Surgical Oncology

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

SAN DIEGO – African Americans and Asian Americans with hepatocellular carcinoma had significantly worse inpatient mortality than did white patients, and the data suggest that socioeconomic disparities in availability of health services may at least partially explain the difference.

In a multivariate analysis that also applied propensity-score matching, African American inpatients with hepatocellular carcinoma (HCC) were 30% more likely to die, compared with their white counterparts, and Asian Americans had a 60% higher inpatient mortality, compared with white Americans who had HCC.

The findings were based on data collected from 27,741 patients during 2002-2011 by the University Health Consortium, Dr. Sabeen F. Medvedev said at the the annual Digestive Disease Week.

The data analyzed by Dr. Medvedev and her associates showed a broad range of disparities by racial and ethnic groups for type of medical coverage, disease severity at the time of hospitalization, presence of metastatic disease, and whether patients received invasive treatment or liver transplantation.

"Despite increased survival due to advances in surveillance and surgical interventions for HCC, we found racial disparities exist in prognosis and disease presentation," said Dr. Medvedev of the division of gastroenterology and liver diseases at the George Washington University in Washington.

After propensity scores to mimic randomization of treatment options were used, a 60% excess mortality in African Americans, compared with whites, was reduced to a 30% excess, "indicating that the observed disparity in deaths might extend beyond disproportionate treatment allocation. The take home message is, due to their insurance and economic status and lack of access to care, African Americans did not have as many treatment options," Dr. Medvedev said. "We think that this is a delivery-of-care issue," she added in an interview.

The University Health Consortium includes 116 U.S. academic medical centers and 272 of their affiliated hospitals – about 90% of America’s nonprofit academic medical centers. HCC patients who were treated during the 9 years studied had a median age of 61 years; 54% of them were white, 16% were African American, 11% Asian, 9% Hispanic, and 10% were from other ethnic groups.

The white subgroup had the highest percentage of patients with private medical insurance (41%) and the lowest rate of Medicaid or uninsured status (15%). In contrast, among African Americans, 30% had private insurance, and 37% received Medicaid or were uninsured. Among Asian Americans, 38% had private insurance, and 30% had Medicaid or were uninsured.

An analysis of disease presentation and treatments applied showed that the African American and Asian American subgroups each had a 20% higher rate of HCC metastasis at the time of hospitalization, compared with the white subgroup.

African Americans also received significantly fewer liver transplants, resections, ablations, and transarterial chemoembolizations, compared with the white subgroup. Asian Americans received significantly fewer transarterial chemoembolizations, compared with whites, but their rates for other types of treatments were similar to the rates seen in the white subgroup. The only treatment received significantly less often by Hispanic patients, compared with whites, was resection.

Dr. Medvedev said that she had no disclosures.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Amidst growing controversy over prostate-specific antigen screening, a new analysis raises the possibility that more men would be diagnosed with advanced prostate cancer without early testing.

The incidence of men presenting with prostate cancer that has already metastasized is three times lower than would be expected, if incidence figures from the pre-PSA era were extrapolated to today’s U.S. population, according to the report published online July 30 in Cancer.

Based on data for diagnoses made from 1983 to 1985, clinicians today could expect to see approximately 25,000 cases of prostate cancer that has already metastasized at presentation. But the actual number of such cases is three times lower, at approximately 8,000, said Emil N. Scosyrev, Ph.D., of the department of urology, University of Rochester (N.Y.) Medical Center, and his associates.

It would be erroneous to assume a causal relationship from these observational data, however, or to conclude that PSA testing alone contributed to this reduction. Temporal changes in other factors that influence prostate cancer almost certainly have contributed to the decrease, the investigators noted.

"Our current findings must be viewed primarily as a description of observed time trends rather than as definitive tests of causal hypotheses about screening," they said.

Dr. Scosyrev and his colleagues assessed age- and race-specific annual rates of presenting with metastatic prostate cancer from 1983 to 2008, using data from Surveillance, Epidemiology, and End Results (SEER) Program registries in San Francisco, Connecticut, Detroit, Hawaii, Iowa, New Mexico, Seattle, Utah, and Atlanta. The Food and Drug Administration approved PSA testing for clinical use in 1986, so the researchers compared prostate cancer data in the pre-PSA era (1983-1985) to that in the PSA era (1986-2008).

When men of all ages and races were considered together, 2,277 men in the SEER registries would be expected to present with metastatic prostate cancer in 2008, the most recent year for which data are available. However, the actual number who presented with metastatic prostate cancer that year was only 739 in the SEER registries.

These registries are thought to capture approximately 25% of all cases of prostate cancer in the U.S. each year. When the study figures are extrapolated to the entire U.S. population in 2008, only about 8,000 cases actually occurred when about 25,000 would have been expected to occur. This suggests that 17,000 cases of metastatic prostate cancer at presentation were prevented in 2008, the investigators said (Cancer 2012 July 30 [doi:1002/cncr.27503]).

It is important to note that other factors besides PSA testing also changed during this time period, which could not be accounted for in this observational study, the authors noted.

For example, obesity may be associated with an increased risk of prostate cancer, and the prevalence of obesity has certainly increased since 1983. "Hence, if obesity had a major influence on the incidence of presenting with [metastatic prostate cancer] during the study period, then the true benefit of screening may be underestimated in our study," Dr. Scosyrev and his associates said.

Medical imaging techniques also have improved over time, however, enabling earlier diagnosis of prostate cancer in more recent years.

"In particular, in the pre-PSA era, CT and bone scans were not as widespread (or of the same quality) as they are today, MRI and PET-CT were not available, and metastatic prostate cancer often was diagnosed because of symptomatic progression of metastatic lesions. In contrast, in the modern PSA era, metastatic prostate cancer is often diagnosed on staging imaging for high-risk disease," the authors added.

Another issue that must be considered, they said, "is the potential lead-time effect resulting from screening." To that end they offered the hypothetical case of a man who develops organ-confined prostate cancer at 70 years of age, micrometastates at 75, and overt metastatic disease at 80, and then dies of prostate cancer when he is 82 years of age.

"If this man were screened between ages 70 and 75 years, then his prostate cancer potentially could be cured. Conversely, screening between ages 75 and 80 years would result in an earlier diagnosis, but not in a cure," they wrote, going on to note substantial stage shifts in newly diagnosed prostate cancer after mass screening programs were introduced.

Because metastatic prostate cancer is highly symptomatic and "rapidly fatal," the authors said they "believe that many men with this disease would likely benefit from earlier diagnosis, either in terms of improved survival or at least from the palliative perspective (e.g., prevention or delay of skeletal complications)."

It also is important to remember that PSA screening has led to overdiagnosis and overtreatment of nonaggressive prostate cancer, another issue that could not be addressed in this study, they added.

"In particular, we could not determine the number of men who would need to undergo a biopsy for an elevated PSA and [be] treated for screen-detected prostate cancer to prevent one case of presenting with metastatic disease. This must be recognized as a limitation of the current study," the researchers said. Likewise, they could not investigate the optimal age to start or to stop screening.

