Lung Cancer

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

A new systematic review and meta-analysis finds that unvaccinated cancer patients who contracted COVID-19 last year, were more than two times more likely – than people without cancer – to develop a case of COVID-19 so severe it required hospitalization in an intensive care unit.

“Our study provides the most precise measure to date of the effect of COVID-19 in cancer patients,” wrote researchers who were led by Paolo Boffetta, MD, MPH, a specialist in population science with the Stony Brook Cancer Center in New York.

Dr. Boffetta and colleagues also found that patients with hematologic neoplasms had a higher mortality rate from COVID-19 comparable to that of all cancers combined.

Cancer patients have long been considered to be among those patients who are at high risk of developing COVID-19, and if they contract the disease, they are at high risk of having poor outcomes. Other high-risk patients include those with hypertension, diabetes, chronic kidney disease, or COPD, or the elderly. But how high the risk of developing severe COVID-19 disease is for cancer patients hasn’t yet been documented on a wide scale.

The study, which was made available as a preprint on medRxiv on Oct. 23, is based on an analysis of COVID-19 cases that were documented in 35 reviews, meta-analyses, case reports, and studies indexed in PubMed from authors in North America, Europe, and Asia.

In this study, the pooled odds ratio for mortality for all patients with any cancer was 2.32 (95% confidence interval, 1.82-2.94; 24 studies). For ICU admission, the odds ratio was 2.39 (95% CI, 1.90-3.02; I2 0.0%; 5 studies). And, for disease severity or hospitalization, it was 2.08 (95% CI, 1.60-2.72; I2 92.1%; 15 studies). The pooled mortality odds ratio for hematologic neoplasms was 2.14 (95% CI, 1.87-2.44; I2 20.8%; 8 studies).

Their findings, which have not yet been peer reviewed, confirmed the results of a similar analysis from China published as a preprint in May 2020. The analysis included 181,323 patients (23,736 cancer patients) from 26 studies reported an odds ratio of 2.54 (95% CI, 1.47-4.42). “Cancer patients with COVID-19 have an increased likelihood of death compared to non-cancer COVID-19 patients,” Venkatesulu et al. wrote. And a systematic review and meta-analysis of five studies of 2,619 patients published in October 2020 in Medicine also found a significantly higher risk of death from COVID-19 among cancer patients (odds ratio, 2.63; 95% confidence interval, 1.14-6.06; P = .023; I2 = 26.4%).

Fakih et al., writing in the journal Hematology/Oncology and Stem Cell Therapy conducted a meta-analysis early last year finding a threefold increase for admission to the intensive care unit, an almost fourfold increase for a severe SARS-CoV-2 infection, and a fivefold increase for being intubated.

The three studies show that mortality rates were higher early in the pandemic “when diagnosis and treatment for SARS-CoV-2 might have been delayed, resulting in higher death rate,” Boffetta et al. wrote, adding that their analysis showed only a twofold increase most likely because it was a year-long analysis.

“Future studies will be able to better analyze this association for the different subtypes of cancer. Furthermore, they will eventually be able to evaluate whether the difference among vaccinated population is reduced,” Boffetta et al. wrote.

The authors noted several limitations for the study, including the fact that many of the studies included in the analysis did not include sex, age, comorbidities, and therapy. Nor were the authors able to analyze specific cancers other than hematologic neoplasms.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

Breast cancer screening using urine samples based on the volatile organic compounds (VOCs) sensed by a trained dog is feasible, according to a preliminary study published in the journal Biology June 10.

“The extrapolation of our results to widespread implementation is still uncertain,” wrote Shoko Kure, MD, PhD, of Nippon Medical School in Tokyo, and colleagues. “However, even if few dogs could be trained to detect breast cancer, the result may open the door to a robust and inexpensive way to detect breast cancer.” They added that “dog cancer detection is entirely noninvasive, safe and easy for both patients and everyone.” 

Early detection of breast cancer, which is the leading cause of death globally, is essential for more efficient treatment. While mammography can detect asymptomatic breast cancer and reduce mortality, it has a poor compliance, is less sensitive in dense breast tissue, detects nonmalignant lesions, and has not been shown to reduce mortality in women younger than 40. VOCs are emitted in the breath, blood, and urine, with different volatile patterns correlated with a variety of diseases including cancers, which dogs can be trained to detect. Breast cancer screening by dog sniffing of the VOCs in urine samples has not been attempted.

Dogs have been used as medical detectives for several cancers and conditions. A study published in 2018 showed that trained dogs who were able to differentiate the specific odor from the metabolic waste of breast cancer in vitro could identify that of colorectal cancer, and vice versa. More recently, research showed that trained dogs could detect advanced prostate cancer in urine samples with high specificity and sensitivity. In this double-blinded pilot study, two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. The canine olfaction system was 71% sensitive and as much as 76% specific at detecting Gleason 9 cancer. Along with cancer, trained dogs have been shown to identify people with COVID-19, even those who were asymptomatic. In this study, dogs who sniffed swab samples of armpit sweat could identify which samples came from patients infected with COVID-19 with up to 100% accuracy, while ruling out infection with up to 99% accuracy.

