

Even though the INWORKS study was conducted on nuclear workers rather than medical professionals, the findings could have implications for those who might be exposed to medical radiation, such as interventional radiologists and radiologic technologists. The study will undoubtedly be examined by radiation protection organizations and government regulators; the question is whether it leads to any changes in rules on occupational radiation exposure.

Theranostics Grabs SNMMI Spotlight

The emerging field of theranostics – in which two radiopharmaceuticals work in tandem for diagnostic and therapeutic purposes – is one of the most exciting new areas of medicine. Nowhere is this more evident than at this week’s SNMMI 2023 meeting in Chicago

Theranostics involves the use first of a highly targeted diagnostic radiotracer to detect pathology with a technology like PET, then sending in another tracer to deliver a stronger radioactive payload to the site of disease – almost the definition of precision medicine. Some estimates are that theranostics could soon develop into a market worth $30B.

In addition to talks on theranostics, SNMMI 2023 highlights so far have included presentations covering the following:

  • An ultra-high-resolution brain PET scanner that can visualize and quantify nuclei in the brainstem for the first time, opening up new inquiries into neurological disorders like Alzheimer’s disease
  • The discovery of the optimal tracer kinetic model for quantifying myocardial uptake of 18F-flutemetamol in patients with transthyretin (ATTR) cardiac amyloidosis, a buildup of amyloid plaque in the heart
  • A technique called augmented whole-body scanning via magnifying PET (AWSM-PET) that uses two high-resolution add-on detectors as an “outsert” to improve image resolution and reduce noise
  • Imaging of rheumatoid arthritis with 68Ga-FAPI PET/CT, which showed a greater number and degree of affected joints than FDG-PET/CT
  • A PET radiotracer called 18F-Cholestify has the potential to improve neuroimaging by visualizing metabolic cholesterol degradation in the brain.

The commercial side of SNMMI 2023 is active as well. Siemens Healthineers, GE HealthCare, and United Imaging Healthcare are launching new hybrid scanners, and other vendor news includes the following: 

  • Blue Earth Diagnostics is touting its recent shipments of Posluma, a PET radiotracer targeting PSMA in prostate cancer patients
  • GE HealthCare is migrating AIR technologies found on its MRI scanners to its new Signa PET/MRI AIR system (see below) 
  • Isotopia is discussing its plans for a US radioisotope manufacturing facility
  • Lantheus researchers are presenting talks on AI-enabled PSMA-PET reporting using its Pylarify AI software
  • Mediso received FDA clearance for its InterView Fusion and InterView XP multimodality image processing and reporting software
  • Siemens Healthineers has launched a new PET/CT scanner, Biograph Vision.X, sporting a 20% improvement in time of flight (see below)
  • Subtle Medical is demonstrating its SubtlePET solution, which uses AI to remove noise for low-count PET images, enabling up to 75% faster PET scans
  • Telix Pharmaceuticals is highlighting clinical results of several agents: the Illuccix gallium-based prostate cancer imaging agent; ProstACT lutetium-based antibody-directed prostate cancer therapy; and TLX250-CDx, a zircon-89-based tracer for diagnosing clear cell renal cell carcinoma.
  • United Imaging Healthcare is launching uMI Panorama, a new wide-bore PET/CT scanner (see below).  

The Takeaway

This week’s proceedings in Chicago illustrate the new energy that theranostics is bringing to nuclear medicine and molecular imaging, one of radiology’s most venerable modalities. Stay tuned for the announcement of SNMMI’s Henry N. Wagner, Jr. Image of the Year award, always a conference highlight.  

Is There Hope for CT Lung Screening?

New data on CT lung cancer screening rates offer a good news/bad news story. The bad news is that only 21.2% of eligible individuals in four US states got screened, far lower than other exams like breast or colon screening.

The good news is that, as low as the rate was relative to other tests, 21.2% is still much higher than previous estimates. And the study itself found that the rate of CT lung screening has risen over 8 percentage points in 3 years. 

Compliance has lagged with CT lung screening ever since Medicare approved payments for the exam in 2015. A recent JACR study found that screening rates were low for eligible people for both Medicare and commercial insurance (3.4% and 1.8%).

Why is screening compliance so low? Explanations have ranged from fatalism among people who smoke to reimbursement requirements for “shared decision-making,” which unlike other screening exams require patients and providers to discuss CT lung screening before an exam can be ordered.

In this new study in JAMA Network Open, researchers examined screening rates in four states – Maine, Michigan, New Jersey, and Rhode Island – from January 2021 to January 2022. The study drew data from the National Health Interview Survey and weighted it to reflect the population of the US of individuals eligible for CT lung screening, based on the criteria of ages 55-79, 30-pack-year smoking history, and having smoked or quit within the past 15 years. Major findings included: 

  • The rate for CT lung cancer screening was 21.2%, up from 12.8% in 2019
  • People with a primary health professional (PHP) were nearly 6 times more likely to get screened (OR=5.62)
  • The age sweet spot for screening was 65-77, with lower odds for those 55-64 (OR=0.43) and 78-79 (OR=0.17)
  • Rates varied between states, with Rhode Island having the highest rate (30.3%) and New Jersey the lowest (17.5%).
  • Of those who got screened, 27.7% were in poor health and 4.5% had no health insurance

The Takeaway

The findings offer some hope for CT lung screening, as the compliance rate is among the highest we’ve seen among recent research studies. On the other hand, many of those screened were in such poor health they might not benefit from treatment. The high rate of compliance in people with PHPs indicates that promoting screening with these providers could pay off, especially given the requirement for shared decision-making. 

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