Ongoing increases in the global number of prostate cancer cases expected to motivate test developers to deliver better screening tests to pathologists and clinical lab scientists
No less an authority than the peer-reviewed healthcare journal The Lancet is drawing attention to predictions of increasing prostate cancer cases across the globe, triggering calls for the development of cheaper, faster, and more accurate assays that pathologists and medical laboratories can use to screen for—and diagnose—prostate cancer.
Swift population growth and rising life expectancy will cause the prostate cancer death rate to nearly double in the next 20 years, according to a new study that has led scientists to call for immediate, critical improvements in clinical laboratory testing for cancer screening, Financial Times (FT) reported.
“Low- and middle-income countries need to prepare to prevent a sharp rise in fatalities while richer nations should pay more attention to young men at higher risk of the disease,” FT noted. The study, titled, “The Lancet Commission on Prostate Cancer: Planning for the Surge in Cases,” predicts cases will jump from 1.4 million in 2020 to 2.9 million by 2040.
“Prostate cancer is the most common cancer in men in 112 countries, and accounts for 15% of cancers. In this Commission, we report projections of prostate cancer cases in 2040 on the basis of data for demographic changes worldwide and rising life expectancy. … This surge in cases cannot be prevented by lifestyle changes or public health interventions alone, and governments need to prepare strategies to deal with it,” the study authors wrote.
“The findings in this Commission provide a pathway forward for healthcare providers and funders, public health bodies, research funders, governments, and the broader patient and clinical community,” the authors noted. In their Lancet paper, the researchers define clear areas for improvement.
Given the shortage worldwide of pathologists—especially highly-trained pathologists—the gap between the demand/need for expanded prostate cancer testing as screens (along with prostate biopsies) and the available supply of pathologists will encourage companies to develop screening and diagnostic tests that are accurate and automated, thus increasing the productivity of the available pathologists.
“As more and more men around the world live to middle and old age, there will be an inevitable rise in the number of prostate cancer cases. We know this surge in cases is coming, so we need to start planning and take action now,” said Nick James, PhD (above), Professor of Prostate and Bladder Cancer Research at The Institute of Cancer Research, in a press release. Pathologists and medical laboratories worldwide will want to monitor progress of The Lancet Commission’s recommendations. (Photo copyright: Institute of Cancer Research.)
“Evidence-based interventions, such as improved early detection and education programs, will help to save lives and prevent ill health from prostate cancer in the years to come. This is especially true for low- and middle-income countries (LMICs) which will bear the overwhelming brunt of future cases,” he said in a press release.
Communication is key. “Improved outreach programs are needed to better inform people of the key signs to look out for and what to do next,” James N’Dow, MD, Professor and Chair in Surgery and Director of the Academic Urology Unit at the University of Aberdeen in the UK, told the Financial Times. “Implementing these in tandem with investments in cost-effective early diagnostic systems will be key to preventing deaths,” he added.
Capitalizing on artificial intelligence (AI) analysis to help translate results was another area The Lancet Commission researchers focused on, Financial Times noted.
AI could “subdivide disease into potentially valuable additional subgroups to help with treatment selection. In environments with few or no pathologists, these changes could be transformational,” the study authors wrote.
High Income Countries (HICs) would benefit from AI by empowering patients. “Linking cloud-based records to artificial intelligence systems could allow access to context-sensitive, up-to-date advice for both patients and health professionals, and could be used to drive evidence-based change in all settings,” the study authors added. Such a trend could lead to specialist prostate cancer pathologists being referred cases from around the world as digital pathology systems become faster and less expensive.
Effective treatment strategies and bolstering areas of need is also key, the study notes. “Many LMICs have urgent need for expansion of radiotherapy and surgery services,” the study authors wrote. The researchers stress the need to immediately implement expansion programs to keep up with anticipated near-future demand.
Cancer drug therapy should follow suit.
“Research and the development of risk-stratified regulatory models need to be facilitated,” the study authors noted, citing a focus on drug repurposing and dose de-escalation. “Novel clinical trial designs, such as multi-arm platforms, should be supported and expanded,” they added.
