Lung cancer screening with low-dose CT can detect extensive coronary artery calcium (CAC), an independent predictor of all-cause death and cardiovascular events, new research suggests.
Gary Small, MBChB, PhD
“The high prevalence of asymptomatic coronary artery disease (83%) was surprising, as was the prevalence of extensive CAC (30%),” principal investigator Gary Small, MBChB, PhD, a cardiologist at the University of Ottawa Heart Institute, Ottawa, Ontario, Canada, told Medscape Medical News.
“The size of effect was also surprising, as was the persistence of the effect even in the presence of elevated mortality risk from other causes,” he said. “Extensive coronary disease was associated with a twofold increase in risk for death or cardiovascular events over 4 years of follow-up,” even after adjustment for risk for death from cancer and other comorbidities such as chronic obstructive pulmonary disease.
“CAC as reported on chest CT exams is often ignored and not factored into clinical practice,” he noted. “The presence of CAC, however, provides a very real and very personal perspective on an individual’s cardiovascular risk. It is a true example of personalized medicine.”
The study was published online on December 2 in the Canadian Medical Association Journal.
Air Pollution Exposure Linked to Higher Breast Cancer Risk
Edited by Gargi Mukherjee
October 24, 2024
TOPLINE:
A recent study found that long-term exposure to fine particulate matter ≤ 2.5 μm (PM2.5) is associated with an increased risk for breast cancer, with the highest risk observed among White women.
METHODOLOGY:
Studies have suggested that exposure to air pollution — specifically PM2.5 — may increase the risk for breast cancer, but data are largely in populations of White women.
The current analysis explored the potential risk among a more racially and ethnically diverse group.
The study included 58,358 women (median age, 60.4 years at enrollment) from the California Cancer Registry, followed over an average of 19.3 years. Overall, 35% were African American, 39% were Latino, 15% were White, and 10% were Japanese American.
Researchers measured PM2.5 exposure using satellite-based data and geocoded addresses. Other pollutants, such as PM10, NO2, NOX, and CO, were also tracked using Environmental Protection Agency data.
TAKEAWAY:
A total of 3524 invasive breast cancer cases were diagnosed over an average follow-up period of 19.3 years. PM2.5 exposure was associated with a 28% increased risk for breast cancer overall (hazard ratio [HR], 1.28; 95% CI, 1.08-1.51).
When looking at risk by racial/ethnic group, the association between PM2.5 exposure and breast cancer risk was strongest among White women (HR, 1.67). PM2.5 exposure was also associated with a higher risk for breast cancer among African American women (HR, 1.14; 95% CI, 0.89-1.46) and Latino women (HR, 1.34; 95% CI, 0.94-1.92), but the associations were not significant.
Overall breast cancer incidence was also positively associated with exposure to NO2, NOX, and CO (HRs, 1.09-1.11), but the associations were not significant. A meta-analysis of this study and ten other cohorts estimated a 5% increased breast cancer incidence per 10-unit increase in PM2.5 (HR, 1.05).
IN PRACTICE:
“Collective findings suggest that PM2.5 exposure should be considered a risk factor for breast cancer, and curtailing air pollution exposures at the population level using regulatory strategies should be a priority,” the authors concluded.
SOURCE:
The study, led by Anna H. Wu, PhD, MPH, Keck School of Medicine, University of Southern California, Los Angeles, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
The study did not include data on nonresidential exposures or residential history before cohort entry, which limited the assessment of earlier exposures. The study also lacked information on specific sources of PM emissions, as well as an explanation for why White women had the highest breast cancer risk compared with other racial/ethnic groups.
DISCLOSURES:
The study was supported by grants from the Health Effects Air Pollution Foundation, the National Cancer Institute, USC Environmental Exposures, Host Factors, and Human Disease, and the California Air Resource Board. One author disclosed being an associate editor for the Journal of Clinical Oncology. No other potential conflicts of interest were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
The American College of Obstetricians and Gynecologists (ACOG) has updated its breast cancer screening guidelines, recommending that individuals at an average risk for breast cancer initiate mammography screening at age 40. This change reflects evolving evidence that starting earlier screening yields greater net benefits in reducing breast cancer mortality, particularly for certain racial groups with higher risk factors.
Breast cancer is the second leading cause of cancer deaths in American women overall and the leading cause of cancer deaths among Black and Hispanic women. Although mammography has long been recognized as a life-saving tool by detecting cancer early, there has been debate on when screening should begin due to concerns about overdiagnosis, false positives, and potential harms such as unnecessary biopsies.