The double-blind study by Dr. Kure aimed to assess the potential of VOCs in urine samples for breast cancer screening by using a single trained sniffer dog – in this case a 9-year-old female Labrador retriever. Urine samples from 40 patients with primary breast cancer and 142 patients with non-breast malignant diseases were included along with samples from 18 healthy volunteers. In 40 times out of 40 runs of the double-blind test, the dog correctly identified urine samples of patients with breast cancer, with 100% sensitivity and 100% specificity.

“The dog in this test successfully differentiated breast cancer from non-breast malignancies and healthy controls,” the authors wrote. “This is the first, preliminary study indicating the feasibility of developing a new breast cancer screening method using urine samples based on VOCs.”

While the authors noted that the study was limited as it relied on one trained dog, they suggested that this method has potential in low-income countries where access to mammography is inadequate.

“Some well-trained sniffing dogs traveling around medically underserved [countries] all over the world could save many lives. Even when a healthy control was indicated by a trained dog, there would be a suspicion of undiagnosed/early-stage cancer, and the person would be advised to undergo medical screening,” the authors wrote.

The authors declared no conflicts of interest.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

The number of same-day discharges has grown with the increase in robotic-assisted surgeries and advances in imaging and pressures to reduce hospital costs. COVID-19 has, perhaps temporarily, increased the same-day surgery numbers as surgeries have been restricted and hospital beds are needed for COVID-19 patients.

Urologist Ronney Abaza, MD, a robotic surgery specialist in Dublin, Ohio, and colleagues, reviewed robotic surgeries at their hospital during COVID-19 restrictions on surgery in Ohio between March 17 and June 5, 2020, and compared them with robotic procedures before COVID-19 and after restrictions were lifted. They published their results in Urology.

Since 2016, the hospital has offered the option of same-day discharge (SDD) to all robotic urologic surgery patients, regardless of procedure or patient-specific factors.

Among patients who had surgery during COVID-19 restrictions, 98% (87/89 patients) opted for SDD versus 52% in the group having surgery before the restrictions (P < .00001). After the COVID-19 surgery restrictions were lifted, the higher rate of SDD remained at 98%.

“There were no differences in 30-day complications or readmissions between SDD and overnight patients,” the authors write.
 

The right patient, the right motivation for successful surgery

Brian Lane, MD, PhD, a urologic oncologist with Spectrum Health in Grand Rapids, Michigan, told this news organization that, for nephrectomies, uptake of same-day discharge will continue to be slow.

“You have to have the right patient, the right patient motivation, and the surgery has to go smoothly,” he said. “If you start sending everyone home the same day, you will certainly see readmissions,” he said.

Dr. Lane is part of the Michigan Urologic Surgery Improvement Collaborative and he said the group recently looked at same-day discharge outcomes after robotic prostatectomies with SDD as compared with 1-2 nights in the hospital.

The work has not yet been published but, “There was a slight signal that there were increased readmissions with same-day discharge vs. 0-1 day,” he said.

A paper on outcomes of same-day discharge in total knee arthroplasty in the Journal of Bone & Joint Surgery found a higher risk of perioperative complications “including component failure, surgical site infection, knee stiffness, and deep vein thrombosis.” Researchers compared outcomes between 4,391 patients who underwent outpatient TKA and 128,951 patients who underwent inpatient TKA.

But for other many surgeries, same-day discharge numbers are increasing without worsening outcomes.

A paper in the Journal of Robotic Surgery found that same-day discharge following robotic-assisted endometrial cancer staging is “safe and feasible.”

Stephen Bradley, MD, MPH, with the Minneapolis Heart Institute in Minneapolis, and colleagues write in the Journal of the American College of Cardiology: Cardiovascular Interventions that they found a large increase in the use of same-day discharge after elective percutaneous coronary intervention (PCI) was not associated with worse 30-day mortality rates or readmission.

In that study, 114,461 patients were discharged the same day they underwent PCI. The proportion of patients who had a same-day discharge increased from 4.5% in 2009 to 28.6% in the fourth quarter of 2017.

Risk-adjusted 30-day mortality did not change in that time, while risk-adjusted rehospitalization decreased over time and more quickly when patients had same-day discharge.

Deepak L. Bhatt, MD, MPH, and Jonathan G. Sung, MBCHB, both of Brigham and Women’s Hospital Heart & Vascular Center, Harvard Medical School, Boston, wrote in an accompanying article that, “Advances in the devices and techniques of PCI have improved the safety and efficacy of the procedure. In selected patients, same-day discharge has become possible, and overnight in-hospital observation can be avoided. By reducing unnecessary hospital stays, both patients and hospitals could benefit.”

