Susan London

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men with prostate cancer who are on active surveillance may be overtreated if their clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw told attendees of a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

Dr. Loblaw said that research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer. This surveillance typically entails some type of PSA monitoring, with the decision to initiate treatment often based on a PSA trigger, said the radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

The investigators therefore tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of progression after a median of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%); first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%); linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%); overall PSA velocity of greater than 2 ng/mL per year (42%); and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a 20-ng/mL threshold has a low false-trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, he said.

My Take

Active Surveillance May Not Catch On

Active surveillance is a hot topic. More and more men with low-risk disease are being diagnosed with prostate cancer in the United States and around the world. Many of these men would be candidates for active surveillance. In real-world practice, however, many questions remain about offering active surveillance to men with localized prostate cancer, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment for a patient with localized prostate cancer?

In their study of 315 men, the researchers found that a PSA threshold of 20 ng/mL had the lowest false-trigger rate for men on active surveillance. In other words, by allowing the PSA to go above 20 before offering active treatment, the authors suggested that this PSA threshold may be the most appropriate marker for switching from active surveillance to active treatment.

Although I applaud the researchers for doing this work, many patients would be very uncomfortable allowing their PSA to go as high as 20 before considering a repeat biopsy or treatment. In the D'Amico risk stratification scheme in localized prostate cancer, men with a PSA rated at 20 have high-risk disease. Therefore, if we allow a PSA to go above 20 in men on active surveillance before we recommend active treatment, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients alike.

The key is that we need more prospective, randomized, controlled trials—such as the multicenter START—that address active surveillance. Again, I congratulate the researchers on excellent work, and look forward to further studies of active surveillance and new information about this hot topic.

Judd W. Moul, M.D., is professor and chief of the Division of Urologic Surgery, and director of the Duke Prostate Center at Duke University, Durham, N.C. He had no relevant conflicts of interest.

Vitals

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men with prostate cancer who are on active surveillance may be overtreated if their clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw told attendees of a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

Dr. Loblaw said that research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer. This surveillance typically entails some type of PSA monitoring, with the decision to initiate treatment often based on a PSA trigger, said the radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

The investigators therefore tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of progression after a median of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%); first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%); linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%); overall PSA velocity of greater than 2 ng/mL per year (42%); and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a 20-ng/mL threshold has a low false-trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, he said.

My Take

Active Surveillance May Not Catch On

Active surveillance is a hot topic. More and more men with low-risk disease are being diagnosed with prostate cancer in the United States and around the world. Many of these men would be candidates for active surveillance. In real-world practice, however, many questions remain about offering active surveillance to men with localized prostate cancer, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment for a patient with localized prostate cancer?

In their study of 315 men, the researchers found that a PSA threshold of 20 ng/mL had the lowest false-trigger rate for men on active surveillance. In other words, by allowing the PSA to go above 20 before offering active treatment, the authors suggested that this PSA threshold may be the most appropriate marker for switching from active surveillance to active treatment.

Although I applaud the researchers for doing this work, many patients would be very uncomfortable allowing their PSA to go as high as 20 before considering a repeat biopsy or treatment. In the D'Amico risk stratification scheme in localized prostate cancer, men with a PSA rated at 20 have high-risk disease. Therefore, if we allow a PSA to go above 20 in men on active surveillance before we recommend active treatment, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients alike.

The key is that we need more prospective, randomized, controlled trials—such as the multicenter START—that address active surveillance. Again, I congratulate the researchers on excellent work, and look forward to further studies of active surveillance and new information about this hot topic.

Judd W. Moul, M.D., is professor and chief of the Division of Urologic Surgery, and director of the Duke Prostate Center at Duke University, Durham, N.C. He had no relevant conflicts of interest.

Vitals

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men with prostate cancer who are on active surveillance may be overtreated if their clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw told attendees of a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

Dr. Loblaw said that research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer. This surveillance typically entails some type of PSA monitoring, with the decision to initiate treatment often based on a PSA trigger, said the radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

The investigators therefore tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of progression after a median of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%); first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%); linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%); overall PSA velocity of greater than 2 ng/mL per year (42%); and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a 20-ng/mL threshold has a low false-trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, he said.

My Take

Active Surveillance May Not Catch On

Active surveillance is a hot topic. More and more men with low-risk disease are being diagnosed with prostate cancer in the United States and around the world. Many of these men would be candidates for active surveillance. In real-world practice, however, many questions remain about offering active surveillance to men with localized prostate cancer, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment for a patient with localized prostate cancer?

In their study of 315 men, the researchers found that a PSA threshold of 20 ng/mL had the lowest false-trigger rate for men on active surveillance. In other words, by allowing the PSA to go above 20 before offering active treatment, the authors suggested that this PSA threshold may be the most appropriate marker for switching from active surveillance to active treatment.

Although I applaud the researchers for doing this work, many patients would be very uncomfortable allowing their PSA to go as high as 20 before considering a repeat biopsy or treatment. In the D'Amico risk stratification scheme in localized prostate cancer, men with a PSA rated at 20 have high-risk disease. Therefore, if we allow a PSA to go above 20 in men on active surveillance before we recommend active treatment, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients alike.

The key is that we need more prospective, randomized, controlled trials—such as the multicenter START—that address active surveillance. Again, I congratulate the researchers on excellent work, and look forward to further studies of active surveillance and new information about this hot topic.

Judd W. Moul, M.D., is professor and chief of the Division of Urologic Surgery, and director of the Duke Prostate Center at Duke University, Durham, N.C. He had no relevant conflicts of interest.

Vitals

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.

Major Finding: Common PSA triggers would have led to overtreatment of prostate cancer in 14%–84% of men on active surveillance.

Data Source: Prospective study of 315 men with localized prostate cancer and PSA levels less than 15 ng/mL at enrollment in monitoring program.

Disclosures: Dr. Loblaw reported having no conflicts of interest related to the study.

SAN FRANCISCO — Men on active surveillance for prostate cancer may be overtreated if clinicians rely strictly on certain commonly used prostate-specific antigen triggers for starting treatment, Dr. Andrew Loblaw said at a symposium on genitourinary cancers.

In a cohort of 315 such men who had no evidence of disease progression, the percentage in whom treatment would have been falsely triggered ranged widely—from 14% to 84%—depending on which of nine PSA measures was used for monitoring. The lowest value seen was with a PSA threshold of 20 ng/mL.

“For patients managed on active surveillance, this raises what we believe is a cautionary tale that strict follow-up with the definitions of either linear regression, threshold, or velocities may lead to a false rate of treatment for patients on surveillance who don't need it,” said Dr. Loblaw, a radiation oncologist at the Sunnybrook Health Sciences Centre in Toronto.

Research shows that active surveillance can achieve good outcomes in men with low-risk prostate cancer, he said. This surveillance typically entails PSA monitoring, with initiatation of treatment often based on a PSA trigger.

The researchers tested the performance of various PSA triggers in 315 men with localized prostate cancer who declined radical treatment, were enrolled in an active surveillance program, and did not have any evidence of disease progression after a median follow-up of 6.8 years (7.2 years for survivors).

At enrollment, the patients' PSA levels were all less than 15 ng/mL. Their monitoring had consisted of periodic physical examination, digital rectal examination, blood work, transrectal ultrasound, bone scans, and repeated prostate biopsies.

“All of the triggers or definitions that we looked at had a false or high trigger for treatment,” Dr. Loblaw reported at the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology.

The false trigger rate was lowest for a PSA threshold of 20 ng/mL (according to which 14% of the men would have been treated) and highest for a successive PSA velocity of greater than 2 ng/mL (84%).