Recent evidence has prompted ACOG to revise its recommendation for individuals assigned female at birth, including cisgender women, transgender men, and nonbinary individuals. This updated guidance includes individuals with dense breast tissue or a family history of breast cancer but excludes those with higher risk factors, such as a personal history of breast cancer or previous high-risk lesion on a breast biopsy, genetic mutations linked to higher cancer risk, or a history of high-dose radiation therapy to their chest at a young age.
Under the new guidelines, routine screening mammography should start at age 40 and can be performed annually or every 2 years, based on an informed, shared decision-making process that considers the benefits and potential harms of frequent screening.
Previously, ACOG recommended initiating screening between ages 40 and 50, depending on individual risk factors and preferences, with screening required by age 50 at the latest. However, several factors, including an increasing incidence of breast cancer in younger women, have influenced the decision to lower the recommended starting age.
Increasing Incidence Among Younger Women
Between 2015 and 2019, the incidence of invasive breast cancer in women aged 40-49 years increased by approximately 2% per year.
“There has been a concerning trend of increasing breast cancer diagnoses among women in their 40s, and new data shows that earlier screening could make a significant difference in decreasing breast cancer deaths,” said Eve Zaritsky, MD, FACOG, co-author of the clinical practice update. “While screening can sometimes cause anxiety for people and even unnecessary follow-up, the benefits of diagnosing breast cancer earlier outweigh those risks enough to warrant starting to get mammograms at age 40.”
Studies commissioned by the US Preventive Services Task Force (USPSTF) show that starting mammography at age 40 provides a greater overall benefit than beginning at age 50. Early screening reduces the number of breast cancer deaths and increases life years gained when weighed against the harms of false positives, overdiagnosis, and benign biopsies.
Addressing Health Inequities
The benefits of earlier screening are expected to be particularly significant for Black women, who have disproportionately high mortality rates from breast cancer. Even though Black women have a lower overall incidence of breast cancer than White women, they have a 40% higher 5-year age-adjusted mortality rate from the disease and a 45% increased incidence of invasive breast cancer before age 50. Black women are also more likely to be diagnosed with aggressive subtypes, such as triple-negative breast cancer, which is harder to detect and treat and occurs at younger ages.
Racial disparities in breast cancer outcomes are deeply rooted in inequities in social determinants of health, such as access to care, housing, and environmental conditions. Black women are also less likely to receive timely or comprehensive treatment than White women, which contributes to worse survival rates even after adjusting for socioeconomic factors and insurance status.
“Our updated recommendation addresses important inequities in breast cancer diagnosis, treatment, and death, and we hope that the earlier initiation of mammography screening across the board will have a great net benefit in outcomes for Black women especially, who have been shown to have the poorest outcomes when it comes to breast cancer, in part because of long-standing inequities in social determinants of health,” added co-author Cherie C. Hill, MD, FACOG.
ACOG’s updated recommendation aligns with that of other leading organizations, including the USPSTF, the National Comprehensive Cancer Network, the American College of Radiology, and the Society of Breast Imaging. This growing consensus among experts is expected to reduce confusion among clinicians and patients regarding when to begin screening, thus improving screening rates in individuals in the 40- to 49-year age group.
Zaritsky and Hill reported no conflicts of interest.
Meg Barbor is a freelance writer for Medscape Medical News.
Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function.
Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.
Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide-1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.
A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments.
In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice.
Simple Prevention and Treatment Strategy
Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week.
With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.)
Although that particular study didn’t identify greater benefit at 3x/week compared with 2x/week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding.
Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ 5 sets per major muscle group per week compared with < 5 sets per week for increasing muscle in the legs, arms, back, chest, and shoulders.
Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative.
A previous commentary outlined an overall approach to preventing loss of muscle mass while taking GLP-1–related medications. Of note, a diet with sufficient protein is critical for optimizing muscle mass gains as part of regular strength-training routines. One study performed in older adults with frailty found an average loss of 0.25 kg of LBM with consumption of 1.0 grams of protein per kilogram of total body weight per day (g/kg/d) despite 2 days of strength training per week for 24 weeks. In that same study, consuming 1.3 g/kg/d of protein led to an average increase of 1.25 kg of LBM during the same period and in association with the same strength-training routine as those consuming 1.0 g/kg/d. Meta-analyses performed to assess an amount of protein to provide optimal benefit to strength and muscle for strength-training individuals determined those amounts to be 1.5 g/kg/d and 1.62 g/kg/d, respectively. While historically a low-protein diet was recommended to prevent disease progression in individuals with chronic kidney disease(CKD), a recent study found reduced risk for death in patients with CKD with greater reported protein consumption. A separate study, using a mendelian randomization methodology, found a similar reduction in mortality risk among individuals with CKD who consumed greater amounts of protein.