Evan Garden, a medical student at Icahn School of Medicine at Mount Sinai in New York, presented findings at the American Urological Association 2021 annual meeting that show patients selected for same-day discharge after partial or radical nephrectomy did not have increased rates of postoperative complications or readmissions in the immediate postoperative period, compared with standard discharge of 1-3 days.
 

Case studies in nephrectomy

While several case studies have looked at the feasibility and safety of performing partial and radical nephrectomy with same-day discharge in select cases, “this topic has not been addressed on a national level,” Mr. Garden said.

Few patients who have partial or radical nephrectomies have same-day discharges. The researchers found that fewer than 1% of patients who have either procedure in the sample studied were discharged the same day.

Researchers used the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, a nationally representative deidentified database that prospectively tracks patient characteristics and 30-day perioperative outcomes for major inpatient and outpatient surgical procedures at more than 700 hospitals.

They extracted all minimally invasive partial and radical nephrectomies from 2012 to 2019 and refined the cohort to 28,140 patients who were theoretically eligible for same-day discharge: Of those, 237 (0.8%) had SSD, and 27,903 (99.2%) had a standard-length discharge (SLD).

The team found that there were no differences in 30-day complications or readmissions between same-day discharge (Clavien-Dindo [CD] I/II, 4.22%; CD III, 0%; CD IV, 1.27%; readmission, 4.64%); and SLD (CD I/II, 4.11%; CD III, 0.95%; CD IV, 0.79%; readmission, 3.90%; all P > .05).

Controlling for demographic and clinical variables, SDD was not associated with greater risk of 30-day complications or readmissions (CD I/II: odds ratio, 1.08; 95% confidence interval, 0.57-2.048; P = .813; CD IV: OR 1.699; 95% CI, 0.537-5.375; P = .367; readmission: OR, 1.254; 95% CI, 0.681-2.31; P = .467).

Mr. Garden and coauthors report no relevant financial relationships.

Dr. Lane reports no relevant financial relationships.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

In patients with advanced cancer who are prescribed immune checkpoint inhibitors, comedications must be carefully assessed before patients start ICI therapy, most notably proton pump inhibitors, glucocorticoids, antibiotics, and psychotropic drugs.

“Our results confirm the detrimental impact on oncological outcomes of antibiotics and glucocorticoids at a dosage ≥10 mg/day when given within 1 month before or after ICI onset,” Marie Kostine, MD, of Bordeaux (France) University Hospital, and colleagues wrote in the European Journal of Cancer. “Moreover, we show that other comedications may significantly alter the antitumoral response of ICI, such as proton pump inhibitors, psychotropic drugs, morphine, aspirin, and insulin, whereas others seem to have no impact.”

While immune checkpoint inhibitors are transforming the treatment of advanced cancers, gut microbiota composition is an important determinant of response to ICIs. Antibiotic treatments are known to alter the gut microbiota. Other drugs, such as proton pump inhibitors, antidiabetic agents, aspirin, NSAIDs, glucocorticoids, immunomodulators, psychotropic drugs, and analgesics, have been associated with changes in microbiome composition. Since many patients with advanced cancer are exposed to such drugs, this study looked at the possible influence of these comedications on the antitumor effect and safety of ICIs.

The observational study included 635 patients with advanced cancer treated with ICIs between May 2015 and September 2017. Comedications given within 1 month before or 1 month after the first administration of an ICI were reviewed from medical records. Psychotropic drugs, proton pump inhibitors, ACE inhibitors and/or angiotensin II receptor blockers (ARBs), glucocorticoids, antibiotics, statins, and morphine were the most prescribed comedications.

Baseline use of antibiotics, glucocorticoids greater than 10 mg/day, proton pump inhibitors, psychotropic drugs, morphine, and insulin was associated with decreased overall survival and tumor response. However, the coadministration of statins, ACE inhibitors and/or ARBs, NSAIDs, aspirin, and oral diabetes drugs did not impact patient outcomes. Additionally, treatments that altered the response to ICIs were associated with a decreased incidence of immune-related adverse events.

“These results suggest some practical advice in a patient candidate to ICIs,” the authors wrote. “First, antibiotic treatment should be limited to documented infections,” and “withdrawal of proton pump inhibitors and psychotropic drugs should be considered.

“Regarding baseline glucocorticoids use, the cutoff of 10 mg/day should be respected, considering the deleterious effect of higher dosage. Moreover, because of the lack of impact of inhaled or topical glucocorticoids, local routes should be preferred,” the authors wrote. “Conversely, our study brings reassuring data regarding the use of glucocorticoids for the management of immune-related adverse events, which did not alter ICI efficacy, confirming previous reports.”

The authors noted that the observational nature of the study does not allow any causal conclusion, adding that it remains unknown whether the effect of comedications “on cancer outcomes is thoroughly mediated by changes in microbiota or other immunomodulatory properties.”