The rate was intermediate for a PSA threshold of 10 ng/mL (38%), first-last PSA doubling times of less than 2 and less than 3 years (39% and 50%), linear regression PSA doubling times of less than 2 and less than 3 years (37% and 48%), overall PSA velocity of greater than 2 ng/mL per year (42%), and a 1-year PSA velocity of greater than 2 ng/mL (51%).

The findings suggest that only a PSA threshold of 20 ng/mL has a low false trigger rate and that men on active surveillance may be overtreated when clinicians rely on the other PSA triggers, Dr. Loblaw said.

To assess PSA changes, he said, clinicians at his center have started using and are validating a general linear mixed model that is freely available online (www.asure.ca

“It allows us to smooth out these PSA variations and helps us interpret the PSA undulations over time,” Dr. Loblaw said. “We are hoping that this will be a beneficial tool … to use in terms of managing patients on active surveillance.”

'All of the triggers or definitions that we looked at had a false or high trigger for treatment.'

Source Dr. Loblaw

My Take

Many Patients and Clinicians May Not Accept 20 ng/mL as Threshold

Active surveillance is a hot topic. Many men with localized prostate cancer may be candidates, but questions remain, including these:

▸ Is it prudent to offer active surveillance to young, healthy men who have a very long life expectancy?

▸ Does a patient on active surveillance need repeat prostate biopsies every year or two, or can we rely on PSA?

▸ As Dr. Loblaw and his colleagues asked, what is the best PSA change determinant to suggest a switch from active surveillance to active treatment?

The researchers found that a PSA above 20 ng/mL may be the most appropriate marker for switching to active treatment. But many patients would be very uncomfortable letting their PSA go as high as 20 before considering a repeat biopsy or treatment. With that strategy, we will be treating only high-risk patients who have progressed on active surveillance. This may be unacceptable to many clinicians and patients.

We need more randomized trials—such as the multicenter START trial—that address active surveillance. I congratulate the researchers on excellent work, and look forward to further studies of and new information about active surveillance.

Major Finding: Cystoscopy alone, the least expensive of five surveillance strategies, picked up two invasive bladder cancers that were missed by urine testing.

Data Source: A study in 200 consecutive patients.

Disclosures: Dr. Karam reported having no conflicts of interest related to the study. A coauthor received honoraria from Abbott Molecular.

SAN FRANCISCO — Cystoscopy alone offers the best combination of cost and sensitivity for surveillance after treatment of superficial bladder cancer, new data show.

In a prospective study comparing five surveillance strategies in 200 patients, the addition of various urine tests to cystoscopy increased the cost per cancer detected, but did not find more invasive tumors, researchers reported at a symposium on genitourinary cancers.

“Our data suggest that cystoscopy alone is the most cost-effective strategy, and that the addition of urinary markers adds to cost without improved detection of invasive disease,” said first author Dr. Jose A. Karam, a urologic oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Evidence-based data are lacking on the outcomes of surveillance strategies among patients who have been treated for superficial (non–muscle invasive) bladder cancer. Many urinary-based markers are now available for use, but cystoscopy remains the standard of care, he said.

In the study, consecutive patients needing surveillance after treatment of superficial bladder cancer underwent these tests at study entry: cystoscopy, urine cytology, NMP22 BladderChek test (a urine test marketed by Inverness Medical Innovations that measures a protein associated with bladder cancer), and FISH (fluorescence in situ hybridization) UroVysion test (a urine test marketed by Abbott Molecular that detects chromosomal abnormalities associated with bladder cancer).

The bladder cancers for which they had been treated were mainly of Ta stage (71%) and low grade (58%). In 25 patients, new tumors were found at study entry or by the first follow-up assessment, a median of 4.1 months later, Dr. Karam reported at the symposium, sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Based on 2009 Medicare reimbursement rates, the cost per cancer detected was lowest with cystoscopy alone ($7,692), and highest with cystoscopy plus FISH ($19,111). Values were intermediate for cystoscopy plus cytology ($10,267), cystoscopy plus NMP ($11,143), and cystoscopy plus NMP with FISH confirmation in the event of a positive NMP result ($9,557).

The cancer detection rate was lowest with cystoscopy alone (52%) and highest with cystoscopy plus FISH (72%). Values were intermediate for cystoscopy plus cytology (60%), cystoscopy plus NMP (56%), and cystoscopy plus NMP with FISH confirmation (56%). Subsequent analyses showed that cystoscopy plus FISH picked up more early, noninvasive (carcinoma in situ and Ta) tumors than did cystoscopy alone. But it similarly missed the two more advanced (T1 and T2) tumors that were found, “which arguably are the ones that matter the most,” Dr. Karam commented.

Cystoscopy alone appears to be the most cost-effective approach, he concluded, cautioning that “these [urinary-based] markers should be used carefully and judiciously in patients with bladder cancer.” Because all patients received care from bladder specialists, the findings may not be generalizable to community practices, he added.

Dr. Nicholas J. Vogelzang, one of the developers of the NMP22 assay, chaired a press briefing at which the study was discussed. Dr. Vogelzang, chair and medical director of the developmental therapeutics committee of U.S. Oncology, said he found the results “very chagrining but nonetheless very important.”

Urinary-based markers 'should be used carefully and judiciously in patients with bladder cancer.'

Source Dr. Karam

Major Finding: Cystoscopy alone, the least expensive of five surveillance strategies, picked up two invasive bladder cancers that were missed by urine testing.

Data Source: A study in 200 consecutive patients.

Disclosures: Dr. Karam reported having no conflicts of interest related to the study. A coauthor received honoraria from Abbott Molecular.

SAN FRANCISCO — Cystoscopy alone offers the best combination of cost and sensitivity for surveillance after treatment of superficial bladder cancer, new data show.

In a prospective study comparing five surveillance strategies in 200 patients, the addition of various urine tests to cystoscopy increased the cost per cancer detected, but did not find more invasive tumors, researchers reported at a symposium on genitourinary cancers.

“Our data suggest that cystoscopy alone is the most cost-effective strategy, and that the addition of urinary markers adds to cost without improved detection of invasive disease,” said first author Dr. Jose A. Karam, a urologic oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Evidence-based data are lacking on the outcomes of surveillance strategies among patients who have been treated for superficial (non–muscle invasive) bladder cancer. Many urinary-based markers are now available for use, but cystoscopy remains the standard of care, he said.

In the study, consecutive patients needing surveillance after treatment of superficial bladder cancer underwent these tests at study entry: cystoscopy, urine cytology, NMP22 BladderChek test (a urine test marketed by Inverness Medical Innovations that measures a protein associated with bladder cancer), and FISH (fluorescence in situ hybridization) UroVysion test (a urine test marketed by Abbott Molecular that detects chromosomal abnormalities associated with bladder cancer).

The bladder cancers for which they had been treated were mainly of Ta stage (71%) and low grade (58%). In 25 patients, new tumors were found at study entry or by the first follow-up assessment, a median of 4.1 months later, Dr. Karam reported at the symposium, sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Based on 2009 Medicare reimbursement rates, the cost per cancer detected was lowest with cystoscopy alone ($7,692), and highest with cystoscopy plus FISH ($19,111). Values were intermediate for cystoscopy plus cytology ($10,267), cystoscopy plus NMP ($11,143), and cystoscopy plus NMP with FISH confirmation in the event of a positive NMP result ($9,557).

The cancer detection rate was lowest with cystoscopy alone (52%) and highest with cystoscopy plus FISH (72%). Values were intermediate for cystoscopy plus cytology (60%), cystoscopy plus NMP (56%), and cystoscopy plus NMP with FISH confirmation (56%). Subsequent analyses showed that cystoscopy plus FISH picked up more early, noninvasive (carcinoma in situ and Ta) tumors than did cystoscopy alone. But it similarly missed the two more advanced (T1 and T2) tumors that were found, “which arguably are the ones that matter the most,” Dr. Karam commented.

