MDedge Surgery

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

In 1974, Tommy John of the Los Angeles Dodgers was 31 and a 12-year veteran of Major League Baseball when he became the unwitting vanguard of a revolution in baseball and orthopedics. Fifty years later, Mr. John might not be a candidate for the latest advances to a procedure that bears his name.

The southpaw pitcher had faced the abrupt end of his career when, after one fateful delivery, he found himself unable to throw to home. So he took a gamble on the surgical equivalent of a Hail Mary: the reconstruction of a torn ligament in his pitching elbow.

The experiment was a wild success. Mr. John pitched— and better than he had before — for another 14 seasons, retiring in 1989 at the age of 46. How much better? After the surgery, he tallied three 20-win seasons compared with none before the operation, and he finished among the top five vote-getters for the annual Cy Young Award three times. He was named an All-Star once before the surgery and three times after.

The triumph notwithstanding, Tommy John now cautions against Tommy John surgery. What’s given him and clinicians pause is a trend in recent years of ever-younger athletes who undergo the procedure.

Along with the surgical improvements in repairing a torn ulnar collateral ligament (UCL) is a demographic shift toward school-aged athletes who get it. By 2014, one study concluded that 67.4% of UCL reconstruction surgeries were performed on athletes between 16 and 20 years of age. Some patients are still in Little League when they undergo the procedure.

Experts say these athletes have weakened their UCLs through overuse. They disagree on whether to call it an “epidemic,” but if it is, “the vaccine is awareness” against throwing too hard and too often, said Eric Makhni, MD, an orthopedic surgeon at Henry Ford Health in Detroit.
 

From Career-Ending to Routine

Mr. John’s entry into baseball and orthopedic lore was initially slow, but the trickle turned into a tide. After Frank Jobe, MD, swapped a healthy tendon from John’s right wrist for his worn and torn left UCL on September 25, 1974, he didn’t perform his second surgery for another 1194 days. By the time “Tommy John surgery” became a recognized phrase, Mr. John was still active but only 14 professional baseball players had undergone the operation.

Prior to the start of spring training this year, an oft-cited database listed 366 pro players who’d undergone the operation. 

“Before Tommy John, that was a career-ending injury,” said Grant E. Garrigues, MD, an orthopedic surgeon at Midwest Orthopaedics at RUSH in Chicago, who called Mr. John “a pure revolutionary.”

Tommy John surgery is “the only one that I can think of that is named after the patient rather than the doctor who first did it,” said Patrick McCulloch, MD, an orthopedic surgeon in Houston and a team physician for the Astros.

Dr. McCulloch, who performs about 25 UCL repairs a year, said that by recent estimates, one-third of pro pitchers had had some sort of surgical repair. He hesitated to call the increasing number of operations an epidemic but acknowledged that the ingredients exist for more elbow trauma among baseball players.

“More people are playing more often, and people are bigger and stronger and throwing harder,” he said.

Either way, Dr. McCulloch said, “the procedure is a victim of its own success” because it is “just done phenomenally well.”

The surgery is now commonplace — perhaps too commonplace, said David W. Altchek, MD, attending surgeon and co-chief emeritus at Hospital for Special Surgery in New York City.

Dr. Altchek played a key role in the popularity of the operation. Twenty-two years after Mr. John’s surgery, he helped develop a variation of the procedure called the docking technique. 

Whereas Dr. Jobe sutured Mr. John’s replacement graft to itself, “we developed a different way of tying it over a bone bridge, which was more secure and more easy to tension,” Dr. Altchek explained.

The advance meant less drilling into bone and enabled surgeons to avoid moving a problem-free ulnar nerve or removing the flexor-pronator muscle that protects the elbow from stress. “The trauma of the surgery is significantly less,” he said. “We just made it a lot easier very quickly,” cutting the surgery time from 2 hours to 30-40 minutes.

Maybe the surgery became too easy, said Dr. Altchek, who estimates he has done 2000 of them over the past 30 years. “I don’t want to condemn my colleagues, but there are a lot of people doing the surgery,” he said. “And not a lot of people are doing a lot of them, and they don’t know the nuances of doing the surgery.”

The older procedures are known as the “full Tommy John”; each has a 12- to 18-month healing process, with a success rate of 80%-85%. Pitchers typically sit out a season while recovering.

Brandon Erickson, MD, an orthopedic surgeon at Rothman Orthopaedic Institute in New York City, said that in younger patients he has recently turned more often to the suture of the future: an internal brace that provides a repair rather than reconstruction.

The procedure, pioneered by Felix H. Savoie III, MD, the Ray J. Haddad Professor of Orthopaedics at Tulane University School of Medicine in New Orleans, and Jeffrey R. Dugas, MD, of Andrews Sports Medicine & Orthopaedic Center in Birmingham, Alabama, uses collagen-coated tape that looks like a shoelace and provides a scaffold that Dr. McCulloch said “is inductive to healing and growth of ligament tissue.”

The brace is intended for an “overhead” athlete (mostly baseball players but also javelin throwers and gymnasts) whose UCL is torn on only one side but is otherwise in good shape. In a pitcher the same age as Mr. John was when Dr. Jobe performed the first procedure, “that ligament may not be of very good quality,” Dr. McCulloch said. “It may have thickened. It may have calcifications.” But for a high-school junior with aspirations to pitch in college or beyond without “way too many miles on the elbow,” the approach is a good fit. The healing process is as little as 6 months.

“The ones who have a good ligament are very likely to do well,” said Dr. Erickson, an assistant team doctor for the Philadelphia Phillies.

“If the patient’s ligament is generally ‘good’ with only a tear, the InternalBrace procedure may be used to repair the native ligament. On the other end of the spectrum, if the patient’s ligament is torn and degenerative the surgeon may opt to do a UCL reconstruction using an auto or allograft — ie, Tommy John surgery,” Allen Holowecky, senior product manager of Arthrex of Naples, Florida, the maker of the InternalBrace, told this news organization. “Before UCL repair, Tommy John surgery was the only real treatment option. We tend to see repairs done on younger patients since their ligament hasn’t seen years of use-damage.”
 

Calls for Caution

Tommy John III wanted to play baseball like his dad until near-fatal complications from shoulder surgery altered his path. He was drawn to chiropractic and consults on injury prevention. “All surgeries and all medical interventions are cut first, ask questions later,” he said. “I was born with that.”

He saw his dad’s slow, heroic comeback from the surgery and described him as the perfect candidate for Dr. Jobe’s experiment. Tommy John spent his recovery time squeezing Silly Putty and throwing tennis balls. “He was willing to do anything necessary. He wanted to throw. That was his brush.” When the son was recovering from his own injury, “he said, ‘Learn the knuckleball.’ I said, ‘I don’t want to. I’ve reached my point.’ ”

He said he tells young patients with UCL injuries to rest. But instead “we have year-round sports with the promise that the more you play, the better,” he said. “They’re over-activitied.”

According to the American Academy of Orthopaedic Surgeons, 6.4 million children and adolescents in the United States played organized baseball in 2022, down from 11.5 million in 2014. Nearly half of pitchers played in a league with no maximum pitch counts, and 43.5% pitched on consecutive days, the group said.

How many UCL repair or reconstruction surgeries are performed on youth athletes each year is unclear. A 2019 study, however, found that although baseball injuries decreased between 2006 and 2016, the elbow was “the only location of injury that saw an increase.”

Dr. Garrigues said some parents of throwing athletes have asked about prophylactic Tommy John surgery for their children. He said it shouldn’t apply to pitchers.

“People have taken it a little too far,” he said. Dr. Garrigues and others argue against children throwing weighted balls when coming back from surgery. Instead, “we’re shutting them down,” he said.

Throwing any pitch is an act of violence on the body, Dr. Garrigues said, with the elbow taking the final brunt of the force. “These pitchers are functioning at the absolute limits of what the human body can take,” he said. “There’s only so many bullets in a gun,” which is why pitchers often feel the twinge of a torn UCL on a routine pitch.

Dr. Makhni suggested cross-training for pitchers in the off-season instead of playing baseball year-round. “If you play soccer, your footwork is going to be better,” he said.

“Kids shouldn’t be doing this all year round,” said Rebecca Carl, MD, associate professor of pediatrics at Northwestern University Feinberg School of Medicine in Chicago. “We are recommending that kids take 2 or 3 months off.” In the off-season, she urges them to strengthen their backs and cores. 

Such advice can “feel like a bombshell,” said Dr. Carl, who chairs the Council on Sports Medicine and Fitness for the American Academy of Pediatrics. ‘Some started at a very young age. They go to camps. If I say to a teenager, ‘If you do this, I can keep you from getting injured,’ they think, ‘I won’t be injured.’” Most parents, however, understand the risk of “doing too much, too soon.”