This study was supported by the Ashley Family Foundation. No financial disclosures were reported.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

Compared with observation, radical prostatectomy failed to reduce either disease-specific or all-cause mortality significantly among men with clinically localized prostate cancer that was diagnosed early in the era of PSA testing, according to a report published online July 18 in the New England Journal of Medicine.

The lack of benefit from prostatectomy was "particularly robust" among men with a PSA value of 10 ng/mL or less, and in those with low-risk tumors. "Our findings support observation for men with localized prostate cancer, especially those who have a low PSA value and those who have low-risk disease," said Dr. Timothy J. Wilt and his associates in the PIVOT (Prostate Cancer Intervention Versus Observation) study.

PIVOT was a randomized trial designed specifically to compare outcomes after radical prostatectomy with those after observation. It involved 731 patients who were diagnosed as having clinically localized prostate cancer in 1994-2002, early in the PSA-testing era.

The participants were treated at 44 Veterans Affairs centers and eight National Cancer Institute sites across the country. Investigators had planned to randomize 2,000 men, but scaled down the trial because of "recruitment difficulties." In all, 364 men were randomly assigned to radical prostatectomy using a technique chosen at the surgeon’s discretion, and 367 were assigned to observation.

Of these, 281 in the surgery group and 36 in the observation group underwent radical prostatectomy, whereas 53 and 292, respectively, underwent observation. Other interventions included external-beam radiotherapy and brachytherapy. Any additional interventions were decided upon by the patient and his physician.

Investigators followed participants every 6 months for 8-15 years. Patients (mean age, 67 years) underwent bone scans every 5 years. Approximately one-third of the patients were black, and 85% were fully independent in performing the activities of daily living.

Some 40% of the men were found to have low-risk tumors, 34% had intermediate-risk, 21% had high-risk, and 5% had unknown risk because of missing data. Findings were reported on an intention-to-treat basis.

During a median follow-up of 10 years, 47.0% of the surgical group and 49.9% of the observation group died from any cause, a difference that was not significant. Median survival was 13.0 years with radical prostatectomy and 12.4 years with observation, also an insignificant difference.

"The absolute reduction in mortality with radical prostatectomy was not significant at any interval and declined over time, from 4.6 percentage points at 4 years to 2.9 percentage points at 12 years," the investigators said (New Engl. J. Med. 2012 July 19 [doi:10.1056/NEJMoa1113162]).

This trend suggests that longer follow-up would not alter the results, added Dr. Wilt of the Center for Chronic Disease Outcomes Research of the Minneapolis VA Health Care System and his coauthors.

The results were similar with prostate cancer–specific mortality.

Death that was definitely attributable to prostate cancer or its treatment occurred in 4.4% of the men in the surgical group and 4.9% of those in the observation group, a nonsignificant difference. Disease-specific mortality was identical between the two groups at 4 years and was not significantly different at 12 years.

Subgroup analyses showed that radical prostatectomy did not improve all-cause mortality according to patient age, race, performance status, or comorbidities, nor did it vary by tumor score on the Gleason histologic scale. However, the surgery was associated with a slight (13.2%) decline in all-cause mortality in the subgroup of men who had PSA values greater than 10 ng/mL.

The finding of no mortality benefit was particularly strong among men with low-risk cancers (defined as those with PSA values of 10 ng/mL or lower, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor). In this subgroup, prostatectomy was actually associated with a nonsignificant 15% increase in mortality, Dr. Wilt and his associates said.

Perioperative complications, including one death, developed in 21.4% of men in the radical prostatectomy group. Wound infection was the most common complication, occurring in 4.3% of the men. Other problems included urinary tract infection, bleeding requiring transfusion, and the need for urinary catheterization for more than 30 days.

At 2 years, urinary incontinence and erectile dysfunction were more common among patients in the surgical group than in those in the observation group.

This study was supported by the Department of Veterans Affairs, the National Cancer Institute, and the Agency for Healthcare Quality and Research. Dr. Wilt reported no financial conflicts of interest, and his associates reported ties to numerous industry sources.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

All newly diagnosed melanoma patients with tumors of intermediate thickness – defined as those with a Breslow thickness of between 1 and 4 mm – should undergo sentinel lymph node biopsy, according to a new guideline from two professional societies.

The guideline, issued jointly July 9 by the American Society of Clinical Oncology and the Society of Surgical Oncology, also advises that while the use of sentinel lymph node biopsy (SLNB) in people with thicker or thinner melanomas remains contentious, both categories of patients could benefit from SLNB in some circumstances.

All melanoma patients with a positive SLNB, the guideline says, should be treated with completion lymph node dissection (CLND), the current standard of care, although, the authors noted, it is not yet known whether CLND after a positive SLN biopsy improves 10-year overall survival. This is the subject of a large, ongoing randomized trial, the Multicenter Selective Lymphadenectomy Trial II (MSLT-11).

The guideline’s authors, led by Dr. Sandra L. Wong of the University of Michigan, Ann Arbor, and Dr. Gary H. Lyman of Duke University, Durham, N.C., aimed to use the most current evidence to clarify both the indications for sentinel node biopsy and the role of completion biopsy in people with melanomas.

"It is critically important to identify those patients for whom the expected benefits of resecting regional lymph nodes outweigh the risks of surgical morbidity," they wrote in their analysis.

To this end, Dr. Wong, Dr. Lyman, and 12 other expert panel members undertook a broad literature search and identified 73 studies (most of them observational in design) that met the criteria for inclusion in their meta-analysis. Some 25,000 patients were enrolled in the included studies.

The authors found that while robust evidence supports routine use of sentinel lymph node biopsy (SLNB) in intermediate melanomas, there is also some evidence to support the procedure in patients with thin melanomas (less than 1 mm) when certain other risk factors are present, and in patients with thick melanomas (greater than 4 mm).

For people with melanomas of less than 1 mm Breslow thickness and one or more risk factors such as tumor ulceration or a mitotic rate of 1/mm² or greater, they wrote, "the benefits of pathologic staging may outweigh the potential risks of the procedure," particularly in the subgroup of patients with melanomas ranging from 0.75 mm to 0.99 mm.

Patients with melanomas of 4 mm or greater may also benefit, the guideline says. "Conventional wisdom asserts that patients with thick melanomas have a high risk of systemic disease at the time of diagnosis and that no survival benefit can be derived from removal of regional lymph nodes," the authors wrote.

"However, among patients without distant disease, it can be argued that those with thick melanomas have indications for SLN biopsy similar to those of patients with intermediate-thickness melanomas and derive the same benefits from SLN biopsy as a pathologic staging procedure. One of the main advantages of SLN biopsy in patients with thick melanomas is better regional disease control."

