Norwegian researchers reviewed large clinical trials of six common cancer screenings, including clinical laboratory tests, but some experts question the findings
Cancer screenings are a critical tool for diagnosis and treatment. But how much do they actually extend the lives of patients? According to researchers at the University of Oslo in Norway, not by much. They recently conducted a review and meta-analysis of 18 long-term clinical trials, five of the six most commonly used types of cancer screening—including two clinical laboratory tests—and found that with few exceptions, the screenings did not significantly extend lifespans.
The 18 long-term clinical trials included in the study were randomized trials that collectively included a total of 2.1 million participants. Median follow-up periods of 10 to 15 years were used to gauge estimated lifetime gain and mortality.
“The findings of this meta-analysis suggest that current evidence does not substantiate the claim that common cancer screening tests save lives by extending lifetime, except possibly for colorectal cancer screening with sigmoidoscopy,” the researchers wrote in their published paper.
The researchers noted, however, that their analysis does not suggest all screenings should be abandoned. They also acknowledged that some lives are saved by screenings.
“Without screening, these patients may have died of cancer because it would have been detected at a later, incurable stage,” the scientists wrote, MedPage Today reported. “Thus, these patients experience a gain in lifetime.”
Still, some independent experts questioned the validity of the findings.
Gastroenterologist Michael Bretthauer, MD, PhD (above), a professor at the University of Oslo in Norway led the research into cancer screenings. In their JAMA Internal Medicine paper, he and his team wrote, “The findings of this meta-analysis suggest that colorectal cancer screening with sigmoidoscopy may extend life by approximately three months; lifetime gain for other screening tests appears to be unlikely or uncertain.” How their findings might affect clinical laboratory and anatomic pathology screening for cancer remains to be seen. (Photo copyright: University of Oslo.)
Pros and Cons of Cancer Screening
The clinical trials, according to MedPage Today and Oncology Nursing News covered the following tests:
Mammography screening for breast cancer (two trials).
As reported in these trials, “colorectal cancer screening with sigmoidoscopy prolonged lifetime by 110 days, while fecal testing and mammography screening did not prolong life,” the researchers wrote. “An extension of 37 days was noted for prostate cancer screening with prostate-specific antigen testing and 107 days with lung cancer screening using computed tomography, but estimates are uncertain.”
The American Cancer Society (ACS) recommends certain types of screening tests to detect cancers and pre-cancers before they can spread, thus improving the chances for survival.
The ACS advises screenings for breast cancer, colorectal cancer, and cervical cancer regardless of whether the individual is considered high risk. Lung cancer screenings are advised for people with a history of smoking. Men who are 45 to 50 or older should discuss the pros and cons of prostate cancer screening with their healthcare providers, the ACS states.
A CNN report about the University of Oslo study noted that the benefits and drawbacks of cancer screening have long been well known to doctors.
“Some positive screening results are false positives, which can lead to unnecessary anxiety as well as additional screening that can be expensive,” CNN reported. “Tests can also give a false negative and thus a false sense of security. Sometimes too, treatment can be unnecessary, resulting in a net harm rather than a net benefit, studies show.”
In their JAMA paper, the University of Oslo researchers wrote, “The critical question is whether the benefits for the few are sufficiently large to warrant the associated harms for many. It is entirely possible that multicancer detection blood tests do save lives and warrant the attendant costs and harms. But we will never know unless we ask,” CNN reported.
Hidden Impact on Cancer Mortality
ACS Chief Scientific Officer William Dahut, MD, told CNN that screenings may have an impact on cancer mortality in ways that might not be apparent from randomized trials. He noted that there’s been a decline in deaths from cervical cancer and prostate cancer since doctors began advising routine testing.
“Cancer screening was never really designed to increase longevity,” Dahut said. “Screenings are really designed to decrease premature deaths from cancer.” For example, “if a person’s life expectancy at birth was 80, a cancer screening may prevent their premature death at 65, but it wouldn’t necessarily mean they’d live to be 90 instead of the predicted 80,” CNN reported.
Dahut told CNN that fully assessing the impact of cancer screenings on life expectancy would require a clinical trial larger than those in the new study, and one that followed patients “for a very long time.”
“From its title, one would have expected this paper to be based on analysis of individual lifetime data. However, it is not,” he wrote in a compilation of expert commentary from the UK’s Science Media Center. “The paper’s conclusions are based on arithmetic manipulation of relative rates of all-cause mortality in some of the screening trials. It is therefore difficult to give credence to the claim that screening largely does not extend expected lifetime.”
