Women's Health

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Patients experiencing memory problems often come to neurologist David Jones, MD, for second opinions. They repeat questions and sometimes misplace items. Their primary care clinician has suggested they may have Alzheimer’s disease or something else.

In many cases, Dr. Jones, a neurologist with Mayo Clinic in Rochester, Minnesota, performs a series of investigations and finds the patient instead has a different type of neurodegenerative syndrome, one that progresses slowly, seems limited chiefly to loss of memory, and which tests show affects only the limbic system.

The news of diagnosis can be reassuring to patients.

“Memory problems are not always Alzheimer’s disease,” Dr. Jones said. “It’s important to broaden the differential diagnosis and seek diagnostic clarity and precision for patients who experience problems with brain functioning later in life.”

Dr. Jones and colleagues recently published clinical criteria for what they call limbic-predominant amnestic neurodegenerative syndrome (LANS).

Various underlying etiologies are known to cause degeneration of the limbic system, the most frequent being a buildup of deposits of the TAR DNA-binding protein 43 (TDP-43) protein referred to as limbic-predominant, age-related TDP-43 encephalopathy neuropathological change (LATE-NC). LATE-NC first involves the amygdala, followed by the hippocampus, and then the middle frontal gyrus, and is found in about 40% of autopsied brains in people over age of 85 years.

By contrast, amnestic syndromes originating from neocortical degeneration are largely caused by neuropathological changes from Alzheimer’s disease and often present with non-memory features.
 

Criteria for LANS

Broken down into core, standard, and advanced features

Core clinical features:

The patient must present with a slow, amnestic, predominant neurodegenerative syndrome — an insidious onset with gradual progression over 2 or more years — without another condition that better accounts for the clinical deficits.

Standard supportive features:

1. Older age at evaluation.

• Most patients are at least the age of 75 years. Older age increases the likelihood that the amnestic syndrome is caused by degeneration of the limbic system.

2. Mild clinical syndrome.

• A diagnosis of mild cognitive impairment or mild amnestic dementia (ie, a score of ≤ 4 on the Clinical Dementia Rating Sum of Boxes [CDR-SB]) at the first visit.

3. Hippocampal atrophy out of proportion to syndrome severity.

• Hippocampal volume was smaller than expected on MRI, compared with the CDR-SB score.

4. Mildly impaired semantic memory.

Advanced supportive features:

1.Limbic hypometabolism and absence of neocortical degenerative pattern on fludeoxyglucose-18-PET imaging.

2. Low likelihood of significant neocortical tau pathology.


Dr. Jones and colleagues also classified a degree of certainty for LANS to use when making a diagnosis. Those with the highest likelihood meet all core, standard, and advanced features.

Patients with a high likelihood of having LANS meet core features, at least three standard features and one advanced feature; or meet core features, at least two standard features as well as two advanced features. Those with a moderate likelihood meet core features and at least three standard features or meet core features and at least two standard features and one advanced feature. Those with a low likelihood of LANS meet core features and two or fewer standard features.

To develop these criteria, the group screened 218 autopsied patients participating in databases for the Mayo Clinic Study of Aging and the multicenter Alzheimer’s Disease Neuroimaging Initiative. They conducted neuropathological assessments, reviewed MRI and PET scans of the brains, and studied fluid biomarkers from samples of cerebrospinal fluid.

In LANS, the neocortex exhibits normal function, Dr. Jones said. High-level language functions, visual spatial functions, and executive function are preserved, and the disease stays mild for many years. LANS is highly associated with LATE, for which no biomarkers are yet available.

The National Institute on Aging in May 2023 held a workshop on LATE, and a consensus group was formed to publish criteria to help with the diagnosis. Many LANS criteria likely will be in that publication as well, Dr. Jones said.

Several steps lay ahead to improve the definition of LANS, the authors wrote, including conducting prospective studies and developing clinical tools that are sensitive and specific to its cognitive features. The development of in vivo diagnostic markers of TDP-43 pathology is needed to embed LANS into a disease state driven by LATE-NC, according to Dr. Jones’ group. Because LANS is newly defined, clinical trials are needed to determine the best treatments.
 

Heterogeneous Dementia

“We are increasingly recognizing that the syndrome of dementia in older adults is heterogeneous,” said Sudha Seshadri, MD, DM, a behavioral neurologist and founding director of the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio.

LANS “is something that needs to be diagnosed early but also needs to be worked up in a nuanced manner, with assessment of the pattern of cognitive deficits, the pattern of brain shrinkage on MRI, and also how the disease progresses over, say, a year,” said Dr. Seshadri. “We need to have both some primary care physicians and geriatricians who are comfortable doing this kind of nuanced advising and others who may refer patients to behavioral neurologists, geriatricians, or psychiatrists who have that kind of expertise.”

About 10% of people presenting to dementia clinics potentially could fit the LANS definition, Dr. Seshadri said. Dr. Seshadri was not a coauthor of the classification article but sees patients in the clinic who fit this description.

“It may be that as we start more freely giving the diagnosis of a possible LANS, the proportion of people will go up,” Dr. Seshadri said.

Primary care physicians can use a variety of assessments to help diagnose dementias, she said. These include the Montreal Cognitive Assessment (MoCA), which takes about 10 minutes to administer, or an MRI to determine the level of hippocampal atrophy. Blood tests for p-tau 217 and other plasma tests can stratify risk and guide referrals to a neurologist. Clinicians also should look for reversible causes of memory complaints, such as deficiencies in vitamin B12, folate, or the thyroid hormone.

“There aren’t enough behavioral neurologists around to work up every single person who has memory problems,” Dr. Seshadri said. “We really need to partner on educating and learning from our primary care partners as to what challenges they face, advocating for them to be able to address that, and then sharing what we know, because what we know is an evolving thing.”

Other tools primary care clinicians can use in the initial evaluation of dementia include the General Practitioner Assessment of Cognition and the Mini-Cog, as part of annual Medicare wellness visits or in response to patient or caregiver concerns about memory, said Allison Kaplan, MD, a family physician at Desert Grove Family Medical in Gilbert, Arizona, who coauthored a point-of-care guide for the American Academy of Family Physicians. Each of these tests takes just 3-4 minutes to administer.

If a patient has a positive result on the Mini-Cog or similar test, they should return for further dementia evaluation using the MoCA, Mini-Mental State Examination, or Saint Louis University Mental Status examination, she said. Physicians also can order brain imaging and lab work, as Dr. Seshadri noted. Dementias often accompany some type of cardiovascular disease, which should be managed.

Even if a patient or family member doesn’t express concern about memory, physicians can look for certain signs during medical visits.

“Patients will keep asking the same question, or you notice they’re having difficulty taking care of themselves, especially independent activities of daily living, which could clue you in to a dementia diagnosis,” she said.

Dr. Jones ,Dr. Seshadri, and Dr. Kaplan disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

A study found significant associations between melasma and several comorbidities, including hypertension and hormonal contraception use, which were the most common.

METHODOLOGY:

• Melasma predominantly affects young women of color and often worsens in hyperestrogen states; understanding the association with comorbidities can improve surveillance and treatment strategies.
• Researchers evaluated 41,283 patients with melasma (mean age, 48.8 years; 93% women) from the TriNetX database and an equal number of matched control individuals.
• The main outcome was comorbidities including allergic rhinitis, atopic dermatitis, anticonvulsants, diabetes, hormonal contraceptives, hypothyroidism, hypertension, lupus, rosacea, skin cancer, and malignancy.