Patients in Need of Sarcopenia Assessments
Although a gradual loss of muscle mass occurs over the course of life, sharp declines can also occur following an illness or an injury involving long bedrest. For example, one studyfound that 5 days of limb immobilization led to a 1.5% loss of quadriceps volume, equivalent to an amount of muscle loss, that, when extrapolated to the full body, may require 10 weeks of strength training twice weekly to regain.
In weight loss, such as from GLP-1–related medications, the sarcopenia risk may accrue long term, as it does in aging. Individuals who lose weight using GLP-1s may experienceimproved physical function in the short term (a little over a year), despite 20%-40% of the total weight lost coming from muscle mass; however, this loss of muscle may cause limitations over time.
If someone lost 20 lb of their total body weight through the use of semaglutide and was not strength training and not consuming enough protein, the amount of LBM lost (assuming 40% of total weight lost) is 8 lb or 3.62 kg. If a body-composition assessment was not performed before and after the weight loss, it won’t be possible to estimate how much of the lost weight is coming from muscle compared with fat. This individual may not yet experience a loss in strength as a result of that muscle loss, particularly if they are in their 50s; however, a person in their 70s is more likely to experience some degree of limitation in their physical function as a result.
For some individuals, that amount of muscle mass reduction can tip them into the sarcopenic range, which increases the risk for hip fractures. Sarcopenia contributed to 71% of hip fractures in one community-level study. Hip fractures are not uncommon. One studyreported a lifetime risk for a hip fracture of 16%-18% in White women of and 5%-6% in White men. Furthermore, 34% of older adult patients who suffer a hip fracture die within 1 year of the fracture, and of those who survive, many experience impaired mobility and quality of life even up to 2 years afterward.
To outline an unfortunate but possible trajectory, an individual could unknowingly lose muscle in association with weight loss achieved in their 50s, acquire a mild case of pneumonia at a social event in their 60s or 70s, end up in the hospital for 7 days undergoing treatment for pneumonia, experience a rapid loss of muscle mass during the hospitalization, leave the hospital after completing pneumonia treatment, only to then fall ascending the stairs to their home, suffer a hip fracture, and end up back in the hospital.
How Do Busy Clinicians Fit In Sarcopenia Screening?
Different sarcopenia-related societies have proposed different criteria and thresholds for diagnosis. Of these different guidelines, those from the European Working Group on Sarcopenia in Older People (EWGSOP) are the most recent and are summarized below:
EWGSOP-defined sarcopenia categories:
One criterion met = Probable sarcopenia
Two criteria met = Sarcopenia
Three or more criteria met = Severe sarcopenia
An assessment for sarcopenia does not require excessive time, cost, or safety risk. Of the tests included for screening for sarcopenia in the EWGSOP criteria, grip strength and the 5-Time Sit-to-Stand (5tStSt) assessments are probably the most feasible to perform in clinic. These are evidence-based and can be performed together in about 2 minutes total time.
Hand Grip Strength
The clinically validated Jamar Hydraulic Hand Dynamometer is available for about $270, but devices priced at $30 are probably reasonably accurate and worthy of consideration for clinics with budgetary limitations. To perform the grip strength test, the patient simply squeezes the device with as much force as they can, once with each hand. The device will display the max force generated with each squeeze.
5-Time Sit Stand to Test
For the 5tStSt, the patient should begin in a seated position, cross their arms over their shoulders (so that their hands are not used to assist in the movement), and rise to a full stand before returning to a seated position. This motion should be completed five times, and the patient should be instructed to complete the five repetitions as quickly as possible, while the time required to complete the five repetitions is recorded.
Ideally, if performed during a clinic visit, the clinicians would show the patient how their results compare with demographic norms for each test; see here for examples of demographic norms for grip strength and here for the 5tStSt.
Body Composition Assessments
Body composition data are also included as part of a sarcopenia assessment and have gender-specific thresholds defined in the EWGSOP criteria. A body composition assessment provides data on LBM (which is a proxy for muscle mass) and fat mass. A recent study demonstrated that percent body fat provides greater sensitivity than body mass index for diagnosing obesity and metabolic syndrome.
When to Consider Sarcopenia Screening
An extensive body of evidence on sarcopenia supports sarcopenia screening for all patients older than age 65. Given the risk for muscle mass reductions that occur with weight loss in general and GLP-1–related medications more specifically, sarcopenia screening is probably appropriate for certain patients younger than 65 years as well.