Along with the retrospective design, study limitations included reporting bias and missing data on baseline comedications, specific prognostic factors and cancer outcomes.

The authors noted no conflicts of interest.

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

Takeda Pharmaceuticals is now the latest pharmaceutical company to offer a value-based agreement on one of its new targeted therapies.

The rebate offer is for brigatinib (Alunbrig) which is approved for the treatment of adults with anaplastic lymphoma kinase positive (ALK+) metastatic non–small cell lung cancer (NSCLC) as detected by an FDA-approved test.

The move follows a rebate offer from Pfizer for crizotinib (Xalkori), which is also approved for ALK+ (as well as ROS1+) NSCLC, and also for ALK+ anaplastic large cell lymphoma

For its offer, Takeda has teamed up with Point32Health, the second-largest health plan in New England with about 2.3 million members. The new agreement will make brigatinib widely available to patients who may benefit from its use, say the companies.

If a patient is unable to remain on brigatinib for 3 months or longer because of effectiveness or tolerability, Takeda will refund a yet unspecified amount of money to Point32Health. Brigatinib’s list price is $17,000 for a month’s treatment.

“Given the importance of facilitating cutting-edge oncology treatment and also the reality that not all patients show a positive response, reimbursement for oncology treatments is an area that is prime for innovative financing approaches,” said Michael Sherman, MD, chief medical officer and executive vice president, Point32Health, in a statement. “Collaborating with Takeda to share risk makes this agreement a crucial milestone in bringing cost-effectiveness to cancer care.”

The Pfizer program for crizotinib is somewhat different. For one thing, Pfizer’s refund is offered to any patient who qualifies and not just those who are covered by a specific plan. Second, Takeda is thus far only refunding money to the insurer, whereas Pfizer will also reimburse patients for out-of-pocket expenses.

There is a similar approach that has been offered by Novartis for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

In addition, Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run health care system collected 200 million euros ($220 million) in refunds.

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

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

Lung cancer screening reduces mortality, but patient adherence to screening intervals is suboptimal in the United States, according to a review and meta-analysis published in the Journal of Thoracic Oncology.

“Lung cancer screening is effective in reducing mortality, particularly when patients adhere to follow-up recommendations standardized by the Lung CT Screening Reporting & Data System (Lung-RADS),” Yannan Lin, MD, MPH, of the University of California, Los Angeles, and colleagues wrote. ”Patient adherence to Lung-RADS–recommended screening intervals is suboptimal across clinical lung cancer screening programs in the U.S., especially among patients with Lung-RADS category 1-2 results.”

Lung cancer screening can identify tumors at earlier, more treatable stages, but patients with lung cancer diagnoses based on new nodules at incidence screening have shown shortened survivals. The National Lung Screening Trial (NLST) has shown a 20% relative reduction in lung cancer mortality with low-dose chest CT screening relative to chest radiography. The Lung-RADS guidelines to standardize the reporting of lung cancer screening were developed based on findings from the NLST and other screening studies, partly to reduce false-positive rates. Lung-RADS scores are based upon nodule size, characteristics and location, with management guidelines specific to Lung-RADS categories, ranging from low-dose chest CT in 12 months for Lung-RADS 1-2 to chest CT, PET/CT, or tissue sampling for Lung-RADS 4B/X.

The rate of adherence to lung cancer screening based on Lung-RADS guidelines is unclear. This systematic review and meta-analysis looked at patient adherence to Lung-RADS recommended screening intervals in clinical practice.

The meta-analysis included 21 studies. The pooled adherence rate was 57% for defined adherence, which included an annual incidence screen performed within 15 months, among 6,689 patients and 65% for anytime adherence among 5,085 patients. The authors noted that overall rates of adherence to Lung-RADS recommended screening intervals in clinical practices is low as compared with the over 90% adherence seen in the NLST, adversely affecting the mortality benefits of lung cancer screening.

Higher adherence rates were found in patients with Lung-RADS 3 (risk for lung cancer, 1%-2%) and 4 (risk, >5%) than Lung-RADS 1 and 2 (risk, <1%; P < .05), which the authors said suggests that tailored interventions based on Lung-RADS categories may be beneficial.

“It is likely that patients and referrers are more concerned about nodules at a higher risk for lung cancer, prompting greater adherence to recommended screening intervals in Lung-RADS 3-4,” the authors wrote. “It is crucial that patients and referrers alike understand that screening is most effective when performed regularly, including for those with negative baseline screens, as de novo nodules, those detected after a negative screen, are more aggressive than those detected at baseline screen.”

These low adherence rates seen in the clinical practices could be explained by patient characteristics, insurance coverage and interventions to ensure adherence, among other factors.

Further, inconsistent reporting of adherence rates was observed. Standardized reporting of adherence rates to lung cancer screening is needed to identify interventions to improve adherence, the authors wrote.

The authors of this study noted no conflicts of interest.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.