The guideline reiterates that CLND should remain the standard of care for patients with tumor-positive SLNs, even absent survival data from the ongoing MSLT-II trial. The authors cited in support of this evidence from studies that saw nodal recurrence after CLND of between 4.2% and 4.9%. By contrast, as Dr. Wong and colleagues reported in an earlier study, patients in whom CLND was not performed saw a 15% rate of regional nodal recurrence as a site of first metastasis and 41% overall regional nodal recurrence rate (Ann Surg Oncol 2006 13:302-309).

"Until final results of MSLT-II are available, we will not be able to determine, with higher-level evidence, the impact of CLND on regional disease control. Until that time, the best available evidence suggests that CLND is effective at achieving regional disease control in the majority of patients with positive SLNs," the authors wrote.

The guideline was commissioned by ASCO and SSO. The authors disclosed no conflicts of interest.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

SAN DIEGO – Removing 12-20 lymph nodes for node-negative patients and 8-25 lymph nodes for node-positive patients confers a survival advantage in esophageal cancer, according to a data analysis of more than 2,100 patients.

"The maximum survival advantage was seen when a minimum of 15 lymph nodes were removed in node-negative patients and 20 in the node-positive patients," Dr. Kenneth L. Meredith said.

The Surveillance Epidemiology and End Results (SEER) analysis also revealed that the benefit of adjuvant radiation therapy on survival in esophageal cancer is limited to those with node-positive disease, suggesting that the management of esophageal cancer remains a work in progress, Dr. Meredith said at the annual Digestive Disease Week.

"Currently the treatment for these patients includes esophagectomy with or without neoadjuvant therapy," Dr. Meredith said. "There are many approaches to esophagectomy, and there are a multitude of recommendations for nodal clearance of these patients. If you look at single and multi-institutional database reviews, their recommendation for nodal harvest is anywhere from 6 to 40. We decided to perform a more recent analysis of the SEER database."

Dr. Meredith, chief of esophagogastric oncology and director of esophageal research at Moffitt Cancer Center, Tampa, Fla., and his associates queried the database for patients who underwent esophagectomy for cancer between 2004 and 2008. They identified 2,109 patients and categorized them by nodal harvest: greater than or less than 5, 8, 10, 12, 15, 20, 25, and 30.

Of the 2,109 patients, 467 were treated with adjuvant radiation and 1,642 were not. Patients treated with neoadjuvant radiation were excluded from the analysis, as were those who had histologic subtypes of cancer that were not adenocarcinoma or squamous cell carcinoma.

Dr. Meredith reported that use of adjuvant radiation was associated with decreased survival in patients with stage I disease (hazard ratio, 2.73; P less than .0001), no benefit in stage II (P = .075), increased survival in stage III (HR, 0.71; P = .005), and no benefit in stage IV (P = .913).

The median number of lymph nodes retracted from all patients was nine, "which is a little low by most standards," said Dr. Meredith.

Multivariate analysis revealed that among node-positive patients, the median survival with and without adjuvant radiation was 23 months and 20 months, respectively, and the 3-year survival rates were 34% and 26.7%, respectively (P = .023). Among node-negative patients, the 3-year survival with and without adjuvant radiation was 48.8% and 68.8%, respectively.

"The only lymph node cutoff we found was significant for all patients was that if you had more than five lymph nodes resected," Dr. Meredith said. "As you [removed more], lymph node harvesting did not translate into a survival benefit. However, when you subclassified whether they were node negative or node positive, a cutoff of 12 and 15, respectively, did translate into a survival benefit. In node-positive patients, those who had more than 8, 10, 12, 15, and 20 lymph nodes did translate into a survival benefit." He added that with regard to extended lymphadenectomy, or more than 20 lymph nodes resected in either cohort, no additional survival benefit was seen.

Dr. Meredith acknowledged certain limitations of the study, including its retrospective design and the fact that SEER lacks information on the nutritional status and performance status of patients. "There is also no information on margin status, chemotherapy, radiation dose, field design, and treatment technique," he said.

Dr. Meredith said that he had no relevant financial conflicts to disclose.

CHICAGO – The diagnostic accuracy of FDG-PET in lung cancer performed below previous reports and varied widely among U.S. centers in a secondary analysis of a large phase III clinical trial.

"FDG-PET performed poorly for diagnosing non–small cell lung cancer in a national sample of clinical stage 1 patients," Dr. Eric L. Grogan said at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

The current National Comprehensive Cancer Network guidelines recommend fluorodeoxyglucose positron emission tomography (FDG-PET) for the diagnosis of NSCLC based on studies showing a high degree of accuracy for this diagnostic tool, notably a sensitivity of 94% and a median specificity of 83% in a meta-analysis of 40 studies (JAMA 2001;285:914-24).

Others have reported, however, that FDG-PET performs poorly at single institutions in regions of endemic fungal lung diseases (Ann. Thor. Surg. 2011;92:428-32 and Lung Cancer 2002;36:297-301), observed Dr. Grogan, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Among 682 patients in the American College of Surgeons Oncology Group (ACOSOG) Z4031 trial, the overall accuracy of FDG-PET was 73%, the sensitivity 82%, and the specificity only 31%.

The series is the largest to date evaluating the accuracy of FDG-PET in patients with known or suspected clinical stage 1 NSCLC. In addition, it is generalizable to clinical practice because multiple FDG-PET scanners were used and the scans were performed in community and academic centers and interpreted by multiple radiologists, Dr. Grogan said.

"Results of PET scans in this population should be interpreted cautiously, and reasons for the poor test performance should be explored in other studies," he said.

Discussant Dr. Tetsuya Mitsudomi, chief of thoracic surgery at Aichi Cancer Center Hospital in Nagoya, Japan, said FDG-PET shows reasonable sensitivity, but very low specificity compared with previous studies.

"I think this reflects the real world," he said. "So, the lung cancer diagnosis cannot be made on the basis of PET positivity alone."

Investigators at 51 sites in 39 cities enrolled 969 patients with known or clinically suspicious stage 1 lesions between 2004 and 2006 to evaluate the value of proteomic analysis in diagnosing NSCLC (the results were presented at ASCO 2010). FDG-PET scans were available for 682 patients. All underwent surgical resection. Analyses were performed for all patients and for sites with more than 25 patients.

PET avidity was determined by the radiologist’s description of lesion activity or by the reported maximum standard uptake value (SUV). Avidity was classified in four categories: category 1 was no avidity/not cancer (SUV = 0), category 2 was low avidity/not likely cancer (SUV 0 to less than 2.5), category 3 was avidity/possibly cancer (SUV 2.5 to less than 5.0), and category 4 was high avidity/likely cancer (SUV 5.0 or more).

Among the 682 patients, there were 566 cancers and 116 benign cases. In all, 82% of the cancerous lesions were PET avid, and "surprisingly, 69% of the benign lesions were avid," Dr. Grogan said.

Patients with cancer were significantly older (67 vs. 61 years; P less than .001) and had larger lesions (26 mm vs. 20 mm; P less than .001).