Clinical judgement should be used to determine when and whom to assess for sarcopenia; however, given that the screening assessments are fast, safe, and have minimal cost, a low threshold for screening appears appropriate. For example, even for a 50-year-old patient who has not been physically active, sarcopenia assessments may indicate below-average performances, and this knowledge can serve as motivation for this patient to adopt an exercise regimen to address strength-related limitations that have already begun to manifest. Further, keeping a record of screenings performed in younger years can serve as points of comparison for repeat assessments later on.
Self-Directed Sarcopenia Screening
Some healthcare providers may not be familiar with the diagnostic criteria for sarcopenia; efforts to promote greater awareness and testing should continue. That said, patients can perform some of the testing themselves if so desired.
The 5tStSt, 400-meter walk test, and Timed Get Up and Go (TUG) tests do not require a clinician. The 400-meter walk test simply evaluates the time required for completion of walking this distance. The TUG test evaluates the time required for a patient to rise from a chair and then walk 3 meters forward. As part of the TUG test, patients can use their arms to assist in rising from the chair.
It has been said that every job has a “sales” component. This is also true of medicine. Doctors must “sell” patients on an explanation for their symptoms and must elicit “buy-in” from them on a treatment plan for it to be most effective. Data from sarcopenia assessments can increase the power of the sales pitch aimed at motivating patients to adopt and/or improve an exercise routine.
Clinically significant extracardiac findings are common on CT and MRI and are especially associated with exam indication and patient age, researchers have reported.
Detecting and interpreting these findings is crucial for patient care, wrote a team led by Dr. Lukas Moser of University Hospital Zurich in Switzerland. The study results were published on 10 October in Radiology: Cardiothoracic Imaging.
“Detecting and interpreting extracardiac findings in cardiovascular CT and MRI remains a challenge … [but] timely evaluation of extracardiac findings can be important in the presence of life-threatening conditions,” the investigators noted.
Cross-sectional imaging such as CT and MRI is a valuable tool for assessing cardiac disease, Moser and colleagues explained, and the volume of cardiac exams continues to increase. The field-of-view for these types of exams includes not just the heart but also adjacent structures such as the lung and abdomen, which can identify incidental extracardiac conditions, according to the team; some of these findings can be benign, but others — such as pulmonary nodules or effusions, structural lung disease, pulmonary embolism, pleural lesions, diffuse liver disease, hernia, or suspicious abdominal lesions — may require follow-up.
The researchers explored the prevalence extracardiac clinically significant findings on CT and MRI by conducting an analysis of data from the European Society of Cardiovascular Radiology MR/CT registry. Their assessment included information from 208,506 cardiac CT exams and 228,462 cardiac MRI exams entered into the registry between January 2011 and November 2023. They defined “clinically relevant extracardiac findings” as those that required follow-up exams or which influenced patient management and evaluated any associations between patient characteristics (including age) with the prevalence of extracardiac findings using incidence rate ratios (IRRs).
The authors found the following:
The prevalence of clinically relevant extracardiac findings was 3.3% on the cardiac CT exams and 1.5% on the cardiac MR scans.
Extracardiac findings were more common on CT exams performed for transcatheter aortic valve replacement (IRR, 2.07, with 1 as reference) and structural heart disease (IRR, 1.44) compared with CT imaging undertaken for coronary artery disease.
Extracardiac findings were more common on MR imaging performed for myocarditis (IRR, 1.36) and structural heart disease (IRR, 1.16) than for coronary artery disease.
Older patient age was significantly associated with higher incidence of extracardiac findings, with an IRR for both CT and MRI examinations of 1.02.
The study results underscore the important role radiologists play in interpreting CT and MRI exams, according to the authors.
“[Our] findings support the role of radiologists in interpretation of cardiac CT and MR images, as they represent imaging experts not only for the heart and vessels but also for other body regions that are simultaneously depicted at cross-sectional imaging examinations,” they concluded. “Future studies of such large-scale registries should evaluate the prognostic implications of extracardiac findings in cardiovascular imaging.”
Instead of delivering an organized breast screening service that treats all women between the ages of 50 and 74 in an identical way, the future is likely to be about the evolution of a more personalized approach, according to Prof. Isabelle Thomassin-Naggara, head of the Specialized Radiological and Interventional Imaging Service (IRIS) at AP-HP Sorbonne University, Tenon Hospital, Paris.
More variations will arise in the age at which screening begins, possibly moving to 40 years of age, and changes will occur in the optimal imaging methods and the frequency of screening. These issues will be determined by a better assessment of each woman’s risk, and the wider implementation of AI will also have a significant impact in the future, she predict.