TAKEAWAY:

• Among those with melasma, 25% had hypertension and 24% used hormonal contraception, the two most commonly associated risk factors identified.
• Rosacea (odds ratio [OR], 5.1), atopic dermatitis (OR, 3.3), lupus (OR, 2.5), history of skin cancer (OR, 2.5), and history of internal malignancy (OR, 2.1) were associated with the highest risk of developing melasma (P < .01 for all).
• Asian (OR, 2.0; P < .01) and “other/unknown” races (OR, 1.7; P < .01) and Hispanic ethnicity (OR, 1.3; P < .01) were also significantly associated with melasma, while the odds were slightly lower among White, Black/African American, and “not Hispanic” groups (ORs, 0.8; P < .01 for all groups).

IN PRACTICE:

“Understanding the potential associations between these risk factors and melasma will better improve the management and monitoring of the most susceptible patients,” the authors wrote.

SOURCE:

The study, led by Ajay N. Sharma, MD, MBA, of the Department of Dermatology at the University of California, Irvine, was published online in Journal of Drugs in Dermatology.

LIMITATIONS:

The study limitations included the retrospective design, potential misclassification of diagnoses, and the inability to establish causality.

DISCLOSURES:

The study did not disclose any funding sources. The authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

An estimated 25 million adult Americans experience temporary or chronic urinary incontinence.

Although urinary incontinence can occur in both women and men at any age, it is more common in women over age 50. According to Rise for Health, a national survey-based research study on bladder health, up to 40% of girls and women experience urinary problems and it may be as high as 50% or 60%.

“The main known predictors of urinary incontinence are age, obesity, diabetes, and pregnancy and childbirth,” said internist Joan M. Neuner MD, MPH, a professor of women’s health at Medical College of Wisconsin, Milwaukee.

courtesy Northwell Health

Other causes are urinary tract infections, pelvic surgery, and in men, of course, prostate problems. Medications such as antihypertensives and antidepressants can promote urinary incontinence. Inexplicably, smokers seem to be at higher risk. Childbearing is a prime reason women are at greater risk. “While C-section can be protective against many pelvic floor issues, vaginal delivery, particularly forceps assisted, increases the risk for urinary incontinence,” said Sarah Friedman, MD, director of the Division of Urogynecology at Staten Island University Hospital, New York City.

Urinary incontinence is underrecognized and undertreated in primary care and may not get enough emphasis in medical schools. Dr. Neuner recently coauthored a small pilot study on developing a primary care pathway to manage urinary incontinence. It suggested that a streamlined paradigm from identification and patient self-care through basic medical care and specialty referral might assist primary care providers as first-line providers in urinary incontinence.

courtesy Medical College of Wisconsin

Urinary incontinence’s impact on quality of life should not be underestimated. “It depends on severity, but people may limit their physical activities and social activities, including work, going out with friends, and sexual activity, which can in turn increase loneliness and depression,” Dr. Neuner said in an interview. “Incontinence products like pads and adult diapers are costly and often not covered by insurance.”

In fact, urinary incontinence costs US men and women more than $20 billion per year, mostly for management supplies such as pads and laundry.
 

Primary Care

While primary care practitioners are well positioned to manage urinary incontinence, the majority of patients remain untreated.

courtesy Corewell Health

The current stepwise approach should start with a knowledge of basic micturition physiology to identify the incontinence type before selecting treatment, said Khaled A. Imam, MD, CMD, a geriatrician at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan. “More important, this working knowledge can prevent the prescription of an inappropriate treatment or drug, thus preventing many adverse effects,”

According to Dr. Imam, urinary incontinence occurs “because the outlet is open when it should be closed, the outlet is closed when it should be open, the detrusor fails to contract, or the detrusor contracts when it should not.”

There are five main types of incontinence: transient, detrusor overactivity (urge), stress, overflow, and functional. The primary care evaluation of urinary incontinence should include history taking, physical examination, post-voiding residual volume measurement, urinalysis, and urine culture, according to Dr. Imam. “The physical examination should include a urine stress test, abdominal examination, pelvic examination in female patients, rectal examination, and neurologic evaluation.”
 

Screening

“I am always careful before recommending additional screening that hasn’t been backed by a large screening study. Incontinence has not,” said Dr. Neuner. “However, at most preventive visits, PC [primary care] doctors do a review of systems that includes common symptoms. And so if a PC is currently asking a more generic question like ‘any problems with urine?’ I recommend they replace it with the more specific ‘during the last 3 months, have you leaked any urine, even a small amount?’ ”

courtesy Medical College of Wisconsin

Added Kathryn E. Flynn, PhD, a professor of medicine at Medical College of Wisconsin and Dr. Neuner’s coauthor on the primary care pilot study: “Routine screening for urinary incontinence in primary care makes a lot of sense because most older women visit a primary care provider regularly, but they often don’t want to bring the topic up to their provider. When providers routinely screen, it can reduce that barrier to disclosure.“
 

Treatment

For many women, DIY measures such as losing weight, restricting badder irritants such as caffeine or alcohol, scheduled or double voiding, and at-home Kegel exercises are not enough. Fortunately, treatment options are expanding.

“Nonpharmacologic interventions such as pelvic physical therapy can strengthen the pelvic floor muscles and improve incontinence as long as the muscle strength is maintained,” said Dr. Friedman. “Some procedural or surgical effects last long term and some are shorter acting and need to be repeated over time, but a medication’s effect on bladder function lasts only as long as you take it.”

Strengthening pelvic floor muscles. Solutions for stress incontinence – leakage during coughing, sneezing, lifting, or jumping – aim to hold the urethra closed in the face of increased pressure. “Strengthening the pelvic floor muscles can help hold the urethra closed, but many of us do not know how to contract our pelvic floor muscles correctly,” said Heidi Brown, MD, MAS, a clinician researcher at Kaiser Permanente Southern California and a urogynecologist at Kaiser Permanente San Diego Medical Center. “Working with a pelvic floor therapist is not an option for many busy people, so devices that can be used at home to help women confirm they’re contracting their muscles correctly and remind them to do their exercises are becoming more popular.”

courtesy Kaiser Permanente Southern California

These trainers include external thigh exercisers and vaginal Kegel balls or weights. Kegel chairs that electromagnetically stimulate pelvic muscle contractions are another option, if more expensive. Some deliver pelvic therapy in clinic sessions, but there are several portable versions for home use available online.

According to Dr. Neuner, “pelvic exercises can reduce incontinence by 50% or more. “Some women stay completely dry with them but many women will need help to do these and I usually recommend a referral to a pelvic floor physical therapist or someone with extensive experience.”

Drugs. Overactive bladder, or urge urinary incontinence, leads to leakage because the bladder muscle contracts strongly at inappropriate times. Anticholinergics/antimuscarinics such as oxybutynin (Oxytrol, Ditropan) have been used for decades to control these spasms by relaxing the bladder muscle. Because of recent concerns about their association with cognitive impairment after long-term use, these agents are now being used more cautiously, said Dr. Brown. “A newer class of medication, the beta-3-adrenergic agonists, has not been shown to have that association with cognitive impairment and this class is now being used more frequently to treat overactive bladder.”

This class includes the beta-3-adrenergic agonists vibegron (Gemtesa) and mirabegron (Myrbetriq), which a recent Japanese crossover study found to be comparably effective in women with overactive bladder.

“While they have fewer safety concerns, these newer agents can be costly or may require lots of insurance paperwork, and while I hope that will improve soon, it hasn’t yet,” said Dr. Neuner.

Another pharmacologic option is botulinum A toxin (Botox). Injected into the bladder, this neurotoxin can ease urgency and frequency by relaxing the bladder muscle, added Dr. Friedman.

In some cases combination pharmacotherapy may be advisable.