The positive predictive value of FDG-PET was 85% and negative predictive value 26%. This translates into 80 false positives and 101 false negatives. The majority of false positives were granulomas (69%), he observed. Eleven of the false negatives were 10 mm or less.

Not surprising, FDG-PET accuracy improved with lesion size, Dr. Grogan said. The accuracy was less than 50% for lesions less than 20 mm, but greater than 80% for lesions larger than 30 mm. "Above 30 mm, the accuracy did not seem to improve," he observed.

In the eight cities with more than 25 patients, the sensitivity varied significantly, from a low of 67% in Los Angeles to a high of 91% in Durham, N.C. (P = .03), Dr. Grogan said, without explanation. Specificity ranged from 15% in Birmingham, Ala., to 46% in Philadelphia, but this did not reach statistical significance because of the small number of benign cases at each institution (P = .72).

Dr. Mitsudomi said he could not explain the reason for the heterogeneity, especially in terms of the specificity, between centers.

"It’s not possible to remove all the false positives if you use FDG, but newer tracers are being developed and they may increase the specificity rate," he added.

Dr. Grogan reported no disclosures. Dr. Mitsudomi reported having a consulting/advisory role with Boehringer Ingelheim, Kyowa Hakko Kirin, Lilly, and Pfizer, and receiving honoraria from AstraZeneca, Chugai Pharma, Lilly, and Roche.

CHICAGO – The diagnostic accuracy of FDG-PET in lung cancer performed below previous reports and varied widely among U.S. centers in a secondary analysis of a large phase III clinical trial.

"FDG-PET performed poorly for diagnosing non–small cell lung cancer in a national sample of clinical stage 1 patients," Dr. Eric L. Grogan said at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

The current National Comprehensive Cancer Network guidelines recommend fluorodeoxyglucose positron emission tomography (FDG-PET) for the diagnosis of NSCLC based on studies showing a high degree of accuracy for this diagnostic tool, notably a sensitivity of 94% and a median specificity of 83% in a meta-analysis of 40 studies (JAMA 2001;285:914-24).

Others have reported, however, that FDG-PET performs poorly at single institutions in regions of endemic fungal lung diseases (Ann. Thor. Surg. 2011;92:428-32 and Lung Cancer 2002;36:297-301), observed Dr. Grogan, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Among 682 patients in the American College of Surgeons Oncology Group (ACOSOG) Z4031 trial, the overall accuracy of FDG-PET was 73%, the sensitivity 82%, and the specificity only 31%.

The series is the largest to date evaluating the accuracy of FDG-PET in patients with known or suspected clinical stage 1 NSCLC. In addition, it is generalizable to clinical practice because multiple FDG-PET scanners were used and the scans were performed in community and academic centers and interpreted by multiple radiologists, Dr. Grogan said.

"Results of PET scans in this population should be interpreted cautiously, and reasons for the poor test performance should be explored in other studies," he said.

Discussant Dr. Tetsuya Mitsudomi, chief of thoracic surgery at Aichi Cancer Center Hospital in Nagoya, Japan, said FDG-PET shows reasonable sensitivity, but very low specificity compared with previous studies.

"I think this reflects the real world," he said. "So, the lung cancer diagnosis cannot be made on the basis of PET positivity alone."

Investigators at 51 sites in 39 cities enrolled 969 patients with known or clinically suspicious stage 1 lesions between 2004 and 2006 to evaluate the value of proteomic analysis in diagnosing NSCLC (the results were presented at ASCO 2010). FDG-PET scans were available for 682 patients. All underwent surgical resection. Analyses were performed for all patients and for sites with more than 25 patients.

PET avidity was determined by the radiologist’s description of lesion activity or by the reported maximum standard uptake value (SUV). Avidity was classified in four categories: category 1 was no avidity/not cancer (SUV = 0), category 2 was low avidity/not likely cancer (SUV 0 to less than 2.5), category 3 was avidity/possibly cancer (SUV 2.5 to less than 5.0), and category 4 was high avidity/likely cancer (SUV 5.0 or more).

Among the 682 patients, there were 566 cancers and 116 benign cases. In all, 82% of the cancerous lesions were PET avid, and "surprisingly, 69% of the benign lesions were avid," Dr. Grogan said.

Patients with cancer were significantly older (67 vs. 61 years; P less than .001) and had larger lesions (26 mm vs. 20 mm; P less than .001).

The positive predictive value of FDG-PET was 85% and negative predictive value 26%. This translates into 80 false positives and 101 false negatives. The majority of false positives were granulomas (69%), he observed. Eleven of the false negatives were 10 mm or less.

Not surprising, FDG-PET accuracy improved with lesion size, Dr. Grogan said. The accuracy was less than 50% for lesions less than 20 mm, but greater than 80% for lesions larger than 30 mm. "Above 30 mm, the accuracy did not seem to improve," he observed.

In the eight cities with more than 25 patients, the sensitivity varied significantly, from a low of 67% in Los Angeles to a high of 91% in Durham, N.C. (P = .03), Dr. Grogan said, without explanation. Specificity ranged from 15% in Birmingham, Ala., to 46% in Philadelphia, but this did not reach statistical significance because of the small number of benign cases at each institution (P = .72).

Dr. Mitsudomi said he could not explain the reason for the heterogeneity, especially in terms of the specificity, between centers.

"It’s not possible to remove all the false positives if you use FDG, but newer tracers are being developed and they may increase the specificity rate," he added.

Dr. Grogan reported no disclosures. Dr. Mitsudomi reported having a consulting/advisory role with Boehringer Ingelheim, Kyowa Hakko Kirin, Lilly, and Pfizer, and receiving honoraria from AstraZeneca, Chugai Pharma, Lilly, and Roche.

CHICAGO – The diagnostic accuracy of FDG-PET in lung cancer performed below previous reports and varied widely among U.S. centers in a secondary analysis of a large phase III clinical trial.

"FDG-PET performed poorly for diagnosing non–small cell lung cancer in a national sample of clinical stage 1 patients," Dr. Eric L. Grogan said at the annual meeting of the American Society of Clinical Oncology.

Patrice Wendling/IMNG Medical Media

The current National Comprehensive Cancer Network guidelines recommend fluorodeoxyglucose positron emission tomography (FDG-PET) for the diagnosis of NSCLC based on studies showing a high degree of accuracy for this diagnostic tool, notably a sensitivity of 94% and a median specificity of 83% in a meta-analysis of 40 studies (JAMA 2001;285:914-24).

Others have reported, however, that FDG-PET performs poorly at single institutions in regions of endemic fungal lung diseases (Ann. Thor. Surg. 2011;92:428-32 and Lung Cancer 2002;36:297-301), observed Dr. Grogan, of Vanderbilt-Ingram Cancer Center in Nashville, Tenn.

Among 682 patients in the American College of Surgeons Oncology Group (ACOSOG) Z4031 trial, the overall accuracy of FDG-PET was 73%, the sensitivity 82%, and the specificity only 31%.

