Dermatology News

Supporters of home phototherapy for patients with plaque and guttate psoriasis had plenty to cheer about at the annual meeting of the American Academy of Dermatology (AAD) in March. There, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, presented results from the LITE study, a trial that tested the hypothesis that narrowband ultraviolet B phototherapy of psoriasis at home is noninferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. While smaller studies have drawn similar conclusions, LITE was the largest trial of its kind to show what many dermatologists have suspected for years: Home phototherapy can be an effective first-line treatment for patients with moderate to severe psoriasis.

The co-primary outcomes in the LITE study were a Physician’s Global Assessment (PGA) score of 0/1 (clear, almost clear) and a Dermatology Life Quality Index (DLQI) score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. Following 12 weeks of treatment, 25.6% of patients in the office-based phototherapy group achieved a PGA score of 0/1 compared with 32.8% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data). Similarly, 33.6% of patients in the office-based phototherapy group achieved a DLQI score of 5 or less compared with 52.4% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data).

Courtesy Dr. Gelfand

A Safe and Effective Option

“I think that it’s important for physicians, insurance companies, and patients with psoriasis to understand that this is a very safe and effective form of therapy,” Craig A. Elmets, MD, professor of dermatology at The University of Alabama at Birmingham, said in an interview. “For people who are not interested in systemic medications or who have contraindications to systemic medications, phototherapy would be ideal,” added Dr. Elmets, first author of the joint AAD–National Psoriasis Foundation (NPF) guidelines for the management and treatment of psoriasis with phototherapy, published in 2019.

Factors beyond efficacy support the role of home phototherapy, Dr. Gelfand said, including the fact that it costs 10-100 times less than biologics for psoriasis and that office-based phototherapy is not available in 90% of counties in the United States. However, insurance coverage of home phototherapy “is highly variable because until the LITE study, there was no large-scale US data to support its use,” he told this news organization.

“Also, insurance companies are broken up into two parts: Durable medical goods and the medical side such as pharmacy costs, and they are siloed. The durable medical goods side views phototherapy as expensive, while the pharmacy side views it as dirt cheap. This is part of the problem with our health system. A lot of things are siloed and don’t make any sense,” said Dr. Gelfand, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania. By working with the NPF and payers, he added, “we’re hoping ... to transform the way insurance companies think about covering home phototherapy.”

In the meantime, he and Dr. Elmets shared practical ways to optimize access to home phototherapy for psoriasis patients:

Have the discussion. Patients “rarely bring this up as an option,” Dr. Elmets said, so the onus is on clinicians to talk about it. In his view, the ideal candidate “is averse to using systemic agents but whose disease is beyond the point where topical medicines alone will work. One of the advantages of phototherapy is that it doesn’t have immunosuppressive effects.”

Clinicians and patients can learn about the efficacy and safety of phototherapy for psoriasis, including home-based options, on the NPF’s web site and by reading the 2019 joint AAD-NPF guidelines.

Shared decision-making is key. “When a patient comes in, I’ll discuss what their treatment options are and [we] will decide upon a course of action based on their unique needs and preferences [and] if it’s medically appropriate, meaning they have the type of psoriasis likely to respond to phototherapy,” Dr. Gelfand said. A patient with psoriasis mainly on the fingernails or genitals “is not a good candidate for phototherapy. If it’s on the trunk or extremities, that patient would be a good candidate.”

Home phototherapy candidates also must be willing and able to operate a machine and have dedicated space in their dwelling for it (most units are about the size of a door). Patients also have to be reliable, follow directions, and come back in person for follow-up appointments “so we can assess their response to treatment and fine-tune things as necessary and make sure they’re not developing any skin damage,” Dr. Gelfand said.

Educate yourself about existing options. Home phototherapy units from manufacturers such as Daavlin, National Biological Corporation, and SolRx range between $1200 and $6000 in cost, Dr. Gelfand said. He and his colleagues used the Daavlin 7 series in the LITE study. That unit features an integrated dosimetry system that delivers the correct dose of energy based on parameters that the prescribing clinician recommends. Settings are based on the patient’s skin type and how much the prescriber wants to increase the dose for each treatment. “The machine does the rest,” he said. “It knows what dose to give, so they get the same dosing as they would in an office situation.”

Smaller home-based phototherapy units designed to treat the hands and feet are available. So are handheld units to treat the scalp. “These can be a nice option for patients who have a few spots, but if the disease is moderate to severe, then it’s going to be pretty laborious to [use them],” Dr. Elmets said.

Remember that phototherapy is not a cure-all. According to the joint AAD-NPF guidelines, most phototherapy regimens require treatments two to three times per week for 10-14 weeks. Once patients achieve their home phototherapy treatment goal, Dr. Elmets often recommends treatments one to two times per week for maintenance.

“Patients with psoriasis have a lifetime condition,” he noted. “There are certainly cases where people have gone on phototherapy, cleared, and then stopped for a period of time. If they flare up, they can always go back to phototherapy. Usually, people who are on phototherapy use some type of topical agents to touch up areas that are resistant.”

Expect pushback from insurers on coverage. While Medicare and some integrated health plans cover home phototherapy, expect to spend time writing letters or placing phone calls to insurance companies to convince them why they should cover home phototherapy for candidate psoriasis patients. “Usually there’s a lot of letter writing and a long delay in getting approval,” Dr. Elmets said.

Dr. Elmets and Dr. Gelfand reported no relevant financial relationships. The LITE study was funded by the Patient-Centered Outcomes Research Institute. Research partners included the National Psoriasis Foundation and Daavlin, which provided the home phototherapy machines and covered the cost of shipping the devices.

A version of this article appeared on Medscape.com.

Supporters of home phototherapy for patients with plaque and guttate psoriasis had plenty to cheer about at the annual meeting of the American Academy of Dermatology (AAD) in March. There, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, presented results from the LITE study, a trial that tested the hypothesis that narrowband ultraviolet B phototherapy of psoriasis at home is noninferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. While smaller studies have drawn similar conclusions, LITE was the largest trial of its kind to show what many dermatologists have suspected for years: Home phototherapy can be an effective first-line treatment for patients with moderate to severe psoriasis.

The co-primary outcomes in the LITE study were a Physician’s Global Assessment (PGA) score of 0/1 (clear, almost clear) and a Dermatology Life Quality Index (DLQI) score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. Following 12 weeks of treatment, 25.6% of patients in the office-based phototherapy group achieved a PGA score of 0/1 compared with 32.8% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data). Similarly, 33.6% of patients in the office-based phototherapy group achieved a DLQI score of 5 or less compared with 52.4% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data).

Courtesy Dr. Gelfand

A Safe and Effective Option

“I think that it’s important for physicians, insurance companies, and patients with psoriasis to understand that this is a very safe and effective form of therapy,” Craig A. Elmets, MD, professor of dermatology at The University of Alabama at Birmingham, said in an interview. “For people who are not interested in systemic medications or who have contraindications to systemic medications, phototherapy would be ideal,” added Dr. Elmets, first author of the joint AAD–National Psoriasis Foundation (NPF) guidelines for the management and treatment of psoriasis with phototherapy, published in 2019.

Factors beyond efficacy support the role of home phototherapy, Dr. Gelfand said, including the fact that it costs 10-100 times less than biologics for psoriasis and that office-based phototherapy is not available in 90% of counties in the United States. However, insurance coverage of home phototherapy “is highly variable because until the LITE study, there was no large-scale US data to support its use,” he told this news organization.

“Also, insurance companies are broken up into two parts: Durable medical goods and the medical side such as pharmacy costs, and they are siloed. The durable medical goods side views phototherapy as expensive, while the pharmacy side views it as dirt cheap. This is part of the problem with our health system. A lot of things are siloed and don’t make any sense,” said Dr. Gelfand, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania. By working with the NPF and payers, he added, “we’re hoping ... to transform the way insurance companies think about covering home phototherapy.”

In the meantime, he and Dr. Elmets shared practical ways to optimize access to home phototherapy for psoriasis patients:

Have the discussion. Patients “rarely bring this up as an option,” Dr. Elmets said, so the onus is on clinicians to talk about it. In his view, the ideal candidate “is averse to using systemic agents but whose disease is beyond the point where topical medicines alone will work. One of the advantages of phototherapy is that it doesn’t have immunosuppressive effects.”

Clinicians and patients can learn about the efficacy and safety of phototherapy for psoriasis, including home-based options, on the NPF’s web site and by reading the 2019 joint AAD-NPF guidelines.

Shared decision-making is key. “When a patient comes in, I’ll discuss what their treatment options are and [we] will decide upon a course of action based on their unique needs and preferences [and] if it’s medically appropriate, meaning they have the type of psoriasis likely to respond to phototherapy,” Dr. Gelfand said. A patient with psoriasis mainly on the fingernails or genitals “is not a good candidate for phototherapy. If it’s on the trunk or extremities, that patient would be a good candidate.”

Home phototherapy candidates also must be willing and able to operate a machine and have dedicated space in their dwelling for it (most units are about the size of a door). Patients also have to be reliable, follow directions, and come back in person for follow-up appointments “so we can assess their response to treatment and fine-tune things as necessary and make sure they’re not developing any skin damage,” Dr. Gelfand said.

Educate yourself about existing options. Home phototherapy units from manufacturers such as Daavlin, National Biological Corporation, and SolRx range between $1200 and $6000 in cost, Dr. Gelfand said. He and his colleagues used the Daavlin 7 series in the LITE study. That unit features an integrated dosimetry system that delivers the correct dose of energy based on parameters that the prescribing clinician recommends. Settings are based on the patient’s skin type and how much the prescriber wants to increase the dose for each treatment. “The machine does the rest,” he said. “It knows what dose to give, so they get the same dosing as they would in an office situation.”

Smaller home-based phototherapy units designed to treat the hands and feet are available. So are handheld units to treat the scalp. “These can be a nice option for patients who have a few spots, but if the disease is moderate to severe, then it’s going to be pretty laborious to [use them],” Dr. Elmets said.

Remember that phototherapy is not a cure-all. According to the joint AAD-NPF guidelines, most phototherapy regimens require treatments two to three times per week for 10-14 weeks. Once patients achieve their home phototherapy treatment goal, Dr. Elmets often recommends treatments one to two times per week for maintenance.

“Patients with psoriasis have a lifetime condition,” he noted. “There are certainly cases where people have gone on phototherapy, cleared, and then stopped for a period of time. If they flare up, they can always go back to phototherapy. Usually, people who are on phototherapy use some type of topical agents to touch up areas that are resistant.”

Expect pushback from insurers on coverage. While Medicare and some integrated health plans cover home phototherapy, expect to spend time writing letters or placing phone calls to insurance companies to convince them why they should cover home phototherapy for candidate psoriasis patients. “Usually there’s a lot of letter writing and a long delay in getting approval,” Dr. Elmets said.