Surgery. Mid-urethral slings are still considered the preferred option for stress urinary incontinence because they are minimally invasive, safe, and very effective, said Dr. Brown. “Single-incisions slings are an emerging treatment for stress incontinence, because they require one incision instead of three, but their effectiveness has not been proven as robustly as that of the traditional mid-urethral slings,” Dr. Brown said.

Urethral bulking. Bulking can reduce incontinence caused by straining as in defecation by thickening the wall of the urethra. This procedure uses a needle to inject a filler material such as collagen. “These injections are gaining more popularity as research uncovers filler materials that are more durable and with fewer potential complications,” Dr. Brown said.

Neuromodulation. This technique works to reprogram communication between the nerves and the bladder. While conventional therapy worked by relaxing the bladder muscle itself, newer approaches target the nerve that controls the muscle. This can be done at home with gentle, acupuncture-like electric stimulation of the S3 sacral nerve.

“Traditional methods of stimulating the S3 nerve involved placing a needle in the ankle and delivering electrical stimulation via that needle in the doctor’s office, or placing a wire in the nerve near the spine and implanting a pacemaker to deliver electrical stimulation,” Dr. Brown explained. “There are now emerging therapies that implant a device in the ankle to allow electrical stimulation of the S3 nerve in the home, providing a minimally invasive option that does not require weekly trips to the office.”

InterStim is a neural pacemaker that is inserted into the fat of the buttocks and patient controlled by a small handheld external device.

Biofeedback is a technique works for some. A patch applied to the skin over the bladder and urethra area and connected to an external monitor allows patients to see the bladder muscle contracting and teaches them to control spasms and prevent leaks.

Dr. Neuner advises primary care doctors to connect with a local incontinence expert and refer patients to a specialist early on if their condition isn’t improving. “There are both surgical and nonsurgical treatments that only those specialists can give and that can be more effective if given before incontinence is severe — or before the patient has been so frustrated with other treatments that she doesn’t want to try anything else.”

When discussing potential outcomes with patients, Dr. Friedman’s advice is to explain that each management option has different success rates. “Patients need to know that urinary incontinence is a very common condition, but it is not a condition you need to live with. There are many treatments available, all with the goal of improving quality of life.”

The primary care pathway pilot study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Study authors Dr. Neuner and Dr. Flynn disclosed no relevant conflicts of interest. Dr. Friedman, Dr. Imam, and Dr. Brown disclosed no relevant conflicts of interest.

*Story was updated on August 7, 2024.

An estimated 25 million adult Americans experience temporary or chronic urinary incontinence.

Although urinary incontinence can occur in both women and men at any age, it is more common in women over age 50. According to Rise for Health, a national survey-based research study on bladder health, up to 40% of girls and women experience urinary problems and it may be as high as 50% or 60%.

“The main known predictors of urinary incontinence are age, obesity, diabetes, and pregnancy and childbirth,” said internist Joan M. Neuner MD, MPH, a professor of women’s health at Medical College of Wisconsin, Milwaukee.

courtesy Northwell Health

Other causes are urinary tract infections, pelvic surgery, and in men, of course, prostate problems. Medications such as antihypertensives and antidepressants can promote urinary incontinence. Inexplicably, smokers seem to be at higher risk. Childbearing is a prime reason women are at greater risk. “While C-section can be protective against many pelvic floor issues, vaginal delivery, particularly forceps assisted, increases the risk for urinary incontinence,” said Sarah Friedman, MD, director of the Division of Urogynecology at Staten Island University Hospital, New York City.

Urinary incontinence is underrecognized and undertreated in primary care and may not get enough emphasis in medical schools. Dr. Neuner recently coauthored a small pilot study on developing a primary care pathway to manage urinary incontinence. It suggested that a streamlined paradigm from identification and patient self-care through basic medical care and specialty referral might assist primary care providers as first-line providers in urinary incontinence.

courtesy Medical College of Wisconsin

Urinary incontinence’s impact on quality of life should not be underestimated. “It depends on severity, but people may limit their physical activities and social activities, including work, going out with friends, and sexual activity, which can in turn increase loneliness and depression,” Dr. Neuner said in an interview. “Incontinence products like pads and adult diapers are costly and often not covered by insurance.”

In fact, urinary incontinence costs US men and women more than $20 billion per year, mostly for management supplies such as pads and laundry.
 

Primary Care

While primary care practitioners are well positioned to manage urinary incontinence, the majority of patients remain untreated.

courtesy Corewell Health

The current stepwise approach should start with a knowledge of basic micturition physiology to identify the incontinence type before selecting treatment, said Khaled A. Imam, MD, CMD, a geriatrician at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan. “More important, this working knowledge can prevent the prescription of an inappropriate treatment or drug, thus preventing many adverse effects,”

According to Dr. Imam, urinary incontinence occurs “because the outlet is open when it should be closed, the outlet is closed when it should be open, the detrusor fails to contract, or the detrusor contracts when it should not.”

There are five main types of incontinence: transient, detrusor overactivity (urge), stress, overflow, and functional. The primary care evaluation of urinary incontinence should include history taking, physical examination, post-voiding residual volume measurement, urinalysis, and urine culture, according to Dr. Imam. “The physical examination should include a urine stress test, abdominal examination, pelvic examination in female patients, rectal examination, and neurologic evaluation.”
 

Screening

“I am always careful before recommending additional screening that hasn’t been backed by a large screening study. Incontinence has not,” said Dr. Neuner. “However, at most preventive visits, PC [primary care] doctors do a review of systems that includes common symptoms. And so if a PC is currently asking a more generic question like ‘any problems with urine?’ I recommend they replace it with the more specific ‘during the last 3 months, have you leaked any urine, even a small amount?’ ”

courtesy Medical College of Wisconsin

Added Kathryn E. Flynn, PhD, a professor of medicine at Medical College of Wisconsin and Dr. Neuner’s coauthor on the primary care pilot study: “Routine screening for urinary incontinence in primary care makes a lot of sense because most older women visit a primary care provider regularly, but they often don’t want to bring the topic up to their provider. When providers routinely screen, it can reduce that barrier to disclosure.“
 

Treatment

For many women, DIY measures such as losing weight, restricting badder irritants such as caffeine or alcohol, scheduled or double voiding, and at-home Kegel exercises are not enough. Fortunately, treatment options are expanding.

“Nonpharmacologic interventions such as pelvic physical therapy can strengthen the pelvic floor muscles and improve incontinence as long as the muscle strength is maintained,” said Dr. Friedman. “Some procedural or surgical effects last long term and some are shorter acting and need to be repeated over time, but a medication’s effect on bladder function lasts only as long as you take it.”

Strengthening pelvic floor muscles. Solutions for stress incontinence – leakage during coughing, sneezing, lifting, or jumping – aim to hold the urethra closed in the face of increased pressure. “Strengthening the pelvic floor muscles can help hold the urethra closed, but many of us do not know how to contract our pelvic floor muscles correctly,” said Heidi Brown, MD, MAS, a clinician researcher at Kaiser Permanente Southern California and a urogynecologist at Kaiser Permanente San Diego Medical Center. “Working with a pelvic floor therapist is not an option for many busy people, so devices that can be used at home to help women confirm they’re contracting their muscles correctly and remind them to do their exercises are becoming more popular.”

courtesy Kaiser Permanente Southern California

These trainers include external thigh exercisers and vaginal Kegel balls or weights. Kegel chairs that electromagnetically stimulate pelvic muscle contractions are another option, if more expensive. Some deliver pelvic therapy in clinic sessions, but there are several portable versions for home use available online.

According to Dr. Neuner, “pelvic exercises can reduce incontinence by 50% or more. “Some women stay completely dry with them but many women will need help to do these and I usually recommend a referral to a pelvic floor physical therapist or someone with extensive experience.”