The series is the largest to date evaluating the accuracy of FDG-PET in patients with known or suspected clinical stage 1 NSCLC. In addition, it is generalizable to clinical practice because multiple FDG-PET scanners were used and the scans were performed in community and academic centers and interpreted by multiple radiologists, Dr. Grogan said.

"Results of PET scans in this population should be interpreted cautiously, and reasons for the poor test performance should be explored in other studies," he said.

Discussant Dr. Tetsuya Mitsudomi, chief of thoracic surgery at Aichi Cancer Center Hospital in Nagoya, Japan, said FDG-PET shows reasonable sensitivity, but very low specificity compared with previous studies.

"I think this reflects the real world," he said. "So, the lung cancer diagnosis cannot be made on the basis of PET positivity alone."

Investigators at 51 sites in 39 cities enrolled 969 patients with known or clinically suspicious stage 1 lesions between 2004 and 2006 to evaluate the value of proteomic analysis in diagnosing NSCLC (the results were presented at ASCO 2010). FDG-PET scans were available for 682 patients. All underwent surgical resection. Analyses were performed for all patients and for sites with more than 25 patients.

PET avidity was determined by the radiologist’s description of lesion activity or by the reported maximum standard uptake value (SUV). Avidity was classified in four categories: category 1 was no avidity/not cancer (SUV = 0), category 2 was low avidity/not likely cancer (SUV 0 to less than 2.5), category 3 was avidity/possibly cancer (SUV 2.5 to less than 5.0), and category 4 was high avidity/likely cancer (SUV 5.0 or more).

Among the 682 patients, there were 566 cancers and 116 benign cases. In all, 82% of the cancerous lesions were PET avid, and "surprisingly, 69% of the benign lesions were avid," Dr. Grogan said.

Patients with cancer were significantly older (67 vs. 61 years; P less than .001) and had larger lesions (26 mm vs. 20 mm; P less than .001).

The positive predictive value of FDG-PET was 85% and negative predictive value 26%. This translates into 80 false positives and 101 false negatives. The majority of false positives were granulomas (69%), he observed. Eleven of the false negatives were 10 mm or less.

Not surprising, FDG-PET accuracy improved with lesion size, Dr. Grogan said. The accuracy was less than 50% for lesions less than 20 mm, but greater than 80% for lesions larger than 30 mm. "Above 30 mm, the accuracy did not seem to improve," he observed.

In the eight cities with more than 25 patients, the sensitivity varied significantly, from a low of 67% in Los Angeles to a high of 91% in Durham, N.C. (P = .03), Dr. Grogan said, without explanation. Specificity ranged from 15% in Birmingham, Ala., to 46% in Philadelphia, but this did not reach statistical significance because of the small number of benign cases at each institution (P = .72).

Dr. Mitsudomi said he could not explain the reason for the heterogeneity, especially in terms of the specificity, between centers.

"It’s not possible to remove all the false positives if you use FDG, but newer tracers are being developed and they may increase the specificity rate," he added.

Dr. Grogan reported no disclosures. Dr. Mitsudomi reported having a consulting/advisory role with Boehringer Ingelheim, Kyowa Hakko Kirin, Lilly, and Pfizer, and receiving honoraria from AstraZeneca, Chugai Pharma, Lilly, and Roche.

BARCELONA – Adding cetuximab to standard adjuvant chemotherapy for resected stage III colon cancer does not benefit patients, according to interim results from a large, phase III, European trial.

In the multicenter randomized study, the combination of FOLFOX4 plus cetuximab (Erbitux) did not prolong disease-free survival compared with FOLFOX4 alone, even in patients with KRAS wild-type tumors. The disease-free survival rate at 3 years was 75.1% in 791 patients given FOLFOX4 with cetuximab and 78% in 811 patients in the control group.

These preliminary results of the PETACC8 cooperative group trial were presented for the first time on June 29 at the European Society for Medical Oncology’s (ESMO’s) 14th World Congress on Gastrointestinal Cancer. The disappointing outcome follows a negative report from the North Central Cancer Treatment Group (NCCTG) N0147 trial, which also looked at the benefit of cetuximab added to FOLFOX in the adjuvant colorectal cancer setting (JAMA 2012;13:1383-93).

The FOLFOX regimen, a combination of oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), has been the standard of care since the MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) reported its results (Cancer Treat. Rev. 2004;30:711-13), said Dr. Julien Taieb, who presented the current study.

The MOSAIC benefit was confirmed by the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial, with attainable 3-year disease-free survival rates of around 70% (J. Clin. Oncol. 2007;25:2198-204), noted Dr. Taieb of Georges Pompidou European Hospital in Paris.

"When [molecularly] targeted agents came for colorectal cancer, of course everyone was wondering if they were [effective] in the adjuvant setting," he said.

In addition to the U.S. trial of cetuximab, two other trials of the antiangiogenesis inhibitor bevacizumab (Avastin) – the AVANT and NSABP C-08 trials – have also failed to show a benefit in disease-free survival at 3 years in this clinical setting, however.

"It is a little bit disappointing," coinvestigator Dr. Michel Ducreux, head of the gastrointestinal unit at the Institût Gustave Roussy in Villejuif, France, said in an interview.

The current study specifically looked at patients with the KRAS wild type, Dr. Ducreux noted. These are patients who should, in theory, still be able to respond to an epidermal growth factor receptor (EGFR) inhibitor, such as cetuximab. It has been known since 2008 that patients with mutated KRAS tumors do not respond to EGFR inhibition.

"The main point now is to go into the details of the biological samples in that study," Dr. Ducreux suggested, to determine whether any subpopulations of patients might benefit, and if not, to find out why.

The PETACC8 trial was originally designed to compare 12 cycles of FOLFOX4 versus FOLFOX4 plus additional cetuximab. The trial protocol was amended in 2008, when it became possible to select patients for cetuximab therapy based on their KRAS status.

Of the 2,559 patients recruited into the trial at 340 sites in Europe, nearly two-thirds had KRAS wild-type disease and 1,602 of them were randomized. The mean age of the KRAS wild-type patients was 58 years. All had completely resected, pathologically confirmed stage III colon cancer, a good WHO performance status, and a life expectancy of at least 5 years at enrollment.

The primary end point was disease-free survival, defined as the period before recurrence, second colorectal cancer, or death. However, the hazard ratio for disease-free-survival was 1.047 (P = .66). The differences in rates at 1, 2, and 4 years were also not statistically significant for FOLFOX4 with cetuximab (90.4%, 79.7%, and 72.4%, respectively) or without (92%, 81.5%, and 75.5%).

"Disease-free survival was really excellent compared to what has been reported with FOLFOX4 in the literature," Dr. Taieb said.

He noted that while cetuximab appeared to give no extra benefit, there might be subgroup of KRAS wild-type patients that could gain some benefit. There were trends for women; patients 70 years and older; and groups with a WHO performance status of 0, pT1-3 and pN1 tumors, and no bowel obstruction or perforation to do a little better.