Dr. Elmets and Dr. Gelfand reported no relevant financial relationships. The LITE study was funded by the Patient-Centered Outcomes Research Institute. Research partners included the National Psoriasis Foundation and Daavlin, which provided the home phototherapy machines and covered the cost of shipping the devices.

A version of this article appeared on Medscape.com.

Supporters of home phototherapy for patients with plaque and guttate psoriasis had plenty to cheer about at the annual meeting of the American Academy of Dermatology (AAD) in March. There, Joel M. Gelfand, MD, professor of dermatology and epidemiology at the University of Pennsylvania in Philadelphia, presented results from the LITE study, a trial that tested the hypothesis that narrowband ultraviolet B phototherapy of psoriasis at home is noninferior to office treatment, based on outcomes that matter to patients, clinicians, and payers. While smaller studies have drawn similar conclusions, LITE was the largest trial of its kind to show what many dermatologists have suspected for years: Home phototherapy can be an effective first-line treatment for patients with moderate to severe psoriasis.

The co-primary outcomes in the LITE study were a Physician’s Global Assessment (PGA) score of 0/1 (clear, almost clear) and a Dermatology Life Quality Index (DLQI) score of 5 or less (small, no effect on health-related quality of life).

Dr. Gelfand and colleagues at 42 sites in the United States enrolled 783 patients aged 12 years and older who had plaque or guttate psoriasis and were candidates for phototherapy at home or in an office setting. Following 12 weeks of treatment, 25.6% of patients in the office-based phototherapy group achieved a PGA score of 0/1 compared with 32.8% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data). Similarly, 33.6% of patients in the office-based phototherapy group achieved a DLQI score of 5 or less compared with 52.4% of patients in the home-based phototherapy group (P > .0001 for noninferiority, non-response imputation for missing data).

Courtesy Dr. Gelfand

A Safe and Effective Option

“I think that it’s important for physicians, insurance companies, and patients with psoriasis to understand that this is a very safe and effective form of therapy,” Craig A. Elmets, MD, professor of dermatology at The University of Alabama at Birmingham, said in an interview. “For people who are not interested in systemic medications or who have contraindications to systemic medications, phototherapy would be ideal,” added Dr. Elmets, first author of the joint AAD–National Psoriasis Foundation (NPF) guidelines for the management and treatment of psoriasis with phototherapy, published in 2019.

Factors beyond efficacy support the role of home phototherapy, Dr. Gelfand said, including the fact that it costs 10-100 times less than biologics for psoriasis and that office-based phototherapy is not available in 90% of counties in the United States. However, insurance coverage of home phototherapy “is highly variable because until the LITE study, there was no large-scale US data to support its use,” he told this news organization.

“Also, insurance companies are broken up into two parts: Durable medical goods and the medical side such as pharmacy costs, and they are siloed. The durable medical goods side views phototherapy as expensive, while the pharmacy side views it as dirt cheap. This is part of the problem with our health system. A lot of things are siloed and don’t make any sense,” said Dr. Gelfand, director of the Psoriasis and Phototherapy Treatment Center at the University of Pennsylvania. By working with the NPF and payers, he added, “we’re hoping ... to transform the way insurance companies think about covering home phototherapy.”

In the meantime, he and Dr. Elmets shared practical ways to optimize access to home phototherapy for psoriasis patients:

Have the discussion. Patients “rarely bring this up as an option,” Dr. Elmets said, so the onus is on clinicians to talk about it. In his view, the ideal candidate “is averse to using systemic agents but whose disease is beyond the point where topical medicines alone will work. One of the advantages of phototherapy is that it doesn’t have immunosuppressive effects.”

Clinicians and patients can learn about the efficacy and safety of phototherapy for psoriasis, including home-based options, on the NPF’s web site and by reading the 2019 joint AAD-NPF guidelines.

Shared decision-making is key. “When a patient comes in, I’ll discuss what their treatment options are and [we] will decide upon a course of action based on their unique needs and preferences [and] if it’s medically appropriate, meaning they have the type of psoriasis likely to respond to phototherapy,” Dr. Gelfand said. A patient with psoriasis mainly on the fingernails or genitals “is not a good candidate for phototherapy. If it’s on the trunk or extremities, that patient would be a good candidate.”

Home phototherapy candidates also must be willing and able to operate a machine and have dedicated space in their dwelling for it (most units are about the size of a door). Patients also have to be reliable, follow directions, and come back in person for follow-up appointments “so we can assess their response to treatment and fine-tune things as necessary and make sure they’re not developing any skin damage,” Dr. Gelfand said.

Educate yourself about existing options. Home phototherapy units from manufacturers such as Daavlin, National Biological Corporation, and SolRx range between $1200 and $6000 in cost, Dr. Gelfand said. He and his colleagues used the Daavlin 7 series in the LITE study. That unit features an integrated dosimetry system that delivers the correct dose of energy based on parameters that the prescribing clinician recommends. Settings are based on the patient’s skin type and how much the prescriber wants to increase the dose for each treatment. “The machine does the rest,” he said. “It knows what dose to give, so they get the same dosing as they would in an office situation.”

Smaller home-based phototherapy units designed to treat the hands and feet are available. So are handheld units to treat the scalp. “These can be a nice option for patients who have a few spots, but if the disease is moderate to severe, then it’s going to be pretty laborious to [use them],” Dr. Elmets said.

Remember that phototherapy is not a cure-all. According to the joint AAD-NPF guidelines, most phototherapy regimens require treatments two to three times per week for 10-14 weeks. Once patients achieve their home phototherapy treatment goal, Dr. Elmets often recommends treatments one to two times per week for maintenance.

“Patients with psoriasis have a lifetime condition,” he noted. “There are certainly cases where people have gone on phototherapy, cleared, and then stopped for a period of time. If they flare up, they can always go back to phototherapy. Usually, people who are on phototherapy use some type of topical agents to touch up areas that are resistant.”

Expect pushback from insurers on coverage. While Medicare and some integrated health plans cover home phototherapy, expect to spend time writing letters or placing phone calls to insurance companies to convince them why they should cover home phototherapy for candidate psoriasis patients. “Usually there’s a lot of letter writing and a long delay in getting approval,” Dr. Elmets said.

Dr. Elmets and Dr. Gelfand reported no relevant financial relationships. The LITE study was funded by the Patient-Centered Outcomes Research Institute. Research partners included the National Psoriasis Foundation and Daavlin, which provided the home phototherapy machines and covered the cost of shipping the devices.

A version of this article appeared on Medscape.com.

Older patients prescribed hydroxychloroquine (HCQ) have a higher risk of developing retinal damage from taking the medication, according to a new analysis.

In addition to known risk factors such as a higher weight-based HCQ dose and higher cumulative dose, researchers also found that female sex, chronic kidney disease stage III, and tamoxifen use were associated with HCQ retinopathy.

The findings provide “evidence for other key risk factors for hydroxychloroquine retinopathy beyond hydroxychloroquine exposure itself,” wrote April M. Jorge, MD, of the Division of Rheumatology, Allergy, and Immunology at Massachusetts General Hospital, Boston, and colleagues.

Baylor College of Medicine

Study Details

Researchers identified patients in the Kaiser Permanente Northern California (KPNC), Oakland, California, health system who began taking HCQ between July 1, 1997, and December 14, 2014. To be included, patients needed to have at least 5 years of continuous enrollment in the KPNC system and at least one prescription for HCQ after more than 5 years of starting the drug. Patients were followed from HCQ initiation to their last retinopathy screening study, up to December 31, 2020.

The study was published May 9 in JAMA Network Open.

Of the 4677 users followed for the study, 83% were women, and the average age starting HCQ was 52. Most patients were White (58.1%), while 13.7% were Asian, 10.5% were Black, and 17.7% were Hispanic.

More than 60% of patients had an initial dose > 5 mg/kg/d, though the mean initial dose of HCQ was 4.4 mg/kg/d. After 5 years, only 34.4% of patients were using a daily dose over 5 mg/kg.

Of the entire cohort, 125 patients (2.7%) developed HCQ retinopathy. As expected, cumulative HCQ exposure was associated with a higher retinopathy risk: For every 100 g of HCQ cumulative exposure, risk rose by 64% (hazard ratio [HR], 1.64; 95% CI, 1.44-1.87).

Age was a significant risk factor for retinal damage from HCQ use. Individuals who began taking the drug at 65 years or older were nearly six times more likely to develop retinopathy than those who started HCQ when they were younger than 45. In people aged 55-64 years, this risk was nearly four times higher, and individuals aged 45-54 years when starting the drug were 2.5 times more likely to have retinal damage than those younger than 45.

Other risk factors were female sex (HR, 3.83; 95% CI, 1.86-7.89), chronic kidney disease stage III (HR, 1.95; 95% CI, 1.25-3.04), and tamoxifen use (HR, 3.43; 95% CI, 1.08-10.89), although only 17 patients were taking tamoxifen during the study.

Researchers also found that the type of HCQ retinopathy varied by race. Of the 125 cases in the cohort, 102 had a parafoveal pattern, and 23 had a pericentral pattern. Asian individuals were 15 times more likely, and Black individuals were more than 5 times more likely to develop this pericentral type than were White patients.

This association in Asian patients has also been found in previous studies, Dr. Weng said, and many eye practices now screen their Asian patients with a 30-2 Humphrey visual field — rather than the more commonly used 10-2 — to examine areas farther outside the center.

This study also found this association in Black patients, though only five Black patients developed HCQ retinopathy over the study period.

“More studies and larger studies will be very helpful in strengthening or dispelling some of the associations that have been seen here,” Dr. Weng said.
 

‘More Room for Personalized Medicine’

The team found a “relatively linear” relationship between HCQ dose and retinopathy risk, with higher daily doses correlating with higher incidence. While 2016 guidelines from the American Academy of Ophthalmology advise using < 5 mg/kg, “what we found is it’s not that straightforward [where there’s] just this one cutoff,” Dr. Jorge told this news organization. “It does seem like the higher the dose of medication per bodyweight and the longer duration of use, there is a higher risk of retinopathy.”

These findings leave “a bit more room for personalized medicine” with patients, she explained. “For an elderly female patient with CKD, aiming for a dose < 5 mg/kg might be more appropriate; however, a young male patient without any additional risk factors may be able to exceed 5 mg/kg and continue to have a low risk for HCQ retinopathy,” she said.

“For anyone, I think it really is more of an individual risk-benefit evaluation,” rather than strict cutoffs, she continued.

“Guidelines are just that: They’re guidelines,” added Dr. Weng, “and treatment plans should be tailored to each individual patient.”

