Nephrology

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN

HOLLYWOOD, FLA. — Targeted renal therapy with the vasodilating drug fenoldopam was effective for treating acute kidney injury and for preventing contrast-induced nephropathy in results from a pair of studies.

By infusing the drug directly into patients' renal arteries with a specially designed catheter, targeted therapy allows the use of a substantial dose of fenoldopam mesylate while avoiding systemic adverse effects such as hypotension, Dr. James A. Tumlin said at ISET 2009, an international symposium on endovascular therapy.

He reported treating a series of 28 patients with oliguria and diuretic-unresponsive acute kidney injury. Their diuretic unresponsiveness was defined as a failure to double their urine output after a single bolus dose of 80–120 mg furosemide. Their average serum creatinine level at entry into the study was about 1.7 mg/dL. Many of the patients had one or more comorbidities, with 57% having respiratory distress, 46% on mechanical ventilation, 43% having sepsis, and 39% with a left ventricular ejection fraction less than 35%.

All patients received intrarenal fenoldopam via a Benephit peripheral vascular catheter made by FlowMedica Inc. The catheter is designed to infuse both renal arteries with a single device, and was approved by the Food and Drug Administration in late 2008 for targeted renal therapy in patients at risk for developing acute kidney injury. Dr. Tumlin is a consultant to and has received grant support from FlowMedica.

Their goal dosage was a fenoldopam infusion of 0.4 mcg/kg per minute, and the actual average dose used was 0.39 mcg/kg per minute, with a maximum dose given to any patient of 0.8 mcg/kg per minute. The target duration of treatment was 48 hours, and the actual average duration was 42 hours, with a maximum of 72 hours.

Renal recovery, defined as a fall in serum creatinine, occurred in 17 patients (61%) by the fourth day after treatment, and in 27 (96%) of patients by a week after treatment. Three of the patients (11%) died during follow-up, and another four (14%) required dialysis during follow-up. (None of the dialysis patients died.) “This was an unusually low mortality rate,” compared with the historic experience with similar patients who did not undergo renal infusion with fenoldopam, said Dr. Tumlin, a nephrologist and professor of medicine at the University of Tennessee in Chattanooga.

The second experience using intrarenal fenoldopam that was presented at the meeting included data from 593 patients who were enrolled in a targeted renal therapy registry. The series included 340 patients who were treated to prevent contrast-induced nephropathy and another 40 patients who were treated for acute kidney injury that they developed following coronary artery bypass grafting. The patients had been treated by 38 different physicians at 19 medical centers.

Intrarenal fenoldopam was given to 94% of the registry's patients, at a median dosage of 0.4 mcg/kg per minute, with a range of 0.05–0.8 mcg/kg per minute. The remaining patients received another drug, such as sodium bicarbonate, reported Dr. John H. Rundback in a separate talk at the meeting. The median duration of the fenoldopam infusion was 180 minutes.

Bilateral renal-artery catheterization was performed successfully in 95% of the registry patients, a procedure that took an average of 2 minutes. Five of the 593 patients in the registry (0.8%) had a complication from renal-artery catheterization: Three had groin complications (the catheter is often inserted through the femoral artery), one had a renal-artery dissection, and one developed hypotension.

Registry outcomes showed that the 0.4-mcg/kg per minute dosage was much more effective than was a 0.2- mcg/kg per minute dosage for preventing contrast-induced nephropathy, and that treatment for at least an hour was more effective than a briefer infusion, said Dr. Rundback, an interventional radiologist and director of the Interventional Institute at Holy Name Hospital, Teaneck, N.J. Dr. Rundback has been a consultant to and a member of the scientific advisory board of FlowMedica.

The predicted incidence of contrast-induced nephropathy was about 27%, yet the rate among 268 patients who were treated with at least 0.4 mcg/kg per minute of fenoldopam for at least 1 hour was less than 1%, Dr. Rundback said.

Patients who received fenoldopam had 'an unusually low mortality rate.' DR. TUMLIN

Sherry Boschert contributed to this story.

Healthy men with a prostate-specific antigen score of 3.0 or lower should consider taking a 5-alpha reductase inhibitor to prevent prostate cancer, according to newly released clinical practice guidelines.