The use of robotically assisted surgical devices for benign and malignant tumors is here to stay, but the decision to perform robot-assisted surgery should be driven by clinical outcomes, not convenience, physicians say.

“The problem in minimally invasive surgery, especially in cancer surgery, is that the concept has been flip-flopped,” said Hooman Noorchashm, MD, PhD, a retired cardiothoracic surgeon turned patient advocate. “The main purpose of surgery should be removal of diseased tissue or repair of damaged tissue with adequate safety. The size of the incision on that triage scheme is secondary.”

In 2013, Dr. Noorchashm’s wife, Amy Reed, MD, an anesthesiologist, had a hysterectomy for treatment of severe uterine fibroids. The surgery was performed with a laparoscopic power morcellator, which led to the dissemination of cells from a previously undetected abdominal lesion. She was later diagnosed with stage 4 leiomyosarcoma and died in May 2017.

Dr. Noorchashm said the problem with robotic surgery isn’t the technology itself or how it’s used, but why it’s used in the first place. “Not only was there an extreme level of laxity with respect to the malignant potential of fibroids, but also that the size of the incision supersedes the safety of the procedure.”

The ultimate goal of oncologic surgery is to achieve an en bloc resection with clean surgical margins and removal of the tumor intact, Dr. Noorchashm said. The only scientific way of showing the benefits or therapeutic equivalence of new technology is through noninferiority comparison trials.
 

Robotic surgery inching toward $14 billion in revenue by 2028

Although robotic surgical technology has been in use since the 1990s, the technology is still considered to be its infancy. The first Food and Drug Administration–approved robotics platform, the da Vinci Surgical System (Intuitive Surgical) was approved by the FDA in 2000. And, now, with its patent expiring in 2022, competitors will be developing and launching new products for abdominal and colorectal surgery, partial knee replacements, cardiovascular procedures, head and neck surgery, and spinal procedures.

Robotic surgery is a rapidly expanding area with new product launches announced daily. In August 2021, the market research firm Grand View Research, reported the surgical robot marketplace is projected to reach $14 billion by 2028, up from $3.6 billion this year.

“This new era of robotic-assisted surgery attracts both surgeons and patients. Robotic surgery has reshaped our surgeries over the last 2 decades, and robots are now used in almost in every surgical field. Still, as surgeons, we continue to look – with great interest – to new robotic companies that may be able to provide better robots in a more cost-effective manner,” wrote urologists Ahmad Almujalhem and Koon Ho Rha in a review published in the journal BJUI Compass.

However, the authors wrote that, although the market is competitive, cost remains an issue, as are competing interests. In addition, many companies are creating replicas of existing technologies instead of focusing on new designs and new technology. “Although the da Vinci system propelled many robots to market, there has been no significant improvement in the console,” they added.

The technology is attractive to both surgeons and patients. “Surgeons are attracted to newer technologies, better vision, and easier learning curves. Patients are also attracted to robotic surgery, as this technology is considered state of the art and is associated with reduced pain and scar size,” the authors wrote.
 

Outcomes depend on many variables

In terms of outcomes, the literature is mixed. It largely depends on a number of variables from the site of surgery, the type of cancer, technology used, and the surgeon’s skill.

Jung Mogg Kim, MD, PhD, a microbiologist with Hanyang University, Seoul, South Korea, published a systemic review and meta-analysis of 27 clinical reports in PLoS ONE assessing clinical outcomes. They found that robot-assisted laparoscopic surgery did not result in statistically superior outcomes, compared with conventional laparoscopic surgery, except for lower estimated blood loss with robots. Operative time and total complications rates were “significantly more favorable” with conventional laparoscopic procedures.

Thomas E. Ahlering, MD, a robotic prostatectomy specialist at the University of California, Irvine, explained that the success or failure of robot-assisted surgery can be highly dependent on the body site and tumor type.

“The oncologic outcome, as long as the surgeon is up to speed, is not going to be better, but the goal is to be as good,” he said in an interview.

In most cases, Dr. Ahlering said, the goal of surgery is to remove a viable tumor with clean margins while leaving the organ intact. But in prostate surgery, the goal is to remove the entire organ while trying to preserve urinary continence and sexual function.

“One of the biggest benefits of the robot is that we’re able to use it in a laparoscopic environment meaning that we need a pneumoperitoneum [which] dramatically decreases bleeding. In prostate cancer, the area is so highly vascular that bleeding is a major issue,” he said.

The same benefits of reduced bleeding, improved visualization, and precision are also seen with robotic-assisted surgery for renal cancer, he noted.

He also emphasized that positive surgical margins, while less desirable than complete elimination of malignant cells, is not nearly as dire in prostate cancer as it is in surgery for other malignancies, such as soft-tissue sarcomas.

“The majority of cases are never going to recur, and if they do recur they essentially never lead to metastatic disease to bone, much less to prostate cancer–related death. The only thing they can do is slightly increase the PSA [prostate-specific antigen] recurrence,” he said.