Justin Orenduff, a former pitching prospect until his arm blew out, has made a career teaching head-to-toe pitching mechanics. He founded DVS Baseball, which uses software to teach pitchers how to properly use every muscle, starting with the orientation of the back foot. He, too, argues against pitching year-round. “Everyone on that travel team expects to get their fair share of playing time,” he said. “It just never stops.”

Organized baseball is paying attention. It has come up with the Pitch Smart program that gives maximum pitch counts for young players, but experts said children often get around that by belonging to several leagues.

Dr. Altchek said some surgeons have added platelet-rich plasma, stem cells, and bone marrow during surgery to quicken the slow healing time from UCL replacement. But he said, “it has to heal. Can you speed up biology?”

Dr. McCulloch said that, all the advances in Tommy John surgery aside, “the next frontier is really trying to crack the code on prevention.”

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

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

Minimally invasive cytoreductive surgery for epithelial ovarian cancer appears to be safe and does not compromise survival, compared with open surgery, when patients have completely resected tumors.

This was a finding of a retrospective study presented by Judy Hayek, MD, during an oral abstract session at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer, in San Diego.

Among 2,412 women in the National Cancer Database with tumor-free surgical margins (R0 resections) after interval debulking surgery (IDS), the median overall survival (OS) was 46 months for those who had undergone an open procedure or minimally invasive surgery (MIS) that was converted to an open procedure. In contrast, the median OS was 51 months for patients who underwent laparoscopic or robot-assisted minimally invasive surgery, reported Dr. Hayek, a gynecologic oncology fellow at SUNY Downstate Health Sciences University in Brooklyn, New York.

“R0 resection at the time of interval debulking surgery has similar survival outcomes by minimally invasive surgery versus laparotomy, while R0 resection via laparotomy is associated with higher perioperative mortality. There is no interaction between the extent of surgery and the impact of MIS on survival,” she said during her presentation.

The session included a debate on the pros and cons of minimally invasive vs. open surgery in this population.
 

Growing Use of MIS

Over the last decade, minimally invasive surgery for interval debulking was shown to be safe and feasible. More recently, two studies using National Cancer Database cohorts showed that survival was similar and perioperative outcomes were better with a minimally invasive approach at the time of IDS for patients with early disease, Dr. Hayek said (Obstet Gynecol 2017 Jul;130(1):71-79; and Gynecol Oncol 2023 May:172:130-137).

Potential limitations of MIS include the absence of haptic feedback compared with open surgery, and the possibility that limited visualization of the surgical field could lead to missed residual disease and subsequent poor outcomes for patients who were presumed to have complete gross resections, she said.
 

Outcomes Compared

Dr. Hayek and colleagues conducted their study to evaluate survival outcomes after R0 resections by MIS or laparotomy in IDS for patients with advanced epithelial ovarian cancer.

As noted before, they looked at outcomes for 2,412 women with stage IIIC or IV cancers of all histology types who were diagnosed from 2010 through 2019. A total of 624 patients (25.9%) had minimally invasive procedures, and 1,788 (74.1%) had open surgery or MIS that had been converted to open procedures.

Of the minimally invasive procedures, 48.7% were robot-assisted, and the remainder were laparoscopic.

Over the decade of the study, the frequency of minimally invasive surgery steadily increased, from 11.9% of all procedures in 2010 to 36.5% in 2019.

Also as noted, there was no difference in median overall survival, at 46 months for open/converted procedures vs. 51 months for minimally invasive procedures.

As might be expected, the mean length of stay was shorter with the less invasive surgery: 3.3 days compared with 5.3 days with open surgery (P less than .001). In addition, 30-day and 90-day mortality rates were also lower with MIS, at 0.8% and 1.9%, respectively, compared with 1.6% and 3.5% with laparotomy (P = .006 for 30-day mortality, and .003 for 90-day).

There were also no differences in overall survival between the procedure types when the cases were stratified according to extent of surgery. Within the minimally invasive surgery groups there were no differences in median OS for patients whose surgery was performed laparoscopically or with robotic assistance.

The study was limited by a lack of data on either patient-specific tumor burden, neoadjuvant chemotherapy use, progression-free survival, cause of death, or surgical morbidity, Dr. Hayek acknowledged.
 

MIS Use Debatable: CON

Despite the good outcomes with minimally invasive techniques in this favorable-risk population, critics contend that MIS interval cytoreduction is too risky in the majority of cases.

In the debate portion of the session, Kara Long Roche, MD, an associate attending in the section of ovarian cancer surgery at Memorial Sloan Kettering Cancer Center in New York, argued that the potential for MIS missing residual disease is too great.

“We know from almost every retrospective and prospective study done that the volume of residual disease after debulking, whether primary or interval, is the most important prognostic factor for our patients that we can modify,” she said.

Rather than debating morbidity, mortality, or criteria for resection, “I would argue that the question we need to debate is can MIS interval debulking achieve a completeness of resection, i.e., volume of residual disease?” she said.

Dr. Roche contended that retrospective studies such as that reported by Dr. Hayek cannot adequately answer this question because of selection bias. Patients selected for MIS have better responses to neoadjuvant chemotherapy and more favorable tumor biology; and, therefore, overall survival may not be the optimal endpoint for retrospective studies.

In addition, neoadjuvant chemotherapy does not automatically preclude the need for extensive upper abdominal surgery since almost half of patients who receive neoadjuvant chemotherapy are found to have bulky upper abdominal disease at the time of debulking.

Dr. Roche especially cautioned against what she called the WNL or “We Never Looked” phenomenon, in which patients are found on open surgery and organ mobilization to have disease that was not evident on presurgical imaging.

She acknowledged that for some patients the risks of laparotomy are likely to outweigh the benefit of a radical resection, and stressed that for such patients forgoing surgery or optimizing perioperative care may be more important than the size of the incision.

MIS IDS should be the exception, not the rule. We need prospective data with appropriate endpoints. We need surgical quality control in both arms, and we need to continue to focus on surgical education and training so that our trainees can graduate doing these procedures via any approach,” she concluded.
 

Debate: PRO

Arguing in favor of MIS for ovarian cancer, J. Alejandro Rauh-Hain, MD, MPH, associate professor of gynecologic oncology at the University of Texas MD Anderson Cancer Center in Houston, told attendees “the only bias I have is that I actually love doing open surgery, but I’m going to try to convince you that there is a potential role for minimally invasive surgery in the future for selected patients with ovarian cancer after neoadjuvant chemotherapy.”

He noted that several studies have convincingly shown that neoadjuvant chemotherapy does not adversely affect oncologic outcomes for patients with advanced-stage ovarian cancer, and decreases perioperative morbidity in patients who receive it, including reductions in serious adverse events, risk of stoma, and 30-day postoperative mortality.

In addition, low use of neoadjuvant chemotherapy is associated with increased risks for 90-day postoperative deaths in both low- and high surgical volume centers in the US, according to unpublished National Cancer Database data.

Dr. Rauh-Hain noted that neoadjuvant chemotherapy use has steadily increased from 2010 through 2020, and added that in 2022, 32% of interval cytoreductive surgeries in the United States were performed with a minimally invasive approach.

To get a better handle on the MIS vs. open-surgery question, Dr. Rauh-Hain and colleagues at MD Anderson and 13 other centers in the United States, Canada, and Europe are currently recruiting patients for the Laparoscopic Cytoreduction After Neoadjuvant Chemotherapy (LANCE) trial. In this phase 3 noninferiority study, patients with stage IIIC-IV ovarian, primary peritoneal, or fallopian tube cancer who have complete or partial responses and CA125 normalization after three or four cycles of neoadjuvant chemotherapy will be randomized to laparotomy or MIS, followed by adjuvant platinum- and taxane-based chemotherapy.

The study by Hayek et al. was internally supported. Dr. Hayek and Dr. Roche reported having no conflicts of interest. Dr. Rauh-Hain disclosed financial relationships with Guidepoint Consulting, and the Schlesinger Group.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

For early-stage cervical cancer, non-radical surgery (simple hysterectomy or cone biopsy plus pelvic lymphadenectomy) appears safe with no lasting negative impact on quality of life, according to results of the GOG-278 trial.

In fact, patients’ quality of life was improved after surgery in both groups, and their concerns about cancer recurrence decreased, especially for those undergoing simple hysterectomy, said Allan Covens, MD, in his late-breaking abstract presentation at the Society of Gynecologic Oncology (SGO)’s Annual Meeting on Women’s Cancer. 

“Cone biopsy patients reported less concerns about reproductive fertility after surgery and over time compared to preop assessments,” he added.

Due to screening in developed countries, a large proportion of cervical cancers are discovered at an early stage. Treatment of these cancers with radical surgery is associated with high cure rates but significant adverse effects on quality of life, said Dr. Covens, who is with the University of Toronto, Toronto, Ontario, Canada.

He and his colleagues wanted to see if non-radical surgery could be safely used instead. “Multiple case series have indicated that non-radical surgery is associated with less morbidity and improved quality of life,” he explained. “If this can be proven in a prospective evaluation, it will change future practice.”