Drugs. Overactive bladder, or urge urinary incontinence, leads to leakage because the bladder muscle contracts strongly at inappropriate times. Anticholinergics/antimuscarinics such as oxybutynin (Oxytrol, Ditropan) have been used for decades to control these spasms by relaxing the bladder muscle. Because of recent concerns about their association with cognitive impairment after long-term use, these agents are now being used more cautiously, said Dr. Brown. “A newer class of medication, the beta-3-adrenergic agonists, has not been shown to have that association with cognitive impairment and this class is now being used more frequently to treat overactive bladder.”

This class includes the beta-3-adrenergic agonists vibegron (Gemtesa) and mirabegron (Myrbetriq), which a recent Japanese crossover study found to be comparably effective in women with overactive bladder.

“While they have fewer safety concerns, these newer agents can be costly or may require lots of insurance paperwork, and while I hope that will improve soon, it hasn’t yet,” said Dr. Neuner.

Another pharmacologic option is botulinum A toxin (Botox). Injected into the bladder, this neurotoxin can ease urgency and frequency by relaxing the bladder muscle, added Dr. Friedman.

In some cases combination pharmacotherapy may be advisable.

Surgery. Mid-urethral slings are still considered the preferred option for stress urinary incontinence because they are minimally invasive, safe, and very effective, said Dr. Brown. “Single-incisions slings are an emerging treatment for stress incontinence, because they require one incision instead of three, but their effectiveness has not been proven as robustly as that of the traditional mid-urethral slings,” Dr. Brown said.

Urethral bulking. Bulking can reduce incontinence caused by straining as in defecation by thickening the wall of the urethra. This procedure uses a needle to inject a filler material such as collagen. “These injections are gaining more popularity as research uncovers filler materials that are more durable and with fewer potential complications,” Dr. Brown said.

Neuromodulation. This technique works to reprogram communication between the nerves and the bladder. While conventional therapy worked by relaxing the bladder muscle itself, newer approaches target the nerve that controls the muscle. This can be done at home with gentle, acupuncture-like electric stimulation of the S3 sacral nerve.

“Traditional methods of stimulating the S3 nerve involved placing a needle in the ankle and delivering electrical stimulation via that needle in the doctor’s office, or placing a wire in the nerve near the spine and implanting a pacemaker to deliver electrical stimulation,” Dr. Brown explained. “There are now emerging therapies that implant a device in the ankle to allow electrical stimulation of the S3 nerve in the home, providing a minimally invasive option that does not require weekly trips to the office.”

InterStim is a neural pacemaker that is inserted into the fat of the buttocks and patient controlled by a small handheld external device.

Biofeedback is a technique works for some. A patch applied to the skin over the bladder and urethra area and connected to an external monitor allows patients to see the bladder muscle contracting and teaches them to control spasms and prevent leaks.

Dr. Neuner advises primary care doctors to connect with a local incontinence expert and refer patients to a specialist early on if their condition isn’t improving. “There are both surgical and nonsurgical treatments that only those specialists can give and that can be more effective if given before incontinence is severe — or before the patient has been so frustrated with other treatments that she doesn’t want to try anything else.”

When discussing potential outcomes with patients, Dr. Friedman’s advice is to explain that each management option has different success rates. “Patients need to know that urinary incontinence is a very common condition, but it is not a condition you need to live with. There are many treatments available, all with the goal of improving quality of life.”

The primary care pathway pilot study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Study authors Dr. Neuner and Dr. Flynn disclosed no relevant conflicts of interest. Dr. Friedman, Dr. Imam, and Dr. Brown disclosed no relevant conflicts of interest.

*Story was updated on August 7, 2024.

An estimated 25 million adult Americans experience temporary or chronic urinary incontinence.

Although urinary incontinence can occur in both women and men at any age, it is more common in women over age 50. According to Rise for Health, a national survey-based research study on bladder health, up to 40% of girls and women experience urinary problems and it may be as high as 50% or 60%.

“The main known predictors of urinary incontinence are age, obesity, diabetes, and pregnancy and childbirth,” said internist Joan M. Neuner MD, MPH, a professor of women’s health at Medical College of Wisconsin, Milwaukee.

courtesy Northwell Health

Other causes are urinary tract infections, pelvic surgery, and in men, of course, prostate problems. Medications such as antihypertensives and antidepressants can promote urinary incontinence. Inexplicably, smokers seem to be at higher risk. Childbearing is a prime reason women are at greater risk. “While C-section can be protective against many pelvic floor issues, vaginal delivery, particularly forceps assisted, increases the risk for urinary incontinence,” said Sarah Friedman, MD, director of the Division of Urogynecology at Staten Island University Hospital, New York City.

Urinary incontinence is underrecognized and undertreated in primary care and may not get enough emphasis in medical schools. Dr. Neuner recently coauthored a small pilot study on developing a primary care pathway to manage urinary incontinence. It suggested that a streamlined paradigm from identification and patient self-care through basic medical care and specialty referral might assist primary care providers as first-line providers in urinary incontinence.

courtesy Medical College of Wisconsin

Urinary incontinence’s impact on quality of life should not be underestimated. “It depends on severity, but people may limit their physical activities and social activities, including work, going out with friends, and sexual activity, which can in turn increase loneliness and depression,” Dr. Neuner said in an interview. “Incontinence products like pads and adult diapers are costly and often not covered by insurance.”

In fact, urinary incontinence costs US men and women more than $20 billion per year, mostly for management supplies such as pads and laundry.
 

Primary Care

While primary care practitioners are well positioned to manage urinary incontinence, the majority of patients remain untreated.

courtesy Corewell Health

The current stepwise approach should start with a knowledge of basic micturition physiology to identify the incontinence type before selecting treatment, said Khaled A. Imam, MD, CMD, a geriatrician at Corewell Health William Beaumont University Hospital in Royal Oak, Michigan. “More important, this working knowledge can prevent the prescription of an inappropriate treatment or drug, thus preventing many adverse effects,”

According to Dr. Imam, urinary incontinence occurs “because the outlet is open when it should be closed, the outlet is closed when it should be open, the detrusor fails to contract, or the detrusor contracts when it should not.”

There are five main types of incontinence: transient, detrusor overactivity (urge), stress, overflow, and functional. The primary care evaluation of urinary incontinence should include history taking, physical examination, post-voiding residual volume measurement, urinalysis, and urine culture, according to Dr. Imam. “The physical examination should include a urine stress test, abdominal examination, pelvic examination in female patients, rectal examination, and neurologic evaluation.”
 

Screening

“I am always careful before recommending additional screening that hasn’t been backed by a large screening study. Incontinence has not,” said Dr. Neuner. “However, at most preventive visits, PC [primary care] doctors do a review of systems that includes common symptoms. And so if a PC is currently asking a more generic question like ‘any problems with urine?’ I recommend they replace it with the more specific ‘during the last 3 months, have you leaked any urine, even a small amount?’ ”

courtesy Medical College of Wisconsin

Added Kathryn E. Flynn, PhD, a professor of medicine at Medical College of Wisconsin and Dr. Neuner’s coauthor on the primary care pilot study: “Routine screening for urinary incontinence in primary care makes a lot of sense because most older women visit a primary care provider regularly, but they often don’t want to bring the topic up to their provider. When providers routinely screen, it can reduce that barrier to disclosure.“
 

Treatment

For many women, DIY measures such as losing weight, restricting badder irritants such as caffeine or alcohol, scheduled or double voiding, and at-home Kegel exercises are not enough. Fortunately, treatment options are expanding.