Cystoscopy alone appears to be the most cost-effective approach, he concluded, cautioning that “these [urinary-based] markers should be used carefully and judiciously in patients with bladder cancer.” Because all patients received care from bladder specialists, the findings may not be generalizable to community practices, he added.

Dr. Nicholas J. Vogelzang, one of the developers of the NMP22 assay, chaired a press briefing at which the study was discussed. Dr. Vogelzang, chair and medical director of the developmental therapeutics committee of U.S. Oncology, said he found the results “very chagrining but nonetheless very important.”

Urinary-based markers 'should be used carefully and judiciously in patients with bladder cancer.'

Source Dr. Karam

Major Finding: Cystoscopy alone, the least expensive of five surveillance strategies, picked up two invasive bladder cancers that were missed by urine testing.

Data Source: A study in 200 consecutive patients.

Disclosures: Dr. Karam reported having no conflicts of interest related to the study. A coauthor received honoraria from Abbott Molecular.

SAN FRANCISCO — Cystoscopy alone offers the best combination of cost and sensitivity for surveillance after treatment of superficial bladder cancer, new data show.

In a prospective study comparing five surveillance strategies in 200 patients, the addition of various urine tests to cystoscopy increased the cost per cancer detected, but did not find more invasive tumors, researchers reported at a symposium on genitourinary cancers.

“Our data suggest that cystoscopy alone is the most cost-effective strategy, and that the addition of urinary markers adds to cost without improved detection of invasive disease,” said first author Dr. Jose A. Karam, a urologic oncology fellow at the University of Texas M.D. Anderson Cancer Center in Houston.

Evidence-based data are lacking on the outcomes of surveillance strategies among patients who have been treated for superficial (non–muscle invasive) bladder cancer. Many urinary-based markers are now available for use, but cystoscopy remains the standard of care, he said.

In the study, consecutive patients needing surveillance after treatment of superficial bladder cancer underwent these tests at study entry: cystoscopy, urine cytology, NMP22 BladderChek test (a urine test marketed by Inverness Medical Innovations that measures a protein associated with bladder cancer), and FISH (fluorescence in situ hybridization) UroVysion test (a urine test marketed by Abbott Molecular that detects chromosomal abnormalities associated with bladder cancer).

The bladder cancers for which they had been treated were mainly of Ta stage (71%) and low grade (58%). In 25 patients, new tumors were found at study entry or by the first follow-up assessment, a median of 4.1 months later, Dr. Karam reported at the symposium, sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, and the Society of Urologic Oncology.

Based on 2009 Medicare reimbursement rates, the cost per cancer detected was lowest with cystoscopy alone ($7,692), and highest with cystoscopy plus FISH ($19,111). Values were intermediate for cystoscopy plus cytology ($10,267), cystoscopy plus NMP ($11,143), and cystoscopy plus NMP with FISH confirmation in the event of a positive NMP result ($9,557).

The cancer detection rate was lowest with cystoscopy alone (52%) and highest with cystoscopy plus FISH (72%). Values were intermediate for cystoscopy plus cytology (60%), cystoscopy plus NMP (56%), and cystoscopy plus NMP with FISH confirmation (56%). Subsequent analyses showed that cystoscopy plus FISH picked up more early, noninvasive (carcinoma in situ and Ta) tumors than did cystoscopy alone. But it similarly missed the two more advanced (T1 and T2) tumors that were found, “which arguably are the ones that matter the most,” Dr. Karam commented.

Cystoscopy alone appears to be the most cost-effective approach, he concluded, cautioning that “these [urinary-based] markers should be used carefully and judiciously in patients with bladder cancer.” Because all patients received care from bladder specialists, the findings may not be generalizable to community practices, he added.

Dr. Nicholas J. Vogelzang, one of the developers of the NMP22 assay, chaired a press briefing at which the study was discussed. Dr. Vogelzang, chair and medical director of the developmental therapeutics committee of U.S. Oncology, said he found the results “very chagrining but nonetheless very important.”

Urinary-based markers 'should be used carefully and judiciously in patients with bladder cancer.'

Source Dr. Karam

Major Finding: A new urinary assay had high specificity for distinguishing between patients with and without cancer (88%–93%).

Data Source: Two cohort studies in men who were scheduled for prostatectomy or prostate biopsy.

Disclosures: Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

“This new … urinary assay has the ability to not only detect prostate cancer, but may help move us forward in our paradigm to also detect clinically significant prostate cancer,” said Dr. John T. Wei, who presented results of the first study on behalf of first author Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer, Dr. Wei observed. “Because of this, many patients will go on to have false-positive PSA tests and unnecessary prostate biopsies, and suffer a significant amount of distress.”

Moreover, these tests are unable to differentiate indolent from aggressive cancer, which becomes more important given current efforts to tailor management to disease characteristics, according to Dr. Wei, professor of urology at the University of Michigan in Ann Arbor. “Taken together, there is a significant unmet need, and that is to develop a highly specific test that can tell us if a patient has clinically significant cancer or not,” he said.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene, Dr. Wei told attendees of the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer.

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged. He said that ongoing discussions are looking at the possibility of incorporating the assay into trials of the Early Detection Research Network.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to presenting author Dr. James B.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems, which performs diagnostic and prognostic testing. Sensitivity was 39%, “in line with the expected gene fusion prevalence in this population of about 50%.”

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, Dr. Amberson said.

The area under the curve was 0.597 for serum PSA level alone, 0.715 for a model using multiple risk factors (serum PSA level, percentage of free PSA, age, prostate volume, family history, race, digital rectal examination result, prior biopsy history, and urine prostate cancer gene 3 level), and 0.754 when the T2:ERG score was added to the model.

Major Finding: A new urinary assay had high specificity for distinguishing between patients with and without cancer (88%–93%).

Data Source: Two cohort studies in men who were scheduled for prostatectomy or prostate biopsy.

Disclosures: Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

“This new … urinary assay has the ability to not only detect prostate cancer, but may help move us forward in our paradigm to also detect clinically significant prostate cancer,” said Dr. John T. Wei, who presented results of the first study on behalf of first author Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer, Dr. Wei observed. “Because of this, many patients will go on to have false-positive PSA tests and unnecessary prostate biopsies, and suffer a significant amount of distress.”

Moreover, these tests are unable to differentiate indolent from aggressive cancer, which becomes more important given current efforts to tailor management to disease characteristics, according to Dr. Wei, professor of urology at the University of Michigan in Ann Arbor. “Taken together, there is a significant unmet need, and that is to develop a highly specific test that can tell us if a patient has clinically significant cancer or not,” he said.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene, Dr. Wei told attendees of the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer.

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged. He said that ongoing discussions are looking at the possibility of incorporating the assay into trials of the Early Detection Research Network.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to presenting author Dr. James B.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems, which performs diagnostic and prognostic testing. Sensitivity was 39%, “in line with the expected gene fusion prevalence in this population of about 50%.”

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, Dr. Amberson said.

The area under the curve was 0.597 for serum PSA level alone, 0.715 for a model using multiple risk factors (serum PSA level, percentage of free PSA, age, prostate volume, family history, race, digital rectal examination result, prior biopsy history, and urine prostate cancer gene 3 level), and 0.754 when the T2:ERG score was added to the model.

Major Finding: A new urinary assay had high specificity for distinguishing between patients with and without cancer (88%–93%).

Data Source: Two cohort studies in men who were scheduled for prostatectomy or prostate biopsy.