As the study authors also discussed, “the goal is to treat the patient with the lowest dose that is still effective and also be mindful of the duration that a patient is left at higher doses,” Dr. Weng said. “But ultimately, we need to control these diseases, which can cause damage across multiple organ systems in the body. While it’s important to be aware of the potential retinopathy adverse events, we also don’t want physicians to feel restricted in their use of this very effective drug.”

The work of three coauthors on the current study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dr. Jorge’s work on the study was supported by an award from the Rheumatology Research Foundation and a grant from NIAMS. Dr. Jorge reported clinical trial agreements with Bristol Myers Squibb and Cabaletta Bio outside of this study. Dr. Weng has served as a consultant for Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, RegenxBio, Iveric Bio, and EyePoint Pharmaceuticals. Dr. Weng disclosed financial relationships with Springer Publishers (royalties) and DRCR Retina Network, Alimera Sciences, and Applied Genetic Technologies Corporation (research).

A version of this article appeared on Medscape.com.

Older patients prescribed hydroxychloroquine (HCQ) have a higher risk of developing retinal damage from taking the medication, according to a new analysis.

In addition to known risk factors such as a higher weight-based HCQ dose and higher cumulative dose, researchers also found that female sex, chronic kidney disease stage III, and tamoxifen use were associated with HCQ retinopathy.

The findings provide “evidence for other key risk factors for hydroxychloroquine retinopathy beyond hydroxychloroquine exposure itself,” wrote April M. Jorge, MD, of the Division of Rheumatology, Allergy, and Immunology at Massachusetts General Hospital, Boston, and colleagues.

Baylor College of Medicine

Study Details

Researchers identified patients in the Kaiser Permanente Northern California (KPNC), Oakland, California, health system who began taking HCQ between July 1, 1997, and December 14, 2014. To be included, patients needed to have at least 5 years of continuous enrollment in the KPNC system and at least one prescription for HCQ after more than 5 years of starting the drug. Patients were followed from HCQ initiation to their last retinopathy screening study, up to December 31, 2020.

The study was published May 9 in JAMA Network Open.

Of the 4677 users followed for the study, 83% were women, and the average age starting HCQ was 52. Most patients were White (58.1%), while 13.7% were Asian, 10.5% were Black, and 17.7% were Hispanic.

More than 60% of patients had an initial dose > 5 mg/kg/d, though the mean initial dose of HCQ was 4.4 mg/kg/d. After 5 years, only 34.4% of patients were using a daily dose over 5 mg/kg.

Of the entire cohort, 125 patients (2.7%) developed HCQ retinopathy. As expected, cumulative HCQ exposure was associated with a higher retinopathy risk: For every 100 g of HCQ cumulative exposure, risk rose by 64% (hazard ratio [HR], 1.64; 95% CI, 1.44-1.87).

Age was a significant risk factor for retinal damage from HCQ use. Individuals who began taking the drug at 65 years or older were nearly six times more likely to develop retinopathy than those who started HCQ when they were younger than 45. In people aged 55-64 years, this risk was nearly four times higher, and individuals aged 45-54 years when starting the drug were 2.5 times more likely to have retinal damage than those younger than 45.

Other risk factors were female sex (HR, 3.83; 95% CI, 1.86-7.89), chronic kidney disease stage III (HR, 1.95; 95% CI, 1.25-3.04), and tamoxifen use (HR, 3.43; 95% CI, 1.08-10.89), although only 17 patients were taking tamoxifen during the study.

Researchers also found that the type of HCQ retinopathy varied by race. Of the 125 cases in the cohort, 102 had a parafoveal pattern, and 23 had a pericentral pattern. Asian individuals were 15 times more likely, and Black individuals were more than 5 times more likely to develop this pericentral type than were White patients.

This association in Asian patients has also been found in previous studies, Dr. Weng said, and many eye practices now screen their Asian patients with a 30-2 Humphrey visual field — rather than the more commonly used 10-2 — to examine areas farther outside the center.

This study also found this association in Black patients, though only five Black patients developed HCQ retinopathy over the study period.

“More studies and larger studies will be very helpful in strengthening or dispelling some of the associations that have been seen here,” Dr. Weng said.
 

‘More Room for Personalized Medicine’

The team found a “relatively linear” relationship between HCQ dose and retinopathy risk, with higher daily doses correlating with higher incidence. While 2016 guidelines from the American Academy of Ophthalmology advise using < 5 mg/kg, “what we found is it’s not that straightforward [where there’s] just this one cutoff,” Dr. Jorge told this news organization. “It does seem like the higher the dose of medication per bodyweight and the longer duration of use, there is a higher risk of retinopathy.”

These findings leave “a bit more room for personalized medicine” with patients, she explained. “For an elderly female patient with CKD, aiming for a dose < 5 mg/kg might be more appropriate; however, a young male patient without any additional risk factors may be able to exceed 5 mg/kg and continue to have a low risk for HCQ retinopathy,” she said.

“For anyone, I think it really is more of an individual risk-benefit evaluation,” rather than strict cutoffs, she continued.

“Guidelines are just that: They’re guidelines,” added Dr. Weng, “and treatment plans should be tailored to each individual patient.”

As the study authors also discussed, “the goal is to treat the patient with the lowest dose that is still effective and also be mindful of the duration that a patient is left at higher doses,” Dr. Weng said. “But ultimately, we need to control these diseases, which can cause damage across multiple organ systems in the body. While it’s important to be aware of the potential retinopathy adverse events, we also don’t want physicians to feel restricted in their use of this very effective drug.”

The work of three coauthors on the current study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dr. Jorge’s work on the study was supported by an award from the Rheumatology Research Foundation and a grant from NIAMS. Dr. Jorge reported clinical trial agreements with Bristol Myers Squibb and Cabaletta Bio outside of this study. Dr. Weng has served as a consultant for Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, RegenxBio, Iveric Bio, and EyePoint Pharmaceuticals. Dr. Weng disclosed financial relationships with Springer Publishers (royalties) and DRCR Retina Network, Alimera Sciences, and Applied Genetic Technologies Corporation (research).

A version of this article appeared on Medscape.com.

Older patients prescribed hydroxychloroquine (HCQ) have a higher risk of developing retinal damage from taking the medication, according to a new analysis.

In addition to known risk factors such as a higher weight-based HCQ dose and higher cumulative dose, researchers also found that female sex, chronic kidney disease stage III, and tamoxifen use were associated with HCQ retinopathy.

The findings provide “evidence for other key risk factors for hydroxychloroquine retinopathy beyond hydroxychloroquine exposure itself,” wrote April M. Jorge, MD, of the Division of Rheumatology, Allergy, and Immunology at Massachusetts General Hospital, Boston, and colleagues.

Baylor College of Medicine

Study Details

Researchers identified patients in the Kaiser Permanente Northern California (KPNC), Oakland, California, health system who began taking HCQ between July 1, 1997, and December 14, 2014. To be included, patients needed to have at least 5 years of continuous enrollment in the KPNC system and at least one prescription for HCQ after more than 5 years of starting the drug. Patients were followed from HCQ initiation to their last retinopathy screening study, up to December 31, 2020.

The study was published May 9 in JAMA Network Open.

Of the 4677 users followed for the study, 83% were women, and the average age starting HCQ was 52. Most patients were White (58.1%), while 13.7% were Asian, 10.5% were Black, and 17.7% were Hispanic.

More than 60% of patients had an initial dose > 5 mg/kg/d, though the mean initial dose of HCQ was 4.4 mg/kg/d. After 5 years, only 34.4% of patients were using a daily dose over 5 mg/kg.

Of the entire cohort, 125 patients (2.7%) developed HCQ retinopathy. As expected, cumulative HCQ exposure was associated with a higher retinopathy risk: For every 100 g of HCQ cumulative exposure, risk rose by 64% (hazard ratio [HR], 1.64; 95% CI, 1.44-1.87).

Age was a significant risk factor for retinal damage from HCQ use. Individuals who began taking the drug at 65 years or older were nearly six times more likely to develop retinopathy than those who started HCQ when they were younger than 45. In people aged 55-64 years, this risk was nearly four times higher, and individuals aged 45-54 years when starting the drug were 2.5 times more likely to have retinal damage than those younger than 45.

Other risk factors were female sex (HR, 3.83; 95% CI, 1.86-7.89), chronic kidney disease stage III (HR, 1.95; 95% CI, 1.25-3.04), and tamoxifen use (HR, 3.43; 95% CI, 1.08-10.89), although only 17 patients were taking tamoxifen during the study.

Researchers also found that the type of HCQ retinopathy varied by race. Of the 125 cases in the cohort, 102 had a parafoveal pattern, and 23 had a pericentral pattern. Asian individuals were 15 times more likely, and Black individuals were more than 5 times more likely to develop this pericentral type than were White patients.

This association in Asian patients has also been found in previous studies, Dr. Weng said, and many eye practices now screen their Asian patients with a 30-2 Humphrey visual field — rather than the more commonly used 10-2 — to examine areas farther outside the center.

This study also found this association in Black patients, though only five Black patients developed HCQ retinopathy over the study period.

“More studies and larger studies will be very helpful in strengthening or dispelling some of the associations that have been seen here,” Dr. Weng said.
 

‘More Room for Personalized Medicine’

The team found a “relatively linear” relationship between HCQ dose and retinopathy risk, with higher daily doses correlating with higher incidence. While 2016 guidelines from the American Academy of Ophthalmology advise using < 5 mg/kg, “what we found is it’s not that straightforward [where there’s] just this one cutoff,” Dr. Jorge told this news organization. “It does seem like the higher the dose of medication per bodyweight and the longer duration of use, there is a higher risk of retinopathy.”

These findings leave “a bit more room for personalized medicine” with patients, she explained. “For an elderly female patient with CKD, aiming for a dose < 5 mg/kg might be more appropriate; however, a young male patient without any additional risk factors may be able to exceed 5 mg/kg and continue to have a low risk for HCQ retinopathy,” she said.

“For anyone, I think it really is more of an individual risk-benefit evaluation,” rather than strict cutoffs, she continued.

“Guidelines are just that: They’re guidelines,” added Dr. Weng, “and treatment plans should be tailored to each individual patient.”

As the study authors also discussed, “the goal is to treat the patient with the lowest dose that is still effective and also be mindful of the duration that a patient is left at higher doses,” Dr. Weng said. “But ultimately, we need to control these diseases, which can cause damage across multiple organ systems in the body. While it’s important to be aware of the potential retinopathy adverse events, we also don’t want physicians to feel restricted in their use of this very effective drug.”

The work of three coauthors on the current study was supported by a grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Dr. Jorge’s work on the study was supported by an award from the Rheumatology Research Foundation and a grant from NIAMS. Dr. Jorge reported clinical trial agreements with Bristol Myers Squibb and Cabaletta Bio outside of this study. Dr. Weng has served as a consultant for Allergan/AbbVie, Alcon, Apellis Pharmaceuticals, Alimera Sciences, DORC, Novartis, Genentech, Regeneron, RegenxBio, Iveric Bio, and EyePoint Pharmaceuticals. Dr. Weng disclosed financial relationships with Springer Publishers (royalties) and DRCR Retina Network, Alimera Sciences, and Applied Genetic Technologies Corporation (research).