GOG-278 was a prospective cohort study of women with stage IA1 (lymph-vascular space invasion+) and IA2-IB1 (≤ 2 cm) carcinoma of the cervix who underwent non-radical surgery (simple hysterectomy or fertility-preserving cone biopsy) and pelvic lymphadenectomy. Criteria included ≤ 10 mm stromal invasion and negative margins on the final cone biopsy.

The primary objectives were to assess changes in functional outcomes of quality of life (bladder/bowel function, sexual function, cancer worry, and reproductive concerns), using validated instruments. Findings were based on 55 patients who underwent cone biopsy and 113 who underwent simple hysterectomy.

Both simple hysterectomy and cone biopsy were associated with “small” declines in sexual function and bladder/bowel function at 4-6 weeks after surgery, but function “quickly” recovered to baseline by 6 months, Dr. Covens reported.

Twelve patients reported a diagnosis of lymphedema, with a Gynecologic Cancer Lymphedema Questionnaire score change of 4 or higher on at least two consecutive evaluations from baseline. This occurred in six cone biopsy and six simple hysterectomy patients.

In a separate presentation, Dr. Covens reported secondary oncologic outcomes from GOG-278, which suggest that non-radical surgery for early-stage cervical cancer is safe, with low perioperative morbidity, although longer follow-up is needed.

He also reported 16 pregnancies in 15 patients who had undergone cone biopsies; 12 of these were successful, and there were four early pregnancy losses.
 

‘Impressive’ Data

Study discussant Kristin Bixel, MD, with The Ohio State University, Columbus, Ohio, said the data are “impressive” and clearly show that non-radical surgery has “minimal impact on bladder/bowel function, with no long-term differences from baseline.”

She added that the incidence of lymphedema was “honestly significantly lower than what I typically counsel patients about” and wondered if the percentage of patients with lymphedema would increase over time.

Dr. Bixel particularly noted the decrease in cancer worry scores after surgery, as sometimes patients who have less radical procedures fear that this comes with an increased risk for recurrence.

The “growing body of data suggests that less radical surgery is safe and effective for early-stage low-risk cervical cancer and highlights the potential reproductive success,” she concluded.

Funding for the study was provided by grants from NRG Oncology. Dr. Covens had no disclosures. Dr. Bixel has received research funding from the Intuitive Foundation.

A version of this article appeared on Medscape.com.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

Widely considered the father of cancer immunotherapy, Steven A. Rosenberg MD, PhD, FAACR, has spent nearly 50 years analyzing the link between patients’ immune reaction and their cancer response.

His pioneering research established interleukin-2 (IL-2) as the first U.S. Food and Drug Administration–approved cancer immunotherapy in 1992.

To recognize his trailblazing work and other achievements, the American Association for Cancer Research (AACR) will award Dr. Rosenberg with the 2024 AACR Award for Lifetime Achievement in Cancer Research at its annual meeting in April.

Dr. Rosenberg: I grew up in the Bronx. My parents both immigrated to the United States from Poland as teenagers.


As a young boy, did you always want to become a doctor?

Dr. Rosenberg: I think some defining moments on why I decided to go into medicine occurred when I was 6 or 7 years old. The second world war was over, and many of the horrors of the Holocaust became apparent to me. I was brought up as an Orthodox Jew. My parents were quite religious, and I remember postcards coming in one after another about relatives that had died in the death camps. That had a profound influence on me.


How did that experience impact your aspirations?

Dr. Rosenberg: It was an example to me of how evil certain people and groups can be toward one another. I decided at that point, that I wanted to do something good for people, and medicine seemed the most likely way to do that. But also, I was developing a broad scientific interest. I ended up at the Bronx High School of Science and knew that I not only wanted to practice the medicine of today, but I wanted to play a role in helping develop the medicine.


What led to your interest in cancer treatment?

Dr. Rosenberg: Well, as a medical student and resident, it became clear that the field of cancer needed major improvement. We had three major ways to treat cancer: surgery, radiation therapy, and chemotherapy. That could cure about half of the people [who] had cancer. But despite the best application of those three specialties, there were over 600,000 deaths from cancer each year in the United States alone. It was clear to me that new approaches were needed, and I became very interested in taking advantage of the body’s immune system as a source of information to try to make progress.


Were there patients who inspired your research?

Dr. Rosenberg: There were two patients that I saw early in my career that impressed me a great deal. One was a patient that I saw when working in the emergency ward as a resident. A patient came in with right upper quadrant pain that looked like a gallbladder attack. That’s what it was. But when I went through his chart, I saw that he had been at that hospital 12 years earlier with a metastatic gastric cancer. The surgeons had operated. They saw tumor had spread to the liver and could not be removed. They closed the belly, not expecting him to survive. Yet he kept showing up for follow-up visits.
Here he was 12 years later. When I helped operate to take out his gallbladder, there was no evidence of any cancer. The cancer had disappeared in the absence of any external treatment. One of the rarest events in medicine, the spontaneous regression of a cancer. Somehow his body had learned how to destroy the tumor.
 

Was the second patient’s case as impressive?

Dr. Rosenberg: This patient had received a kidney transplant from a gentleman who died in an auto accident. [The donor’s] kidney contained a cancer deposit, a kidney cancer, unbeknownst to the transplant surgeons. [When the kidney was transplanted], the recipient developed widespread metastatic kidney cancer.
[The recipient] was on immunosuppressive drugs, and so the drugs had to be stopped. [When the immunosuppressive drugs were stopped], the patient’s body rejected the kidney and his cancer disappeared.
That showed me that, in fact, if you could stimulate a strong enough immune reaction, in this case, an [allogeneic] reaction, against foreign tissues from a different individual, that you could make large vascularized, invasive cancers disappear based on immune reactivities. Those were clues that led me toward studying the immune system’s impact on cancer.


From there, how did your work evolve?

Dr. Rosenberg: As chief of the surgery branch at NIH, I began doing research. It was very difficult to manipulate immune cells in the laboratory. They wouldn’t stay alive. But I tried to study immune reactions in patients with cancer to see if there was such a thing as an immune reaction against the cancer. There was no such thing known at the time. There were no cancer antigens and no known immune reactions against the disease in the human.


Around this time, investigators were publishing studies about interleukin-2 (IL-2), or white blood cells known as leukocytes. How did interleukin-2 further your research?

Dr. Rosenberg: The advent of interleukin-2 enabled scientists to grow lymphocytes outside the body. [This] enabled us to grow t-lymphocytes, which are some of the major warriors of the immune system against foreign tissue. After [studying] 66 patients in which we studied interleukin-2 and cells that would develop from it, we finally saw a disappearance of melanoma in a patient that received interleukin-2. And we went on to treat hundreds of patients with that hormone, interleukin-2. In fact, interleukin-2 became the first immunotherapy ever approved by the Food and Drug Administration for the treatment of cancer in humans.

Dr. Rosenberg: [It] led to studies of the mechanism of action of interleukin-2 and to do that, we identified a kind of cell called a tumor infiltrating lymphocyte. What better place, intuitively to look for cells doing battle against the cancer than within the cancer itself?
In 1988, we demonstrated for the first time that transfer of lymphocytes with antitumor activity could cause the regression of melanoma. This was a living drug obtained from melanoma deposits that could be grown outside the body and then readministered to the patient under suitable conditions. Interestingly, [in February the FDA approved that drug as treatment for patients with melanoma]. A company developed it to the point where in multi-institutional studies, they reproduced our results.
And we’ve now emphasized the value of using T cell therapy, t cell transfer, for the treatment of patients with the common solid cancers, the cancers that start anywhere from the colon up through the intestine, the stomach, the pancreas, and the esophagus. Solid tumors such as ovarian cancer, uterine cancer and so on, are also potentially susceptible to this T cell therapy.
We’ve published several papers showing in isolated patients that you could cause major regressions, if not complete regressions, of these solid cancers in the liver, in the breast, the cervix, the colon. That’s a major aspect of what we’re doing now.
I think immunotherapy has come to be recognized as a major fourth arm that can be used to attack cancers, adding to surgery, radiation, and chemotherapy.


What guidance would you have for other physician-investigators or young doctors who want to follow in your path?

Dr. Rosenberg: You have to have a broad base of knowledge. You have to be willing to immerse yourself in a problem so that your mind is working on it when you’re doing things where you can only think. [When] you’re taking a shower, [or] waiting at a red light, your mind is working on this problem because you’re immersed in trying to understand it.
You need to have a laser focus on the goals that you have and not get sidetracked by issues that may be interesting but not directly related to the goals that you’re attempting to achieve.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

NATIONAL HARBOR, MARYLAND — Implementation of a standardized induction of labor protocol had no significant effect on the rates of cesarean delivery in patients with obesity, based on data from more than 5000 individuals.

Previous research has shown that the risk for cesarean delivery increases by 5% with each 1-kg/m² increase in body mass index (BMI) among nulliparous patients, said Melissa Riegel, MD, of the University of Pennsylvania, Philadelphia, in a presentation at the meeting sponsored by the Society for Maternal-Fetal Medicine. (abstract 82).