“Nonpharmacologic interventions such as pelvic physical therapy can strengthen the pelvic floor muscles and improve incontinence as long as the muscle strength is maintained,” said Dr. Friedman. “Some procedural or surgical effects last long term and some are shorter acting and need to be repeated over time, but a medication’s effect on bladder function lasts only as long as you take it.”

Strengthening pelvic floor muscles. Solutions for stress incontinence – leakage during coughing, sneezing, lifting, or jumping – aim to hold the urethra closed in the face of increased pressure. “Strengthening the pelvic floor muscles can help hold the urethra closed, but many of us do not know how to contract our pelvic floor muscles correctly,” said Heidi Brown, MD, MAS, a clinician researcher at Kaiser Permanente Southern California and a urogynecologist at Kaiser Permanente San Diego Medical Center. “Working with a pelvic floor therapist is not an option for many busy people, so devices that can be used at home to help women confirm they’re contracting their muscles correctly and remind them to do their exercises are becoming more popular.”

courtesy Kaiser Permanente Southern California

These trainers include external thigh exercisers and vaginal Kegel balls or weights. Kegel chairs that electromagnetically stimulate pelvic muscle contractions are another option, if more expensive. Some deliver pelvic therapy in clinic sessions, but there are several portable versions for home use available online.

According to Dr. Neuner, “pelvic exercises can reduce incontinence by 50% or more. “Some women stay completely dry with them but many women will need help to do these and I usually recommend a referral to a pelvic floor physical therapist or someone with extensive experience.”

Drugs. Overactive bladder, or urge urinary incontinence, leads to leakage because the bladder muscle contracts strongly at inappropriate times. Anticholinergics/antimuscarinics such as oxybutynin (Oxytrol, Ditropan) have been used for decades to control these spasms by relaxing the bladder muscle. Because of recent concerns about their association with cognitive impairment after long-term use, these agents are now being used more cautiously, said Dr. Brown. “A newer class of medication, the beta-3-adrenergic agonists, has not been shown to have that association with cognitive impairment and this class is now being used more frequently to treat overactive bladder.”

This class includes the beta-3-adrenergic agonists vibegron (Gemtesa) and mirabegron (Myrbetriq), which a recent Japanese crossover study found to be comparably effective in women with overactive bladder.

“While they have fewer safety concerns, these newer agents can be costly or may require lots of insurance paperwork, and while I hope that will improve soon, it hasn’t yet,” said Dr. Neuner.

Another pharmacologic option is botulinum A toxin (Botox). Injected into the bladder, this neurotoxin can ease urgency and frequency by relaxing the bladder muscle, added Dr. Friedman.

In some cases combination pharmacotherapy may be advisable.

Surgery. Mid-urethral slings are still considered the preferred option for stress urinary incontinence because they are minimally invasive, safe, and very effective, said Dr. Brown. “Single-incisions slings are an emerging treatment for stress incontinence, because they require one incision instead of three, but their effectiveness has not been proven as robustly as that of the traditional mid-urethral slings,” Dr. Brown said.

Urethral bulking. Bulking can reduce incontinence caused by straining as in defecation by thickening the wall of the urethra. This procedure uses a needle to inject a filler material such as collagen. “These injections are gaining more popularity as research uncovers filler materials that are more durable and with fewer potential complications,” Dr. Brown said.

Neuromodulation. This technique works to reprogram communication between the nerves and the bladder. While conventional therapy worked by relaxing the bladder muscle itself, newer approaches target the nerve that controls the muscle. This can be done at home with gentle, acupuncture-like electric stimulation of the S3 sacral nerve.

“Traditional methods of stimulating the S3 nerve involved placing a needle in the ankle and delivering electrical stimulation via that needle in the doctor’s office, or placing a wire in the nerve near the spine and implanting a pacemaker to deliver electrical stimulation,” Dr. Brown explained. “There are now emerging therapies that implant a device in the ankle to allow electrical stimulation of the S3 nerve in the home, providing a minimally invasive option that does not require weekly trips to the office.”

InterStim is a neural pacemaker that is inserted into the fat of the buttocks and patient controlled by a small handheld external device.

Biofeedback is a technique works for some. A patch applied to the skin over the bladder and urethra area and connected to an external monitor allows patients to see the bladder muscle contracting and teaches them to control spasms and prevent leaks.

Dr. Neuner advises primary care doctors to connect with a local incontinence expert and refer patients to a specialist early on if their condition isn’t improving. “There are both surgical and nonsurgical treatments that only those specialists can give and that can be more effective if given before incontinence is severe — or before the patient has been so frustrated with other treatments that she doesn’t want to try anything else.”

When discussing potential outcomes with patients, Dr. Friedman’s advice is to explain that each management option has different success rates. “Patients need to know that urinary incontinence is a very common condition, but it is not a condition you need to live with. There are many treatments available, all with the goal of improving quality of life.”

The primary care pathway pilot study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. Study authors Dr. Neuner and Dr. Flynn disclosed no relevant conflicts of interest. Dr. Friedman, Dr. Imam, and Dr. Brown disclosed no relevant conflicts of interest.

*Story was updated on August 7, 2024.

This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Lawyers have the saying, “Bad facts make for bad cases; bad cases make for bad laws.” What we’re seeing, I fear, all too often in discussions about reproductive rights, reproductive behavior, and attempts to regulate and legislate with respect to abortion and contraception are many bad facts.

I do think it’s important that science and medicine speak up in local settings and every opportunity they have, not so much to say what government should do or to say whether they think a particular law is good or bad, but certainly to get the facts straight in their role as doctors, sometimes as scientists, and as caregivers.

Bad facts are making many bad policies in the reproductive behavior space. For example, there are many people, mainly on the conservative side, who are saying things like intrauterine devices, emergency contraception, and even birth control cause abortions. That is simply not true.

There are interventions that prevent fertilization from occurring. There are also interventions that prevent implantation from occurring. Neither of those are abortions. If an embryo has not implanted into a womb, it is not, by any biological definition, a pregnancy. 

In situations where a barrier method or something else prevents sperm and egg from meeting or if there is an agent that prevents an egg from implanting, these are facts that legislators, the public, and even your patients need to understand if they’re going to make sound policy about access to methods used to control reproduction.

Similarly, you can see debates about whether embryos are deserving of rights. An Alabama court has ruled that embryos are tiny children. A court can say what it wishes in terms of legal status, but it shouldn’t be deviating from the facts. 

The facts are clear. Embryos outside of a uterus implanted are not babies. They are not children. At most, an embryo in a dish might be considered, let’s say, a possible person. Once it implants in a uterus, it may become a potential person because it then still has a failure rate, postimplantation, of not becoming a baby that’s very high. Approximately 40%-50% of such embryos are genetically flawed and aren’t going to be able to turn into a child.

The notion that every embryo, whether it’s stored in a tank or sitting in a dish, is somehow a tiny child, factually is just not true. You can’t make good policy if you ignore the facts. People may wish to protect embryos. They may wish to restrict in vitro fertilization. They may wish to have people implant any embryo that is created and mandate that it has to happen because they don’t want any tiny children not to be brought to term.

Factually, they’re operating outside the realm of what biology and medicine know. There’s no tiny baby, no homunculus, or no preformed baby inside an embryo. An egg that simply fails to implant is not technically even a pregnancy. 

I think all of us have an obligation when we’re in disputes, wherever they occur, whether we’re fighting about laws, having an argument with the neighbors, or speaking to younger high school students or even patients, we need to try to make clear the facts about what we know about eggs, how birth control works, and embryos and their failure rate. 

We also have to be clear about the significance of saying the facts have to guide public policy. I think the facts should, but unfortunately, I don’t think that’s always been true in recent years. As efforts heat up to intervene more with things like contraception, getting the facts straight becomes even more important and more of a duty for those who know best.