Assuming that outcomes are comparable between an open procedure, conventional laparoscopic procedure, or robot-assisted approach, surgeons “will almost all go for the robot. It’s easier on the surgeon and it’s easier on the system,” Dr. Ahlering said.

In skilled hands for select patients, the use of a carefully researched and well-designed surgical assistive device can result in outcomes that are comparable with those seen in open surgical procedures, with robot-assisted surgery offering the possibility of less perioperative bleeding, lower postoperative morbidity, and faster recovery times.

“In our program we have been using robots to perform robotic radical prostatectomy and nephron-sparing surgery – partial nephrectomy and we’re also using them to perform intracorporeal bowel reconstruction and robotic radical cystectomy,” said Ashutosh Tewari, MD, of the Icahn School of Medicine at Mount Sinai, New York.

Robot-assisted surgery can be used “anywhere where you have to be selective, anywhere where you have to be reconstructive, anywhere where [assisted] vision can help, anywhere where the lack of bleeding will be of help to patients, and anywhere where a smaller incision can achieve the same goals,” Dr. Tewari said in an interview. Dr. Tewari’s Mount Sinai colleagues reported at the 2021 American Urological Association annual meeting, robotic-assisted salvage radical and partial nephrectomies were found to be safe and feasible procedures in patients with metachronous kidney tumors. For patients with early invasive cancer (stage pT1), oncologic outcomes with robotic-assisted partial nephrectomy were similar to those of patients who underwent radical surgery. The authors concluded that salvage robotic-assisted partial nephrectomy “can be considered in this group of patients due to the risk of future recurrences and need to preserve renal function.”

The National Comprehensive Cancer Network guideline for prostate cancer, updated in September 2021, states that “laparoscopic and robot-assisted radical prostatectomy are commonly used and are considered comparable to conventional approaches in experienced hands.”

In 2018, researchers in a multinational comparison trial reported that patients with cervical cancer who were randomly assigned to minimally invasive robot-assisted radical hysterectomy had significantly lower rates of both disease-free survival and overall survival than women randomized to open abdominal radical hysterectomy. The study results were published in the New England Journal of Medicine.

The use of robotically assisted surgical (RAS) devices could possibly create a “shielding layer” between the surgical team and patient reducing the risk of infection, according to Ajmal Zemmar, MD, PhD, FMH, a neurosurgeon with the University of Louisville (Ky.) Dr. Zemmar and colleagues recently published a perspective in Nature Machine Intelligence on trends in the use of surgical robots.

“In the operating theatre, robots can place intravascular lines, intubate the patient and manage the airway. The integration of a robot as a shielding layer, physically separating the health care worker and patient, is a powerful tool to combat the omnipresent fear of pathogen contamination and maintain surgical volumes,” Dr. Zemmar and colleagues wrote.
 

Surgical vs. clinical outcomes

In July 2021, this news organization reported that clinical trials of RAS for nipple-sparing mastectomy procedures were looking primarily at cosmetic or surgical outcomes and were not collecting cancer outcomes and if they were, it was secondary to cosmetic or surgical outcomes.

The FDA followed up by issuing a safety communication in August warning patients and providers that neither the safety nor efficacy of RAS for use in mastectomy procedures or treatment of breast cancer have been established.

“In addition, the FDA is aware of allegations that clinical studies are being conducted using RAS devices to perform mastectomies for the prevention or treatment of cancer without the FDA oversight required for such significant risk studies,” the communication stated.

Dr. Tewari disclosed relationships with various companies. Dr. Noorchashm had no relevant disclosures. Dr. Ahlering disclosed past funding or other considerations from Intuitive Robotics.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

A fungal infection typically seen in the lungs may have a variety of unusual clinical presentations elsewhere in the body, even raising suspicion of cancer in some cases, a medical resident reported at the annual meeting of the American College of Chest Physicians.

In one recent and unusual presentation, a 58-year-old woman with persistent headaches had skull lesions on computed tomography (CT) was eventually diagnosed with disseminated coccidioidomycosis (Valley fever), a fungal infection endemic to the Southwestern U.S.

The imaging pattern of her head CT was initially concerning for cancer metastasis, according to Sharjeel Israr, MD, a third-year internal medicine resident at Creighton University in Phoenix, Ariz.

However, the subsequent chest CT revealed a suspicious chest mass. A biopsy of that mass led to the correct diagnosis of disseminated coccidioidomycosis, according to Dr. Israr, who presented the case report in an e-poster at the CHEST meeting, which was held virtually this year.
 

Mistaken identity

Coccidioidomycosis, caused by the fungus Coccidioides, usually affects the lungs, according to the Centers for Disease Control and Prevention. However, in severe cases it can spread to other parts of the body. In those cases, it’s referred to as disseminated coccidioidomycosis.