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Benlysta (belimumab) autoinjector for patients aged 5 years or older with active systemic lupus erythematosus (SLE) on standard therapy. This is the first time that children with SLE can receive this treatment at home, according to a GSK press release.

Prior to this approval, pediatric patients aged 5 years or older could receive belimumab only intravenously via a 1-hour infusion in a hospital or clinic setting.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“Going to the doctor’s office once every 4 weeks can be a logistical hurdle for some children and their caregivers, so having the option to administer Benlysta in the comfort of their home provides much-needed flexibility,” Mary Crimmings, the interim CEO and senior vice president for marketing and communications at the Lupus Foundation of America, said in a statement. 

An estimated 5000-10,000 children in the United States are living with SLE.

Belimumab is a B-lymphocyte stimulator–specific inhibitor approved for the treatment of active SLE and active lupus nephritis in patients aged 5 years or older receiving standard therapy. This approval of the subcutaneous administration of belimumab applies only to pediatric patients with SLE.

The 200-mg injection can be administered once every week for children who weigh ≥ 40 kg and should be given once every 2 weeks for children weighing between 15 and 40 kg. 

The autoinjector “will be available immediately” for caregivers, the company announcement said.

“Patients are our top priority, and we are always working to innovate solutions that can improve lives and address unmet needs,” Court Horncastle, senior vice president and head of US specialty at GSK, said in the press release. “This approval for an at-home treatment is the first and only of its kind for children with lupus and is a testament to our continued commitment to the lupus community.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Benlysta (belimumab) autoinjector for patients aged 5 years or older with active systemic lupus erythematosus (SLE) on standard therapy. This is the first time that children with SLE can receive this treatment at home, according to a GSK press release.

Prior to this approval, pediatric patients aged 5 years or older could receive belimumab only intravenously via a 1-hour infusion in a hospital or clinic setting.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“Going to the doctor’s office once every 4 weeks can be a logistical hurdle for some children and their caregivers, so having the option to administer Benlysta in the comfort of their home provides much-needed flexibility,” Mary Crimmings, the interim CEO and senior vice president for marketing and communications at the Lupus Foundation of America, said in a statement. 

An estimated 5000-10,000 children in the United States are living with SLE.

Belimumab is a B-lymphocyte stimulator–specific inhibitor approved for the treatment of active SLE and active lupus nephritis in patients aged 5 years or older receiving standard therapy. This approval of the subcutaneous administration of belimumab applies only to pediatric patients with SLE.

The 200-mg injection can be administered once every week for children who weigh ≥ 40 kg and should be given once every 2 weeks for children weighing between 15 and 40 kg. 

The autoinjector “will be available immediately” for caregivers, the company announcement said.

“Patients are our top priority, and we are always working to innovate solutions that can improve lives and address unmet needs,” Court Horncastle, senior vice president and head of US specialty at GSK, said in the press release. “This approval for an at-home treatment is the first and only of its kind for children with lupus and is a testament to our continued commitment to the lupus community.”

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Benlysta (belimumab) autoinjector for patients aged 5 years or older with active systemic lupus erythematosus (SLE) on standard therapy. This is the first time that children with SLE can receive this treatment at home, according to a GSK press release.

Prior to this approval, pediatric patients aged 5 years or older could receive belimumab only intravenously via a 1-hour infusion in a hospital or clinic setting.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“Going to the doctor’s office once every 4 weeks can be a logistical hurdle for some children and their caregivers, so having the option to administer Benlysta in the comfort of their home provides much-needed flexibility,” Mary Crimmings, the interim CEO and senior vice president for marketing and communications at the Lupus Foundation of America, said in a statement. 

An estimated 5000-10,000 children in the United States are living with SLE.

Belimumab is a B-lymphocyte stimulator–specific inhibitor approved for the treatment of active SLE and active lupus nephritis in patients aged 5 years or older receiving standard therapy. This approval of the subcutaneous administration of belimumab applies only to pediatric patients with SLE.

The 200-mg injection can be administered once every week for children who weigh ≥ 40 kg and should be given once every 2 weeks for children weighing between 15 and 40 kg. 

The autoinjector “will be available immediately” for caregivers, the company announcement said.

“Patients are our top priority, and we are always working to innovate solutions that can improve lives and address unmet needs,” Court Horncastle, senior vice president and head of US specialty at GSK, said in the press release. “This approval for an at-home treatment is the first and only of its kind for children with lupus and is a testament to our continued commitment to the lupus community.”

A version of this article appeared on Medscape.com.

Patients with metastatic or advanced cancer treated in practices that have high rates of giving systemic care in the last two weeks of life do not have longer survival rates than patients in practices that have low rates of such care.

This conclusion of a new study published online May 16 in JAMA Oncology may help reassure oncologists that giving systemic anticancer therapy (SACT) at the most advanced stages of cancer will not improve the patient’s life, the authors wrote. It also may encourage them to instead focus more on honest communication with patients about their choices, Maureen E. Canavan, PhD, at the Cancer and Outcomes, Public Policy and Effectiveness Research (COPPER) Center at the Yale School of Medicine in New Haven, Connecticut, and colleagues, wrote in their paper.
 

How Was the Study Conducted?

Researchers used Flatiron Health, a nationwide electronic health records database of academic and community practices throughout the United State. They identified 78,446 adults with advanced or metastatic stages of one of six common cancers (breast, colorectal, urothelial, non–small cell lung cancer [NSCLC], pancreatic and renal cell carcinoma) who were treated at healthcare practices from 2015 to 2019. They then stratified practices into quintiles based on how often the practices treated patients with any systemic therapy, including chemotherapy and immunotherapy, in their last 14 days of life. They compared whether patients in practices with greater use of systemic treatment at very advanced stages had longer overall survival.

What Were the Main Findings?

“We saw that there were absolutely no survival differences between the practices that used more systemic therapy for very advanced cancer than the practices that use less,” said senior author Kerin Adelson, MD, chief quality and value officer at MD Anderson Cancer Center in Houston, Texas. In some cancers, those in the lowest quintile (those with the lowest rates of systemic end-of-life care) lived fewer years compared with those in the highest quintiles. In other cancers, those in the lowest quintiles lived more years than those in the highest quintiles.

“What’s important is that none of those differences, after you control for other factors, was statistically significant,” Dr. Adelson said. “That was the same in every cancer type we looked at.”

An example is seen in advanced urothelial cancer. Those in the first quintile (lowest rates of systemic care at end of life) had an SACT rate range of 4.0-9.1. The SACT rate range in the highest quintile was 19.8-42.6. But the median overall survival (OS) rate for those in the lowest quintile was 12.7 months, not statistically different from the median OS in the highest quintile (11 months.)
 

How Does This Study Add to the Literature?

The American Society of Clinical Oncology (ASCO) and the National Quality Forum (NQF) developed a cancer quality metric to reduce SACT at the end of life. The NQF 0210 is a ratio of patients who get systemic treatment within 14 days of death over all patients who die of cancer. The quality metric has been widely adopted and used in value-based care reporting.

But the metric has been criticized because it focuses only on people who died and not people who lived longer because they benefited from the systemic therapy, the authors wrote.

Dr. Canavan’s team focused on all patients treated in the practice, not just those who died, Dr. Adelson said. This may put that criticism to rest, Dr. Adelson said.

“I personally believed the ASCO and NQF metric was appropriate and the criticisms were off base,” said Otis Brawley, MD, associate director of community outreach and engagement at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine in Baltimore. “Canavan’s study is evidence suggesting the metrics were appropriate.”

This study included not just chemotherapy, as some other studies have, but targeted therapies and immunotherapies as well. Dr. Adelson said some think that the newer drugs might change the prognosis at end of life. But this study shows “even those drugs are not helping patients to survive with very advanced cancer,” she said.

 

Could This Change Practice?

The authors noted that end-of life SACT has been linked with more acute care use, delays in conversations about care goals, late enrollment in hospice, higher costs, and potentially shorter and poorer quality life.

Dr. Adelson said she’s hoping that the knowledge that there’s no survival benefit for use of SACT for patients with advanced solid tumors who are nearing the end of life will lead instead to more conversations about prognosis with patients and transitions to palliative care.

“Palliative care has actually been shown to improve quality of life and, in some studies, even survival,” she said.

“I doubt it will change practice, but it should,” Dr. Brawley said. “The study suggests that doctors and patients have too much hope for chemotherapy as patients’ disease progresses. In the US especially, there is a tendency to believe we have better therapies than we truly do and we have difficulty accepting that the patient is dying. Many patients get third- and fourth-line chemotherapy that is highly likely to increase suffering without realistic hope of prolonging life and especially no hope of prolonging life with good quality.”

Dr. Adelson disclosed ties with AbbVie, Quantum Health, Gilead, ParetoHealth, and Carrum Health. Various coauthors disclosed ties with Roche, AbbVie, Johnson & Johnson, Genentech, the National Comprehensive Cancer Network, and AstraZeneca. The study was funded by Flatiron Health, an independent member of the Roche group. Dr. Brawley reports no relevant financial disclosures.

Patients with metastatic or advanced cancer treated in practices that have high rates of giving systemic care in the last two weeks of life do not have longer survival rates than patients in practices that have low rates of such care.

This conclusion of a new study published online May 16 in JAMA Oncology may help reassure oncologists that giving systemic anticancer therapy (SACT) at the most advanced stages of cancer will not improve the patient’s life, the authors wrote. It also may encourage them to instead focus more on honest communication with patients about their choices, Maureen E. Canavan, PhD, at the Cancer and Outcomes, Public Policy and Effectiveness Research (COPPER) Center at the Yale School of Medicine in New Haven, Connecticut, and colleagues, wrote in their paper.
 

How Was the Study Conducted?

Researchers used Flatiron Health, a nationwide electronic health records database of academic and community practices throughout the United State. They identified 78,446 adults with advanced or metastatic stages of one of six common cancers (breast, colorectal, urothelial, non–small cell lung cancer [NSCLC], pancreatic and renal cell carcinoma) who were treated at healthcare practices from 2015 to 2019. They then stratified practices into quintiles based on how often the practices treated patients with any systemic therapy, including chemotherapy and immunotherapy, in their last 14 days of life. They compared whether patients in practices with greater use of systemic treatment at very advanced stages had longer overall survival.

What Were the Main Findings?