Disclosures: Dr. Wei and Dr. Amberson reported receiving research funding from Gen-Probe Inc. Some coauthors of both studies disclosed employment or leadership roles and stock ownership in Gen-Probe.

SAN FRANCISCO — A new urinary assay for a common gene rearrangement in prostate cancer improves the detection of this disease and the differentiation of its more aggressive forms, according to two cohort studies reported at a symposium on genitourinary cancers.

The studies, conducted among men who were scheduled for prostate biopsy or prostatectomy, found that the assay supplemented conventional risk factors for accurately identifying those having prostate cancer. In addition, higher assay scores correlated with the presence of adverse tumor features.

“This new … urinary assay has the ability to not only detect prostate cancer, but may help move us forward in our paradigm to also detect clinically significant prostate cancer,” said Dr. John T. Wei, who presented results of the first study on behalf of first author Sheila M.J. Aubin, Ph.D., of Gen-Probe Inc., the company that is developing the assay.

Prostate-specific antigen (PSA) level and digital rectal examination both have poor specificity for detecting prostate cancer, Dr. Wei observed. “Because of this, many patients will go on to have false-positive PSA tests and unnecessary prostate biopsies, and suffer a significant amount of distress.”

Moreover, these tests are unable to differentiate indolent from aggressive cancer, which becomes more important given current efforts to tailor management to disease characteristics, according to Dr. Wei, professor of urology at the University of Michigan in Ann Arbor. “Taken together, there is a significant unmet need, and that is to develop a highly specific test that can tell us if a patient has clinically significant cancer or not,” he said.

About half of prostate cancers exhibit fusion of the androgen-regulated TMPRSS2 gene and the ERG oncogene, Dr. Wei told attendees of the symposium, which was sponsored by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society of Urologic Oncology. Cancers that harbor this fusion gene (abbreviated T2:ERG) have increased cell growth, invasion, and metastasis, and decreased apoptosis.

In the first study, the investigators assessed the performance of the novel assay, which measures levels of T2:ERG messenger RNA in urine, using urine specimens collected after digital rectal examination and before either prostate biopsy (623 men) or prostatectomy (142 men).

Analyses of biopsy-based indicators showed that the T2:ERG score was correlated with the number of cores that were positive, the percentage of cores that were positive, and the greatest percentage involvement of any core by cancer, according to Dr. Wei. Also, the median score was higher among patients with biopsy-significant cancer as defined by Epstein criteria.

Analyses of prostatectomy-based indicators showed that the T2:ERG score was correlated with the maximum tumor dimension. In addition, the median score was higher among patients who had an upgrade of the Gleason score between biopsy and prostatectomy, a prostatectomy Gleason score of greater than 6, and prostatectomy-significant cancer as defined from tumor characteristics.

Compared with the PCPT (Prostate Cancer Prevention Trial) risk score alone, the combination of this score with the T2:ERG score more accurately identified men who had prostate cancer.

Dr. Wei noted that at cutoff scores of 100 and 200, the T2:ERG assay had high specificity for distinguishing between patients with and without cancer (88%–93%), with biopsy-significant and -insignificant cancer (85%–95%), and with prostatectomy-significant and -insignificant cancer (95%–100%).

Independent trials of the assay are needed, Dr. Wei acknowledged. He said that ongoing discussions are looking at the possibility of incorporating the assay into trials of the Early Detection Research Network.

In the second study, investigators tested the same T2:ERG assay using urine specimens that were collected after digital rectal examination from 471 men who were scheduled for prostate cancer biopsy at community clinics, according to presenting author Dr. James B.

Some 44% of patients had positive biopsies, he reported. The median age was 66 years in the patients with cancer and 63 years in the patients without it. The median serum PSA level was 5.0 and 4.3 ng/mL, respectively.

When used alone, the T2:ERG score had a high specificity (87%) for detection of biopsy-proven cancer, reported Dr. Amberson, divisional medical director of Dianon Systems, which performs diagnostic and prognostic testing. Sensitivity was 39%, “in line with the expected gene fusion prevalence in this population of about 50%.”

The median T2:ERG score was higher in patients who had a Gleason score of 7 or greater, involvement of more than 50% of positive cores by cancer, and three or more positive cores.

“The T2:ERG assay significantly improved the diagnostic accuracy of a logistic regression model” for prostate cancer detection, Dr. Amberson said.

The area under the curve was 0.597 for serum PSA level alone, 0.715 for a model using multiple risk factors (serum PSA level, percentage of free PSA, age, prostate volume, family history, race, digital rectal examination result, prior biopsy history, and urine prostate cancer gene 3 level), and 0.754 when the T2:ERG score was added to the model.

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls (P less than .05 for each). For distinguishing between these groups, this panel had an area under a receiver operating characteristic curve of 0.92.

In a logistic regression model focusing on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9). For distinguishing between patients with stage I lung cancer and at-risk controls, a panel consisting of these three biomarkers had an area under the curve of 0.93, a sensitivity of 97%, and a specificity of 77%.

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Dr. Lee reported that she had no conflicts of interest related to the study.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer.

In the training set, the signature's sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

In the investigation, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 patients (19%) had chemoresistance (defined as progression despite receiving chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression. Polymerase chain reaction analyses validated that three of them were indeed associated with progression, according to Dr. Weiss, who has filed patents to use them as “theranostics.”

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment of this disease, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls.

In a logistic regression model that focused on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9).

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Therefore, she and her colleagues will evaluate the 40 biomarkers in pre- and postresection serum samples from patients in the ACOSOG (American College of Surgeons Oncology Group) Z4031 trial. Roughly one-fifth of patients undergoing resection for lung nodules in that trial were found to have benign lung disease.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). They were divided into training and verification sets.

Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer, including cell adhesion molecules, cytokines, angiogenesis markers, and tyrosine kinases, among others.

The signature had an area under the curve of 0.91 in the training set and 0.90 in the verification set, Dr. Ostroff reported. In the training set, sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

The signature has also been tested in breast, prostate, and other cancers. “Certainly, some of the markers are also differentially expressed in those cancers, as you would expect,” Dr. Ostroff said. “But … when you combine all of those 12 markers together, it is much more specific for lung cancer than those others.”

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

“Small cell lung cancer patients have not had key breakthroughs for improved therapy in years, in part, because a one-size-fits-all approach for treatment is the current standard,” he commented in an interview.

In the study, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 (19%) had chemoresistance (defined as progression despite chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression.

Polymerase chain reaction analyses validated that three of them—miR-92a-2*, miR-147, and miR-574-5p—were indeed associated with progression, Dr. Weiss said.

The investigators are currently assessing how the identified microRNAs may reduce a tumor's sensitivity to chemotherapy, according to Dr. Weiss.

“If we can independently validate our findings in other tumor sample sets collected from small cell lung cancer patients, we can begin to explore [by] using these microRNAs to design better clinical trials and perhaps find new therapies that help patients at higher risk for resistance to current standard chemotherapy treatment,” he concluded.

Disclosures: Dr. Lee reported that she had no conflicts of interest related to the study. Dr. Ostroff's employer is the manufacturer of the study assay. Dr. Weiss has filed patents for the use of microRNAs as theranostics, and has received funding from the Sylvia-Chase Foundation, the American Cancer Society, the IBIS Foundation of Arizona, the TGen Foundation, and Scottsdale Healthcare to conduct this work.

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment of this disease, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls.

In a logistic regression model that focused on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9).

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Therefore, she and her colleagues will evaluate the 40 biomarkers in pre- and postresection serum samples from patients in the ACOSOG (American College of Surgeons Oncology Group) Z4031 trial. Roughly one-fifth of patients undergoing resection for lung nodules in that trial were found to have benign lung disease.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). They were divided into training and verification sets.

Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer, including cell adhesion molecules, cytokines, angiogenesis markers, and tyrosine kinases, among others.

The signature had an area under the curve of 0.91 in the training set and 0.90 in the verification set, Dr. Ostroff reported. In the training set, sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

The signature has also been tested in breast, prostate, and other cancers. “Certainly, some of the markers are also differentially expressed in those cancers, as you would expect,” Dr. Ostroff said. “But … when you combine all of those 12 markers together, it is much more specific for lung cancer than those others.”

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

“Small cell lung cancer patients have not had key breakthroughs for improved therapy in years, in part, because a one-size-fits-all approach for treatment is the current standard,” he commented in an interview.

In the study, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 (19%) had chemoresistance (defined as progression despite chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression.

Polymerase chain reaction analyses validated that three of them—miR-92a-2*, miR-147, and miR-574-5p—were indeed associated with progression, Dr. Weiss said.

The investigators are currently assessing how the identified microRNAs may reduce a tumor's sensitivity to chemotherapy, according to Dr. Weiss.

“If we can independently validate our findings in other tumor sample sets collected from small cell lung cancer patients, we can begin to explore [by] using these microRNAs to design better clinical trials and perhaps find new therapies that help patients at higher risk for resistance to current standard chemotherapy treatment,” he concluded.

Disclosures: Dr. Lee reported that she had no conflicts of interest related to the study. Dr. Ostroff's employer is the manufacturer of the study assay. Dr. Weiss has filed patents for the use of microRNAs as theranostics, and has received funding from the Sylvia-Chase Foundation, the American Cancer Society, the IBIS Foundation of Arizona, the TGen Foundation, and Scottsdale Healthcare to conduct this work.

CORONADO, CALIF. — A variety of lung cancer–associated biomarkers are being tested in assays that may improve diagnosis and treatment of this disease, according to three studies reported at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Blood-Based Biomarker Profile

A blood-based biomarker profile discriminates well between patients who have early-stage lung cancer and those individuals who are cancer free but at high risk, reported Dr. Gina Lee, a pulmonary and critical care physician at the University of California, Los Angeles.

She and her colleagues hypothesized that molecular changes in the developing tumor environment would be reflected in changes in levels of inflammatory, angiogenic, and tumorigenic proteins that can be detected in peripheral blood.

They used a bead-based multiplex immunoassay to assess levels of 40 biomarkers in serum samples from 90 patients who had lung cancer of any stage and from 56 cancer-free controls who were at high risk because of lengthy former smoking status and older age.

Levels of 21 biomarkers differed significantly between the 28 patients with stage I lung cancer and the cancer-free controls.

In a logistic regression model that focused on selected biomarkers, participants were more likely to have stage I cancer if they had higher levels of interleukin 2 (odds ratio, 51.4), interleukin 3 (OR, 11.0), and macrophage-derived chemokine (OR, 10.9).

“Our results suggest that we can find tumor-associated biomarkers that are differentially expressed in stage I vs. at-risk controls,” Dr. Lee said. “However, we are also interested in the clinical scenario where individuals present to clinicians with a lung nodule seen on chest x-ray or a CT scan of indeterminate significance.”

Therefore, she and her colleagues will evaluate the 40 biomarkers in pre- and postresection serum samples from patients in the ACOSOG (American College of Surgeons Oncology Group) Z4031 trial. Roughly one-fifth of patients undergoing resection for lung nodules in that trial were found to have benign lung disease.

High-Throughput Protein Assay

A protein signature identified by a high-throughput assay correctly classifies the large majority of patients with and without lung cancer, reported Dr. Rachel Ostroff, clinical research director at SomaLogic Inc., a diagnostic development company in Boulder, Colo.

The SOMAmer technology used in the study relies on aptamers (oligonucleotides that bind to specific proteins with high affinity) to measure 825 proteins in serum simultaneously with subpicomolar sensitivity, she explained.

The investigators analyzed more than 1,300 serum samples from patients with stage I-III non–small cell lung cancer (20%) and two control groups: individuals with benign calcified pulmonary nodules (40%) and long-term smokers with no evidence of cancer (40%). They were divided into training and verification sets.

Analyses identified a signature of 12 proteins that were differentially expressed between the groups with and without lung cancer, including cell adhesion molecules, cytokines, angiogenesis markers, and tyrosine kinases, among others.

The signature had an area under the curve of 0.91 in the training set and 0.90 in the verification set, Dr. Ostroff reported. In the training set, sensitivity was 91% for cancer of all stages (90% for stage I) and specificity was 84%. In the verification set, sensitivity was 89% for cancer of all stages (87% for stage I) and specificity was 84%.

The signature has also been tested in breast, prostate, and other cancers. “Certainly, some of the markers are also differentially expressed in those cancers, as you would expect,” Dr. Ostroff said. “But … when you combine all of those 12 markers together, it is much more specific for lung cancer than those others.”

Tumor MicroRNA Analysis

A trio of tumor microRNAs predict de novo resistance to first-line chemotherapy among patients with small cell lung cancer, reported Dr. Glenn J. Weiss, a pulmonary oncologist with Scottsdale (Ariz.) Healthcare and the Translational Genomics Research Institute (TGen) in Phoenix.

“Small cell lung cancer patients have not had key breakthroughs for improved therapy in years, in part, because a one-size-fits-all approach for treatment is the current standard,” he commented in an interview.

In the study, which was funded in part by the TGen Foundation, he and his colleagues extracted RNA from formalin-fixed, paraffin-embedded tumor specimens obtained from 34 patients with small cell lung cancer before they started chemotherapy, which was a platinum-based regimen in most cases.

Study results, reported in a poster, showed that of 21 evaluable patients, 4 (19%) had chemoresistance (defined as progression despite chemotherapy).

MicroRNA array analyses identified 16 microRNA biomarkers as possible predictors of progression.

Polymerase chain reaction analyses validated that three of them—miR-92a-2*, miR-147, and miR-574-5p—were indeed associated with progression, Dr. Weiss said.

The investigators are currently assessing how the identified microRNAs may reduce a tumor's sensitivity to chemotherapy, according to Dr. Weiss.

“If we can independently validate our findings in other tumor sample sets collected from small cell lung cancer patients, we can begin to explore [by] using these microRNAs to design better clinical trials and perhaps find new therapies that help patients at higher risk for resistance to current standard chemotherapy treatment,” he concluded.

Disclosures: Dr. Lee reported that she had no conflicts of interest related to the study. Dr. Ostroff's employer is the manufacturer of the study assay. Dr. Weiss has filed patents for the use of microRNAs as theranostics, and has received funding from the Sylvia-Chase Foundation, the American Cancer Society, the IBIS Foundation of Arizona, the TGen Foundation, and Scottsdale Healthcare to conduct this work.

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentation. Accumulating evidence suggests that melanoma may encompass several different diseases with differing biology, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. “Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy,” he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913-7).“But we'll never know the depth of the lesion” with an incisional or shave biopsy, he pointed out, “so we'll never have the right prognosis.”

Accurate diagnosis of melanoma requires permanent sections. “Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives,” Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570-9). “There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests,” he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

“I send everybody who has a melanoma that is 1 mm or greater to an oncologist,” he added. “I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials.” Whenever possible, patients with advanced disease should be referred for clinical trials. “Investigational therapies—I think this is where the promise is,” Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1-3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1-2 cm and larger margins of 3-5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. “There is a lot of distortion when you do Mohs,” he noted. “It's really easy to get false-negatives and false-positives.” To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307-17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302-13). “So right now, the recommendation is that it does take probably 30 cases for that learning curve,” he said.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566-76).