Research on the relationship between obesity and higher cesarean delivery rates “has been clouded by the inability to reduce variation in care,” Dr. Riegel said at the meeting sponsored by the Society for Maternal Fetal Medicine. Failed induction of labor (IOL) is a leading indicator for cesarean delivery, and cesarean delivery is 80% more likely in patients with obesity undergoing IOL than in normal-weight patients, Dr. Riegel said.

Possible explanations for these differences include provider factors such as variability in care management, conscious and unconscious biases, or physiologic differences in patients with obesity such as elevated hormones, differences in the labor curve, and higher doses of oxytocin and prostaglandins, Dr. Riegel said.

Dr. Riegel and colleagues hypothesized that differences in cesarean delivery rates would persist despite a standardized labor induction protocol, thereby supporting the effects of factors other than variations in care on increased cesarean delivery risk after IOL in patients with obesity.

The researchers reviewed data from two sites comparing 2-year periods before and after implementation of an IOL protocol from 2018 to 2022. The study population included nulliparous women with singleton pregnancies at term who underwent IOL with intact membranes and unfavorable cervices, and had a BMI of at least 30 kg/m² at delivery. The preimplementation group (PRE) included 2480 individuals and the postimplementation group (POST) included 2651 individuals. Patients were divided into weight classes based on BMI: 30-34.9; 35-39.9; ≥40.

The standardized protocol consisted of active labor management with cervical exams, with an amniotomy by the time of the first exam with 4 cm or greater cervical dilation, and further intervention with medication such as oxytocin or an intrauterine pressure catheter if no cervical change was noted after 2 hours.

In a multivariate analysis, the overall cesarean delivery rate was 24.9% before the protocol implementation and 26.0% in the postimplementation group. There were no differences in the risk of cesarean delivery in any obesity class from the PRE to POST period.

In addition, no significant differences appeared in the secondary outcomes of duration of labor, maternal morbidity, or neonatal morbidity, Dr. Riegel said. Nonreassuring fetal heart rate tracing was the most common reason for cesarean delivery across all obesity classes and the PRE and POST groups.

Study limitations included the use of data from only two sites, but the results were strengthened by the large sample size, said Dr. Reigel. The results indicate that reducing variation in IOL management had no significant effect on the relationship between obesity and cesarean delivery and support underlying physiologic explanations, she said.
 

Making the Case for Physiology

“By standardizing induction practices, we were able to minimize differences in care and better answer why the increased cesarean delivery rate exists in this patient population,” Dr. Riegel said in an interview. The findings were in line with the primary hypothesis that standardized induction would not affect cesarean delivery rates in patients with obesity, she said. Instead, the findings support potential physiologic differences as “the driving force behind this relationship,” she added.

Looking ahead, “There is a role for translational work to investigate the specific biological changes in patients with obesity that might contribute to an increased risk of cesarean delivery and there is also a role for investigating the effectiveness of different labor induction interventions specifically in patients with obesity,” Dr. Riegel said.
 

Different Induction Protocols Needed for Obese Patients?

“Given that severe maternal morbidity and mortality are continuing to increase in the United States, this study is critical, as we know that both cesarean delivery and obesity are driving factors in increasing maternal morbidity,” said Marissa Platner, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, Georgia, in an interview.

However, the novel takeaway message from the current study is that patients with obesity were more likely to require cesarean delivery even with a protocol in which variation in labor induction techniques are minimized, said Dr. Platner, who was not involved in the study. “This leads to the question of [whether] we should have different standards or protocols for our patients with obesity, as well as a need for clear counseling for these patients early on in pregnancy,” she said.

As for further research, “It would be interesting to see if the risk of cesarean delivery changed based on class of obesity, and the primary drivers of cesarean delivery in this study,” Dr. Platner said. “Additionally, it would be helpful to know how much pitocin was needed for patients, based on their BMI category, to achieve successful vaginal delivery,” she noted.

The study was supported by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Development. The researchers had no financial conflicts to disclose. Dr. Platner had no financial conflicts to disclose.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

President Joe Biden on March 9 signed into law a measure that softened — but did not completely eliminate — a 2024 cut in a key rate used to determine how physicians are paid for treating Medicare patients.

While physician groups hailed the move as partial relief, they say they’ll continue to press for broader changes in the Medicare physician fee schedule.

The Medicare provision was tucked into a larger spending package approved by the US House and Senate.

The American Academy of Family Physicians (AAFP), the American Medical Association (AMA), and other groups have lobbied Congress for months to undo a 3.4% cut in the base rate, or conversion factor, in the physician fee schedule for 2024.

The conversion factor is used in calculations to determine reimbursement for myriad other services. Federal Medicare officials said the cut would mean a 1.25% decrease in overall payments in 2024, compared with 2023.

“With the passage of this legislation, Congress has offset 2.93% of that payment cut,” said Steven P. Furr, MD, AAFP’s president in a statement. “We appreciate this temporary measure but continue to urge Congress to advance comprehensive, long-term Medicare payment reform.”

In a statement, Representative Larry Bucshon, MD (R-IN), said the payment cut could not be completely eliminated because of budget constraints.

The Medicare physician fee schedule covers much of the care clinicians provide to people older than 65 and those with disabilities. It covers about 8000 different types of services, ranging from office visits to surgical procedures, imaging, and tests, according to the Medicare Payment Advisory Commission (MedPAC).

Along with physicians, the fee schedule sets payments for nurse practitioners, physician assistants, podiatrists, physical therapists, psychologists, and other clinicians.

In 2021, the Medicare program and its beneficiaries paid $92.8 billion for services provided by almost 1.3 million clinicians, MedPAC said.
 

Larger Changes Ahead?

Rep. Bucshon is among the physicians serving in the House who are pressing for a permanent revamp of the Medicare physician fee schedule. He cosponsored a bill (HR 2474) that would peg future annual increases in the physician fee schedule to the Medicare Economic Index, which would reflect inflation’s effect.

In April, more than 120 state and national medical groups signed onto an AMA-led letter urging Congress to pass this bill.

The measure is a key priority for the AMA. The organization reached out repeatedly last year to federal officials about it through its own in-house lobbyists, this news organization found through a review of congressional lobbying forms submitted by AMA.

These required disclosure forms reveal how much AMA and other organizations spend each quarter to appeal to members of Congress and federal agencies on specific issues. The disclosure forms do not include a detailed accounting of spending on each issue.

But they do show which issues are priorities for an organization. AMA’s in-house lobbyists reported raising dozens of issues in 2024 within contacts in Congress and federal agencies. These issues included abortion access, maternal health, physician burnout, and potential for bias in clinical use of algorithms, as well as Medicare payment for physicians.

AMA reported spending estimated cost of $20.6 million. (AMA spent $6.7 million in the first quarter, $4.75 million in the second quarter, $3.42 million in the third quarter, and $5.74 million in the fourth quarter.)

In a March 6 statement, Jesse M. Ehrenfeld, MD, MPH, AMA president, urged Congress to turn to more serious consideration of Medicare physician pay beyond short-term tweaks attached to other larger bills.

“As physicians, we are trained to run toward emergencies. We urge Congress to do the same,” Dr. Ehrenfeld said. “We encourage Congress to act if this policy decision is an emergency because — in fact — it is. It is well past time to put an end to stopgap measures that fail to address the underlying causes of the continuing decline in Medicare physician payments.”

There’s bipartisan interest in a revamp of the physician fee schedule amid widespread criticism of the last such overhaul, the Medicare Access and CHIP Reauthorization Act of 2015.

For example, Senate Budget Chairman Sheldon Whitehouse (D-RI) has proposed the creation of a technical advisory committee to improve how Medicare sets the physician fee schedule. The existing fee schedule provides too little money for primary care services and primary care provider pay, contributing to shortages, Sen. Whitehouse said.

Sen. Whitehouse on March 6 held a hearing on ways to beef up US primary care. Among the experts who appeared was Amol Navathe, MD, PhD, of the University of Pennsylvania, Philadelphia, Pennsylvania.

Dr. Navathe said the current Medicare physician fee schedule tilts in favor of procedural services, leading to “underinvestment in cognitive, diagnostic, and supportive services such as primary care.”

In addition, much of what primary care clinicians do, “such as addressing social challenges, is not included in the codes of the fee schedule itself,” said Dr. Navathe, who also serves as the vice chairman of MedPAC.

It’s unclear when Congress will attempt a serious revision to the Medicare physician fee schedule. Lawmakers are unlikely to take on such a major challenge in this election year.

There would be significant opposition and challenges for lawmakers in trying to clear a bill that added an inflation adjustment for what’s already seen as an imperfect physician fee schedule, said Mark E. Miller, PhD, executive vice president of healthcare at the philanthropy Arnold Ventures, which studies how payment decisions affect medical care.