Dr. Caplan is director, Division of Medical Ethics, New York University Langone Medical Center, New York. He served as a director, officer, partner, employee, adviser, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position). He is a contributing author and adviser for Medscape.

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

A version of this article first appeared on Medscape.com.

The US Food and Drug Administration (FDA) has expanded the approval of dostarlimab-gxly (Jemperli, GSK) in conjunction with carboplatin and paclitaxel, followed by single-agent dostarlimab-gxly, for adults with primary advanced or recurrent endometrial cancer.

Prior FDA approval of the combination was granted for adults with primary advanced or recurrent endometrial cancer that was mismatch repair deficient (dMMR) or microsatellite instability–high (MSI-H).

The expanded approval, granted following a priority review, was based on efficacy and safety demonstrated in the randomized, controlled, multicenter RUBY trial, which included 494 patients who were randomized to receive the dostarlimab-gxly regimen or placebo plus carboplatin and paclitaxel, followed by placebo.

Researchers observed a significant improvement in median overall survival with treatment vs placebo in the overall population — 44.6 vs 28.2 months, respectively (hazard ratio [HR], 0.69). Median progression-free survival was also significantly better in the treatment vs placebo group — 11.8 vs 7.9 months, respectively (HR, 0.64).

“Today’s expanded approval will offer even more patients the opportunity for improved outcomes,” Matthew Powell, MD, of Washington University School of Medicine, and principal investigator on the RUBY trial, said in a press release. “This is the only immuno-oncology treatment regimen that has shown a statistically significant overall survival benefit for the full patient population, which is a meaningful step forward in treating this challenging cancer.”

Adverse reactions occurring in at least 20% of patients receiving dostarlimab-gxly include anemia, increased creatinine levels, peripheral neuropathy, decreased white blood cell counts, fatigue, nausea, alopecia, low platelet counts, increased glucose levels, lymphopenia, neutropenia, liver function test abnormalities, arthralgia, rash, constipation, diarrhea, decreased albumin levels, abdominal pain, dyspnea, decreased appetite, increased amylase levels, urinary tract infection, and vomiting. Immune-mediated adverse reactions with dostarlimab-gxly were similar to those previously reported.

The recommended dostarlimab-gxly dose, according to the full prescribing information, is 500 mg every 3 weeks for six cycles administered before carboplatin and paclitaxel if given on the same day, followed by 1000 mg monotherapy every 6 weeks until disease progression or unacceptable toxicity, or up to 3 years.
 

A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Oncologists show significant variability in prescribing systemic cancer therapies in the last 30 days of life. Patients treated by oncologists in the top quartile for end-of-life prescribing behavior were almost four and a half times more likely to receive end-of-life therapy than those treated by these specialists in the bottom quartile.

METHODOLOGY:

• Researchers analyzed data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, focusing on patients who died of cancer between 2012 and 2017.
• A total of 17,609 patients with breast, lung, colorectal, or prostate cancer were included, treated by 960 oncologists across 388 practices.
• Patients were required to have had at least one systemic cancer therapy claim in the last 180 days of life, with the treating oncologist identified on the basis of the therapy claim closest to the time of death.
• The study used multilevel models to estimate oncologists’ rates of providing cancer therapy in the last 30 days of life, adjusting for patient characteristics and practice variation.
• Functional status was assessed on the basis of paid claims for durable medical equipment in the last 60 months of life, with scores categorized as 0, 1, ≥ 2, or unknown.

TAKEAWAY:

• Oncologists in the 95th percentile for high end-of-life prescribing behavior had a 45% adjusted rate of treating patients in the last 30 days of life, compared with 17% among those in the 5th percentile.
• Patients treated by high end-of-life prescribing oncologists had over four times higher odds of receiving systemic therapy in the last 30 days of life (odds ratio [OR], 4.42; 95% CI, 4.00-4.89).
• Higher end-of-life prescribing oncologists also had a higher proportion of patients hospitalized in the last 30 days of life than low prescribers (58% vs 51.9%).
• No significant association was found between oncologist prescribing behavior and patient race or ethnicity, except for Black patients who had lower odds of receiving treatment (OR, 0.77; P < .001).

IN PRACTICE:

“Given calls to rein in overutilization of end-of-life six to eight cancer therapies, our findings highlight an underappreciated area for further research: How treatment discontinuation before death is shaped by oncologists’ unique treatment propensities. Elucidating the reasons for this remarkable variability in oncologist treatment behavior could inform efforts to reduce end-of-life cancer treatment overutilization,” wrote the authors of the study.

SOURCE:

The study was led by Login S. George, PhD, Institute for Health, Health Care Policy and Aging Research, Rutgers University in New Brunswick, New Jersey. It was published online in Cancer.

LIMITATIONS:

The study’s reliance on SEER-Medicare data may limit the generalizability of the findings to patients with Medicare Advantage, private insurance, or Medicaid, as well as younger patients. The lack of data on patient preferences and other health characteristics could confound the results. The study focused on systemic therapies and may not be generalizable to other treatments such as clinical trial drugs, oral therapies, surgery, or radiation. The data from 2012 to 2017 may not reflect more recent trends in cancer treatment.

DISCLOSURES:

The study was supported by grants from the National Cancer Institute and the Rutgers Cancer Institute of New Jersey. George disclosed receiving grants from these organizations. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

A version of this article first appeared on Medscape.com.

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

A version of this article first appeared on Medscape.com.

Federal officials intend to compel US hospitals to improve obstetrical services, with a plan that could result in a potential loss of Medicare and Medicaid funds for institutions that fail to comply with the demands.

The Centers for Medicare and Medicaid Services (CMS) on July 10 announced this proposal, tucking its plan for new conditions of participation (COP) for obstetrician services into the draft 2025 rule on Medicare payments for outpatient hospital services.

The COP requirements are considered the most powerful tool CMS has for trying to improve the quality of medical care. With the new obstetric COP requirement, CMS said it intends to address what it sees as potential shortfalls in training, staffing, transfer protocols, and emergency services readiness.

In practice, hospitals, CMS, and accrediting bodies such as the Joint Commission usually try to address deficiencies to prevent what would be a devastating financial loss for a hospital.

“CMS is using all of our tools to improve the safety, quality, and timeliness of the care that hospitals provide to pregnant women,” Dora Hughes, MD, MPH, acting chief medical officer of the agency, said in a press release about the proposal.

CMS estimated the proposal may add new annual expenses of $70,671 per hospital. For comparison, this figure would represent far less than 1% of the total $1.4 trillion spent on hospital care in the United States in 2022.

CMS said it is trying to address the reasons women in the United States face more risk in giving birth than those in other nations. There were 22 maternal deaths for every 100,000 live births in this country in 2022, compared with 8.6 deaths per 100,000 live births or lower that year in Canada, France, the United Kingdom, Germany, and Japan, CMS said.

But CMS is seeking to impose this new requirement at a time amid growing concerns about “maternity care deserts.”
 

Reasonable Asks?

Between 2011 and 2021, one out of every four rural hospitals in America stopped providing obstetrics services, Senate Finance Chairman Ron Wyden (D-Ore.) said at a May hearing. Mr. Wyden last year was part of a fight to try to prevent the closure of a birthing center in Baker City in rural eastern Oregon.

The federal government should focus first on helping hospitals keep obstetrical facilities open, said Elizabeth Powers, MD, MHA, the health services officer of the Winding Waters Clinic in Enterprise, Oregon.