Unique Needs of LMICs, HICs
The Lancet Commission researchers’ recommendations shift depending on the financial health of a specific area. HICs are experiencing a 30-year decline in the number of deaths resulting from prostate cancer, presumably from additional testing measures and public health campaigns that may be lacking in LMICs, Financial Times reported. And as population growth soars, low-to-middle income populations “will need to be prepared for the strain the expected surge in cases will put on health resources.”
For HICs, the study dissected the limitations of prostate-specific antigen (PSA) testing. The researchers pointed out that PSA’s inaccuracies in screening symptomless patients can pinpoint “cancers that may never cause symptoms and need no treatment,” Financial Times reported.
Missing high-risk cases was also a cause for concern. “Diagnostic pathways should be modified to facilitate early detection of prostate cancer while avoiding overdiagnosis and overtreatment of trivial disease,” the study notes.
Screenings for high-risk younger men, and continuing public campaigns about prostate cancer, should be a focus for HICs, the study authors noted. “These would include people who have a family history of the disease, are of African ancestry, or carry a genetic mutation known as BRCA2,” Financial Times reported.
While the undertaking may sound intimidating—there is already such a heavy impact worldwide from prostate cancer—the researchers are optimistic of their recommendations.
“Options to improve care are already available at moderate cost. We found that late diagnosis is widespread worldwide, but especially in LMICs, where it is the norm. Early diagnosis improves prognosis and outcomes, and reduces societal and individual costs, and we recommend changes to the diagnostic pathway that can be immediately implemented,” the study authors wrote.
What Comes Next
“More research is needed among various ethnic groups to expand understanding of prostate cancer beyond the findings from studies that were largely based on data from white men,” The Lancet Commission told the Financial Times.
Astute pathologists and medical laboratories will want to monitor efforts to develop assays that are inexpensive, more accurate, and produce faster answers. Demand for these tests will be substantial—both in developed and developing nations.
By emphasizing HPV vaccinations while having clinical laboratories continue to perform Pap smears, Australia’s rate of cervical cancer has dropped notably
There is currently a global push to completely eradicate cervical cancer and Australia is leading the way with increased funding. It is also focusing on hard-to-reach and underserved populations. Australia is hoping to be first in the world to accomplish this feat by 2035.
For a number of decades, the Pap smear has been the primary screening tool for cervical cancer, as most pathologists and clinical laboratory managers know. However, today it plays a lesser role due to the effectiveness of HPV (human papillomavirus) diagnostic testing, which was put into cervical cancer screening guidelines in 2004.
Then came the first HPV vaccine in 2006. Australia was one of the first nations to implement HPV vaccination programs. By 2010, Australia was working to vaccinate every child. Now, 14 years later, the pool of adults vaccinated against HPV in that nation is causing the rates of cervical cancer to fall.
That means much less cervical cancer test volume for cytotechnologists and cytopathologists, freeing them up to devote their skills to other diagnostic tests.
As the country continues to funnel resources into hitting a zero cancer status, the additional drive will “connect Australia’s world-leading cervical cancer expertise with governments across the region to get HPV vaccine programs up and running, expand screening and treatment, and build health workforce capacity,” said Australia’s Minister for Foreign Affairs office in a press release.
“Australia has always punched above its weight when it comes to cervical cancer, and now Australia is on track to be the first country in the world to eliminate this deadly disease,” said Hon Ged Kearney, MP, RN (above), Assistant Minister for Health and Aged Care and a member of the government’s House of Representatives, in a press release. “By supporting the Pacific and Southeast Asia region [to] eliminate cervical cancer, we are another step closer to ridding the world of this disease.” Clinical laboratories and cytopathologists may soon see less reliance on Pap smears for screening and a shift toward HPV vaccinations to lower the rate of cervical cancer in the US as well. (Photo copyright: Australian Labor Party.)
90% of eligible people will be vaccinated against HPV (including girls and boys).
70% of eligible people will be screened every five years.
95% of eligible people will receive the best possible treatment for precancer and cancer.