“That bill could cost a lot of money and raise a lot of questions,” Dr. Miller said.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

Medtronic Neurosurgery has recalled Duet External Drainage and Monitoring System (EDMS) catheter tubing because the catheter may disconnect from the patient line stopcock connectors.

If this happens, potential harm to patients may include infections, cerebrospinal fluid (CSF) leakage, overdrainage of CSF, and abnormality of the ventricles. Uncontrolled overdrainage of CSF could lead to neurological injury or death if the disconnection is undetected.

The Food and Drug Administration has identified this as a Class I recall — the most serious type — due to the risk for serious injury or death. To date, there have been 26 reported injuries and no deaths related to this issue. 

The recall includes 45,176 devices distributed in the United States between May 3, 2021, and January 9, 2024, with model numbers 46913, 46914, 46915, 46916, and 46917.

The Duet EDMS is used for temporary CSF drainage or sampling in patients who have surgery for open descending thoracic aortic aneurysm (TAA) or descending thoraco-abdominal aortic aneurysm (TAAA) or patients who have TAA/TAAA repair surgery and develop symptoms such as paraplegia.

Medtronic has sent an urgent medical device recall letter to all affected customers asking them to identify, quarantine, and return any unused recalled products. 

Customers are also advised to check all Duet EDMS components for damage and ensure that all connections are secure and leak-free. 

If a patient is currently connected to an impacted Duet EDMS and a leak or disconnection is detected, the device should be changed to a new alternative device utilizing a sterile technique. 

It is not recommended that a Duet system device that is connected to a patient and working as intended be removed or replaced.

Customers in the United States with questions about this recall should contact Medtronic at 1-800-874-5797.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. We are coming to you live from the Mayo Clinic Urology Conference in Maui, Hawaii, with the world’s leading experts in men’s health, sexual health, and quality of life. I’m bringing in Dr. Allen Morey from the North Dallas area, one of the world’s leading experts in reconstructive urology. He deals with all things urinary incontinence, penile curvature, and sexual health.

Dr. Morey said something at this conference that really put my chin on the floor. He said, “The urethra is a sex organ. It is androgen dependent.” This is so important because it’s true for all genders. So, Dr. Morey, tell us more about why you made that comment and about the incontinence in men that you deal with all the time.

Allen F. Morey, MD: For many years, I’ve worked at cancer centers where, through the various treatments for prostate cancer, the men suffered from urinary incontinence and we put a lot of artificial urinary sphincters in those patients. I had one patient who asked, “Why do I keep having this erosion?” Of course, the erosion is where the cuff compresses the tissue surrounding the urethra, and the tissue gives way, leaving a hole in the urethra. I looked at him and noticed that he was pale. And I thought, Let me check his testosterone level. We started checking it on everybody who had this problem, and sure enough, the ones who had the cup erosion — who had the atrophic tissue around the urethra — most of them had low testosterone levels. Some of this was due to the cancer treatment, but in other men, it was just due to old age.

We started thinking that this is a causal relationship. And we tested it. I had a fellow who was a board-certified pathologist before becoming a urologist. He obtained some specimens from the urethra and did very sophisticated, elegant stains on that tissue. We found that it’s just erectile tissue surrounding the urethra. That’s why I call it a sex organ. I tell my patients, “When you are a teenager, this tissue is thin, like on your pinky finger. As you get older, it becomes thicker. And then as you get even older, and you may be having cancer treatment, that tissue is gone.” You can show them your little finger; it’s about that size. All the meat is off the bone. There’s nothing left protecting the urinary mucosa from the device.

That’s why it’s important to maintain the optimal health of those tissues and for them to remain dry. Because let’s face it: Urinary incontinence is a horrible quality of life. These are my happiest patients when we fix it. Before that, when they go on vacation, they have a separate suitcase filled with diapers. They can’t go anywhere. They can’t do anything. When they become incontinent after the prostatectomy, they gain weight. And when you put in the device to treat it, they lose weight and you can track it. The urinary incontinence patients really suffer. And we need to consider the medical optimization of those patients.

Dr. Rubin: It’s so important, and I love how analogous this is to our female patients. We know that incontinence is devastating to our female patients as well, and there’s a lot of hope. As we get older we start to pee every time we cough, laugh, or sneeze. Men are a little more bothered by it when it happens; they don’t expect it. Among women, it’s thought of as normal, but it’s not normal. There is so much we can do to help these patients, ranging from conservative treatment to surgical therapies.

The connection between hormones and urethral health is true on the female side as well. As you go through menopause, the urethral tissue thins out, gets dry, gets irritated, and can cause worsening incontinence, pain with sex, and genital urinary syndrome of menopause. It’s really important.

For our primary care doctors, how should we talk about stress incontinence in men? How do we diagnose it?

Dr. Morey: It’s easy to diagnose. Just do a quick history. Find out how many pads a day they are using. You have to ask the question, and then you have them stand up and look inside their underwear. You’ll see what kind of pad they are wearing. Is it just a shield or are they actually wearing full diapers? Then I have them do a standing cough test. I stand off to the side, holding a couple of towels, and have the patient cough four times. I can tell if it’s a full stream or just a couple of drops. Is it nothing but they are wearing a pad? You match up what you see with their experience, and in an instant it tells you how severe their problem is and it helps you direct them on to further treatment, because many patients have treatment fatigue. They’ve already been through the system. They have really suffered and they don’t know which way to go. They don’t know what’s available.

Dr. Rubin: On the female side, we have pelvic floor physical therapy. We have pads and devices that you can wear, and pessaries. We have surgical options, like bulking agents into the urethra as well as urethral slings, which can be quite helpful for women. So there’s a lot of hope out there for women, and from what I learned from you at this conference, there’s a lot of hope for men as well. So talk us through treatment, from conservative to surgical options.

Dr. Morey: There hasn’t been much innovation in male incontinence treatment over the past few decades, but we’re starting to see signs of new products appearing on the horizon, so I’m very optimistic that in the next 5 or 10 years, we’ll have more. But right now it comes down to slings and artificial sphincters, which are devices with little pumps and hydraulics, and they’re very good. But they’ve been around for 50 years, and they have this other potential risk factor of the erosion of the tissue.

We don’t have a pill that we can give the patient to tighten up those muscles. We can help them with overactive bladder. But maybe the hormonal influence is a way to optimize the health of the tissue so that these surgical treatments can really deliver the best outcomes. And as I always say, and having treated so many of these patients, it’s really a game of millimeters — how much coaptation you get. If you’re off by the slightest amount, that’s an unhappy patient. So it doesn’t take much to make it a lot better.

Dr. Rubin: There’s so much hope for our patients, and this can really have an effect on sexual health. You know the benefits you see in their quality of life and sexual health when you can stop leakage.

Dr. Morey: I always take care of the waterworks first. Many of the men have both urinary problems and erectile problems. Nobody feels sexy when they’re leaking urine all over their partner. So first we take care of that. And then, in the motivated younger patients, we bring them back and talk to them about potentially having a second operation.

Dr. Rubin: And so similarly, in women with urinary incontinence, it can have a major impact on sexual health — how they show up and how they talk to their partner. So, it is really important for our primary care docs to talk to patients about urinary incontinence and not just say, “Oh, well, you’re getting older. There’s nothing that you can do.” There’s actually no age at which there is nothing that we can do. And it’s really important to refer patients to those urologists who have extra training in incontinence and sexual health, because we do care about these quality-of-life measures and there is a lot we can do, ranging from conservative to more invasive treatments. But patients really should have options.

Dr. Morey: I heard during this meeting that urinary incontinence was the number-one source of treatment regret among patients who had their prostate treated for cancer. So, this is a really big deal for our patients. And it impacts wellness, quality of life, and overall well-being.

Dr. Rubin: When we are counseling patients for cancer surgeries or cancer treatments such as radiation therapy, it’s really hard for the patients who have never had urinary incontinence to imagine what that might be like. When you’re telling them they could have a stroke or a heart attack, or they could have erectile dysfunction or urinary incontinence, it all sounds similar to them. It could happen to someone else. It’s very hard to truly counsel patients on these quality-of-life issues that they’ve never encountered before.

Dr. Morey: We have found that it takes a long time for patients to get into our office for treatment, and it’s unbelievable — often 5 years in diapers before they find us.

Dr. Rubin: Hopefully videos like this will teach our docs and our patients that there is hope out there, that you don’t need to wait through years of suffering from incontinence. So, how does somebody find a reconstructive urologist or a sexual medicine urologist?

Dr. Morey: There are a couple of good websites out there, such as fixincontinence.com and edcure.org. The device manufacturers have pretty good information for patients.

Dr. Rubin: The Sexual Medicine Society of North America (SMSNA) has a great find-a-provider website, which provides a list of urologists who are trained in both sexual health and urinary incontinence, because they both matter. Our patients deeply care about these issues.