In a video interview recorded ahead of the French national radiology congress, JFR 2024, Thomassin-Naggara, who is president of the Women’s Imaging Society (SIFEM), discusses the latest trends in breast imaging. She also looks ahead to sessions at JFR 2024, which runs from 4 to 7 October in Paris.
Video produced by Christof.G.Pelz | GRAFIFANT Creation | www.grafifant.at | 2024
Skipping systematic biopsy in men with elevated prostate-specific antigen (PSA) levels but negative MRI results reduces overdiagnosis by more than 50% — and doesn’t boost risk of missing clinically significant disease, researchers have reported.
The study results could help clinicians tailor care for men with elevated PSAs, wrote a team led by Dr. Jonas Hugosson, PhD, of the University of Göthenburg in Sweden. The group’s findings were published on 25 September in the New England Journal of Medicine.
“Many studies have shown that men with an elevated PSA level and negative MRI results (i.e., a PI-RADS score of 1 or 2) still have a substantial risk of having clinically significant cancer detected if systematic biopsy is performed,” Hugosson and colleagues wrote. “[But in] many cases, these cancers are low-volume [International Society of Urological Pathology] grade 2 cancers that are of questionable clinical significance at the time of diagnosis.”
No consensus exists as to whether population-based prostate cancer screening should be recommended, according to the investigators, who noted that “the largest obstacle has been the high rate of overdiagnosis when prostate-specific antigen (PSA) is used as the identifying marker of risk.” MRI for prostate cancer screening tends to have lower rates of overdiagnosis when only MRI-targeted biopsy is performed and systematic biopsy omitted, the team explained.
In an attempt to clarify MRI’s role in prostate cancer screening, Hugosson and colleagues conducted an analysis of data from the GÖTEBORG-2 screening trial, the main objective of which was “to evaluate, in a long-term screening program, whether a strategy of omitting systematic biopsy in men with a PSA level of 3 ng/ml higher and performing only targeted biopsy of MRI-positive lesions would reduce the risk of detecting clinically insignificant prostate cancer while still enabling the detection of clinically significant prostate cancer at a curable stage.”
The trial began in 2015 and included 38,316 men between the ages of 50 and 60 invited for PSA screening. Of these, 19,733 attended at least one screening. Men with a PSA level of 3 ng/ml or higher were recommended to have an MRI prostate exam and a systematic biopsy; those with suspicious findings on this MRI exam were recommended to have an MRI-targeted biopsy. Of the men who attended at least one screening, 6,578 were placed in a systematic biopsy group (that is, one that takes multiple tissue samples from the prostate) and 6,575 in an MRI-targeted biopsy group (performed due to suspicious lesions found on MR imaging).
The percentage of men with an indication for biopsy was 2.8% of the MRI-targeted biopsy group (elevated PSA/suspicious lesion on MRI) and 6.9% of the systematic biopsy group (all study participants with an elevated PSA level).
The authors found that the risk of detecting clinically insignificant cancer was 57% lower in the MRI-targeted biopsy group than in the systematic biopsy group (relative risk, 0.43, with 1 as reference).
Biopsy type performance
Category of cancer
Systematic biopsy
MRI-targeted biopsy
Relative risk (with 1 as reference)
Screening-detected cancer and interval cancer, overall
Clinically insignificant
2.4%
1%
0.43
The study results could translate to better patient care, according to Hugosson and colleagues.
“In this trial, omitting [systematic] biopsy in patients with negative MRI results eliminated more than half of diagnoses of clinically insignificant prostate cancer, and the associated risk of having incurable cancer diagnosed at screening or as interval cancer was very low,” they concluded. “These results should encourage guideline committees to update recommendations around prostate cancer diagnosis and screening.”
CT screening for lung cancer continues to gather momentum across Europe. Ahead of the French national radiology congress, JFR 2024, we caught up with Prof. Marie-Pierre Revel, PhD, to get her latest thoughts on the progress made in lung cancer screening.
In a video interview, she provides an update on the CASCADE study (Lung Cancer Screening in French women using low-dose CT and AI for DEtection) and speaks about the urgent need to boost awareness and increase the participation of women in deprived areas. She also gives details on SOLACE, an EU4Health project aimed at strengthening lung cancer screening strategies using structured low-dose CT. The plan is to break down the barriers to screening to ensure people across all social and economic groups can access it (go to www.solacelung.eu for more details).
On a personal level, Revel reflects on the 2.5 km sea swim she undertook in Spain on 22 September 2024 – the day before the video interview was recorded.