The guidelines, issued by the American Urological Association and the American Society of Clinical Oncology, apply to men who plan to get yearly PSA tests or regular prostate cancer screening and who have no signs of prostate cancer. In addition, for men who already are taking the drugs (to treat benign prostatic hyperplasia or male-pattern baldness, for example), physicians should discuss continuing the drug specifically to prevent prostate cancer (J. Urol. 2009;181:1642–57; J. Clin Oncol. 2009 Feb. 24 [doi:10.1200/JCO.2008.16.9599]; www.asco.org/guidelines

The guidelines are based on evidence from nine randomized, controlled clinical trials, including the Prostate Cancer Prevention Trial (PCPT). “That body of evidence provided proof” that the 5-alpha reductase inhibitors will decrease the risk of prostate cancer in men being regularly screened for the disease, Dr. Barnett S. Kramer said at a press conference held in conjunction with a symposium on genitourinary cancers.

All nine trials have enrolled men undergoing regular screening for prostate cancer. This fact is important, because it has been well-established that screening doubles the risk of being diagnosed with prostate cancer, added Dr. Kramer, cochair of the panel that produced the guidelines.

The PCPT found an overall 25% relative risk reduction for prostate cancer in men who took the 5-alpha reductase inhibitor finasteride for 1–7 years. Because most of the men in this study were white, the results “principally apply only to white men,” he noted, adding that subanalyses found no substantive differences among racial or ethnic groups.

It's not clear whether preventive treatment will affect mortality from prostate cancer or whether doses lower than those currently used would be effective in prevention, said Dr. Kramer, associate director of disease prevention at the National Institutes of Health. In addition, “we can't be confident of its effect in men who choose not to be screened.”

The 5-alpha reductase inhibitors are known to lower levels of dihydrotestosterone, which can contribute to prostate cancer growth. Their most common side effects include erectile dysfunction, decreased libido, and ejaculatory dysfunction, with rarer cases of gynecomastia.

When the PCPT was published, there was concern over what appeared to be an increase in the rate of high-grade tumors diagnosed among those randomized to finasteride (37% of the prostate cancers in the finasteride arm were high grade, vs. 22% of those in the placebo arm). But a subsequent analysis determined this increase was likely to be spurious, Dr. Kramer said, adding that his comments represented those of ASCO and the AUA, not the U.S. government or NIH.

Although Dr. Kramer said he believed that cost needs to be part of this discussion, the available data were not strong enough to calculate cost-effectiveness.

Currently, approximately one in six U.S. men gets diagnosed with prostate cancer, the second-leading cause of death from cancer in men and, after skin cancer, the most common cancer diagnosed in men in the United States.

He pointed out that prostate cancer rates in the United States are among the highest in the world. In addition, since the principal driver of prostate cancer risk is age, the recommendations target “healthy men who fulfill risk criteria by virtue of age.”

The guidelines could apply to millions of men. During the briefing, Dr. Howard Sandler, a prostate cancer specialist at Cedars-Sinai Medical Center in Los Angeles, said he expects there will be many different attitudes about taking a pill every day “for preventing a condition that may not occur.”

He said he personally might consider a trial of over a month, and if he developed side effects to the drug, it would not be worth the potential benefits. But if he did not develop adverse effects, “ultimately, I would become reassured that taking one pill per day … might decrease my risk for prostate cancer,” he said, adding that he had not yet decided whether to pursue such preventive treatment.

The ASCO Web site offers physicians a “Decision Aid Tool,” composed of charts and diagrams to help explain the risks and benefits of 5-alpha reductase inhibitors to patients and their families. ASCO also has produced a corresponding patient guide, which is available at www.cancer.net

Dr. Schellhammer has received research funds or support from GlaxoSmithKline, which markets the 5-alpha reductase inhibitor dutasteride, and from other pharmaceutical companies. Dr. Kramer has no conflicts of interest related to the guidelines.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

Sherry Boschert contributed to this story.

Healthy men with a prostate-specific antigen score of 3.0 or lower should consider taking a 5-alpha reductase inhibitor to prevent prostate cancer, according to newly released clinical practice guidelines.