Rachel S. Rubin, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. We are coming to you live from the Mayo Clinic Urology Conference in Maui, Hawaii, with the world’s leading experts in men’s health, sexual health, and quality of life. I’m bringing in Dr. Allen Morey from the North Dallas area, one of the world’s leading experts in reconstructive urology. He deals with all things urinary incontinence, penile curvature, and sexual health.

Dr. Morey said something at this conference that really put my chin on the floor. He said, “The urethra is a sex organ. It is androgen dependent.” This is so important because it’s true for all genders. So, Dr. Morey, tell us more about why you made that comment and about the incontinence in men that you deal with all the time.

Allen F. Morey, MD: For many years, I’ve worked at cancer centers where, through the various treatments for prostate cancer, the men suffered from urinary incontinence and we put a lot of artificial urinary sphincters in those patients. I had one patient who asked, “Why do I keep having this erosion?” Of course, the erosion is where the cuff compresses the tissue surrounding the urethra, and the tissue gives way, leaving a hole in the urethra. I looked at him and noticed that he was pale. And I thought, Let me check his testosterone level. We started checking it on everybody who had this problem, and sure enough, the ones who had the cup erosion — who had the atrophic tissue around the urethra — most of them had low testosterone levels. Some of this was due to the cancer treatment, but in other men, it was just due to old age.

We started thinking that this is a causal relationship. And we tested it. I had a fellow who was a board-certified pathologist before becoming a urologist. He obtained some specimens from the urethra and did very sophisticated, elegant stains on that tissue. We found that it’s just erectile tissue surrounding the urethra. That’s why I call it a sex organ. I tell my patients, “When you are a teenager, this tissue is thin, like on your pinky finger. As you get older, it becomes thicker. And then as you get even older, and you may be having cancer treatment, that tissue is gone.” You can show them your little finger; it’s about that size. All the meat is off the bone. There’s nothing left protecting the urinary mucosa from the device.

That’s why it’s important to maintain the optimal health of those tissues and for them to remain dry. Because let’s face it: Urinary incontinence is a horrible quality of life. These are my happiest patients when we fix it. Before that, when they go on vacation, they have a separate suitcase filled with diapers. They can’t go anywhere. They can’t do anything. When they become incontinent after the prostatectomy, they gain weight. And when you put in the device to treat it, they lose weight and you can track it. The urinary incontinence patients really suffer. And we need to consider the medical optimization of those patients.

Dr. Rubin: It’s so important, and I love how analogous this is to our female patients. We know that incontinence is devastating to our female patients as well, and there’s a lot of hope. As we get older we start to pee every time we cough, laugh, or sneeze. Men are a little more bothered by it when it happens; they don’t expect it. Among women, it’s thought of as normal, but it’s not normal. There is so much we can do to help these patients, ranging from conservative treatment to surgical therapies.

The connection between hormones and urethral health is true on the female side as well. As you go through menopause, the urethral tissue thins out, gets dry, gets irritated, and can cause worsening incontinence, pain with sex, and genital urinary syndrome of menopause. It’s really important.

For our primary care doctors, how should we talk about stress incontinence in men? How do we diagnose it?

Dr. Morey: It’s easy to diagnose. Just do a quick history. Find out how many pads a day they are using. You have to ask the question, and then you have them stand up and look inside their underwear. You’ll see what kind of pad they are wearing. Is it just a shield or are they actually wearing full diapers? Then I have them do a standing cough test. I stand off to the side, holding a couple of towels, and have the patient cough four times. I can tell if it’s a full stream or just a couple of drops. Is it nothing but they are wearing a pad? You match up what you see with their experience, and in an instant it tells you how severe their problem is and it helps you direct them on to further treatment, because many patients have treatment fatigue. They’ve already been through the system. They have really suffered and they don’t know which way to go. They don’t know what’s available.

Dr. Rubin: On the female side, we have pelvic floor physical therapy. We have pads and devices that you can wear, and pessaries. We have surgical options, like bulking agents into the urethra as well as urethral slings, which can be quite helpful for women. So there’s a lot of hope out there for women, and from what I learned from you at this conference, there’s a lot of hope for men as well. So talk us through treatment, from conservative to surgical options.

Dr. Morey: There hasn’t been much innovation in male incontinence treatment over the past few decades, but we’re starting to see signs of new products appearing on the horizon, so I’m very optimistic that in the next 5 or 10 years, we’ll have more. But right now it comes down to slings and artificial sphincters, which are devices with little pumps and hydraulics, and they’re very good. But they’ve been around for 50 years, and they have this other potential risk factor of the erosion of the tissue.

We don’t have a pill that we can give the patient to tighten up those muscles. We can help them with overactive bladder. But maybe the hormonal influence is a way to optimize the health of the tissue so that these surgical treatments can really deliver the best outcomes. And as I always say, and having treated so many of these patients, it’s really a game of millimeters — how much coaptation you get. If you’re off by the slightest amount, that’s an unhappy patient. So it doesn’t take much to make it a lot better.

Dr. Rubin: There’s so much hope for our patients, and this can really have an effect on sexual health. You know the benefits you see in their quality of life and sexual health when you can stop leakage.

Dr. Morey: I always take care of the waterworks first. Many of the men have both urinary problems and erectile problems. Nobody feels sexy when they’re leaking urine all over their partner. So first we take care of that. And then, in the motivated younger patients, we bring them back and talk to them about potentially having a second operation.

Dr. Rubin: And so similarly, in women with urinary incontinence, it can have a major impact on sexual health — how they show up and how they talk to their partner. So, it is really important for our primary care docs to talk to patients about urinary incontinence and not just say, “Oh, well, you’re getting older. There’s nothing that you can do.” There’s actually no age at which there is nothing that we can do. And it’s really important to refer patients to those urologists who have extra training in incontinence and sexual health, because we do care about these quality-of-life measures and there is a lot we can do, ranging from conservative to more invasive treatments. But patients really should have options.

Dr. Morey: I heard during this meeting that urinary incontinence was the number-one source of treatment regret among patients who had their prostate treated for cancer. So, this is a really big deal for our patients. And it impacts wellness, quality of life, and overall well-being.

Dr. Rubin: When we are counseling patients for cancer surgeries or cancer treatments such as radiation therapy, it’s really hard for the patients who have never had urinary incontinence to imagine what that might be like. When you’re telling them they could have a stroke or a heart attack, or they could have erectile dysfunction or urinary incontinence, it all sounds similar to them. It could happen to someone else. It’s very hard to truly counsel patients on these quality-of-life issues that they’ve never encountered before.

Dr. Morey: We have found that it takes a long time for patients to get into our office for treatment, and it’s unbelievable — often 5 years in diapers before they find us.

Dr. Rubin: Hopefully videos like this will teach our docs and our patients that there is hope out there, that you don’t need to wait through years of suffering from incontinence. So, how does somebody find a reconstructive urologist or a sexual medicine urologist?

Dr. Morey: There are a couple of good websites out there, such as fixincontinence.com and edcure.org. The device manufacturers have pretty good information for patients.

Dr. Rubin: The Sexual Medicine Society of North America (SMSNA) has a great find-a-provider website, which provides a list of urologists who are trained in both sexual health and urinary incontinence, because they both matter. Our patients deeply care about these issues.

Rachel S. Rubin, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, Endo.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Rachel S. Rubin, MD: I’m Dr. Rachel Rubin, urologist and sexual medicine specialist in the Washington, DC, area. We are coming to you live from the Mayo Clinic Urology Conference in Maui, Hawaii, with the world’s leading experts in men’s health, sexual health, and quality of life. I’m bringing in Dr. Allen Morey from the North Dallas area, one of the world’s leading experts in reconstructive urology. He deals with all things urinary incontinence, penile curvature, and sexual health.

Dr. Morey said something at this conference that really put my chin on the floor. He said, “The urethra is a sex organ. It is androgen dependent.” This is so important because it’s true for all genders. So, Dr. Morey, tell us more about why you made that comment and about the incontinence in men that you deal with all the time.

Allen F. Morey, MD: For many years, I’ve worked at cancer centers where, through the various treatments for prostate cancer, the men suffered from urinary incontinence and we put a lot of artificial urinary sphincters in those patients. I had one patient who asked, “Why do I keep having this erosion?” Of course, the erosion is where the cuff compresses the tissue surrounding the urethra, and the tissue gives way, leaving a hole in the urethra. I looked at him and noticed that he was pale. And I thought, Let me check his testosterone level. We started checking it on everybody who had this problem, and sure enough, the ones who had the cup erosion — who had the atrophic tissue around the urethra — most of them had low testosterone levels. Some of this was due to the cancer treatment, but in other men, it was just due to old age.

We started thinking that this is a causal relationship. And we tested it. I had a fellow who was a board-certified pathologist before becoming a urologist. He obtained some specimens from the urethra and did very sophisticated, elegant stains on that tissue. We found that it’s just erectile tissue surrounding the urethra. That’s why I call it a sex organ. I tell my patients, “When you are a teenager, this tissue is thin, like on your pinky finger. As you get older, it becomes thicker. And then as you get even older, and you may be having cancer treatment, that tissue is gone.” You can show them your little finger; it’s about that size. All the meat is off the bone. There’s nothing left protecting the urinary mucosa from the device.