“We saw that there were absolutely no survival differences between the practices that used more systemic therapy for very advanced cancer than the practices that use less,” said senior author Kerin Adelson, MD, chief quality and value officer at MD Anderson Cancer Center in Houston, Texas. In some cancers, those in the lowest quintile (those with the lowest rates of systemic end-of-life care) lived fewer years compared with those in the highest quintiles. In other cancers, those in the lowest quintiles lived more years than those in the highest quintiles.

“What’s important is that none of those differences, after you control for other factors, was statistically significant,” Dr. Adelson said. “That was the same in every cancer type we looked at.”

An example is seen in advanced urothelial cancer. Those in the first quintile (lowest rates of systemic care at end of life) had an SACT rate range of 4.0-9.1. The SACT rate range in the highest quintile was 19.8-42.6. But the median overall survival (OS) rate for those in the lowest quintile was 12.7 months, not statistically different from the median OS in the highest quintile (11 months.)
 

How Does This Study Add to the Literature?

The American Society of Clinical Oncology (ASCO) and the National Quality Forum (NQF) developed a cancer quality metric to reduce SACT at the end of life. The NQF 0210 is a ratio of patients who get systemic treatment within 14 days of death over all patients who die of cancer. The quality metric has been widely adopted and used in value-based care reporting.

But the metric has been criticized because it focuses only on people who died and not people who lived longer because they benefited from the systemic therapy, the authors wrote.

Dr. Canavan’s team focused on all patients treated in the practice, not just those who died, Dr. Adelson said. This may put that criticism to rest, Dr. Adelson said.

“I personally believed the ASCO and NQF metric was appropriate and the criticisms were off base,” said Otis Brawley, MD, associate director of community outreach and engagement at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine in Baltimore. “Canavan’s study is evidence suggesting the metrics were appropriate.”

This study included not just chemotherapy, as some other studies have, but targeted therapies and immunotherapies as well. Dr. Adelson said some think that the newer drugs might change the prognosis at end of life. But this study shows “even those drugs are not helping patients to survive with very advanced cancer,” she said.

 

Could This Change Practice?

The authors noted that end-of life SACT has been linked with more acute care use, delays in conversations about care goals, late enrollment in hospice, higher costs, and potentially shorter and poorer quality life.

Dr. Adelson said she’s hoping that the knowledge that there’s no survival benefit for use of SACT for patients with advanced solid tumors who are nearing the end of life will lead instead to more conversations about prognosis with patients and transitions to palliative care.

“Palliative care has actually been shown to improve quality of life and, in some studies, even survival,” she said.

“I doubt it will change practice, but it should,” Dr. Brawley said. “The study suggests that doctors and patients have too much hope for chemotherapy as patients’ disease progresses. In the US especially, there is a tendency to believe we have better therapies than we truly do and we have difficulty accepting that the patient is dying. Many patients get third- and fourth-line chemotherapy that is highly likely to increase suffering without realistic hope of prolonging life and especially no hope of prolonging life with good quality.”

Dr. Adelson disclosed ties with AbbVie, Quantum Health, Gilead, ParetoHealth, and Carrum Health. Various coauthors disclosed ties with Roche, AbbVie, Johnson & Johnson, Genentech, the National Comprehensive Cancer Network, and AstraZeneca. The study was funded by Flatiron Health, an independent member of the Roche group. Dr. Brawley reports no relevant financial disclosures.

Patients with metastatic or advanced cancer treated in practices that have high rates of giving systemic care in the last two weeks of life do not have longer survival rates than patients in practices that have low rates of such care.

This conclusion of a new study published online May 16 in JAMA Oncology may help reassure oncologists that giving systemic anticancer therapy (SACT) at the most advanced stages of cancer will not improve the patient’s life, the authors wrote. It also may encourage them to instead focus more on honest communication with patients about their choices, Maureen E. Canavan, PhD, at the Cancer and Outcomes, Public Policy and Effectiveness Research (COPPER) Center at the Yale School of Medicine in New Haven, Connecticut, and colleagues, wrote in their paper.
 

How Was the Study Conducted?

Researchers used Flatiron Health, a nationwide electronic health records database of academic and community practices throughout the United State. They identified 78,446 adults with advanced or metastatic stages of one of six common cancers (breast, colorectal, urothelial, non–small cell lung cancer [NSCLC], pancreatic and renal cell carcinoma) who were treated at healthcare practices from 2015 to 2019. They then stratified practices into quintiles based on how often the practices treated patients with any systemic therapy, including chemotherapy and immunotherapy, in their last 14 days of life. They compared whether patients in practices with greater use of systemic treatment at very advanced stages had longer overall survival.

What Were the Main Findings?

“We saw that there were absolutely no survival differences between the practices that used more systemic therapy for very advanced cancer than the practices that use less,” said senior author Kerin Adelson, MD, chief quality and value officer at MD Anderson Cancer Center in Houston, Texas. In some cancers, those in the lowest quintile (those with the lowest rates of systemic end-of-life care) lived fewer years compared with those in the highest quintiles. In other cancers, those in the lowest quintiles lived more years than those in the highest quintiles.

“What’s important is that none of those differences, after you control for other factors, was statistically significant,” Dr. Adelson said. “That was the same in every cancer type we looked at.”

An example is seen in advanced urothelial cancer. Those in the first quintile (lowest rates of systemic care at end of life) had an SACT rate range of 4.0-9.1. The SACT rate range in the highest quintile was 19.8-42.6. But the median overall survival (OS) rate for those in the lowest quintile was 12.7 months, not statistically different from the median OS in the highest quintile (11 months.)
 

How Does This Study Add to the Literature?

The American Society of Clinical Oncology (ASCO) and the National Quality Forum (NQF) developed a cancer quality metric to reduce SACT at the end of life. The NQF 0210 is a ratio of patients who get systemic treatment within 14 days of death over all patients who die of cancer. The quality metric has been widely adopted and used in value-based care reporting.

But the metric has been criticized because it focuses only on people who died and not people who lived longer because they benefited from the systemic therapy, the authors wrote.

Dr. Canavan’s team focused on all patients treated in the practice, not just those who died, Dr. Adelson said. This may put that criticism to rest, Dr. Adelson said.

“I personally believed the ASCO and NQF metric was appropriate and the criticisms were off base,” said Otis Brawley, MD, associate director of community outreach and engagement at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine in Baltimore. “Canavan’s study is evidence suggesting the metrics were appropriate.”

This study included not just chemotherapy, as some other studies have, but targeted therapies and immunotherapies as well. Dr. Adelson said some think that the newer drugs might change the prognosis at end of life. But this study shows “even those drugs are not helping patients to survive with very advanced cancer,” she said.

 

Could This Change Practice?

The authors noted that end-of life SACT has been linked with more acute care use, delays in conversations about care goals, late enrollment in hospice, higher costs, and potentially shorter and poorer quality life.

Dr. Adelson said she’s hoping that the knowledge that there’s no survival benefit for use of SACT for patients with advanced solid tumors who are nearing the end of life will lead instead to more conversations about prognosis with patients and transitions to palliative care.

“Palliative care has actually been shown to improve quality of life and, in some studies, even survival,” she said.

“I doubt it will change practice, but it should,” Dr. Brawley said. “The study suggests that doctors and patients have too much hope for chemotherapy as patients’ disease progresses. In the US especially, there is a tendency to believe we have better therapies than we truly do and we have difficulty accepting that the patient is dying. Many patients get third- and fourth-line chemotherapy that is highly likely to increase suffering without realistic hope of prolonging life and especially no hope of prolonging life with good quality.”

Dr. Adelson disclosed ties with AbbVie, Quantum Health, Gilead, ParetoHealth, and Carrum Health. Various coauthors disclosed ties with Roche, AbbVie, Johnson & Johnson, Genentech, the National Comprehensive Cancer Network, and AstraZeneca. The study was funded by Flatiron Health, an independent member of the Roche group. Dr. Brawley reports no relevant financial disclosures.

PHOENIX — Immunotherapy has revolutionized outcomes for patients with metastatic Merkel cell carcinoma (MCC). However, findings from a new study suggest that many patients who are eligible for immunotherapy are not receiving this treatment, despite guideline recommendations, and survival outcomes are better at high-volume centers.

The study has important implications, said study author Shayan Cheraghlou, MD, an incoming fellow in Mohs surgery at New York University, New York City. “We can see that in a real-world setting, these agents have an impact on survival,” he said. “We also found high-volume centers were significantly more likely to use the agents than low-volume centers.” He presented the findings at the annual meeting of the American College of Mohs Surgery.

MCC is a neuroendocrine skin cancer with a high rate of mortality, and even though it remains relatively rare, its incidence has been rising rapidly since the late 1990s and continues to increase. There were no approved treatments available until 2017, when the US Food and Drug Administration (FDA) approved the immunotherapy drug avelumab (Bavencio) to treat advanced MCC. Two years later, pembrolizumab (Keytruda) also received regulatory approval for MCC, and these two agents have revolutionized outcomes.

“In clinical trial settings, these agents led to significant and durable responses, and they are now the recommended treatments in guidelines for metastatic Merkel cell carcinoma,” said Dr. Cheraghlou. “However, we don’t have data as to how they are being used in the real-world setting and if survival outcomes are similar.”

Real World vs Clinical Trials

Real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. The goal of this study was to see if clinical trial data matched what was being observed in actual clinical use and if the agents were being used uniformly in centers across the United States.

The authors used data from the National Cancer Database that included patients diagnosed with cancer from 2004 to 2019 and identified 1017 adult cases of metastatic MCC. They then looked at the association of a variety of patient characteristics, tumors, and system factors with the likelihood of receiving systemic treatment for their disease.

“Our first finding was maybe the least surprising,” he said. “Patients who received these therapeutic agents had significantly improved survival compared to those who have not.”

Those who received immunotherapy had a 35% decrease in the risk for death per year compared with those who did not. The 1-, 3-, and 5-year survival rates were 47.2%, 21.8%, and 16.5%, respectively, for patients who did not receive immunotherapy compared with 62.7%, 34.4%, and 23.6%, respectively, for those who were treated with these agents.

Dr. Cheraghlou noted that they started to get some “surprising” findings when they looked at utilization data. “While it has been increasing over time, it is not as high as it should be,” he emphasized.

From 2017 to 2019, 54.2% of patients with metastatic MCC received immunotherapy. The data also showed an increase in use from 45.1% in 2017 to 63.0% in 2019. “This is an effective treatment for aggressive malignancy, so we have to ask why more patients aren’t getting them,” said Dr. Cheraghlou.

Their findings did suggest one possible reason, and that was that high-volume centers were significantly more likely to use the agents than low-volume centers. Centers that were in the top percentile for MCC case volume were three times as likely to use immunotherapy for MCC compared with other institutions. “So, if you have metastatic Merkel cell carcinoma and go to a low volume center, you may be less likely to get potential lifesaving treatment,” he noted.
 