In addition to $48.2 million in funding over four years, the program provides:
On the spot testing of samples in First Nations [aka, First Peoples] communities, allowing immediate follow up.
Support for nurses, First Nations health practitioners, and midwives to request pathology for cervical screening.
Increasing support for GPs to undertake colposcopies.
Helping the Underserved
Reaching a wider audience is a large part of Australia’s focus.
“One of my priorities is to address inequities in our health system. I want to make sure that everyone can get access to screening—and all healthcare—no matter where [they] live,” Kearney added. Among the populations sought are First Nations, LGBTIQA+, disabled individuals, and those living away from large cities.
“$8.3 million has been allocated to implement innovate screening models to support such communities,” the Minister for Foreign Affairs office noted in the press release.
Meeting people where they are, and reaching underserved populations, can make a huge difference, especially considering how cervical cancer affects these people. “First Nations women are almost twice as likely to be diagnosed with cervical cancer and face significant barriers to participating in cervical screening compared to non-indigenous women,” the press release notes.
“These tests allow privacy and help to break down barriers for thousands of people who have never screened—including women who have experienced sexual violence, LGBTIQA+ people, and culturally and linguistically diverse and First Nations communities,” the Minister for Foreign Affairs office stated.
There is hope that the push will cause a great shift to other underserved communities as well.
“A quarter of global cervical cancer cases occur in our region, the Indo-Pacific. Tragically, in the Pacific, women are dying at up to 13 times the rate of women in Australia,” said Penny Wong, Australian Minister for Foreign Affairs, in the press release.
How the US Fares in Cervical Cancer Vaccinations
Australia’s vaccination rates far exceed those in the United States. The US government currently recommends HPV vaccination between the ages of 11-12 years old, though it could be administered starting at age nine.
“HPV vaccination is recommended for all persons through age 26 years who were not adequately vaccinated earlier,” the NIH’s National Cancer Institute (NCI) reports.
For years the standard focus for cervical cancer screening has been on the Pap smear. Data show the US lags behind many countries on the rate of HPV vaccination. NCI data show that, as of 2021, in the US just 58.5% of 13-15 year-olds “had received two or three doses of HPV vaccine as recommended,” NCI reported.
With the US’s standard of care still focused on the Pap smear, patients are beginning their cervical cancer prevention journey at a later age. This is because the preliminary age to get a Pap smear in the US is 21 years old, with follow-up exams every three years, the NCI reported.
Even those in this country who are sexually active are not recommended to get screening earlier than 21.
The NCI recommends HPV testing every five years starting at age 30 until 65, with Pap tests every three years.
Clinical laboratories may soon find that, while the US has been slower to get on board with HPV vaccinations, trends in other nations indicate that this may soon change. The reliance that was once placed on the Pap smears prior to 2000 will likely give way to HPV vaccinations at ages and vaccination rates that mirror programs in countries like Australia—where marked reductions in the rate of cervical cancer demonstrate the effectiveness of a successful HPV vaccination program.
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.
In the same way that BRCA1 and BRCA2 mutations helped pathologists identify women with increased breast cancer risks in the late 1990s, this new study isolates an additional 72 mutations medical laboratories may soon use to diagnose breast cancer and assess risk factors
For 20 years genetic scientists, anatomic pathologists, and medical laboratories have employed the BRCA1/BRCA2 genes to identify women at higher risk for breast cancer. And, because pathologists receive a high number of breast biopsies to diagnose, physicians and clinical laboratories already have collaborative experience working with genetic mutations supported by ample published evidence outlining their relationship with cancer.
Now, a global research study is adding 72 more mutations to the list of mutations already known to be associated with breast cancer.
In coming years, physicians and anatomic pathologists can expect to use the knowledge of these 72 genetic mutations when diagnosing breast cancer and possibly other types of cancers in which these mutations may be involved.
New Precision Medicine Tools to Improve Breast Cancer Survival
Combining the efforts of more than 550 researchers across 300 institutions and six continents, the OncoArray Consortium analyzed the DNA of nearly 300,000 blood samples. The analysis included samples of both estrogen receptor (ER-positive and ER-negative) cases.