That’s why it’s important to maintain the optimal health of those tissues and for them to remain dry. Because let’s face it: Urinary incontinence is a horrible quality of life. These are my happiest patients when we fix it. Before that, when they go on vacation, they have a separate suitcase filled with diapers. They can’t go anywhere. They can’t do anything. When they become incontinent after the prostatectomy, they gain weight. And when you put in the device to treat it, they lose weight and you can track it. The urinary incontinence patients really suffer. And we need to consider the medical optimization of those patients.

Dr. Rubin: It’s so important, and I love how analogous this is to our female patients. We know that incontinence is devastating to our female patients as well, and there’s a lot of hope. As we get older we start to pee every time we cough, laugh, or sneeze. Men are a little more bothered by it when it happens; they don’t expect it. Among women, it’s thought of as normal, but it’s not normal. There is so much we can do to help these patients, ranging from conservative treatment to surgical therapies.

The connection between hormones and urethral health is true on the female side as well. As you go through menopause, the urethral tissue thins out, gets dry, gets irritated, and can cause worsening incontinence, pain with sex, and genital urinary syndrome of menopause. It’s really important.

For our primary care doctors, how should we talk about stress incontinence in men? How do we diagnose it?

Dr. Morey: It’s easy to diagnose. Just do a quick history. Find out how many pads a day they are using. You have to ask the question, and then you have them stand up and look inside their underwear. You’ll see what kind of pad they are wearing. Is it just a shield or are they actually wearing full diapers? Then I have them do a standing cough test. I stand off to the side, holding a couple of towels, and have the patient cough four times. I can tell if it’s a full stream or just a couple of drops. Is it nothing but they are wearing a pad? You match up what you see with their experience, and in an instant it tells you how severe their problem is and it helps you direct them on to further treatment, because many patients have treatment fatigue. They’ve already been through the system. They have really suffered and they don’t know which way to go. They don’t know what’s available.

Dr. Rubin: On the female side, we have pelvic floor physical therapy. We have pads and devices that you can wear, and pessaries. We have surgical options, like bulking agents into the urethra as well as urethral slings, which can be quite helpful for women. So there’s a lot of hope out there for women, and from what I learned from you at this conference, there’s a lot of hope for men as well. So talk us through treatment, from conservative to surgical options.

Dr. Morey: There hasn’t been much innovation in male incontinence treatment over the past few decades, but we’re starting to see signs of new products appearing on the horizon, so I’m very optimistic that in the next 5 or 10 years, we’ll have more. But right now it comes down to slings and artificial sphincters, which are devices with little pumps and hydraulics, and they’re very good. But they’ve been around for 50 years, and they have this other potential risk factor of the erosion of the tissue.

We don’t have a pill that we can give the patient to tighten up those muscles. We can help them with overactive bladder. But maybe the hormonal influence is a way to optimize the health of the tissue so that these surgical treatments can really deliver the best outcomes. And as I always say, and having treated so many of these patients, it’s really a game of millimeters — how much coaptation you get. If you’re off by the slightest amount, that’s an unhappy patient. So it doesn’t take much to make it a lot better.

Dr. Rubin: There’s so much hope for our patients, and this can really have an effect on sexual health. You know the benefits you see in their quality of life and sexual health when you can stop leakage.

Dr. Morey: I always take care of the waterworks first. Many of the men have both urinary problems and erectile problems. Nobody feels sexy when they’re leaking urine all over their partner. So first we take care of that. And then, in the motivated younger patients, we bring them back and talk to them about potentially having a second operation.

Dr. Rubin: And so similarly, in women with urinary incontinence, it can have a major impact on sexual health — how they show up and how they talk to their partner. So, it is really important for our primary care docs to talk to patients about urinary incontinence and not just say, “Oh, well, you’re getting older. There’s nothing that you can do.” There’s actually no age at which there is nothing that we can do. And it’s really important to refer patients to those urologists who have extra training in incontinence and sexual health, because we do care about these quality-of-life measures and there is a lot we can do, ranging from conservative to more invasive treatments. But patients really should have options.

Dr. Morey: I heard during this meeting that urinary incontinence was the number-one source of treatment regret among patients who had their prostate treated for cancer. So, this is a really big deal for our patients. And it impacts wellness, quality of life, and overall well-being.

Dr. Rubin: When we are counseling patients for cancer surgeries or cancer treatments such as radiation therapy, it’s really hard for the patients who have never had urinary incontinence to imagine what that might be like. When you’re telling them they could have a stroke or a heart attack, or they could have erectile dysfunction or urinary incontinence, it all sounds similar to them. It could happen to someone else. It’s very hard to truly counsel patients on these quality-of-life issues that they’ve never encountered before.

Dr. Morey: We have found that it takes a long time for patients to get into our office for treatment, and it’s unbelievable — often 5 years in diapers before they find us.

Dr. Rubin: Hopefully videos like this will teach our docs and our patients that there is hope out there, that you don’t need to wait through years of suffering from incontinence. So, how does somebody find a reconstructive urologist or a sexual medicine urologist?

Dr. Morey: There are a couple of good websites out there, such as fixincontinence.com and edcure.org. The device manufacturers have pretty good information for patients.

Dr. Rubin: The Sexual Medicine Society of North America (SMSNA) has a great find-a-provider website, which provides a list of urologists who are trained in both sexual health and urinary incontinence, because they both matter. Our patients deeply care about these issues.

Rachel S. Rubin, MD, has disclosed the following relevant financial relationships: Serve(d) as a speaker for Sprout; received research grant from Maternal Medical; received income in an amount equal to or greater than $250 from Absorption Pharmaceuticals, GSK, Endo.

A version of this article appeared on Medscape.com.

A new drug-device combo aimed at detecting residual cancer in real time during lumpectomy is one step closer to gaining federal approval, but some physicians aren’t convinced the technology is safe — or effective enough — to start using on patients.

A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.

LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.

Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.

“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.

However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.

In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.

“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”

The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.

On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.

“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”

Is the Technology Safe?

Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.

After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.

If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.

In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.

Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.

Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.

“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”

During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.

Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.

David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.

“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.

Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.

She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.

MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.

Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.

“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”

During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.

“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
 

Committee Expresses Support

During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.

Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.

Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.

“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”

Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.

“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”

Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.

The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.

If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.

Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.

The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.

A new drug-device combo aimed at detecting residual cancer in real time during lumpectomy is one step closer to gaining federal approval, but some physicians aren’t convinced the technology is safe — or effective enough — to start using on patients.

A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.

LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.

Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.

“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.

However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.

In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.

“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”

The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.

On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.

“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”

Is the Technology Safe?

Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.

After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.

If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.

In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.

Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.

Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.

“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”

During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.

Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.

David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.

“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.

Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.

She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.

MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.

Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.

“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”

During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.

“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
 

Committee Expresses Support

During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.

Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.

Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.

“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”

Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.

“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”

Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.

The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.

If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.

Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.

The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.

A new drug-device combo aimed at detecting residual cancer in real time during lumpectomy is one step closer to gaining federal approval, but some physicians aren’t convinced the technology is safe — or effective enough — to start using on patients.

A majority of the US Food and Drug Administration’s Medical Imaging Drugs Advisory Committee (MIDAC) on March 5 voted in support of LUMISIGHT’s (pegulicianine) benefit-risk profile.

LUMISIGHT is an optical imaging agent used in combination with Lumicell Direct Visualization System (DVS), a fluorescence-guided imaging system. The technology, developed by Lumicell Inc., helps surgeons identify cancer that may remain in the breast after they’ve completed the main resection of tissue.

Following MIDAC’s positive vote, the FDA will move on to reviewing Lumicell’s new drug application for LUMISIGHT and its premarket approval application for Lumicell DVS.

“We are proud of the efforts and look forward to the next steps as we work with the FDA to finalize the approval process so that women with breast cancer can access the therapy,” Jorge Ferrer, PhD, Lumicell’s chief scientific officer, said in an interview.

However, Freya Schnabel, MD, professor of surgery and director of breast surgery at NYU Perlmutter Cancer Center, said there are some “real concerns” with the technology. She expressed surprise at MIDAC’s overall favorable vote.

In a recently published study, she noted that the use of pegulicianine fluorescence-guided surgery (pFGS) did not meet the prespecified threshold for sensitivity.

“It did meet thresholds for removal of residual tumor and specificity — but this is still basically a negative study, and a low sensitivity raises concerns regarding false negative readings,” she said in an interview. “I’m surprised [the committee] is supportive in light of this result. Also, the technique is logistically challenging, as patients need to be injected 2 to 6 hours before their surgeries, very challenging timing for patients having ambulatory procedures.”