He also questioned the inclusion of one particular trial in the University of Oslo study—the Canadian National Breast Screening Study—“as there is now public domain evidence of subversion of the randomization in this trial,” he added.
Another expert, Leigh Jackson, PhD, of the University of Exeter in the UK, described the University of Oslo study as “methodologically sound with some limitations which the authors clearly state.”
But he observed that “the focus on 2.1 million individuals is slightly misleading. The study considered many different screening tests and 2.1 million was indeed the total number of included patients, however, no calculation included that many people.”
Jackson also characterized the length of follow-up as a limitation. “This may have limited the amount of data included and also not considering longer follow-up may tend to underestimate the effects of screening,” he said.
This published study—along with the range of credible criticisms offered by other scientists—demonstrates how analysis of huge volumes of data is making it possible to tease out useful new insights. Clinical laboratory managers and pathologists can expect to see other examples of researchers assembling large quantities of data across different areas of medicine. This huge pools of data will be analyzed to determine the effectiveness of many medical procedures that have been performed for years with a belief that they are helpful.
Only 3% of histopathology departments that responded to the Royal College of Pathologists’ workforce census reported enough staff to meet clinical demand
There is a chronic shortage of histopathologists in the United Kingdom (UK) and it is being blamed for cancer treatment waiting times that now reach the worst-ever levels, as National Health Service (NHS) training initiatives and other steps fail to keep pace with growing demand for diagnostic services.
For US anatomic pathologists and clinical laboratory managers, headlines from the UK reveal the impact a shortage of trained histopathologists (UK’s version of anatomic pathologists) and support technical staff can have on patient care when longer wait times for pathology support and diagnosis become the norm.
Royal College of Pathologists Report
The extent of the UK-wide histopathology staff shortages was highlighted in a recently released 2017 workforce census by the Royal College of Pathologists (RCPath). Of the 103 histopathology departments that responded to a survey, only 3% said they had enough staff to meet the current clinical demand! And 45% of departments had to outsource work, while half of the departments were forced to use more expensive temporary workers.
“The cost of staff shortages across histopathology departments is high for both patients and for our health services,” Jo Martin, PhD, President of the Royal College of Pathologists, noted in a statement announcing the survey results. “For patients, it means worrying delays in diagnosis and treatment. For NHS hospitals, it means spending more resources on [temporary] doctors to fill staffing gaps, or outsourcing services. We estimate this cost [to be] £27 million ($35.2 million) each year across the UK health service—money that could be better invested in staff and new diagnostic equipment.”
Royal College of Pathologists President Jo Martin, PhD, is calling on the National Health Service to take additional steps to increase the number of pathologists working in the United Kingdom, including more funded training places. That’s following the release of a Royal College of Pathologists workforce survey, which reported only 3% of histopathology departments in the UK have enough staff to meet clinical demand. (Photo copyright: Twitter.)
According to iNews, NHS England recorded its worst cancer treatment waiting times on record in July 2018, with more than 3,000 people waiting longer than two months for cancer treatment to begin. NHS’ target is for 85% of patients to begin cancer treatment within 62 days of being referred by their general practitioner.
Anatomic pathologists in the United States should consider how the UK’s average delay in starting cancer treatment affects patients in that country. It is a metric that patients in the US would not tolerate. However, in the UK’s single payer system, the government’s National Health Service sets the budgets for training new physicians, including histopathologists. For many years, the pathology profession in the UK has regularly advocated for increasing the number of histopathologists trained each year by the medical schools in that country.
In July, the number of patients waiting for treatment longer than 60 days fell to 78.2%, the 31st month in a row the target was breached, iNews reported.
“We know that histopathology consultant shortages contribute to at least part of that problem,” Martin told iNews.
The RCPath report highlights the intense pressures on histopathologists—most of whom working in understaffed laboratories—face from increased workloads, as new NHS cancer screening initiatives, an aging population, and a shift toward precision medicine result in a rising number of cases being referred to labs.
“Demand for pathology services has grown significantly in recent years and continues to grow,” Martin noted in the RCPath statement. “The pathology workforce has not increased in line with this demand. If this trend continues unchecked, clinical services could be in jeopardy. Making sure pathology services can cope with current and future demand is essential if we are to ensure early diagnosis and improve outcomes for patients.”
Lack/Loss of Trained Histopathologists an Ongoing Problem
In its most recent workforce report, The Royal College of Pathologists is reiterating its call for:
Increased funding for training;
Better information technology (IT) for day-to-day work;
Capital investment to implement digital pathology more widely; and,
Development of advanced clinical practitioner apprenticeships to help more biomedical scientists become independent practitioners who would work alongside medically-qualified histopathologists.