“Complete lymph node dissection is a curative procedure,” he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. “In most of my axillary dissections, I will remove 35-40 lymph nodes,” Dr. Dzwierzynski said.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. “But there may be a subgroup in which interferon is useful,” he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically “because it's the only thing that's available,” he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

In the one-quarter of patients who have a recurrence of melanoma after primary treatment, a variety of treatment options are used, including wide local excision, therapeutic lymph node dissection, isolated limb perfusion, radiation therapy, and various systemic therapies.

Disclosures: Dr. Dzwierzynski reported that he had no relevant conflicts of interest.

Optimal follow-up has not been established, but it is typically lifelong and multidisciplinary.

Source DR. DZWIERZYNSKI

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentation. Accumulating evidence suggests that melanoma may encompass several different diseases with differing biology, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. “Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy,” he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913-7).“But we'll never know the depth of the lesion” with an incisional or shave biopsy, he pointed out, “so we'll never have the right prognosis.”

Accurate diagnosis of melanoma requires permanent sections. “Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives,” Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570-9). “There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests,” he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

“I send everybody who has a melanoma that is 1 mm or greater to an oncologist,” he added. “I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials.” Whenever possible, patients with advanced disease should be referred for clinical trials. “Investigational therapies—I think this is where the promise is,” Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1-3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1-2 cm and larger margins of 3-5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. “There is a lot of distortion when you do Mohs,” he noted. “It's really easy to get false-negatives and false-positives.” To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307-17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302-13). “So right now, the recommendation is that it does take probably 30 cases for that learning curve,” he said.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566-76).

“Complete lymph node dissection is a curative procedure,” he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. “In most of my axillary dissections, I will remove 35-40 lymph nodes,” Dr. Dzwierzynski said.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. “But there may be a subgroup in which interferon is useful,” he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically “because it's the only thing that's available,” he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

In the one-quarter of patients who have a recurrence of melanoma after primary treatment, a variety of treatment options are used, including wide local excision, therapeutic lymph node dissection, isolated limb perfusion, radiation therapy, and various systemic therapies.

Disclosures: Dr. Dzwierzynski reported that he had no relevant conflicts of interest.

Optimal follow-up has not been established, but it is typically lifelong and multidisciplinary.

Source DR. DZWIERZYNSKI

SEATTLE — Evidence from recent and ongoing trials is helping to clarify the best strategies for managing cutaneous melanoma.

A hurdle to better melanoma management has been the high variability of the disease, exemplified in part by its wide-ranging presentation. Accumulating evidence suggests that melanoma may encompass several different diseases with differing biology, said Dr. William Dzwierzynski, professor of plastic and reconstructive surgery at the Medical College of Wisconsin in Milwaukee.

When initially evaluating a suspicious skin lesion, the type of biopsy is critical. “Excisional biopsy is probably the most key thing. You really try not to do an incisional or a shave biopsy,” he said, unless the latter is deep and removes the whole lesion. Reassuringly, though, the type of biopsy does not affect survival (Am. J. Surg. 2005;190:913-7).“But we'll never know the depth of the lesion” with an incisional or shave biopsy, he pointed out, “so we'll never have the right prognosis.”

Accurate diagnosis of melanoma requires permanent sections. “Melanoma is not accurately diagnosed on frozen sections. Don't do frozen sections on melanoma—you get a lot of false-negatives and a lot of false-positives,” Dr. Dzwierzynski said at the annual meeting of the American Society of Plastic Surgeons.

Positron emission tomography (PET) imaging is unreliable for staging in patients with melanoma, yielding a false-negative rate of 79% when used preoperatively to identify occult nodal metastases (Cancer 2005;104:570-9). “There is not any conclusive data that PET scan is any more accurate than a chest x-ray or lab tests,” he added. On the flip side, patients should not be assumed to have metastases solely based on a positive PET scan.

“I send everybody who has a melanoma that is 1 mm or greater to an oncologist,” he added. “I tell them that the oncologist probably won't have anything to offer you, and that's a good thing. But they are the ones who are going to know if there are any investigational studies or treatment trials.” Whenever possible, patients with advanced disease should be referred for clinical trials. “Investigational therapies—I think this is where the promise is,” Dr. Dzwierzynski commented.

When it comes to resecting the tumor, contemporary margins are 1-3 cm for most invasive melanomas. Prospective studies have found no difference in survival between margins of 1-2 cm and larger margins of 3-5 cm, but methodologic limitations leave the issue unresolved, he said.

Mohs surgery for invasive melanoma remains controversial. “There is a lot of distortion when you do Mohs,” he noted. “It's really easy to get false-negatives and false-positives.” To date, controlled survival data and randomized trials are lacking.

Sentinel node biopsy (SNB) is recommended for patients whose tumors have a Breslow thickness of greater than 1 mm and for those whose tumors are thinner but have adverse features, such as ulceration or a Clark level of IV or V. Currently, it is done to obtain prognostic information and identify the roughly 20% of patients who may benefit from a complete lymph node dissection, Dr. Dzwierzynski noted.

The results of the first Multicenter Selective Lymphadenectomy Trial (MSLT-1) raised the possibility that SNB also may be curing disease in some patients and improving survival (N. Engl. J. Med. 2006;355;1307-17). An ongoing follow-up trial, MSLT-2, is looking more closely at the issue and the possibility that patients with only microscopic disease in the sentinel node may be spared further surgery.

Importantly, there is a learning curve to the SNB procedure. In MSLT-1, the false-negative rate was 10% in a physician's first 25 cases, but fell to 5% thereafter (Ann. Surg. 2005;242:302-13). “So right now, the recommendation is that it does take probably 30 cases for that learning curve,” he said.

The National Comprehensive Cancer Network recommends complete lymph node dissection for patients with a positive SNB, but a recent analysis of national data found that only half of such patients underwent the procedure (Ann. Surg. Oncol. 2008;15:1566-76).

“Complete lymph node dissection is a curative procedure,” he commented. As such, it is extensive, more so than the lymph node sampling done for, say, breast cancer. “In most of my axillary dissections, I will remove 35-40 lymph nodes,” Dr. Dzwierzynski said.

Several trials have shown that adjuvant high-dose interferon therapy modestly improves outcomes among patients with melanoma at high risk for recurrence, but with the tradeoff of substantial toxicity. The benefits are lost when the dose is reduced and therapy is shortened. “But there may be a subgroup in which interferon is useful,” he added, so an individualized approach, with discussion of risks and benefits, is needed. It should not be given automatically “because it's the only thing that's available,” he said.

The optimal approach to follow-up of patients with treated melanoma has not been established, but follow-up is typically lifelong and multidisciplinary, according to Dr. Dzwierzynski. Importantly, all patients must have lymph node palpation for detection of recurrences, and full-body skin checks for detection of second primaries.

In the one-quarter of patients who have a recurrence of melanoma after primary treatment, a variety of treatment options are used, including wide local excision, therapeutic lymph node dissection, isolated limb perfusion, radiation therapy, and various systemic therapies.

Disclosures: Dr. Dzwierzynski reported that he had no relevant conflicts of interest.

Optimal follow-up has not been established, but it is typically lifelong and multidisciplinary.

Source DR. DZWIERZYNSKI

CORONADO, CALIF. — Current and former smokers who do not drink any green tea are nearly 13 times more likely to develop lung cancer than are their counterparts who consume at least one cup daily, according to a study conducted in Taiwan.

“Our results suggest that green tea consumption inhibits the lung cancer risk elicited by smoking,” lead investigator I-Hsin Lin said in an interview. “So we suggest that smokers should drink more than one cup a day.”