Implications Going Forward

Dr. Cheraghlou concluded his presentation by pointing out that this study has important implications. The data showed that in a real-world setting, these agents have an impact on survival, but all eligible patients do not have access. “In other countries, there are established referral patterns for all patients with aggressive rare malignancies and really all cancers,” he added. “But in the US, cancer care is more decentralized. Studies like this and others show that high-volume centers have much better outcomes for aggressive rare malignancies, and we should be looking at why this is the case and mitigating these disparities and outcomes.”

Commenting on the study results, Jeffrey M. Farma, MD, co-director of the Melanoma and Skin Cancer Program and professor of surgical oncology at Fox Chase Cancer Center, Philadelphia, referred to the two immunotherapies that have been approved for MCC since 2017, which have demonstrated a survival benefit and improved outcomes in patients with metastatic MCC.

Fox Chase Cancer Center

“In their study, immunotherapy was associated with improved outcomes,” said Dr. Farma. “This study highlights the continued lag of implementation of guidelines when new therapies are approved, and that for rare cancers like Merkel cell carcinoma, being treated at high-volume centers and the regionalization of care can lead to improved outcomes for patients.”

Dr. Cheraghlou and Dr. Farma had no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Immunotherapy has revolutionized outcomes for patients with metastatic Merkel cell carcinoma (MCC). However, findings from a new study suggest that many patients who are eligible for immunotherapy are not receiving this treatment, despite guideline recommendations, and survival outcomes are better at high-volume centers.

The study has important implications, said study author Shayan Cheraghlou, MD, an incoming fellow in Mohs surgery at New York University, New York City. “We can see that in a real-world setting, these agents have an impact on survival,” he said. “We also found high-volume centers were significantly more likely to use the agents than low-volume centers.” He presented the findings at the annual meeting of the American College of Mohs Surgery.

MCC is a neuroendocrine skin cancer with a high rate of mortality, and even though it remains relatively rare, its incidence has been rising rapidly since the late 1990s and continues to increase. There were no approved treatments available until 2017, when the US Food and Drug Administration (FDA) approved the immunotherapy drug avelumab (Bavencio) to treat advanced MCC. Two years later, pembrolizumab (Keytruda) also received regulatory approval for MCC, and these two agents have revolutionized outcomes.

“In clinical trial settings, these agents led to significant and durable responses, and they are now the recommended treatments in guidelines for metastatic Merkel cell carcinoma,” said Dr. Cheraghlou. “However, we don’t have data as to how they are being used in the real-world setting and if survival outcomes are similar.”

Real World vs Clinical Trials

Real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. The goal of this study was to see if clinical trial data matched what was being observed in actual clinical use and if the agents were being used uniformly in centers across the United States.

The authors used data from the National Cancer Database that included patients diagnosed with cancer from 2004 to 2019 and identified 1017 adult cases of metastatic MCC. They then looked at the association of a variety of patient characteristics, tumors, and system factors with the likelihood of receiving systemic treatment for their disease.

“Our first finding was maybe the least surprising,” he said. “Patients who received these therapeutic agents had significantly improved survival compared to those who have not.”

Those who received immunotherapy had a 35% decrease in the risk for death per year compared with those who did not. The 1-, 3-, and 5-year survival rates were 47.2%, 21.8%, and 16.5%, respectively, for patients who did not receive immunotherapy compared with 62.7%, 34.4%, and 23.6%, respectively, for those who were treated with these agents.

Dr. Cheraghlou noted that they started to get some “surprising” findings when they looked at utilization data. “While it has been increasing over time, it is not as high as it should be,” he emphasized.

From 2017 to 2019, 54.2% of patients with metastatic MCC received immunotherapy. The data also showed an increase in use from 45.1% in 2017 to 63.0% in 2019. “This is an effective treatment for aggressive malignancy, so we have to ask why more patients aren’t getting them,” said Dr. Cheraghlou.

Their findings did suggest one possible reason, and that was that high-volume centers were significantly more likely to use the agents than low-volume centers. Centers that were in the top percentile for MCC case volume were three times as likely to use immunotherapy for MCC compared with other institutions. “So, if you have metastatic Merkel cell carcinoma and go to a low volume center, you may be less likely to get potential lifesaving treatment,” he noted.
 

Implications Going Forward

Dr. Cheraghlou concluded his presentation by pointing out that this study has important implications. The data showed that in a real-world setting, these agents have an impact on survival, but all eligible patients do not have access. “In other countries, there are established referral patterns for all patients with aggressive rare malignancies and really all cancers,” he added. “But in the US, cancer care is more decentralized. Studies like this and others show that high-volume centers have much better outcomes for aggressive rare malignancies, and we should be looking at why this is the case and mitigating these disparities and outcomes.”

Commenting on the study results, Jeffrey M. Farma, MD, co-director of the Melanoma and Skin Cancer Program and professor of surgical oncology at Fox Chase Cancer Center, Philadelphia, referred to the two immunotherapies that have been approved for MCC since 2017, which have demonstrated a survival benefit and improved outcomes in patients with metastatic MCC.

Fox Chase Cancer Center

“In their study, immunotherapy was associated with improved outcomes,” said Dr. Farma. “This study highlights the continued lag of implementation of guidelines when new therapies are approved, and that for rare cancers like Merkel cell carcinoma, being treated at high-volume centers and the regionalization of care can lead to improved outcomes for patients.”

Dr. Cheraghlou and Dr. Farma had no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — Immunotherapy has revolutionized outcomes for patients with metastatic Merkel cell carcinoma (MCC). However, findings from a new study suggest that many patients who are eligible for immunotherapy are not receiving this treatment, despite guideline recommendations, and survival outcomes are better at high-volume centers.

The study has important implications, said study author Shayan Cheraghlou, MD, an incoming fellow in Mohs surgery at New York University, New York City. “We can see that in a real-world setting, these agents have an impact on survival,” he said. “We also found high-volume centers were significantly more likely to use the agents than low-volume centers.” He presented the findings at the annual meeting of the American College of Mohs Surgery.

MCC is a neuroendocrine skin cancer with a high rate of mortality, and even though it remains relatively rare, its incidence has been rising rapidly since the late 1990s and continues to increase. There were no approved treatments available until 2017, when the US Food and Drug Administration (FDA) approved the immunotherapy drug avelumab (Bavencio) to treat advanced MCC. Two years later, pembrolizumab (Keytruda) also received regulatory approval for MCC, and these two agents have revolutionized outcomes.

“In clinical trial settings, these agents led to significant and durable responses, and they are now the recommended treatments in guidelines for metastatic Merkel cell carcinoma,” said Dr. Cheraghlou. “However, we don’t have data as to how they are being used in the real-world setting and if survival outcomes are similar.”

Real World vs Clinical Trials

Real-world outcomes can differ from clinical trial data, and the adoption of novel therapeutics can be gradual. The goal of this study was to see if clinical trial data matched what was being observed in actual clinical use and if the agents were being used uniformly in centers across the United States.

The authors used data from the National Cancer Database that included patients diagnosed with cancer from 2004 to 2019 and identified 1017 adult cases of metastatic MCC. They then looked at the association of a variety of patient characteristics, tumors, and system factors with the likelihood of receiving systemic treatment for their disease.

“Our first finding was maybe the least surprising,” he said. “Patients who received these therapeutic agents had significantly improved survival compared to those who have not.”

Those who received immunotherapy had a 35% decrease in the risk for death per year compared with those who did not. The 1-, 3-, and 5-year survival rates were 47.2%, 21.8%, and 16.5%, respectively, for patients who did not receive immunotherapy compared with 62.7%, 34.4%, and 23.6%, respectively, for those who were treated with these agents.

Dr. Cheraghlou noted that they started to get some “surprising” findings when they looked at utilization data. “While it has been increasing over time, it is not as high as it should be,” he emphasized.

From 2017 to 2019, 54.2% of patients with metastatic MCC received immunotherapy. The data also showed an increase in use from 45.1% in 2017 to 63.0% in 2019. “This is an effective treatment for aggressive malignancy, so we have to ask why more patients aren’t getting them,” said Dr. Cheraghlou.

Their findings did suggest one possible reason, and that was that high-volume centers were significantly more likely to use the agents than low-volume centers. Centers that were in the top percentile for MCC case volume were three times as likely to use immunotherapy for MCC compared with other institutions. “So, if you have metastatic Merkel cell carcinoma and go to a low volume center, you may be less likely to get potential lifesaving treatment,” he noted.
 

Implications Going Forward

Dr. Cheraghlou concluded his presentation by pointing out that this study has important implications. The data showed that in a real-world setting, these agents have an impact on survival, but all eligible patients do not have access. “In other countries, there are established referral patterns for all patients with aggressive rare malignancies and really all cancers,” he added. “But in the US, cancer care is more decentralized. Studies like this and others show that high-volume centers have much better outcomes for aggressive rare malignancies, and we should be looking at why this is the case and mitigating these disparities and outcomes.”

Commenting on the study results, Jeffrey M. Farma, MD, co-director of the Melanoma and Skin Cancer Program and professor of surgical oncology at Fox Chase Cancer Center, Philadelphia, referred to the two immunotherapies that have been approved for MCC since 2017, which have demonstrated a survival benefit and improved outcomes in patients with metastatic MCC.

Fox Chase Cancer Center

“In their study, immunotherapy was associated with improved outcomes,” said Dr. Farma. “This study highlights the continued lag of implementation of guidelines when new therapies are approved, and that for rare cancers like Merkel cell carcinoma, being treated at high-volume centers and the regionalization of care can lead to improved outcomes for patients.”

Dr. Cheraghlou and Dr. Farma had no disclosures.

A version of this article appeared on Medscape.com.

PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — The use of radiotherapy has been steadily increasing by dermatologists, according to new findings from a study analyzing trends in Medicare claims from 2016 to 2021. More specifically, the persistent growth in the use of superficial radiotherapy (SRT) devices and electronic brachytherapy (eBT) to treat nonmelanoma skin cancer (NMSC) has exceeded that of traditional procedures among dermatologists using these modalities, according to Christian Gronbeck, MD, a resident in dermatology at the University of Connecticut Health Center, Farmington.

“These services increased substantially over the study period,” Dr. Gronbeck said at the annual meeting of the American College of Mohs Surgery, where he presented the results of the study. “Our findings suggest that those using eBT/SRT were frequently general dermatologists and non-fellowship–trained Mohs surgeons who have less formalized surgical training.”

He also noted that billing for these services also rose substantially, which is being driven by growing utilization and an increased SRT payment rate.

Surgical approaches are standard for most NMSC cases, but some patients are not good surgical candidates because of medical comorbidities and/or other factors, and radiotherapy is emerging as a potential treatment option for those patients. Traditionally, radiotherapy was administered by radiation oncologists, but with the growing availability of SRT devices and the introduction of eBT, dermatologists are now treating patients with these modalities.