“Until we can ensure access to services, we can’t even work on quality,” Dr. Powers told this news organization. “If you’re thinking about a Maslow’s hierarchy of achieving health outcomes, access is your foundation, and without a shift in payment, that foundation is eroded.”

In the draft rule, CMS sketched broad mandates about staffing and training. For example, the agency proposes requiring if a hospital offers obstetrical services, “the services must be well organized and provided in accordance with nationally recognized acceptable standards of practice.”

That means CMS likely will need to provide further guidance for hospitals if it proceeds with this plan for obstetric COP requirements, said Soumi Saha, PharmD, JD, senior vice president of government affairs at Premier Inc., a healthcare consultancy and purchasing organization.

Premier is among the many groups, including the American Hospital Association, that oppose the COP proposal.

Dr. Saha said a better approach would be to consolidate the work being done through the US Department of Health and Human Services (HHS), including earlier CMS projects, to address maternal health in a cohesive way. The Centers for Disease Control and Prevention has programs, as does the HHS Office on Women’s Health.

“How do we really get to a holistic, national, unified approach to addressing this issue that is led by HHS at the top level as the top agency and trickles down consistently versus having all of these kinds of disparate programs in place?” she said.

In recent years, the federal and state governments have taken many steps to try to improve maternal healthcare.

These include the extension of Medicaid benefits to new mothers out to 12 months following delivery in most states. CMS also has encouraged hospitals to participate in voluntary statewide or national programs to improve the quality of perinatal care. Last year the agency launched a “Birthing-Friendly” designation icon for qualifying hospitals on its Care Compare online tool.
 

Support and Opposition

CMS is accepting comments on the draft 2025 hospital outpatient rule, which includes the obstetric COP proposal, through September 9.

Supporters of the obstetric COP approach included the American Nurses Association (ANA), which urged CMS to consider how staffing shortages can undermine patient care in creating COP requirements.

“Nurses are professionals providing critical healthcare services to patients; they should not have to fight for allotted breaks and other challenges created by antiquated views of the profession and payment policies that disincentivize adequate nurse staffing,” Debbie Hatmaker, PhD, RN, ANA’s chief nursing officer, wrote in a June 7 comment to CMS.

The American College of Obstetricians and Gynecologists (ACOG) and the Association of American Medical Colleges (AAMC) also objected to the prospect of new COP for maternal healthcare. They detailed their concerns in separate comments submitted in June 2024.

ACOG said it feared many hospitals might opt to close labor and delivery (L&D) units due to new CMS COP requirements, especially if these take effect “without important and direct stakeholder engagement and buy-in.” More than 200 rural hospitals across the United States stopped providing L&D services in the last decade, Christopher M. Zahn, MD, ACOG’s interim chief executive officer, wrote in a comment to CMS.

“The reason for these closures is varied. Many rural hospitals that still have L&D units continue to lose money on patient services overall, and their ability to continue to deliver maternity care is at risk,” Dr. Zahn wrote.

The AAMC urged CMS to focus on using other strategies such as quality measures to try to improve maternal health and to drop the COP approach. CMS must consider how many clinicians play a role in successful births, including those who see patients during their pregnancies, Jonathan Jaffery, MD, MS, AAMC’s chief healthcare officer, wrote in a comment to the agency.

“Hospitals do have a critical role in improving maternal healthcare equity, especially for labor and delivery outcomes,” he wrote, “but cannot be held solely responsible for implementing much-needed improvements and solutions.”
 

A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Elevated blood levels of estradiol are associated with an increased risk for corneal ectasia, characterized by thinning and outward bulging of the tissue, in premenopausal women.

METHODOLOGY:

• Researchers conducted an observational case-control study of premenopausal women with naturally occurring corneal ectasia, named keratoconus (n = 36), or those who developed ectasia after refractive surgery (n = 29) from an eye clinic in Israel between 2019 and 2022, and healthy women from hospital staff (n = 31).
• The median age of the participants was 29, 33, and 31 years, respectively.
• Levels of estradiol in the study participants were measured on the second day of their menstrual cycles.

TAKEAWAY:

• The mean levels of estradiol were 38.0 pg/mL in patients with keratoconus, 43.4 pg/mL in those who developed ectasia after surgery, and 28.6 pg/mL in the healthy controls (all P = .001).
• Increased levels of estradiol were associated with corneal ectasia (adjusted odds ratio, 2.44; P < .001).
• Age and use of oral contraceptives were not associated with the risk for corneal ectasia.

IN PRACTICE:

“Our results could have an impact on patient selection for refractive surgery and on better management of patients with keratoconus,” the authors wrote.

SOURCE:

The study was led by Nir Stanescu, MD, of the Department of Ophthalmology at Assuta Samson Hospital, in Ashdod, Israel. It was published online in the European Journal of Ophthalmology.

LIMITATIONS:

The sample size of the study was relatively small. Causality could not be established due to cross-sectional design. The control group consisting of hospital staff may have led to selection bias. The study did not account for factors such as body mass index, diet, smoking status, alcohol consumption, and exercise, which may affect the circulating levels of estradiol.

DISCLOSURES:

The study did not receive any financial support. The authors declared no conflicts of interests.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

The CDK4/6 inhibitors abemaciclib and ribociclib were independently associated with better progression-free survival (PFS) when compared with palbociclib in a real-world comparison of the agents as first line treatment, along with endocrine therapy (ET), for patients with hormone receptor–positive, HER2-negative advanced breast cancer.

Lead investigator Claudio Vernieri, MD, PhD, presented these findings of the PALMARES-2 study at the annual meeting of the American Society of Clinical Oncology.

“Along with different safety profiles, drug-drug interactions, and costs of the three available CDK4/6 inhibitor molecules, our efficacy data may help clinicians and patients in choosing the most appropriate CDK4/6 inhibitor in specific clinical contexts,” Dr. Vernieri, who is from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy, said during the meeting.

CDK4/6 inhibitors combined with ET, are the standard of care as first line treatment for this population, noted Dr. Vernieri. However, their efficacy has never been directly compared in a large clinical trial.

“Since these compounds have different pharmacokinetics, pharmacodynamics, safety profiles, costs, and drug-drug interactions, identifying which of the three CDK4/6 inhibitors may be more effective in specific clinical contexts is a highly clinically relevant issue,” he said. “Real-world data represent a key source to perform direct comparisons.”

The PALMARES-2 study was a retrospective, multicenter, population-based study, in 18 Italian cancer centers. Its two main objectives were to compare the real-world PFS of abemaciclib versus ribociclib versus palbociclib, in combination with ET, in the whole study cohort, as well as in various subgroups including patients with endocrine-resistant disease, luminal B-like disease, or in premenopausal women.

A total of 1,850 patients (median age, 63 years) were enrolled between January 1, 2016 and September 1, 2023, with 750 (40.6%) receiving palbociclib, and 676 (36.5%) and 424 (22.9%) receiving ribociclib and abemaciclib, respectively.
 

Baseline imbalance

Importantly, there were significant imbalances in baseline characteristics of the patients, with those receiving abemaciclib being more likely to have endocrine-resistant disease, low progesterone receptor expression, and liver metastasis, and less likely to have de novo metastatic disease, compared with other patients, said Dr. Vernieri.

The analysis showed that across the entire cohort, the median real-world PFS and overall survival (OS) were 34.7 months and 66.6 months, respectively, by a January 1, 2024, data cutoff date. “I believe that the overall survival data are still immature to make a definitive conclusion,” he commented, noting that at enrollment only about half of patients had undergone disease progression, and at the close of the study only about 25% had died.

After adjusting for clinically relevant patient- and tumor-related covariates, “we found that both abemaciclib and ribociclib were more effective than palbociclib, whereas we did not find statistically significant differences between abemaciclib and ribociclib,” he reported.