Prof. Revel is head of radiology at Hôpital Cochin in Paris and former president of the European Society of Thoracic Imaging (ESTI). She is chairperson of the ESR’s Communication and Interdisciplinary Affairs Committee.
For Patients With Elevated PSA, Which Type of Biopsy Is Best?
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September 25, 2024
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Employing MRI-targeted biopsy instead of systematic biopsy reduces overdiagnosis of low-grade prostate cancer by more than half, although diagnoses may be delayed among a small minority of patients with higher-risk disease, according to the authors of a new paper.
Considered alongside the reduced biopsy burden at a population level, and the fact that very few patients in the higher risk group had incurable cancer when they were diagnosed, these findings suggest that guidelines should be updated to favor the MRI-targeted approach,reported lead author Jonas Hugosson, MD, PhD, of the University of Gothenburg, Sweden, and colleagues.
What Clinical Question Did This Study Address?
The above support for MRI-targeted biopsy over systematic biopsy addresses a long-standing debate about prostate cancer screening.
“Several large randomized trials of screening for prostate cancer have been published, but no consensus has emerged as to whether population-based screening should be recommended,” Hugosson and colleagues wrote in The New England Journal of Medicine. “The largest obstacle has been the high rate of overdiagnosis when prostate-specific antigen (PSA) is used as the identifying marker of risk.”
The central issue concerns overdiagnosis of patients with low-grade (International Society of Urological Pathology [ISUP] grade 1, also called Gleason grade group 1) disease, which must be balanced against underdiagnosis of grade 2 and higher disease.
In an accompanying editorial, Paul F. Pinsky, PhD, of the National Cancer Institute, Bethesda, Maryland, described how patients with ISUP grade 1 disease are typically advised to undergo active surveillance, as outcomes are no worse than with curative treatment.
While this path avoids treatment, it can still be a thorny one.
“Active surveillance has its own costs and harms, and a substantial proportion of patients eventually choose curative therapy as a result of psychological and family pressures, even in the absence of evidence of disease progression (which is relatively infrequent),” Pinsky wrote. “Furthermore, even for patients who continue to undergo active surveillance in the long term, important downsides include anxiety, healthcare system costs, and complications of the required periodic biopsies.”
The emerging consensus aims to avoid detection of ISUP grade 1 disease altogether, according to Pinsky, as this circumvents decisions about active surveillance. Ideally, patients would be diagnosed at ISUP grade 2, which is considered “clinically significant.”
How exactly to hit this sweet spot remains unclear, however, prompting the present study.
With MRI-targeted biopsy, “[w]ill the cancer progress and later become visible on MRI but still be at a curable stage, or will it be diagnosed too late for cure?” Hugosson and colleagues asked.
How Did This Study Compare Systematic and MRI-Targeted Biopsy?
The population-based trial, conducted in Sweden, invited men aged 50-60 years to undergo PSA screening. Those with a PSA level of at least 3 ng/mL underwent MRI. From there, participants were randomized into the MRI-targeted biopsy group or the systematic biopsy group.
In the systematic biopsy group, systematic biopsy was performed regardless of MRI findings, with MRI-targeted biopsy added if suspicious lesions were found. In the MRI-targeted biopsy group, only MRI-targeted biopsy was performed if suspicious lesions were found.
These two strategies were compared across a range of metrics, including detection of clinically significant vs insignificant cancer, need for biopsy, and adverse events.
Which Biopsy Strategy Was Superior?
The final dataset included 6575 men in the systematic biopsy group and 6578 men in the MRI-targeted biopsy group. After a median follow-up of 3.9 years, prostate cancer was detected in 4.5% of patients in the systematic biopsy group vs 2.8% in the MRI-targeted biopsy group.
The risk of detecting grade 1 prostate cancer in the MRI-targeted biopsy group was 57% lower than in the systematic biopsy group (relative risk [RR], 0.43; 95% CI, 0.32-0.57), and risk of undergoing biopsy was reduced by the same percentage (RR, 0.43; 95% CI, 0.37-0.50).
Severe adverse events were also less common with MRI-targeted biopsy than systematic biopsy, with just two occurring in the former group, and five occurring in the latter.
Still, not all findings favored MRI-targeted biopsy.
RR of detecting grades 2-5 prostate cancer was 16% lower in the MRI-targeted biopsy group, although this was not statistically significant (RR, 0.84; 95% CI 0.66-1.07). Similarly, MRI-targeted biopsy was 35% less likely to detect advanced or high-risk cancers; however, again, this was not statistically significant (RR, 0.65; 95% CI, 0.34-1.24).