“It is a potential treatment option for nonmelanoma skin cancer and keloids, and these lower energy devices can be used in the outpatient setting,” said Dr. Gronbeck. “Treatment typically involves a series of fractions over a period of several weeks. There has been recent growth in the use of radiotherapy despite this being a secondary option in skin cancer, primarily when surgery is contraindicated.”

Steady Expansion of Use

Dr. Gronbeck and colleagues sought to gain a better understanding of the use of SRT and eBT for NMSC among dermatologists, as well as trends in cost. Data were obtained from the 2016-2021 Medicare Public Use Files to evaluate the trend in the volume of Medicare Part B claims for eBT (CPT 0394T) and SRT (CPT 77401) by dermatologists, and they also looked at related billable services for radiotherapy.

Of 12,050 dermatologists, 293 (2.4%) were identified as utilizing eBT or SRT in 2021, representing a 75.4% increase from 2016. The usage of both eBT and SRT increased by 59.6% and 148.4%, respectively, from 2016 to 2021.

There were notable geographic differences in the utilization of radiotherapy. “Florida, California, Texas, and Arizona had the highest utilization,” Dr. Gronbeck said, although during the study period, utilization increased in other states, including North Carolina and Alabama.

When looking at geographic regions as a whole, the highest number of dermatologists using radiotherapy were located in the South (n = 143, 50.9%), followed by the West (n = 69, 23.6%). Utilization was more common in metro areas than in nonmetro/rural areas (86% vs 14%).

Differences were also noted among dermatologists. Those who performed eBT/SRT than those who did not were significantly more likely to have had 15 or more years of independent practice (70.1% vs 48.6%), be in a small private dermatology practice (62.7% vs 47.5%), and be non–fellowship-trained Mohs surgeons (33.5% vs 10.2%). Dermatologists utilizing radiotherapy were also more likely to treat Medicare beneficiaries who were older, with a mean age over 75 years (39.3% vs 31.1%) and a mean hierarchical condition category (HCC) score, above the national average (55.2% vs 44.6%).

Dr. Gronbeck and colleagues also looked at cost. The number of direct payments for eBT/SRT payments increased throughout the study period, from 3,678,224 in 2016 to 11,680,925 in 2021, nearly a 218% increase. The change in payments for services related to eBT/SRT, such as radiotherapy simulation, radiotherapy dosing, and ultrasound guidance, increased by 621.4% during this same timeframe.

Radiotherapy in dermatology has primarily been assessed through retrospective studies. “Our findings suggest that eBT and SRT are more frequently utilized by dermatologists managing older and sicker patients, but further studies are needed to identify whether these interventions are truly addressing poor surgical candidates,” Dr. Gronbeck said.

The Centers for Medicare & Medicaid Services (CMS) has recently proposed changes in Medicare coverage in seven states for Image-Guided Superficial Radiation Therapy (image-guided SRT or IGSRT) for the treatment of NMSC. The proposed local coverage determination, or LCD, if finalized in its current form, would affect residents in North Carolina, South Carolina, Virginia, West Virginia, Alabama, Georgia, and Tennessee.

“These changes would mean more restrictive coverage,” said Dr. Gronbeck, and further support the need for “improved clinical data and development of guidelines to support evidence-based utilization.”

Surgical Management Standard, but SRT Has a Role

Asked to comment on the findings, Seemal R. Desai, MD, president of the American Academy of Dermatology (AAD), who was not involved with the study, reiterated that according to this abstract, efficacy has mainly been assessed through retrospective studies, and results are likely inferior to Mohs surgery, require multiple treatment visits, and are associated with significant costs. More study is needed for the use of radiation therapy in dermatology, he told this news organization.

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

PHOENIX — Certain minority populations may be at a higher absolute risk of being prescribed opioids after undergoing dermatologic surgery, according to a new study. The study also found that patients who do receive opioids postoperatively are at an increased risk for chronic opioid use and complications.

This report represents the largest analysis to date of opioid prescribing after dermatologic surgery, said lead author Kyle C. Lauck, MD, a dermatology resident at Baylor University Medical Center, Dallas, Texas. “Females, African Americans, and Latino patients may be at a higher risk of opioid prescription after dermatologic surgery. Surgeons should be aware of these populations and the risks they face when determining candidacy for postsurgical opioid analgesia.”

He presented the results at the annual meeting of the American College of Mohs Surgery.

The opioid epidemic is a concern across all areas of medicine, and the majority of opioid prescriptions in dermatology are given following surgery. Dr. Lauck noted that even though guidelines delegate opioids as second line for pain control, the existing data on opioid prescribing in dermatologic surgery is mixed. For example, some reports have shown that up to 58% of patients receive opioids postoperatively. “No consensus exists when we should routinely give opioids to these patients,” he said.

Even though most surgeons prescribe short courses of opioids, even brief regimens are associated with increased risks for overuse and substance abuse. Population-level data are limited concerning opioid prescriptions in dermatologic surgery, and in particular, there is an absence of data on the risk for long-term complications associated with use.

Certain Populations at Risk

To evaluate opioid prescription rates in dermatologic surgery, focusing on disparities between demographic populations, as well as the risk for long-term complications of postoperative opioid prescriptions, Dr. Lauck and colleagues conducted a retrospective study that included 914,721 dermatologic surgery patients, with billing codes for Mohs micrographic surgery. Patient data were obtained from TriNetX, a federated health research network.

The mean age of patients in this cohort was 54 years, and 124,494 (13.6%) were prescribed postsurgical oral opioids. The most common was oxycodone, prescribed to 43% of patients. Dr. Lauck noted that, according to their data, certain groups appeared more likely to receive a prescription for opioids following surgery. These included Black or African American patients (23.75% vs 12.86% for White patients), females (13.73% vs 13.16% for males), and Latino or Hispanic patients (17.02% vs 13.61% non-Latino/Hispanic patients).

Patients with a history of prior oral opioid prescription, prior opioid abuse or dependence, and any type of substance abuse had a significant increase in absolute risk of being prescribed postsurgical opioids (P < .0001). 

The type of surgery also was associated with prescribed postop opioids. For a malignant excision, 18.29% of patients were prescribed postop opioids compared with 14.9% for a benign excision. About a third of patients (34.9%) undergoing a graft repair received opioids.

There was an elevated rate of postop opioid prescribing that was specific to the site of surgery, with the highest rates observed with eyelids, scalp and neck, trunk, and genital sites. The highest overall rates of opioid prescriptions were for patients who underwent excisions in the genital area (54.5%).
 

Long-Term Consequences

The authors also looked at the longer-term consequences of postop opioid use. “Nearly one in three patients who were prescribed opioids needed subsequent prescriptions down the line,” said Dr. Lauck. 

From 3 months to 5 years after surgery, patients who received postsurgical opioids were at significantly higher risk for not only subsequent oral opioid prescription but also opiate abuse, any substance abuse, overdose by opioid narcotics, constipation, and chronic pain. “An opioid prescription may confer further risks of longitudinal complications of chronic opioid use,” he concluded.

Commenting on the study, Jesse M. Lewin, MD, chief of Mohs micrographic and dermatologic surgery at Icahn School of Medicine at Mount Sinai, New York City, noted an important finding of this study was the long-term sequelae of patients who did receive postop opioids.

“This is striking given that postsurgical opiate prescriptions are for short durations and limited number of pills,” he told this news organization. “This study highlights the potential danger of even short course of opiates and should serve as a reminder to dermatologic surgeons to be judicious about opiate prescribing.”

Dr. Lauck and Dr. Lewin had no disclosures. 
 

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Atopic dermatitis (AD) among older individuals presented most frequently on the extensor surfaces and trunk, with lichenification and nummular lesions being the most frequent rash characteristics, in a retrospective study of almost 800 patients aged 60 years and older.

The researchers reviewed charts of patients aged 60 years and older who were seen at either a private or county dermatology clinic in Houston between 2009 and 2020 and had been diagnosed with AD by a dermatologist. The findings of their cross-sectional study further supports that AD in this age group “presents as a unique phenotype compared to AD in younger ages, which may inform dermatologists’ diagnosis of AD in these patients” they wrote.

The 791 patients in the study had an average age of 69.3 years, were predominantly women (60.1%), and were racially diverse, with almost 40% being non-Hispanic White individuals. Others were non-Hispanic Black individuals (21.8%), Hispanics (20.4%), and non-Hispanic Asian/Pacific Islanders (11.7%).

Use of topicals, mainly topical corticosteroids (92.2%), was the most frequent treatment prescribed. Oral corticosteroids and antihistamines were “frequent systemic treatments” in this population, prescribed to 10.4% and 12.1%, respectively, “likely due to management prior to a diagnosis of AD by a dermatologist,” wrote first author Hannah Y. Wang, Baylor College of Medicine, Houston, and her coauthors, including Soo Jung Kim, MD, PhD, of the department of dermatology at Baylor.

Other treatments included dupilumab in 5.4%, systemic immunosuppressants (including methotrexate, cyclosporine, and mycophenolate) in 5.4%, and UVB-phototherapy in 2.7%.

Approximately 40% of the patients had a history of allergic rhinitis, while 20% had a history of asthma. Lichenification was noted in 14.5% of patients and nummular lesions in almost 13%. Other rash characteristics — ichthyosis and hyperpigmented patches — were less frequent, seen in 9.7% and 9.1%, respectively.

AD in this older population was most commonly documented on the extensors (49.9%) and the trunk (46%) and less commonly on the hands (19.8%) and feet (9%) — a distribution that is similar to past reports, the authors wrote.

Asked to comment on the findings, Adam Friedman, MD, professor and chair of dermatology at George Washington University, Washington, DC, told this news organization that the data relating to clinical morphology are consistent with past reports and with his own experiences. Lichenification is a “tell-tale sign of chronic disease” and may indicate undertreatment, and the frequency of nummular plaques is unsurprising because “nummular dermatitis as an independent eczema tends to occur more so in the elderly.”

A version of this article appeared on Medscape.com.

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

Local injection of tranexamic acid (TXA) effectively reduced the risk for clinically significant bleeding following Mohs micrographic surgery (MMS), results from a single-center cohort study showed.

“Though Mohs micrographic surgery is associated with low bleeding complication rates, around 1% of patients in the literature report postoperative bleeding,” corresponding author Abigail H. Waldman, MD, director of the Mohs and Dermatologic Surgery Center, at Brigham and Women’s Hospital, Boston, and colleagues wrote in the study, which was published online in the Journal of the American Academy of Dermatology. “Intravenous tranexamic acid has been used across surgical specialties to reduce perioperative blood loss. Prior studies have shown topical TXA, an antifibrinolytic agent, following MMS may be effective in reducing postoperative bleeding complications, but there are no large cohort studies on injectable TXA utilization in all patients undergoing MMS.”