The guidelines, issued by the American Urological Association and the American Society of Clinical Oncology, apply to men who plan to get yearly PSA tests or regular prostate cancer screening and who have no signs of prostate cancer. In addition, for men who already are taking the drugs (to treat benign prostatic hyperplasia or male-pattern baldness, for example), physicians should discuss continuing the drug specifically to prevent prostate cancer (J. Urol. 2009;181:1642–57; J. Clin Oncol. 2009 Feb. 24 [doi:10.1200/JCO.2008.16.9599]; www.asco.org/guidelines

The guidelines are based on evidence from nine randomized, controlled clinical trials, including the Prostate Cancer Prevention Trial (PCPT). “That body of evidence provided proof” that the 5-alpha reductase inhibitors will decrease the risk of prostate cancer in men being regularly screened for the disease, Dr. Barnett S. Kramer said at a press conference held in conjunction with a symposium on genitourinary cancers.

All nine trials have enrolled men undergoing regular screening for prostate cancer. This fact is important, because it has been well-established that screening doubles the risk of being diagnosed with prostate cancer, added Dr. Kramer, cochair of the panel that produced the guidelines.

The PCPT found an overall 25% relative risk reduction for prostate cancer in men who took the 5-alpha reductase inhibitor finasteride for 1–7 years. Because most of the men in this study were white, the results “principally apply only to white men,” he noted, adding that subanalyses found no substantive differences among racial or ethnic groups.

It's not clear whether preventive treatment will affect mortality from prostate cancer or whether doses lower than those currently used would be effective in prevention, said Dr. Kramer, associate director of disease prevention at the National Institutes of Health. In addition, “we can't be confident of its effect in men who choose not to be screened.”

The 5-alpha reductase inhibitors are known to lower levels of dihydrotestosterone, which can contribute to prostate cancer growth. Their most common side effects include erectile dysfunction, decreased libido, and ejaculatory dysfunction, with rarer cases of gynecomastia.

When the PCPT was published, there was concern over what appeared to be an increase in the rate of high-grade tumors diagnosed among those randomized to finasteride (37% of the prostate cancers in the finasteride arm were high grade, vs. 22% of those in the placebo arm). But a subsequent analysis determined this increase was likely to be spurious, Dr. Kramer said, adding that his comments represented those of ASCO and the AUA, not the U.S. government or NIH.

Although Dr. Kramer said he believed that cost needs to be part of this discussion, the available data were not strong enough to calculate cost-effectiveness.

Currently, approximately one in six U.S. men gets diagnosed with prostate cancer, the second-leading cause of death from cancer in men and, after skin cancer, the most common cancer diagnosed in men in the United States.

He pointed out that prostate cancer rates in the United States are among the highest in the world. In addition, since the principal driver of prostate cancer risk is age, the recommendations target “healthy men who fulfill risk criteria by virtue of age.”

The guidelines could apply to millions of men. During the briefing, Dr. Howard Sandler, a prostate cancer specialist at Cedars-Sinai Medical Center in Los Angeles, said he expects there will be many different attitudes about taking a pill every day “for preventing a condition that may not occur.”

He said he personally might consider a trial of over a month, and if he developed side effects to the drug, it would not be worth the potential benefits. But if he did not develop adverse effects, “ultimately, I would become reassured that taking one pill per day … might decrease my risk for prostate cancer,” he said, adding that he had not yet decided whether to pursue such preventive treatment.

The ASCO Web site offers physicians a “Decision Aid Tool,” composed of charts and diagrams to help explain the risks and benefits of 5-alpha reductase inhibitors to patients and their families. ASCO also has produced a corresponding patient guide, which is available at www.cancer.net

Dr. Schellhammer has received research funds or support from GlaxoSmithKline, which markets the 5-alpha reductase inhibitor dutasteride, and from other pharmaceutical companies. Dr. Kramer has no conflicts of interest related to the guidelines.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

Sherry Boschert contributed to this story.

Healthy men with a prostate-specific antigen score of 3.0 or lower should consider taking a 5-alpha reductase inhibitor to prevent prostate cancer, according to newly released clinical practice guidelines.