Tolerability was as might be expected for the agents tested, but with a higher chance of hypersensitivity reactions, acnelike rash, diarrhea, and mucositis in the cetuximab-containing arm. There was an overall 15% difference in the occurrence of grade 3 and 4 adverse events between the FOLFOX4 with cetuximab and FOLFOX4 arms (80.9% vs. 66.2%, respectively).

"The probability for a positive result in the final analysis is very low," Dr. Taieb said, suggesting that "cetuximab might have a different form of activity on micrometastatic disease compared to that observed in stage IV disease."

Merck Serono and Sanofi-Aventis provided grants to fund the trial. Dr. Taieb has received consultancy and advisory board honoraria from Merck. Dr. Ducreux has received consultancy fees from Merck Serono and Roche.

BARCELONA – Adding cetuximab to standard adjuvant chemotherapy for resected stage III colon cancer does not benefit patients, according to interim results from a large, phase III, European trial.

In the multicenter randomized study, the combination of FOLFOX4 plus cetuximab (Erbitux) did not prolong disease-free survival compared with FOLFOX4 alone, even in patients with KRAS wild-type tumors. The disease-free survival rate at 3 years was 75.1% in 791 patients given FOLFOX4 with cetuximab and 78% in 811 patients in the control group.

These preliminary results of the PETACC8 cooperative group trial were presented for the first time on June 29 at the European Society for Medical Oncology’s (ESMO’s) 14th World Congress on Gastrointestinal Cancer. The disappointing outcome follows a negative report from the North Central Cancer Treatment Group (NCCTG) N0147 trial, which also looked at the benefit of cetuximab added to FOLFOX in the adjuvant colorectal cancer setting (JAMA 2012;13:1383-93).

The FOLFOX regimen, a combination of oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), has been the standard of care since the MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) reported its results (Cancer Treat. Rev. 2004;30:711-13), said Dr. Julien Taieb, who presented the current study.

The MOSAIC benefit was confirmed by the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial, with attainable 3-year disease-free survival rates of around 70% (J. Clin. Oncol. 2007;25:2198-204), noted Dr. Taieb of Georges Pompidou European Hospital in Paris.

"When [molecularly] targeted agents came for colorectal cancer, of course everyone was wondering if they were [effective] in the adjuvant setting," he said.

In addition to the U.S. trial of cetuximab, two other trials of the antiangiogenesis inhibitor bevacizumab (Avastin) – the AVANT and NSABP C-08 trials – have also failed to show a benefit in disease-free survival at 3 years in this clinical setting, however.

"It is a little bit disappointing," coinvestigator Dr. Michel Ducreux, head of the gastrointestinal unit at the Institût Gustave Roussy in Villejuif, France, said in an interview.

The current study specifically looked at patients with the KRAS wild type, Dr. Ducreux noted. These are patients who should, in theory, still be able to respond to an epidermal growth factor receptor (EGFR) inhibitor, such as cetuximab. It has been known since 2008 that patients with mutated KRAS tumors do not respond to EGFR inhibition.

"The main point now is to go into the details of the biological samples in that study," Dr. Ducreux suggested, to determine whether any subpopulations of patients might benefit, and if not, to find out why.

The PETACC8 trial was originally designed to compare 12 cycles of FOLFOX4 versus FOLFOX4 plus additional cetuximab. The trial protocol was amended in 2008, when it became possible to select patients for cetuximab therapy based on their KRAS status.

Of the 2,559 patients recruited into the trial at 340 sites in Europe, nearly two-thirds had KRAS wild-type disease and 1,602 of them were randomized. The mean age of the KRAS wild-type patients was 58 years. All had completely resected, pathologically confirmed stage III colon cancer, a good WHO performance status, and a life expectancy of at least 5 years at enrollment.

The primary end point was disease-free survival, defined as the period before recurrence, second colorectal cancer, or death. However, the hazard ratio for disease-free-survival was 1.047 (P = .66). The differences in rates at 1, 2, and 4 years were also not statistically significant for FOLFOX4 with cetuximab (90.4%, 79.7%, and 72.4%, respectively) or without (92%, 81.5%, and 75.5%).

"Disease-free survival was really excellent compared to what has been reported with FOLFOX4 in the literature," Dr. Taieb said.

He noted that while cetuximab appeared to give no extra benefit, there might be subgroup of KRAS wild-type patients that could gain some benefit. There were trends for women; patients 70 years and older; and groups with a WHO performance status of 0, pT1-3 and pN1 tumors, and no bowel obstruction or perforation to do a little better.

Tolerability was as might be expected for the agents tested, but with a higher chance of hypersensitivity reactions, acnelike rash, diarrhea, and mucositis in the cetuximab-containing arm. There was an overall 15% difference in the occurrence of grade 3 and 4 adverse events between the FOLFOX4 with cetuximab and FOLFOX4 arms (80.9% vs. 66.2%, respectively).

"The probability for a positive result in the final analysis is very low," Dr. Taieb said, suggesting that "cetuximab might have a different form of activity on micrometastatic disease compared to that observed in stage IV disease."

Merck Serono and Sanofi-Aventis provided grants to fund the trial. Dr. Taieb has received consultancy and advisory board honoraria from Merck. Dr. Ducreux has received consultancy fees from Merck Serono and Roche.

BARCELONA – Adding cetuximab to standard adjuvant chemotherapy for resected stage III colon cancer does not benefit patients, according to interim results from a large, phase III, European trial.

In the multicenter randomized study, the combination of FOLFOX4 plus cetuximab (Erbitux) did not prolong disease-free survival compared with FOLFOX4 alone, even in patients with KRAS wild-type tumors. The disease-free survival rate at 3 years was 75.1% in 791 patients given FOLFOX4 with cetuximab and 78% in 811 patients in the control group.

These preliminary results of the PETACC8 cooperative group trial were presented for the first time on June 29 at the European Society for Medical Oncology’s (ESMO’s) 14th World Congress on Gastrointestinal Cancer. The disappointing outcome follows a negative report from the North Central Cancer Treatment Group (NCCTG) N0147 trial, which also looked at the benefit of cetuximab added to FOLFOX in the adjuvant colorectal cancer setting (JAMA 2012;13:1383-93).

The FOLFOX regimen, a combination of oxaliplatin, leucovorin, and 5-fluorouracil (5-FU), has been the standard of care since the MOSAIC trial (Multicenter International Study of Oxaliplatin/5FU-LV in the Adjuvant Treatment of Colon Cancer) reported its results (Cancer Treat. Rev. 2004;30:711-13), said Dr. Julien Taieb, who presented the current study.

The MOSAIC benefit was confirmed by the National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07 trial, with attainable 3-year disease-free survival rates of around 70% (J. Clin. Oncol. 2007;25:2198-204), noted Dr. Taieb of Georges Pompidou European Hospital in Paris.

"When [molecularly] targeted agents came for colorectal cancer, of course everyone was wondering if they were [effective] in the adjuvant setting," he said.