Arizona accounted for about 10,000 out of 18,000 reported Valley fever cases in 2019, according to the latest statistics from the CDC.

Coccidioidomycosis is frequently mistaken not only for cancer, but also for rheumatic conditions and bacterial infections, according to Valley fever specialist John Galgiani, MD, director of the Valley Fever Center for Excellence at the University of Arizona in Tucson.

“Where Valley fever is common, it should very frequently be in the differential for masses that are thought to be cancer,” Dr. Galgiani said in an interview. “This case is a good example of that.”
 

Challenging case

In an interview, Dr. Israr said the case was challenging to crack despite the fact that Valley fever is very common in Phoenix.

“It was definitely on the differential from the get-go, but it was very, very low our differential, just based on the presentation that she had,” said Dr. Israr.

The patient had history of diabetes and presented with headaches for 4 weeks. However, she had no pulmonary symptoms or meningeal signs, according to Dr. Israr.

A head CT revealed multiple osseous skull lesions and a left temporal lobe lesion.

“The fact that this patient had lesions in the skull, specifically, is something that raised our initial red flags for cancer – especially since she presented with just a headache as her only complaint,” he said.

The imaging pattern was concerning for metastasis, according to Dr. Israr, particularly since a subsequent CT of the chest showed multiple pulmonary nodules plus a 7.7-cm mass in the right lower lobe.

Once the biopsy confirmed coccidioidomycosis, the patient was started on fluconazole 600 mg twice daily, according to Dr. Israr.

Although severe disseminated coccidioidomycosis can be difficult to treat, the lung lesion had decreased in size from 7.7 cm to 4.2 cm about 3 months later, Dr. Israr said.

“At the end of the day, she didn’t have cancer, and it’s something that we’re treating and she’s actually doing better right now,” Dr. Israr said in the interview.

Dr. Israr and coauthors of the case reported they had no relevant relationships to disclose.

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

The high cost of new cancer drugs has been the subject of many debates and discussions, but the issue remains largely unresolved.

Now, one pharmaceutical company is offering a refund if its drug “doesn’t work.”

For what it says is the first time in the industry, Pfizer has issued a warranty on crizotinib (Xalkori) and will refund the cost that was paid for the medicine if it doesn’t work within the first 3 months of use.

“Through this pilot program, Pfizer will offer a warranty to patients and health plans -- Medicare Part D, commercial and those who pay cash -- who are prescribed Xalkori for an FDA [US Food and Drug Administration]–approved indication,” said a company spokesperson.

Although Pfizer claims that its pilot program is a first in the industry, there have been others that are similar.

In 2017, Novartis offered something similar for tisagenlecleucel (Kymriah), the CAR T-cell therapy that launched with a daunting price tag of $475,000. After receiving backlash over the cost, Novartis announced that if the drug does not work after the first month, patients pay nothing.

Italy has been using this system for several years. Pharmaceutical companies must refund money if the drug fails to work. In 2015, the state-run healthcare system collected €200 million ($220 million) in refunds.
 

Pfizer pledge

Crizotinib is a selective tyrosine kinase inhibitor used mainly in the treatment of metastatic non–small cell lung cancer for patients whose tumors are positive for ALK or ROS1, as detected by an FDA-approved test. This indication was approved a decade ago. Another indication, ALK-positive anaplastic large cell lymphoma, was added earlier this year.

Details of the Pfizer Pledge are posted on Pfizer’s website. Eligible patients are those for whom crizotinib is discontinued before the fourth 30-day supply is dispensed by the patient’s pharmacy.

“The warranty will reimburse an amount equal to the cost paid for the medicine,” the spokesperson added. “The insurance-backed warranty pilot program will be insured and managed by AIG.”

This program is only available for patients who reside in the United States.

If use of crizotinib is discontinued and documentation of ineffectiveness is provided, Pfizer will refund the out-of-pocket amount that was paid for up to the first three bottles (30-day supply) of crizotinib, up to a maximum of $19,144 for each month’s supply, or a total of $57,432. Pfizer will also refund the cost that was paid by Medicare or a commercial insurer.

“Also, we have made sure to develop a program that also allows for Medicare patients to be eligible, since they are exempt from copay cards and at risk for significant financial burden when starting an oncology treatment,” said the spokesperson.

The pilot program is available to patients who began taking crizotinib from June 1, 2021, through December 31, 2021.

So far, Pfizer is offering this warranty only for crizotinib, but that may change in the future.

“Once the pilot is complete, we will assess learnings and consider whether to build a more robust, scalable program capable of supporting multiple products,” the Pfizer spokesperson commented.
 

Previous scheme ended in court

Pfizer had previously tried a different approach to reducing drug costs: it had attempted to offer copay support programs to Medicare patients who were prescribed its cardiac drug tafamidis (Vyndaqe, Vyndamax).