Long-term, the organization is calling for additional training slots for pathologists in universities as well as other changes to draw more scientists into the field.
Aging Pathology Staff Means Shortages in US a Possibility
The NHS has stopped short of declaring the pathologist shortage a crisis. Instead, a Department of Health and Social Care spokesperson in an interview with the BBC highlighted recent initiatives taken in response to the shortage. “There are hundreds more pathologists in the NHS compared to 2010 and hospitals have reduced spending on temporary agency staff by over half a billion pounds in the last year,” the spokesperson noted. “We are listening to staff, encouraging more flexible working, and have increased medical training places for home-grown doctors by 25%, to ensure the NHS has the workforce it needs for the future.”
Despite those steps, the NHS may have more work to do. According to the Royal College of Pathologists workplace survey, a quarter of all histopathologists in the UK are 55 or older, adding an approaching retirement crisis to the existing shortage.
US anatomic pathology groups and clinical laboratories should monitor these events with a keen eye. The American pathology industry is challenged by many of the same trends, such as an aging workforce and lackluster replacement initiatives. Time will tell if the US learns from the UK’s experience.
UK study shows how LDTs may one day enable physicians to identify patients genetically predisposed to chronic disease and prescribe lifestyle changes before medical treatment becomes necessary
Could genetic predisposition lead to clinical laboratory-developed tests (LDTs) that enable physicians to assess patients’ risk for specific diseases years ahead of onset of symptoms? Could these LDTs inform treatment/lifestyle changes to help reduce the chance of contracting the disease?
A UK study into the genetics of one million people with high blood pressure reveals such tests could one day exist.
They also confirmed 274 loci (gene locations) and replicated 92 loci for the first time.
“This is the most major advance in blood pressure genetics to date. We now know that there are over 1,000 genetic signals which influence our blood pressure. This provides us with many new insights into how our bodies regulate blood pressure and has revealed several new opportunities for future drug development,” said Mark Caulfield, MD,
The researchers believe “this means almost a third of the estimated heritability for blood pressure is now explained,” the news release noted.
Clinical Laboratories May Eventually Get a Genetic Test Panel for Hypertension
Of course, more research is needed. But the study suggests a genetic test panel for hypertension may be in the future for anatomic pathologists and medical laboratories. Physicians might one day be able to determine their patients’ risks for high blood pressure years in advance and advise treatment and lifestyle changes to avert medical problems.
By involving more than one million people, the study also demonstrates how ever-growing pools of data will be used in research to develop new diagnostic assays.
The video above summarizes research led by Queen Mary University of London and Imperial College London, which found over 500 new gene regions that influence people’s blood pressure, in the largest global genetic study of blood pressure to date. Click here to view the video. (Photo and caption copyright: Queen Mary University of London.)
Genetics Influence Blood Pressure More Than Previously Thought
In addition to identifying hundreds of new genetic regions influencing blood pressure, the researchers compared people with the highest genetic risk of high blood pressure to those in the low risk group. Based on this comparison, the researchers determined that all genetic variants were associated with:
“having around a 13 mm Hg higher blood pressure;
“having 3.34 times the odds for increased risk of hypertension; and,
“1.52 times the odds for increased risk of poor cardiovascular outcomes.”
“We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation, but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future,” the researchers wrote in Nature Genetics.
Other Findings Link Known Genes and Drugs to Hypertension
The UK researchers also revealed the Apolipoprotein E (ApoE) gene’s relation to hypertension. This gene has been associated with both Alzheimer’s and coronary artery diseases, noted LabRoots. The study also found that Canagliflozin, a drug used in type 2 diabetes treatment, could be repurposed to also address hypertension.
“Identifying genetic signals will increasingly help us to split patients into groups based on their risk of disease,” Paul Elliott, PhD, Professor, Imperial College London Faculty of Medicine, School of Public Health, and co-lead author, stated in the news release. “By identifying those patients who have the greatest underlying risk, we may be able to help them to change lifestyle factors which make them more likely to develop disease, as well as enabling doctors to provide them with targeted treatments earlier.”
Working to Advance Precision Medicine
The study shares new and important information about how genetics may influence blood pressure. By acquiring data from more than one million people, the UK researchers also may be setting a new expectation for research about diagnostic tests that could become part of the test menu at clinical laboratories throughout the world. The work could help physicians and patients understand risk of high blood pressure and how precision medicine and lifestyle changes can possibly work to prevent heart attacks and strokes among people worldwide.