“From a public health perspective, these results are best expressed in absolute terms,” Pinsky wrote. “[P]er 1000 enrolled men, the MRI-targeted biopsy approach led to 51 fewer men undergoing biopsy and 14 fewer men receiving a diagnosis of ISUP grade 1 disease, but it also led to a delay in the diagnosis of ISUP grade 2 or higher disease in three men. The meaning of this delay is not immediately clear, but such a delay could lead to worse outcomes in a fraction of those men.”
Should MRI-Targeted Biopsy Be Adopted Instead of Systematic Biopsy?
In their concluding remarks, Hugosson and colleagues emphasized the benefits of MRI-targeted biopsy.
“In this trial, omitting biopsy in patients with negative MRI results eliminated more than half of diagnoses of clinically insignificant prostate cancer, and the associated risk of having incurable cancer diagnosed at screening or as interval cancer was very low,” they wrote. “These results should encourage guideline committees to update recommendations around prostate cancer diagnosis and screening.”
After noting that an MRI-targeted approach may be more cost-effective than performing systematic biopsies, Pinsky maintained a neutral perspective, suggesting that more data may be needed before amending screening protocols.
“The way in which MRI is used in the context of PSA-based screening is evolving,” he wrote. “This trial gives additional evidence regarding the comparative effectiveness and resource utilization of MRI-based strategies designed to reduce biopsies and the diagnosis of clinically insignificant…disease. This information contributes to the ultimate goal of designing screening strategies that preserve most of the benefits of PSA-based screening while reducing harms and costs.”
The study was supported by Karin and Christer Johansson’s Foundation, the Swedish Cancer Society, the Swedish state under an agreement between the Swedish government and the county councils, and others. The investigators and editorialist disclosed no relevant conflicts of interest.
Prostate cancer presents a tricky screening challenge. Catching it early could mean dodging a painful journey with advanced cancer. Yet a sizable majority of prostate cancers are “indolent” — slow growing tumors that most likely would never metastasize during the patient’s lifetime, and whose treatment would do more harm than good.
Experts have long clashed over these considerations, with some arguing that the harms of PSA testing outstrip the benefits and others adamant that lives are saved with screening. The balance may now be shifting as researchers and physicians find methods that reduce the harms of screening, in particular with the use of MRI. A new study published in the New England Journal of Medicine on Wednesday showed using MRI scans can reduce unnecessary diagnosis and treatment of screen-detected prostate cancer by more than half.
That result should be a reason for experts to rethink prostate cancer screening guidelines with MRI in mind, according to Jonas Hugosson, a professor of urology at the University of Gothenburg in Sweden and the study’s lead author. “In my opinion, this is the last piece of the puzzle to have real evidence that the benefits of prostate screening exceed the harms on a population level,” he said. “This paper is the message to healthcare authorities around the world to look over recommendations for men.”
That may be easier said than done, other experts said. There may not be enough MRI infrastructure to support a prostate screening program requiring the scans.
Prostate cancer is one of the most common cancers, afflicting about one in eight men at some point in their lifetimes. It’s also the second highest cause of cancer-related death in men, killing roughly 35,000 people each year. The PSA test can help detect prostate cancer early, including aggressive disease, but it mostly catches low-grade, indolent tumors that probably wouldn’t have been an issue for the patient. The problem then is that diagnosing these patients and treating them for cancer subjects them to radiation and surgery, which has side effects including harming sexual health and urinary function.
That’s what scientists call overdiagnosis and overtreatment, and it probably would’ve been better if the patient had never been treated at all. On top of that, clinical trials in the late 2000s suggested that the PSA test likely only had a modest reduction in mortality, said Paul Pinsky, chief of early detection at the National Cancer Institute, who did not work on the study.
“When we thought about overdiagnosis and mortality reduction which was not great, some people started to sour on screening with PSA,” Pinsky said. Currently, most health authorities recommend people make a shared decision with their physician about prostate screening. “That’s mainly because we think there’s some benefit, but we know there’s a lot of harm.”
So scientists and clinicians began pushing to reduce the harms of screening. Active surveillance was the first way to do that. Doctors wouldn’t treat low-grade prostate cancer unless it seemed to progress on subsequent testing. The problem with that is patients may need to come back multiple times a year for more PSA testing and potentially MRIs and more biopsies, too. Plus, the anxiety and pressure of having a cancer diagnosis can drive some people with low-grade prostate cancer to seek curative treatment anyway. Considering most of these cancers don’t progress, experts began wondering if it’d be better to not even bother finding low-grade cancers in the first place.