Taken from a study published in the British Journal of Cancer, the graph above illustrates “proportions of familial risk of breast cancer explained by hereditary variants.” It is expected that anatomic pathologists will eventually incorporate these genetic variants into diagnostic test for breast and other cancers. (Graphic copyright: British Journal of Cancer.)
The results of their research were published in two separate studies: one in the scientific journal Nature and the other in Nature Genetics. The studies outlined 72 newly isolated genetic mutations that might help quantify the risk of a woman developing breast cancer in her lifetime.
Among the 72 mutations, seven genes were specifically associated with ER-negative cases. ER-negative breast cancer often fails to respond to hormone therapy. Thus, this discovery could be crucial to developing and administering precision medicine therapies tailored to specific patients’ physiologies and conditions. Treatments that improve patient outcomes and overall survival rates in ER-negative and ER-positive breast cancers.
Genetics Could Help Clinical Laboratories Wage War on All Cancers
According to data published by the Centers for Disease Control and Prevention (CDC), breast cancer is the most common form of cancer among women of all races. It’s the second-leading cause of all cancer deaths among most races and first among Hispanic women.
In the past, it was estimated that 5-10% of breast cancers were inherited through the passing of abnormal genes. However, Lisa Schlager, Vice President of community affairs and public policy for FORCE (Facing Our Risk of Cancer Empowered), told CNN, “This new information may mean that that estimate is low.” FORCE is a national nonprofit organization dedicated to fighting hereditary breast, ovarian, and related cancers.
Schlager calls upon health systems to “embrace the ability to use genetic information to tailor healthcare by providing affordable access to the needed screening and preventive interventions.” As precision therapy and genetic analysis continue to shape the way patients are treated, medical laboratories will play a significant role in providing the information powering these innovative approaches.
Identifying Women at Increased Risk for Breast Cancer
Peter Kraft, PhD, Professor of Epidemiology at Harvard’s T.H. Chan School of Public Health, and a study author, told CNN, “Taken together, these risk variants may identify a small proportion of women who are at three-times increased risk of breast cancer.”
Kraft notes that samples were sourced from women of primarily European ancestry. Further study of other ethnic populations could lead to yet more mutations and indicators for cancers more common outside of the European region.
Research authors also highlight the importance of continued standard screening, such as mammograms. However, they suggest that genetic mutations, such as those found in the OncoArray study, might be used to highlight high-risk individuals and screen sooner, or conduct more in-depth genetic analyses, to catch potential cancer cases earlier and improve outcomes.
“Many women are offered mammogram screening when they are middle-aged,” Georgia Chenevix-Trench, PhD, co-author of the Nature Genetics study and researcher at the QIMR Berghofer Medical Research Institute in Australia, told LabRoots. “But if we know a woman has genetic markers that place her at higher risk of breast cancer, we can recommend more intensive screening at a younger age.”
Anatomic pathologists and clinical laboratories can use these new insights to offer increased options for oncologists and physicians on the front lines of the battle against cancer. While the list of genetic mutations related to cancer is far from complete, each added mutation holds the potential to power a new treatment, improve early detection rates, and improve survival rates of this global killer.
Steady progress is happening in consumer self-test kits as new diagnostic technology supports at-home kits that produce results with accuracy approaching 90%
Because screening for colon cancer represents a potentially huge number of medical laboratory tests each year, many biotech companies are racing to develop reliable test kits that patients can use at home. But to be successful, the test kit must be cheap, easy for a consumer to use, and produce clinically useful results.
Home Test Promises Same Accuracy as Clinical Laboratory Test
That’s the goal of Mode Diagnostics, Ltd., a Scottish company that is poised to sell a consumer device that can detect signs of colon cancer at home in three minutes at an accuracy rate of 98%. Mode’s new device is an example of how innovative diagnostic technology is driving the market for fast, accurate consumer self-test kits—and pushing these tests out of the central clinical laboratory and into the home. (more…)