Regardless of the participants' smoking status, the study also found that green tea intake was associated with a lower risk of lung cancer among individuals who had insulinlike growth factor (IGF) genotypes that reduce levels of this protein.

Tea polyphenols have antioxidant activity, and data from previous studies suggest that some preparations inhibit the development of tumors—including lung tumors. In addition, IGFs and their binding proteins influence cell proliferation, differentiation, and apoptosis, noted Ms. Lin, a graduate student at Chung Shan Medical University in Taichung City, Taiwan.

In the hospital-based, case-control study, the investigators identified 170 patients with primary lung cancer and matched them in a 1:2 ratio with 340 healthy control individuals according to age and sex.

All participants completed questionnaires on demographics and lifestyle factors, including cigarette smoking, green tea consumption, dietary intake of fruits and vegetables, cooking practices, and family history of lung cancer, according to Ms. Lin's poster, which was presented at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Genotypes for three IGF-related polymorphisms that influence IGF levels and cancer risk were assessed by polymerase chain reaction.

Some 60% of study participants were male, and 71% were aged 60 years or older; 54% of the lung cancer group and 27% of the control group were current or former smokers. Of the lung cancer group, 4% drank at least one cup of green tea daily, compared with 19% of the control group.

In a multivariate analysis, current and former smokers who did not drink any green tea had almost 13 times the risk of developing lung cancer (odds ratio, 12.7; P less than .001), compared with current and former smokers who drank at least one cup of green tea daily.

In contrast, higher green tea consumption was not significantly associated with lower lung cancer risk in never-smokers.

Among green tea drinkers, those carrying the nonsusceptible genotypes IGF-1 (CA)₁₉/(CA)₁₉ and (CA)₁₉/X had a significantly lower risk of developing lung cancer, compared with those carrying the IGF-1 X/X genotype. This finding suggests that green tea may have a greater protective effect among individuals who already have reduced cancer risk because of their genetic makeup, Ms. Lin said.

“Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body,” Ms. Lin speculated.

Ms. Lin acknowledged several limitations of her study, including the fact that recall bias regarding smoking habits and green tea consumption could have been a problem.

A selection bias also may have occurred, with generally healthy people choosing to enroll in the study as controls.

Disclosures: Ms. Lin reported that she did not have any conflicts of interest.

'Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body.'

Source MS. LIN

CORONADO, CALIF. — Current and former smokers who do not drink any green tea are nearly 13 times more likely to develop lung cancer than are their counterparts who consume at least one cup daily, according to a study conducted in Taiwan.

“Our results suggest that green tea consumption inhibits the lung cancer risk elicited by smoking,” lead investigator I-Hsin Lin said in an interview. “So we suggest that smokers should drink more than one cup a day.”

Regardless of the participants' smoking status, the study also found that green tea intake was associated with a lower risk of lung cancer among individuals who had insulinlike growth factor (IGF) genotypes that reduce levels of this protein.

Tea polyphenols have antioxidant activity, and data from previous studies suggest that some preparations inhibit the development of tumors—including lung tumors. In addition, IGFs and their binding proteins influence cell proliferation, differentiation, and apoptosis, noted Ms. Lin, a graduate student at Chung Shan Medical University in Taichung City, Taiwan.

In the hospital-based, case-control study, the investigators identified 170 patients with primary lung cancer and matched them in a 1:2 ratio with 340 healthy control individuals according to age and sex.

All participants completed questionnaires on demographics and lifestyle factors, including cigarette smoking, green tea consumption, dietary intake of fruits and vegetables, cooking practices, and family history of lung cancer, according to Ms. Lin's poster, which was presented at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Genotypes for three IGF-related polymorphisms that influence IGF levels and cancer risk were assessed by polymerase chain reaction.

Some 60% of study participants were male, and 71% were aged 60 years or older; 54% of the lung cancer group and 27% of the control group were current or former smokers. Of the lung cancer group, 4% drank at least one cup of green tea daily, compared with 19% of the control group.

In a multivariate analysis, current and former smokers who did not drink any green tea had almost 13 times the risk of developing lung cancer (odds ratio, 12.7; P less than .001), compared with current and former smokers who drank at least one cup of green tea daily.

In contrast, higher green tea consumption was not significantly associated with lower lung cancer risk in never-smokers.

Among green tea drinkers, those carrying the nonsusceptible genotypes IGF-1 (CA)₁₉/(CA)₁₉ and (CA)₁₉/X had a significantly lower risk of developing lung cancer, compared with those carrying the IGF-1 X/X genotype. This finding suggests that green tea may have a greater protective effect among individuals who already have reduced cancer risk because of their genetic makeup, Ms. Lin said.

“Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body,” Ms. Lin speculated.

Ms. Lin acknowledged several limitations of her study, including the fact that recall bias regarding smoking habits and green tea consumption could have been a problem.

A selection bias also may have occurred, with generally healthy people choosing to enroll in the study as controls.

Disclosures: Ms. Lin reported that she did not have any conflicts of interest.

'Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body.'

Source MS. LIN

CORONADO, CALIF. — Current and former smokers who do not drink any green tea are nearly 13 times more likely to develop lung cancer than are their counterparts who consume at least one cup daily, according to a study conducted in Taiwan.

“Our results suggest that green tea consumption inhibits the lung cancer risk elicited by smoking,” lead investigator I-Hsin Lin said in an interview. “So we suggest that smokers should drink more than one cup a day.”

Regardless of the participants' smoking status, the study also found that green tea intake was associated with a lower risk of lung cancer among individuals who had insulinlike growth factor (IGF) genotypes that reduce levels of this protein.

Tea polyphenols have antioxidant activity, and data from previous studies suggest that some preparations inhibit the development of tumors—including lung tumors. In addition, IGFs and their binding proteins influence cell proliferation, differentiation, and apoptosis, noted Ms. Lin, a graduate student at Chung Shan Medical University in Taichung City, Taiwan.

In the hospital-based, case-control study, the investigators identified 170 patients with primary lung cancer and matched them in a 1:2 ratio with 340 healthy control individuals according to age and sex.

All participants completed questionnaires on demographics and lifestyle factors, including cigarette smoking, green tea consumption, dietary intake of fruits and vegetables, cooking practices, and family history of lung cancer, according to Ms. Lin's poster, which was presented at a joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer.

Genotypes for three IGF-related polymorphisms that influence IGF levels and cancer risk were assessed by polymerase chain reaction.

Some 60% of study participants were male, and 71% were aged 60 years or older; 54% of the lung cancer group and 27% of the control group were current or former smokers. Of the lung cancer group, 4% drank at least one cup of green tea daily, compared with 19% of the control group.

In a multivariate analysis, current and former smokers who did not drink any green tea had almost 13 times the risk of developing lung cancer (odds ratio, 12.7; P less than .001), compared with current and former smokers who drank at least one cup of green tea daily.

In contrast, higher green tea consumption was not significantly associated with lower lung cancer risk in never-smokers.

Among green tea drinkers, those carrying the nonsusceptible genotypes IGF-1 (CA)₁₉/(CA)₁₉ and (CA)₁₉/X had a significantly lower risk of developing lung cancer, compared with those carrying the IGF-1 X/X genotype. This finding suggests that green tea may have a greater protective effect among individuals who already have reduced cancer risk because of their genetic makeup, Ms. Lin said.

“Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body,” Ms. Lin speculated.

Ms. Lin acknowledged several limitations of her study, including the fact that recall bias regarding smoking habits and green tea consumption could have been a problem.

A selection bias also may have occurred, with generally healthy people choosing to enroll in the study as controls.

Disclosures: Ms. Lin reported that she did not have any conflicts of interest.

'Green tea polyphenols may decrease lung cancer risk by decreasing IGF-1 levels in the body.'