One way to do that is to only biopsy men who have a suspicious lesion on an MRI scan, and only sample the lesion instead of systematically taking pieces from all around the prostate, which is typical. This is the route that University of Gothenburg’s Hugosson tested in the NEJM study.
The study enrolled about 13,000 men in Sweden. For all the men, if they had an elevated PSA of over 3 nanograms per milliliter of blood, they would receive an MRI. Then, about half were randomized to get systematic biopsy regardless of the MRI result — as well as a biopsy targeted on a lesion if one was visible. The other half received a targeted biopsy only if a lesion was present on MRI. After a median of four years, Hugosson found that those in the targeted biopsy-only group got significantly fewer biopsies and diagnoses of clinically insignificant cancers.
“We reduce biopsy frequency by about 60%. If you look at the overdiagnosis rate, we reduce that by approximately 57%,” said Hugosson. “That is very valuable.”
That was expected, Hugosson said. Other scientists have shown that only taking a biopsy if the MRI is positive can reduce the harms of screening. “We wanted to show that it’s a safe strategy, because many urologists around the world have been afraid that if you do not biopsy MRI-negative men, some will develop advanced cancers for sure,” he said.
Notably, Hugosson didn’t see a statistically significant increase in advanced, incurable cancers among men who only had biopsies when there was a visible lesion on MRI. Put another way, using the MRI-targeted approach would spare 51 men from undergoing biopsy and 14 men from receiving grade 1 prostate cancer diagnoses out of every 1,000 men. The strategy also missed a few men with clinically significant prostate cancer on a first screen, but was able to catch them on subsequent testing some years later. It delayed the diagnosis of clinically significant cancer in three men.
“They did not find evidence that patients were at all failed by the system because an MRI was negative,” said Tyler Seibert, a radiation oncologist and prostate cancer researcher at the University of California, San Diego who didn’t work on the study. Some patients might still slip through the cracks and present with incurable cancer, but Seibert said it’s impossible to prevent every single case. In the MRI-targeted group, five men had advanced or incurable cancer detected in a follow-up. Four of them originally had a PSA under 3, however, and the last had a false-negative biopsy.
Overall, Seibert said, the strategy “worked to avoid clinically insignificant cancer. It seemed to find almost all the cancers if you did the systematic biopsy approach. This is a great result for patients.”
The result may tip the balance towards a broader screening recommendation, if MRI can be done. “I think it does swing the pendulum in a favorable direction,” said Oliver Sartor, an oncologist and cancer researcher at the Mayo Clinic who did not work on the study. “This method of screening diminishes the risk of overdiagnosis. It diminishes the risk of infections from biopsy.”
But it simply may not be feasible to implement a wide-scale MRI program. Urologists and genitourinary oncologists have already begun pushing for MRI before biopsy for prostate screening, Seibert said. This study strengthens the evidence that this strategy is a good one, but it may not be feasible on a large scale. Currently, only a third of patients in urban areas receive MRI before a prostate biopsy, even less in rural areas.
“We know MRI should happen before biopsy. It’s already in the guidelines. It’s not happening because there aren’t enough MRI scanners,” Seibert said. Not only that, but getting a good scan on the prostate isn’t straightforward. “It’s not like pushing a button. These are like DSLR cameras on steroids. You need experts to do it, experts to interpret it, and that just doesn’t exist everywhere yet.”
Scientists like Seibert are working on improving this by essentially creating presets for prostate imaging on MRI machines and AI for interpreting them. That could increase the efficiency of MRI scanning for prostate screening and reduce the need for specialized radiologists for this strategy. Researchers are also working on ways other than MRI to reduce the harms of prostate screening, including developing other blood or urine biomarkers or personalized prostate screening programs based on individual genetic risk factors.
Whether all this reduction in harms actually changes whether people get screened may depend on their personal preferences, Seibert said. “This study won’t make it so that everybody jumps on the pro-screening side of things. Some people will say, we’re only doing a big screening program if we save lots of lives,” Seibert said. “If we don’t know that this will make you live longer, then is it worth it to you, and opinions vary on that.”
For Seibert, personally, he will be getting screened for prostate cancer, because even if it doesn’t help him live a longer life, it will help him avoid metastatic prostate cancer. “Even if I die of a heart attack, I don’t want to spend those years being treated for metastatic prostate cancer, because the treatment is really rough. So yes, I would prefer to be screened. But others do not,” he said.
That’s why these conversations with physicians are important, he said. The only problem with that is finding a primary care physician with the time for it.