Specifically, the adjusted hazard ratio (aHR) for PFS was 0.71 for abemaciclib versus palbociclib (95% CI, 0.56-0.90; P = .005), 0.81 for ribociclib versus palbociclib (95% CI, 0.65-0.99; P = .048), and 0.91 for abemaciclib versus ribociclib (95% CI, 0.70-1.19; P = .505).

“Regarding subgroup analysis, we found that abemaciclib and ribociclib were more effective than palbociclib in patients with endocrine-resistant or luminal B-like disease, as well as in premenopausal women. Abemaciclib was superior to palbociclib in patients with poorer ECOG [Eastern Cooperative Oncology Group] performance status and to both palbociclib and ribociclib in patients with de novo metastatic disease. Both ribociclib and abemaciclib showed a trend toward higher efficacy in patients with liver metastases. However, this difference only reached statistical significance in patients treated with ribociclib. And finally, the three CDK4/6 inhibitors were similarly effective in patients who were older or at bone-only disease,” he concluded.
 

Justifying adjustment

Speaking during the audience question period Giuseppe Del Priore, MD, from Morehouse School of Medicine in Atlanta, Georgia, said he preferred unadjusted results when examining real-world data, “because that’s the benefit,” and he questioned why the researchers had adjusted their numbers.

Dr. Vernieri explained that the adjustments were made to account for the important imbalances in the baseline characteristics of the patients.

“When we plotted unadjusted curves, we did not find statistically significant differences between these three drugs, only a trend toward the direction that I showed you today,” he said. “However, as you saw from the tables showing the characteristics of patients, there were important imbalances in terms of important prognostic factors in the three patient cohorts. So, I think that, for this kind of data and based on this level of imbalance, adjustment is necessary.

“To reinforce our conclusions, what we did was also to perform a propensity score match–based analysis,” Dr. Vernieri continued. “I did not have the time to show the results today, but these data were fully in line with the study conclusions. And we also performed a backward selection of variables. So, we basically selected variables more likely to be associated with patient prognosis. And also those models confirm the study conclusion. So I think the conclusions are quite solid.”

Dr. Del Priore, an adjunct professor of obstetrics and gynecology with a specialty in oncology, on the other hand, said he was not convinced that any of the drugs might be better or worse in the actual population treated.

“I still maintain that unadjusted real-world data should be presented and then only a limited adjusted analysis performed using the most unbalanced variables,” he said. “To do more elaborate adjustments may falsely imply a difference in drug choice and outcomes which never should be the conclusion with observational studies. Instead, the conclusions should be that, with typical use, the following similarities in PFS and OS were observed. Then point out how drug choice and important prognostic variables might be linked, thus limiting the generalizable conclusions even further.

“I would conclude that prospective studies should balance for the variables used in the PALMARES-2 analyses, which actually may have been chosen for adjustment post hoc,” Dr. Del Priore said.

The study was funded by the Italian Association for Cancer Research, the European Research Council, the Ministero della Salute, the Scientific Directorate of Fondazione IRCCS Istituto Nazionale dei Tumori, Giuliani’s Foundation and Roche. Dr. Vernieri reported consulting or advisory roles with Daiichi Sankyo/Astra Zeneca, Novartis, and Pfizer; speakers’ bureau roles with Accademia Nazionale Di Medicina (ACCMED), Istituto Gentili, Lilly and Novartis; and research funding from Roche. Dr. Del Priore reported no conflicts of interest and disclosed that he is chief medical officer at BriaCell.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

A version of this article first appeared on Medscape.com.

TOPLINE:

Patients with stage I triple-negative breast cancer (TNBC) who have higher levels of stromal tumor-infiltrating lymphocytes (TILs) demonstrate “excellent” 10-year breast cancer–specific survival without chemotherapy, according to new findings, which suggest that stromal TILs could be a useful biomarker to optimize treatment decisions in this patient population.

METHODOLOGY:

• The absolute benefit of chemotherapy remains unclear among patients with stage I TNBC. High levels of stromal TILs, a promising biomarker, have been linked to better survival in patients with TNBC, but data focused on stage I disease are lacking.
• In the current analysis, researchers identified a cohort of 1041 women (mean age at diagnosis, 64.4 years) from the Netherlands Cancer Registry with stage I TNBC who had an available TIL score and had undergone a lumpectomy or a mastectomy but had not received neoadjuvant or adjuvant chemotherapy.
• Patients’ clinical data were matched to their corresponding pathologic data provided by the Dutch Pathology Registry, and a pathologist blinded to outcomes scored stromal TIL levels according to the International Immuno-Oncology Biomarker Working Group guidelines.
• The primary endpoint was breast cancer–specific survival at prespecified stromal TIL cutoffs of 30%, 50%, and 75%. Secondary outcomes included specific survival by pathologic tumor stage and overall survival.

TAKEAWAY:

• Overall, 8.6% of women had a pT1a tumor, 38.7% had a pT1b tumor, and 52.6% had a pT1c tumor. In the cohort, 25.6% of patients had stromal TIL levels of 30% or higher, 19.5% had levels of 50% or higher, and 13.5% had levels of 75% or higher.
• Over a median follow-up of 11.4 years, 335 patients died, 107 (32%) of whom died from breast cancer. Patients with smaller tumors (pT1abNO) had better survival outcomes than those with larger tumors (pT1cNO) — a 10-year breast cancer–specific survival of 92% vs 86%, respectively.
• In the overall cohort, stromal TIL levels of 30% or higher were associated with better breast cancer–specific survival than those with stromal TIL levels below 30% (96% vs 87%; hazard ratio [HR], 0.45). Stromal TIL levels of 50% or greater were also associated with better 10-year breast cancer–specific survival than those with levels below 50% (92% vs 88%; HR, 0.59). A similar pattern was observed for stromal TIL levels and overall survival.
• In patients with pT1c tumors, the 10-year breast cancer–specific survival among those with stromal TIL levels of 30% or higher was 95% vs 83% for levels below the 30% cutoff (HR, 0.24). Similarly, the 10-year breast cancer–specific survival for those in the 50% or higher group was 95% vs 84% for levels below that cutoff (HR, 0.27). The 10-year breast cancer–specific survival improved to 98% among patients with stromal TIL levels of 75% or higher (HR, 0.09).

IN PRACTICE:

The results supported the establishment of “treatment-optimization clinical trials in patients with stage I TNBC, using [stromal] TIL level as an integral biomarker to prospectively confirm the observed excellent survival when neoadjuvant or adjuvant chemotherapy is not administered,” the authors wrote. Assessing stromal TILs is also “inexpensive,” the authors added.

SOURCE:

The research, conducted by Marleen Kok, MD, PhD, Department of Medical Oncology, the Netherlands Cancer Institute, Amsterdam, and colleagues, was published online in JAMA Oncology.

LIMITATIONS:

The authors noted that the study was limited by its observational nature. The patients were drawn from a larger cohort, about half of whom received adjuvant chemotherapy, and the patients who did not receive chemotherapy may have had favorable tumor characteristics. There were also no data on BRCA1 or BRCA2 germline mutation status and recurrences and/or distant metastases. The database did not include data on patient ethnicity because most Dutch patients were White.

DISCLOSURES:

Research at the Netherlands Cancer Institute was supported by institutional grants from the Dutch Cancer Society and the Dutch Ministry of Health, Welfare and Sport. Dr. Kok declared financial relationships with several organizations including Gilead and Domain Therapeutics, as well as institutional grants from AstraZeneca, BMS, and Roche. Other authors also declared numerous financial relationships for themselves and their institutions with pharmaceutical companies.

A version of this article first appeared on Medscape.com.