The study, published in the April 2023 NEJM Evidence, analyzed 357 patients who received 1.0 mg/kg intravenous pegulicianine followed by lumpectomy. Tumor left behind after standard lumpectomy was removed in 27 of 357 patients through use of pFGS. Of the 27, 22 patients had cavity orientations deemed “negative” on standard margin evaluation, according to the study. A margin is described as negative or clean when there are no further cancer cells at the edge of the tissue, suggesting that all of the cancer has been removed. Second surgeries were avoided by pFGS in 9 of 62 patients with positive margins, the analysis found.

On per-margin analysis, pFGS specificity was 85.2%, and sensitivity was 49.3%. While the sensitivity endpoint missed the lower boundary of the 95% confidence interval, the LUM system exceeded the specificity endpoint of 60% with a point estimate of 86%, and an accuracy of 84% for imaging residual cancer in the lumpectomy cavity, coinvestigator E. Shelley Hwang, MD, MPH, said during the MIDAC meeting.

“The pivotal study was an adequate and well-controlled study demonstrating the effectiveness of the LUM system to detect residual cancer in the lumpectomy cavity, following the standard of care procedure,” she said. “These results also demonstrate clinical benefit that improves the current standard of care. This is the first and only imaging system that provides results in the lumpectomy cavity in real time, allowing surgeons to use this information at the time of the initial procedure.”

Is the Technology Safe?

Pegulicianine is an imaging agent that contains a fluorescent dye. The agent is given to patients as a 3-minute intravenous infusion 2 to 6 hours before surgery.

After removal of the main tumor specimen, the surgeon inserts a handheld probe into the breast cavity and in combination with the detection software, searches for residual cancer that may have been left behind, Dr. Ferrer explained during the MIDAC meeting.

If the software identifies areas suspicious for residual cancer, those areas display in red on an overhead screen. The surgeon then takes a targeted shave to resect the suspicious tissue. Once the tissue has been removed, the surgeon can rescan the cavity with the probe to ensure a more complete resection has been performed. Use of the LUM system typically takes surgeons less than 7 minutes to use, Dr. Ferrer said.

In the study, a total of 406 patients received the intravenous pegulicianine, but 14 patients were withdrawn before randomization. After a standard lumpectomy procedure, 357 patients were assigned to the pFGS group and 35 patients to the control group.

Of the 406 patients, pegulicianine administration was stopped for adverse events in 6 patients (1.5%). Two patients had grade 3 serious adverse events related to pegulicianine; one had hypersensitivity, and one had an anaphylactic reaction. The other four pegulicianine-related adverse events included allergic reaction, milder hypersensitivity, nausea, and pegulicianine extravasation.

Dr. Schnabel said these reactions are worrisome. While any effort to reduce the need for patients to have more than one surgery to complete a breast conserving approach would be a “real advance,” Dr. Schnabel said she would not feel comfortable using pFGS in her own practice if approved by the FDA as is.

“This is clearly a major issue in terms of incorporating this technique into practice,” she said. “I could go on, but in light of the above, I’m surprised that [the committee] is supportive. I would hope for some refinement of the technique to reduce the risks to patients and improve the results before I’d consider utilizing this approach.”

During the MIDAC meeting, Dr. Ferrer said the company takes the safety events seriously and has developed mitigation strategies to further reduce the risk of patient hypersensitivity. These strategies include: clear labeling that informs users of anaphylaxis risk, incorporating a new section into the device training program to address warnings and precautions, an enhanced pharmacovigilance program to closely track and report hypersensitivity events, and a postmarket study to access the incidence rate and risk of such events in a broader population.

Several MIDAC members raised questions about the adverse reactions observed and about the safety of the technology.

David B. Hackney, MD, a neuroradiologist at Beth Israel Deaconess Medical Center in Boston, questioned the recommendation that patients only be monitored for 15 minutes after the injection.

“Since you don’t have enough data to know how long after injection reactions could occur, why not keep them under monitoring until after the surgery is over?” he said.

Barbara Smith, MD, PhD, lead investigator of the study, explained that per the protocol, there would be frequent monitoring, with a nurse at bedside, and patients would be monitored after injection, on their way to the procedure, and afterward.

She suggested, during the meeting, that more intense monitoring early in the process would be beneficial as that is when investigators observed side effects believed to be attributed to LUMISIGHT.

MIDAC member Kimberly E. Applegate, MD, a retired radiology professor, asked about the learning curve for surgeons and how long it generally takes for physicians to become familiar with the system.

Coinvestigator Kelly Hunt, MD, explained that all surgeons who participated in the trial completed a training program.

“Certainly, there’s a learning curve anytime we introduce new technology in the operating room,” she said. “Surgeons said it usually takes about three procedures before they’re comfortable with the system, including the camera and the software.”

During a presentation period by FDA officials, Anil Rajpal, MD, MPH, FDA, Deputy Division Director for Safety, said it’s important that prescribing information for LUMISIGHT communicate the risk of anaphylaxis and other hypersensitivity reactions, the need to monitor patients, and the need for the appropriate available personnel, medications, and equipment.

“This would be done by warnings and precautions and a boxed warning,” he said. “Note, that [such warnings] would only communicate the risks, it would not further characterize the risk.”
 

Committee Expresses Support

During a subsequent vote among committee members, most expressed support for the technology and its benefits. Sixteen members voted in support, one abstained, and two voted against the benefit-risk profile.

Andrea Richardson, MD, PhD, professor of pathology at Johns Hopkins in Baltimore, said she voted yes because the incremental benefits of avoiding additional surgeries outweigh the small risk of anaphylaxis.

Henry Royal, MD, MIDAC chair and professor of radiology at Washington University School of Medicine in St. Louis, agreed.

“Even though the benefit of this is on average, quite small, the benefit to the woman who has positive margins that’s converted to negative margins because of use of [LUMISIGHT] is really quite great,” he said. “The risk from this procedure is certainly very manageable.”

Harold J. Burstein, MD, PhD, a professor of medicine at Harvard Medical School and oncologist at Dana-Farber Cancer Institute in Boston, voted against the benefit-risk profile. He said the technology merits more research and that he does not believe it was proven the technology reduces the risk of reoperation.

“I think it’s a great technology,” he said. “I would like to see a well-conducted, randomized, phase III study with the endpoint of reoperation,” he said. “That would really prove the usefulness and benefit of the intervention in my mind.”

Chengjie Xiong, PhD, professor of biostatistics at Washington University School of Medicine in St. Louis, chose to abstain from voting because he said there was not enough data.

The FDA will now complete its review of Lumicell’s new drug application for LUMISIGHT and review of its premarket approval application for Lumicell DVS. The FDA review team has 6-10 months to make a decision. As part of the process, the FDA will evaluate clinical data, travel to clinical study sites to conduct inspections, and assemble a final action package for a senior FDA official to make a final decision.

If deemed safe and effective, the FDA will then work with Lumicell on developing and refining prescribing information.

Dr. Ferrer said his team expects to receive FDA approval in the coming weeks and will continue to work collaboratively with the FDA to expedite approval where possible.

The purpose of the MIDAC is to review and evaluate data about the safety and effectiveness of marketed and investigational human drug products for use in diagnostic and therapeutic procedures using radioactive pharmaceuticals and make appropriate recommendations to the FDA Commissioner.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.

Lawmakers have added a provision to raise Medicare payments to clinicians to a $460 billion bipartisan package of federal spending bills that passed in the House on March 6 and is expected to be passed in the Senate and signed by President Biden before then end of March 8, but industry groups have criticized it as paltry.

Lawmakers often tweak Medicare policy by adding provisions to other kinds of legislation, including the spending bills Congress must pass to keep the federal government running.

Physicians’ groups and some lawmakers have long pressed Congress to change Medicare payment rules with little success, even as inflation has caused physicians’ expenses to rise. Doctors now face a 3.4% cut to Medicare reimbursements in 2024, which would be only partly mitigated by the recently announced provision.

The Medical Group Management Association (MGMA) said the proposed increase would total 1.68%. The increase, part of a bipartisan package of bills released by the House and Senate Appropriations committees on March 3, would apply to the budget for fiscal 2024, which began on October 1, 2023.

“We are deeply disappointed with Congress’ half-hearted attempt to remedy the devastating blow physician practices were dealt by the 2024 Medicare Physician Fee Schedule,” Anders Gilberg, senior vice president of MGMA, said in a statement. “Anything less than a full reversal of the 3.4% cut is appallingly inadequate.”

The American Medical Association said it was “extremely disappointed” that the boost only eased, but did not fully reverse, a deeper planned cut.

The American Academy of Family Physicians (AAFP) also expressed disappointment with the proposed increase.

“The AAFP has repeatedly told Congress that the 3.4% Medicare payment reduction that went into effect on January 1 is untenable for family physicians and threatens patients’ access to primary care,” the group said in a statement.

“While we appreciate the partial relief, family physicians continue to face an annual threat of payment cuts that are detrimental to practices and patients,” AAFP said.

A version of this article appeared on Medscape.com.