In addition to the U.S. trial of cetuximab, two other trials of the antiangiogenesis inhibitor bevacizumab (Avastin) – the AVANT and NSABP C-08 trials – have also failed to show a benefit in disease-free survival at 3 years in this clinical setting, however.

"It is a little bit disappointing," coinvestigator Dr. Michel Ducreux, head of the gastrointestinal unit at the Institût Gustave Roussy in Villejuif, France, said in an interview.

The current study specifically looked at patients with the KRAS wild type, Dr. Ducreux noted. These are patients who should, in theory, still be able to respond to an epidermal growth factor receptor (EGFR) inhibitor, such as cetuximab. It has been known since 2008 that patients with mutated KRAS tumors do not respond to EGFR inhibition.

"The main point now is to go into the details of the biological samples in that study," Dr. Ducreux suggested, to determine whether any subpopulations of patients might benefit, and if not, to find out why.

The PETACC8 trial was originally designed to compare 12 cycles of FOLFOX4 versus FOLFOX4 plus additional cetuximab. The trial protocol was amended in 2008, when it became possible to select patients for cetuximab therapy based on their KRAS status.

Of the 2,559 patients recruited into the trial at 340 sites in Europe, nearly two-thirds had KRAS wild-type disease and 1,602 of them were randomized. The mean age of the KRAS wild-type patients was 58 years. All had completely resected, pathologically confirmed stage III colon cancer, a good WHO performance status, and a life expectancy of at least 5 years at enrollment.

The primary end point was disease-free survival, defined as the period before recurrence, second colorectal cancer, or death. However, the hazard ratio for disease-free-survival was 1.047 (P = .66). The differences in rates at 1, 2, and 4 years were also not statistically significant for FOLFOX4 with cetuximab (90.4%, 79.7%, and 72.4%, respectively) or without (92%, 81.5%, and 75.5%).

"Disease-free survival was really excellent compared to what has been reported with FOLFOX4 in the literature," Dr. Taieb said.

He noted that while cetuximab appeared to give no extra benefit, there might be subgroup of KRAS wild-type patients that could gain some benefit. There were trends for women; patients 70 years and older; and groups with a WHO performance status of 0, pT1-3 and pN1 tumors, and no bowel obstruction or perforation to do a little better.

Tolerability was as might be expected for the agents tested, but with a higher chance of hypersensitivity reactions, acnelike rash, diarrhea, and mucositis in the cetuximab-containing arm. There was an overall 15% difference in the occurrence of grade 3 and 4 adverse events between the FOLFOX4 with cetuximab and FOLFOX4 arms (80.9% vs. 66.2%, respectively).

"The probability for a positive result in the final analysis is very low," Dr. Taieb said, suggesting that "cetuximab might have a different form of activity on micrometastatic disease compared to that observed in stage IV disease."

Merck Serono and Sanofi-Aventis provided grants to fund the trial. Dr. Taieb has received consultancy and advisory board honoraria from Merck. Dr. Ducreux has received consultancy fees from Merck Serono and Roche.

MIAMI BEACH – When you are called to assess a patient before cancer surgery, how do you know when noninvasive cardiovascular testing is warranted?

Start by asking patients to describe their functional status before they started any treatment to combat their cancer, Dr. Sunil K. Sahai said.

Also assess for any ischemia preoperatively, because its presence might direct a surgeon to prescribe a less cardiotoxic postoperative treatment for your patient, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami. Occult ischemia might be found if a patient reports shortness of breath during prior chemotherapy administration, he added.

"Everything you’ve heard about perioperative medicine is true for cancer patients, but they are also unique," Dr. Sahai said. The physiologic burden of cancer and its treatment makes preoperative evaluation challenging, but it’s worth doing right to ensure the patient receives the optimal therapy. Also, in some cases, either the patient or surgeon will decide not to proceed with surgery based on your risk assessment, said Dr. Sahai, medical director of the Internal Medicine Perioperative Assessment Center at the University of Texas M.D. Anderson Cancer Center in Houston.

To illustrate some of the challenges, Dr. Sahai described an actual patient, a 60-year-old man referred for preoperative assessment 1 week before a scheduled neck dissection and total laryngectomy. He presented with dysphagia and sore throat. A biopsy revealed postcricoid squamous cell carcinoma. He was otherwise healthy, except for psoriasis and benign prostatic hyperplasia. He had undergone surgery and radiation for nasopharyngeal cancer 15 years earlier. The current physical examination was unremarkable, except for bilateral carotid bruits. Doppler ultrasound findings led to a diagnosis of radiation-induced carotid stenosis with diffuse, bilateral atherosclerosis and greater than 70% stenosis.

Head and neck cancer patients can have double the risk of transient ischemic attack or cerebrovascular accident, compared with a patient with normal pathologic narrowing of the carotid arteries, Dr. Sahai said. This is a controversial area because "data are not clear on what to do."

"We postponed and all discussed with all the providers involved," Dr. Sahai said. A stent was placed in the patient’s right internal carotid artery, and cancer surgery was delayed for 1 month while the patient took clopidogrel and aspirin. "He then went to the operating room on aspirin, and he did well."

Another case, a 70-year-old woman scheduled for a 6-hour cystectomy for bladder cancer, raised issues around preoperative cardiovascular assessment. "She reports fatigue and shortness of breath with exertion on her evening walks," Dr. Sahai said. "Before chemotherapy, she was able to walk eight blocks and up two flights of stairs without stopping. Now she can walk only four blocks and stops to rest between flights." She does not describe typical angina symptoms, he added.

The patient is obese, has diabetes mellitus, and is taking a statin for hyperlipidemia. She does not report any angina symptoms. Her history includes a myocardial infarction 5 years earlier addressed with medical management only.

Cancer can sap a patient’s energy, but the precise etiology in this case was unclear, Dr. Sahai said. Was her shortness of breath related to coronary artery disease, heart failure, pulmonary hypertension, or treatment with cardiotoxic chemotherapy? Should the patient be tested, for example, with an echocardiogram for heart function, stress test for ischemia, or both?

"Because this patient had received cardiotoxic chemotherapy ... we would do a stress echo on this patient," Dr. Sahai said. "In addition, BNP [B-type natriuretic peptide] levels may be helpful to detect cardiomyopathy. I would also optimize cardiac function and heart rate and send her to the operating room with the statin on board."

Patients with no cardiovascular symptoms can generally go to the operating room. If a patient is symptomatic, however, especially if the symptoms are new since cancer therapy was begun, Dr. Sahai said he generally considers further testing and work-up.

Dr. Sahai had no relevant financial disclosures.

MIAMI BEACH – When you are called to assess a patient before cancer surgery, how do you know when noninvasive cardiovascular testing is warranted?

Start by asking patients to describe their functional status before they started any treatment to combat their cancer, Dr. Sunil K. Sahai said.