To improve the understanding of this intervention, the researchers examined the impact of off-label, locally injected TXA on postoperative bleeding outcomes following MMS conducted at Brigham and Women’s Hospital. They evaluated two cohorts: 1843 patients who underwent MMS from January 1, 2019, to December 31, 2019 (the pre-TXA cohort), and 2101 patients who underwent MMS from July 1, 2022, to June 30, 2023 (the TXA cohort), and extracted data, including patient and tumor characteristics, MMS procedure details, antithrombotic medication use, systemic conditions that predispose to bleeding, encounters reporting postoperative bleeding, and interventions required for postoperative bleeding, from electronic medical records. Patients reconstructed by a non-MMS surgeon were excluded from the analysis.

Overall, 2509 cases among 1843 patients and 2818 cases among 2101 were included in the pre-TXA and TXA cohorts, respectively. The researchers found that local subcutaneous injection of TXA reduced the risk for postoperative phone calls or visits for bleeding by 25% (RR [risk ratio], 0.75; 0.57-0.99) and risk for bleeding necessitating a medical visit by 51% (RR, 0.49; 0.32-0.77).

The use of preoperative TXA in several subgroups of patients also was also associated with a reduction in visits for bleeding, including those using alcohol (52% reduction; RR, 0.47; 0.26-0.85), cigarettes (57% reduction; RR, 0.43; 0.23-0.82), oral anticoagulants (61% reduction; RR, 0.39; 0.20-0.77), or antiplatelets (60% reduction; RR, 0.40; 0.20-0.79). The use of TXA was also associated with reduced visits for bleeding in tumors of the head and neck (RR, 0.45; 0.26-0.77) and tumors with a preoperative diameter > 2 cm (RR, 0.37; 0.15-0.90).

Impact of Surgical Repair Type

In other findings, the type of surgical repair was a potential confounder, the authors reported. Grafts and flaps were associated with an increased risk for bleeding across both cohorts (RR, 2.36 [1.5-3.6] and 1.7 [1.1-2.6], respectively) and together comprised 15% of all procedures in the pre-TXA cohort compared with 11.1% in TXA cohort. Two patients in the TXA cohort (0.11%) developed deep vein thrombosis (DVT) 10- and 20-days postoperation, a rate that the authors said is comparable to that of the general population. The two patients had risk factors for hypercoagulability, including advanced cancer and recurrent DVT.

“Overall, local injection of TXA was an effective method for reducing the risk of clinically significant bleeding following MMS,” the researchers concluded. “Perioperative TXA may help to limit the risk of bleeding overall, as well as in populations predisposed to bleeding.” Adverse events with TXA use were rare “and delayed beyond the activity of TXA, indicating a low likelihood of being due to TXA,” they wrote.

“Dermatologists performing MMS may consider incorporating local TXA injection into their regular practice,” they noted, adding that “legal counsel on adverse effects in the setting of off-label pharmaceutical usage may be advised.”

In an interview, Patricia M. Richey, MD, director of Mohs surgery at Boston Medical Center, who was asked to comment on the study, said that postoperative bleeding is one of the most commonly encountered Mohs surgery complications. “Because of increased clinic visits and phone calls, it can also often result in decreased patient satisfaction,” she said.

“This study is particularly notable in that we see that local subcutaneous TXA injection decreased visits for bleeding even in those using oral anticoagulants, antiplatelets, alcohol, and cigarettes. Dermatologic surgery has a very low complication rate, even in patients on anticoagulant and antiplatelet medications, but this study shows that TXA is a fantastic option for Mohs surgeons and patients.”

Neither the study authors nor Dr. Richey reported having financial disclosures.

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

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.

The next frontier in cancer detection could be the humble urine test.

Emerging science suggests that the body’s “liquid gold” could be particularly useful for liquid biopsies, offering a convenient, pain-free, and cost-effective way to spot otherwise hard-to-detect cancers.

“The search for cancer biomarkers that can be detected in urine could provide an enormous step forward to decrease cancer patient mortality,” said Kenneth R. Shroyer, MD, PhD, a pathologist at Stony Brook University, Stony Brook, New York, who studies cancer biomarkers.

Physicians have long known that urine can reveal a lot about our health — that’s why urinalysis has been part of medicine for 6000 years. Urine tests can detect diabetes, pregnancy, drug use, and urinary or kidney conditions.

But other conditions leave clues in urine, too, and cancer may be one of the most promising. “Urine testing could detect biomarkers of early-stage cancers, not only from local but also distant sites,” Dr. Shroyer said. It could also help flag recurrence in cancer survivors who have undergone treatment.

Granted, cancer biomarkers in urine are not nearly as widely studied as those in the blood, Dr. Shroyer noted. But a new wave of urine tests suggests research is gaining pace.

“The recent availability of high-throughput screening technologies has enabled researchers to investigate cancer from a top-down, comprehensive approach,” said Pak Kin Wong, PhD, professor of mechanical engineering, biomedical engineering, and surgery at The Pennsylvania State University. “We are starting to understand the rich information that can be obtained from urine.”

Urine is mostly water (about 95%) and urea, a metabolic byproduct that imparts that signature yellow color (about 2%). The other 3% is a mix of waste products, minerals, and other compounds the kidneys removed from the blood. Even in trace amounts, these substances say a lot.

Among them are “exfoliated cancer cells, cell-free DNA, hormones, and the urine microbiota — the collection of microbes in our urinary tract system,” Dr. Wong said.

“It is highly promising to be one of the major biological fluids used for screening, diagnosis, prognosis, and monitoring treatment efficiency in the era of precision medicine,” Dr. Wong said.

How Urine Testing Could Reveal Cancer

Still, as exciting as the prospect is, there’s a lot to consider in the hunt for cancer biomarkers in urine. These biomarkers must be able to pass through the renal nephrons (filtering units), remain stable in urine, and have high-level sensitivity, Dr. Shroyer said. They should also have high specificity for cancer vs benign conditions and be expressed at early stages, before the primary tumor has spread.

“At this stage, few circulating biomarkers have been found that are both sensitive and specific for early-stage disease,” said Dr. Shroyer.

But there are a few promising examples under investigation in humans:

Prostate cancer. Researchers at the University of Michigan have developed a urine test that detects high-grade prostate cancer more accurately than existing tests, including PHI, SelectMDx, 4Kscore, EPI, MPS, and IsoPSA.

The MyProstateScore 2.0 (MPS2) test, which looks for 18 genes associated with high-grade tumors, could reduce unnecessary biopsies in men with elevated prostate-specific antigen levels, according to a paper published in JAMA Oncology.

It makes sense. The prostate gland secretes fluid that becomes part of the semen, traces of which enter urine. After a digital rectal exam, even more prostate fluid enters the urine. If a patient has prostate cancer, genetic material from the cancer cells will infiltrate the urine.

In the MPS2 test, researchers used polymerase chain reaction (PCR) testing in urine. “The technology used for COVID PCR is essentially the same as the PCR used to detect transcripts associated with high-grade prostate cancer in urine,” said study author Arul Chinnaiyan, MD, PhD, director of the Michigan Center for Translational Pathology at the University of Michigan, Ann Arbor. “In the case of the MPS2 test, we are doing PCR on 18 genes simultaneously on urine samples.”

A statistical model uses levels of that genetic material to predict the risk for high-grade disease, helping doctors decide what to do next. At 95% sensitivity, the MPS2 model could eliminate 35%-45% of unnecessary biopsies, compared with 15%-30% for the other tests, and reduce repeat biopsies by 46%-51%, compared with 9%-21% for the other tests.

Head and neck cancer. In a paper published in JCI Insight, researchers described a test that finds ultra-short fragments of DNA in urine to enable early detection of head and neck cancers caused by human papillomavirus.

“Our data show that a relatively small volume of urine (30-60 mL) gives overall detection results comparable to a tube of blood,” said study author Muneesh Tewari, MD, PhD, professor of hematology and oncology at the University of Michigan .

A larger volume of urine could potentially “make cancer detection even more sensitive than blood,” Dr. Tewari said, “allowing cancers to be detected at the earliest stages when they are more curable.”

The team used a technique called droplet digital PCR to detect DNA fragments that are “ultra-short” (less than 50 base pairs long) and usually missed by conventional PCR testing. This transrenal cell-free tumor DNA, which travels from the tumor into the bloodstream, is broken down small enough to pass through the kidneys and into the urine. But the fragments are still long enough to carry information about the tumor’s genetic signature.

This test could spot cancer before a tumor grows big enough — about a centimeter wide and carrying a billion cells — to spot on a CT scan or other imaging test. “When we are instead detecting fragments of DNA released from a tumor,” said Dr. Tewari, “our testing methods are very sensitive and can detect DNA in urine that came from just 5-10 cells in a tumor that died and released their DNA into the blood, which then made its way into the urine.”

Pancreatic cancer. Pancreatic ductal adenocarcinoma is one of the deadliest cancers, largely because it is diagnosed so late. A urine panel now in clinical trials could help doctors diagnose the cancer before it has spread so more people can have the tumor surgically removed, improving prognosis.

Using enzyme-linked immunosorbent assay test, a common lab method that detects antibodies and other proteins, the team measured expression levels for three genes (LYVE1, REG1B, and TFF1) in urine samples collected from people up to 5 years before they were diagnosed with pancreatic cancer. The researchers combined this result with patients’ urinary creatinine levels, a common component of existing urinalysis, and their age to develop a risk score.

This score performed similarly to an existing blood test, CA19-9, in predicting patients’ risk for pancreatic cancer up to 1 year before diagnosis. When combined with CA19-9, the urinary panel helped spot cancer up to 2 years before diagnosis.

According to a paper in the International Journal of Cancer, “the urine panel and affiliated PancRISK are currently being validated in a prospective clinical study (UroPanc).” If all goes well, they could be implemented in clinical practice in a few years as a “noninvasive stratification tool” to identify patients for further testing, speeding up diagnosis, and saving lives.

Limitations and Promises

Each cancer type is different, and more research is needed to map out which substances in urine predict which cancers and to develop tests for mass adoption. “There are medical and technological hurdles to the large-scale implementation of urine analysis for complex diseases such as cancer,” said Dr. Wong.

One possibility: Scientists and clinicians could collaborate and use artificial intelligence techniques to combine urine test results with other data.

“It is likely that future diagnostics may combine urine with other biological samples such as feces and saliva, among others,” said Dr. Wong. “This is especially true when novel data science and machine learning techniques can integrate comprehensive data from patients that span genetic, proteomic, metabolic, microbiomic, and even behavioral data to evaluate a patient’s condition.”

One thing that excites Dr. Tewari about urine-based cancer testing: “We think it could be especially impactful for patients living in rural areas or other areas with less access to healthcare services,” he said.
 

A version of this article appeared on Medscape.com.