Tafamidis, launched in 2019, is used for patients with transthyretin amyloid cardiomyopathy. For those patients, it has been shown to reduce all-cause mortality and cardiovascular hospitalizations. It costs about $225,000 a year and has been described as the most expensive cardiovascular drug in the United States.

Earlier this month, a court dismissed Pfizer’s challenge to an anti-kickback law that prevented the company from offering copay support programs to Medicare patients.

The judge ruled that Pfizer’s plan to offer direct payments to patients violated a federal ban on “knowingly or willfully” providing financial support to induce drug purchases, even in the absence of corrupt intent.

Pharmaceutical manufacturers are forbidden from subsidizing copayments for Medicare beneficiaries but are allowed to donate to independent nonprofit organizations that offer copay assistance. Pfizer sued the U.S. Department of Health and Human Services in June 2020 to get a court ruling that their proposed programs were legal.

The new pledge program for crizotinib operates from a different premise, the Pfizer spokesperson commented.

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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

Untreated PD-L1 non–small cell lung cancer (NSCLC). Patients with previously untreated, PD-L1-selected, locally advanced, unresectable, or metastatic NSCLC are sought for a phase 3 trial comparing pembrolizumab to the investigational immunotherapies ociperlimab (an anti-TIGIT antibody) and tislelizumab (an anti-PD-1 checkpoint inhibitor). Participants will be treated until death or progression of disease, whichever comes first, up to approximately 39 months. The multinational study started recruiting June 8 and hopes to enroll 605 participants. U.S. trial centers are in Alabama, Alaska, California, Florida, Hawaii, Kentucky, Maine, and Virginia. Overall survival (OS) is a primary outcome, and quality of life (QoL) will be tracked. More details are avaiable at clinicaltrials.gov.

Newly diagnosed, locally advanced, unresectable NSCLC. Adult patients with newly diagnosed, histologically confirmed, locally advanced, stage III unresectable NSCL are being recruited for a phase 3 study comparing sequential combinations of concurrent chemoradiotherapy and the immunotherapies ociperlimab, tislelizumab, and durvalumab (Imfinzi). Participants will receive therapy until disease progression or up to 16 months from randomization, whichever occurs first. The trial began recruiting on June 17 at the Central Care Cancer Center, in Bolivar, Mo. OS and QoL over 16 months are secondary outcomes. More details are avaiable at clinicaltrials.gov.

Limited-stage small cell lung cancer. Patients with untreated small cell lung cancer and documented limited-stage disease (stages Tx, T1-T4, N0-3, M0; AJCC staging, eighth edition) can join a phase 2 study comparing the immunotherapies ociperlimab and tislelizumab plus concurrent chemoradiotherapy to concurrent chemoradiotherapy alone. The trial will last 30 months from the date of the study’s first recruitment. Investigators are aiming to recruit 120 people globally. U.S. sites are in Alaska, Hawaii, Kansas, Missouri, Pennsylvania, Texas, and Wisconsin. Progression-free survival is the primary outcome. OS over 30 months is a secondary outcome. QoL will not be tracked. More details are avaiable at clinicaltrials.gov.

Stage III unresectable NSCLC. Patients with stage III unresectable NSCLC with positive circulating tumor DNA are being recruited for a phase 3 study testing whether or not circulating cancer cells in the blood can be decreased by combining standard treatment durvalumab with platinum-doublet chemotherapy (carboplatin/pemetrexed or carboplatin/paclitaxel). Patients will receive durvalumab for 1 year, with or without four cycles of chemotherapy. The study opened on August 25 at Stanford University, in California. OS over 2 years is a secondary outcome. QoL will not be assessed. More details are avaiable at clinicaltrials.gov.

Untreated stage IV NSCLC. Patients with nonsquamous stage IV NSCLC not treated for metastatic disease are being recruited for a phase 2 study of the experimental immunotherapy SEA-CD40 in combination with pembrolizumab, pemetrexed, and carboplatin. Participants will be treated for approximately 2 years. Objective response rate is the primary outcome. OS over 4 years is a secondary outcome. QoL will not be assessed. The study opened on September 30 in Arkansas, California, Minnesota, Ohio, and Texas. More details are avaiable at clinicaltrials.gov.

Untreated metastatic NSCLC. Patients with metastatic squamous or nonsquamous NSCLC are sought for a phase 3 trial that will compare a new subcutaneous formulation of pembrolizumab with standard intravenous pembrolizumab, both given in combination with chemotherapy. Patients will be treated with immunotherapy for up to approximately 2 years until the occurrence of disease progression or intolerable adverse events or the participant/physician decides to stop. Drug pharmacokinetic performance is the primary outcome measure. OS over 5 years will be analyzed as a secondary outcome. QoL will not be assessed. The international trial has U.S. sites in Florida, Montana, Tennessee, Texas, and Virginia. More details are available at clinicaltrials.gov.

All trial information is from the National Institutes of Health U.S. National Library of Medicine (online at clinicaltrials.gov).

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