Source MS. LIN

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.

NEW ORLEANS — Rivaroxaban, an oral anticoagulant that does not require monitoring, produced a dramatic long-term decline in recurrent venous thromboembolism in results from the EINSTEIN-Extension Study.

Patients treated with rivaroxaban had an 82% reduction in the risk of a recurrence, compared with their counterparts treated with placebo—without an increase in the risks of major bleeding or hepatotoxicity, according to a late-breaker presentation at the annual meeting of the American Society of Hematology.

Rivaroxaban has been approved in several countries, according to a statement from Bayer HealthCare, a partner in the drug's development. Despite a Food and Drug Administration advisory panel vote favoring approval in the United States, an application is on hold pending additional data.

Rivaroxaban is a direct factor Xa inhibitor, with pharmacokinetics and other characteristics that give it several advantages over vitamin K antagonists such as warfarin (Coumadin), said Dr. Harry R. Büller, a vascular medicine specialist at the Academic Medical Center in Amsterdam. Namely, this drug does not require regular laboratory monitoring, dose adjustments, or dietary restrictions.

He and his coinvestigators enrolled patients from 28 countries who had completed 6–12 months of anticoagulant therapy for a confirmed symptomatic VTE and did not have any clear indication for either continuing or discontinuing this therapy.

The patients were randomly assigned to double-blind treatment for an additional 6–12 months with a placebo or rivaroxaban at a fixed dose of 20 mg once daily. Intent-to-treat analyses were based on 602 patients assigned to rivaroxaban and 594 patients assigned to placebo. They were 58 years old on average, and 58% were male.

The mean duration of anticoagulant therapy before trial entry was about 8 months, and the mean duration of treatment on the trial was about 6 months.

Compared with their counterparts in the placebo group, patients in the rivaroxaban group were less likely to experience symptomatic recurrent VTE—the composite of recurrent deep venous thrombosis, nonfatal pulmonary embolism (PE), fatal PE, or unexplained death where PE could not be excluded (1.3% vs. 7.1%).

The difference between groups corresponded to an 82% relative reduction in risk with rivaroxaban (hazard ratio, 0.18), Dr. Büller reported. The number needed to treat to prevent one VTE event was 15.

The incidence of major bleeding was essentially the same in the two groups (0.7% with rivaroxaban and 0% with placebo). No events were fatal or located in a critical site, he noted. However, patients in the rivaroxaban group were more likely to experience clinically relevant nonmajor bleeding (for example, prolonged nosebleeds, large skin hematomas, and macroscopic hematuria): 5.4% vs. 1.2%.

In 7–8 months, the results of EINSTEIN-DVT, a head-to-head comparison between rivaroxaban and warfarin, will be available, he said.

Disclosures: Dr. Büller reported that he has received research funding from and been a consultant and advisory board member for Bayer HealthCare.

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick

SEATTLE — Successful reconstruction of facial defects created by Mohs surgery requires knowledge not only of appropriate operative techniques, but also of patients and their cancers.

Assessing a patient's skin cancer risk factors is key before repairing any Mohs defect, according to Dr. Michael L. Bentz, professor and chairman of the division of plastic and reconstructive surgery at the University of Wisconsin, Madison' “It's important to know who is more likely to come back with other skin cancers because it may change the way you stage and think about the reconstruction,” he said.

A prerequisite for successful reconstruction is ensuring that the cancer has been adequately treated, Dr. Bentz said at the annual meeting of the American Society of Plastic Surgeons.

“The first thing you are going to throw at these patients reconstructively is your best option, so you want to make sure that you have not compromised that by inadequate primary tumor treatment.” He recommended a good working relationship between the Mohs and reconstructing surgeon (if applicable), a careful review of pathology reports, and, if necessary, a reassessment of margins.

“Knowing your tumor is important,” he said. It is prudent to avoid initial definitive reconstruction of defects from dermatofibrosarcoma protuberans because of its high recurrence rate. “My goal with these is to get them grafted, let them sit a year or two, and then come back and do the definitive reconstruction,” he explained.

Maximizing the likelihood of a successful and uneventful reconstruction also requires a thorough preoperative assessment of the patient, given that most patients with skin cancer are older, with comorbidities, and that many take medications, particularly anticoagulants, that may need to be tapered.

Dr. Bentz and Dr. Frederick J. Menick, a plastic surgeon in private practice in Tucson, Ariz., went on to discuss the best way to repair defects and the best flaps to use.

▸ Pericranial flaps. These flaps are often a good option for repairing Mohs defects of the forehead, especially if bone is exposed, noted Dr. Bentz. “For patients who particularly are at risk of other skin cancers, you want to use big flaps because if you use small flaps, you will have difficulty using them again,” he said.

▸ Cheek flaps. If they are elevated to reconstruct lateral forehead defects, cheek flaps should be suspended from bone. “They weigh a fair amount and there is some tension on them,” he said. “So taking a permanent suture and suspending them to the appropriate tension point in bone, with or without drilling holes, helps avoid postoperative complications.”

Reconstructing Mohs cheek defects poses several challenges, including the limited number of lines available for hiding donor sites and the potential for distorting the eyelid. “You want to be thoughtful about how you reallocate cheek tissue, trying to hide your donor site and yet minimize the associated complications,” he said.

▸ Lip defects. Principles of cleft lip repair are often helpful in reconstructing larger Mohs defects of the lip, according to Dr. Bentz. “Don't be afraid to take the whole lip down to full-thickness fashion and put it back together,” he advised.

▸ Ear defects. Small defects can be reconstructed with full-thickness grafts, ideally taken from somewhere other than the ipsilateral retroauricular area, given the possibility of subsequent cancers of that ear requiring a retroauricular flap. Large ear defects can be reconstructed with a variety of techniques, but they all require attention to avoid constricting or accentuating the ear.

▸ Nose defects. When reconstructing small, superficial Mohs defects of the nose, Dr. Menick said that he mainly uses secondary healing, small composite grafts (for minor rim defects), and one-stage nasolabial flaps (for alar sidewall defects), along with a lot of full-thickness forehead skin grafts.

When reconstructing Mohs defects of the nose that are large (over 1.5 cm in diameter), deep, or adversely located (affecting the tip or columella), he recommended a forehead flap over the two-stage nasolabial flap. The forehead flap does not distort the nasolabial fold, is less obvious during the maturation phase, and never dies or contracts excessively.

▸ Forehead grafts. The secret to getting good results with a forehead skin graft is to not apply it right after the Mohs excision or if a Bovie has been used in the area, noted Dr. Menick. “I send the patient home, have them put Vaseline on the defect, wash it with soap and water, [and] wait about 14 days till it starts to granulate and all that burn injury is spit out,” he explained.

As to the type of forehead flap, he expressed a preference for the vertical flap, which, compared with the oblique flap, is much less likely to distort the eyebrow and leaves more options if patients need a second flap. “The vertical forehead flap is reliable, efficient, more vascular, and more widely applicable—it works like a charm,” he said.

Dr. Menick also endorsed the three-stage forehead flap over the two-stage because the added intermediate operation provides the ability to sculpt and contour the nose. Other relative merits include its provision of a thin, supple cover; a maximal blood supply; and an ideal framework. Adding an intermediate operation lengthens reconstruction from a 1-month procedure to a 2-month procedure, he acknowledged, but patients generally tolerate it, especially given the aesthetic outcome.

Disclosures: Dr. Bentz and Dr. Menick had no relevant conflicts of interest.

This patient's defect from Mohs surgery was repaired with a modified folding line technique developed by Dr. Frederick J. Menick as part of his three-stage forehead flap approach.

Source Photos courtesy Dr. Frederick J. Menick