Also assess for any ischemia preoperatively, because its presence might direct a surgeon to prescribe a less cardiotoxic postoperative treatment for your patient, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami. Occult ischemia might be found if a patient reports shortness of breath during prior chemotherapy administration, he added.

"Everything you’ve heard about perioperative medicine is true for cancer patients, but they are also unique," Dr. Sahai said. The physiologic burden of cancer and its treatment makes preoperative evaluation challenging, but it’s worth doing right to ensure the patient receives the optimal therapy. Also, in some cases, either the patient or surgeon will decide not to proceed with surgery based on your risk assessment, said Dr. Sahai, medical director of the Internal Medicine Perioperative Assessment Center at the University of Texas M.D. Anderson Cancer Center in Houston.

To illustrate some of the challenges, Dr. Sahai described an actual patient, a 60-year-old man referred for preoperative assessment 1 week before a scheduled neck dissection and total laryngectomy. He presented with dysphagia and sore throat. A biopsy revealed postcricoid squamous cell carcinoma. He was otherwise healthy, except for psoriasis and benign prostatic hyperplasia. He had undergone surgery and radiation for nasopharyngeal cancer 15 years earlier. The current physical examination was unremarkable, except for bilateral carotid bruits. Doppler ultrasound findings led to a diagnosis of radiation-induced carotid stenosis with diffuse, bilateral atherosclerosis and greater than 70% stenosis.

Head and neck cancer patients can have double the risk of transient ischemic attack or cerebrovascular accident, compared with a patient with normal pathologic narrowing of the carotid arteries, Dr. Sahai said. This is a controversial area because "data are not clear on what to do."

"We postponed and all discussed with all the providers involved," Dr. Sahai said. A stent was placed in the patient’s right internal carotid artery, and cancer surgery was delayed for 1 month while the patient took clopidogrel and aspirin. "He then went to the operating room on aspirin, and he did well."

Another case, a 70-year-old woman scheduled for a 6-hour cystectomy for bladder cancer, raised issues around preoperative cardiovascular assessment. "She reports fatigue and shortness of breath with exertion on her evening walks," Dr. Sahai said. "Before chemotherapy, she was able to walk eight blocks and up two flights of stairs without stopping. Now she can walk only four blocks and stops to rest between flights." She does not describe typical angina symptoms, he added.

The patient is obese, has diabetes mellitus, and is taking a statin for hyperlipidemia. She does not report any angina symptoms. Her history includes a myocardial infarction 5 years earlier addressed with medical management only.

Cancer can sap a patient’s energy, but the precise etiology in this case was unclear, Dr. Sahai said. Was her shortness of breath related to coronary artery disease, heart failure, pulmonary hypertension, or treatment with cardiotoxic chemotherapy? Should the patient be tested, for example, with an echocardiogram for heart function, stress test for ischemia, or both?

"Because this patient had received cardiotoxic chemotherapy ... we would do a stress echo on this patient," Dr. Sahai said. "In addition, BNP [B-type natriuretic peptide] levels may be helpful to detect cardiomyopathy. I would also optimize cardiac function and heart rate and send her to the operating room with the statin on board."

Patients with no cardiovascular symptoms can generally go to the operating room. If a patient is symptomatic, however, especially if the symptoms are new since cancer therapy was begun, Dr. Sahai said he generally considers further testing and work-up.

Dr. Sahai had no relevant financial disclosures.

MIAMI BEACH – When you are called to assess a patient before cancer surgery, how do you know when noninvasive cardiovascular testing is warranted?

Start by asking patients to describe their functional status before they started any treatment to combat their cancer, Dr. Sunil K. Sahai said.

Also assess for any ischemia preoperatively, because its presence might direct a surgeon to prescribe a less cardiotoxic postoperative treatment for your patient, Dr. Sahai said at a meeting on perioperative medicine sponsored by the University of Miami. Occult ischemia might be found if a patient reports shortness of breath during prior chemotherapy administration, he added.

"Everything you’ve heard about perioperative medicine is true for cancer patients, but they are also unique," Dr. Sahai said. The physiologic burden of cancer and its treatment makes preoperative evaluation challenging, but it’s worth doing right to ensure the patient receives the optimal therapy. Also, in some cases, either the patient or surgeon will decide not to proceed with surgery based on your risk assessment, said Dr. Sahai, medical director of the Internal Medicine Perioperative Assessment Center at the University of Texas M.D. Anderson Cancer Center in Houston.

To illustrate some of the challenges, Dr. Sahai described an actual patient, a 60-year-old man referred for preoperative assessment 1 week before a scheduled neck dissection and total laryngectomy. He presented with dysphagia and sore throat. A biopsy revealed postcricoid squamous cell carcinoma. He was otherwise healthy, except for psoriasis and benign prostatic hyperplasia. He had undergone surgery and radiation for nasopharyngeal cancer 15 years earlier. The current physical examination was unremarkable, except for bilateral carotid bruits. Doppler ultrasound findings led to a diagnosis of radiation-induced carotid stenosis with diffuse, bilateral atherosclerosis and greater than 70% stenosis.

Head and neck cancer patients can have double the risk of transient ischemic attack or cerebrovascular accident, compared with a patient with normal pathologic narrowing of the carotid arteries, Dr. Sahai said. This is a controversial area because "data are not clear on what to do."

"We postponed and all discussed with all the providers involved," Dr. Sahai said. A stent was placed in the patient’s right internal carotid artery, and cancer surgery was delayed for 1 month while the patient took clopidogrel and aspirin. "He then went to the operating room on aspirin, and he did well."

Another case, a 70-year-old woman scheduled for a 6-hour cystectomy for bladder cancer, raised issues around preoperative cardiovascular assessment. "She reports fatigue and shortness of breath with exertion on her evening walks," Dr. Sahai said. "Before chemotherapy, she was able to walk eight blocks and up two flights of stairs without stopping. Now she can walk only four blocks and stops to rest between flights." She does not describe typical angina symptoms, he added.

The patient is obese, has diabetes mellitus, and is taking a statin for hyperlipidemia. She does not report any angina symptoms. Her history includes a myocardial infarction 5 years earlier addressed with medical management only.

Cancer can sap a patient’s energy, but the precise etiology in this case was unclear, Dr. Sahai said. Was her shortness of breath related to coronary artery disease, heart failure, pulmonary hypertension, or treatment with cardiotoxic chemotherapy? Should the patient be tested, for example, with an echocardiogram for heart function, stress test for ischemia, or both?

"Because this patient had received cardiotoxic chemotherapy ... we would do a stress echo on this patient," Dr. Sahai said. "In addition, BNP [B-type natriuretic peptide] levels may be helpful to detect cardiomyopathy. I would also optimize cardiac function and heart rate and send her to the operating room with the statin on board."

Patients with no cardiovascular symptoms can generally go to the operating room. If a patient is symptomatic, however, especially if the symptoms are new since cancer therapy was begun, Dr. Sahai said he generally considers further testing and work-up.

Dr. Sahai had no relevant financial disclosures.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.