The guidelines, issued by the American Urological Association and the American Society of Clinical Oncology, apply to men who plan to get yearly PSA tests or regular prostate cancer screening and who have no signs of prostate cancer. In addition, for men who already are taking the drugs (to treat benign prostatic hyperplasia or male-pattern baldness, for example), physicians should discuss continuing the drug specifically to prevent prostate cancer (J. Urol. 2009;181:1642–57; J. Clin Oncol. 2009 Feb. 24 [doi:10.1200/JCO.2008.16.9599]; www.asco.org/guidelines

The guidelines are based on evidence from nine randomized, controlled clinical trials, including the Prostate Cancer Prevention Trial (PCPT). “That body of evidence provided proof” that the 5-alpha reductase inhibitors will decrease the risk of prostate cancer in men being regularly screened for the disease, Dr. Barnett S. Kramer said at a press conference held in conjunction with a symposium on genitourinary cancers.

All nine trials have enrolled men undergoing regular screening for prostate cancer. This fact is important, because it has been well-established that screening doubles the risk of being diagnosed with prostate cancer, added Dr. Kramer, cochair of the panel that produced the guidelines.

The PCPT found an overall 25% relative risk reduction for prostate cancer in men who took the 5-alpha reductase inhibitor finasteride for 1–7 years. Because most of the men in this study were white, the results “principally apply only to white men,” he noted, adding that subanalyses found no substantive differences among racial or ethnic groups.

It's not clear whether preventive treatment will affect mortality from prostate cancer or whether doses lower than those currently used would be effective in prevention, said Dr. Kramer, associate director of disease prevention at the National Institutes of Health. In addition, “we can't be confident of its effect in men who choose not to be screened.”

The 5-alpha reductase inhibitors are known to lower levels of dihydrotestosterone, which can contribute to prostate cancer growth. Their most common side effects include erectile dysfunction, decreased libido, and ejaculatory dysfunction, with rarer cases of gynecomastia.

When the PCPT was published, there was concern over what appeared to be an increase in the rate of high-grade tumors diagnosed among those randomized to finasteride (37% of the prostate cancers in the finasteride arm were high grade, vs. 22% of those in the placebo arm). But a subsequent analysis determined this increase was likely to be spurious, Dr. Kramer said, adding that his comments represented those of ASCO and the AUA, not the U.S. government or NIH.

Although Dr. Kramer said he believed that cost needs to be part of this discussion, the available data were not strong enough to calculate cost-effectiveness.

Currently, approximately one in six U.S. men gets diagnosed with prostate cancer, the second-leading cause of death from cancer in men and, after skin cancer, the most common cancer diagnosed in men in the United States.

He pointed out that prostate cancer rates in the United States are among the highest in the world. In addition, since the principal driver of prostate cancer risk is age, the recommendations target “healthy men who fulfill risk criteria by virtue of age.”

The guidelines could apply to millions of men. During the briefing, Dr. Howard Sandler, a prostate cancer specialist at Cedars-Sinai Medical Center in Los Angeles, said he expects there will be many different attitudes about taking a pill every day “for preventing a condition that may not occur.”

He said he personally might consider a trial of over a month, and if he developed side effects to the drug, it would not be worth the potential benefits. But if he did not develop adverse effects, “ultimately, I would become reassured that taking one pill per day … might decrease my risk for prostate cancer,” he said, adding that he had not yet decided whether to pursue such preventive treatment.

The ASCO Web site offers physicians a “Decision Aid Tool,” composed of charts and diagrams to help explain the risks and benefits of 5-alpha reductase inhibitors to patients and their families. ASCO also has produced a corresponding patient guide, which is available at www.cancer.net

Dr. Schellhammer has received research funds or support from GlaxoSmithKline, which markets the 5-alpha reductase inhibitor dutasteride, and from other pharmaceutical companies. Dr. Kramer has no conflicts of interest related to the guidelines.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

A molecular urine test that detects the fusion of two genes associated with more aggressive prostate cancers was highly specific for prostate cancer in a study in men undergoing prostate biopsies, investigators report based on an interim review.

The test, which is not available commercially, detects fusions between TMPRSS2 (T2), an androgen-responsive gene, and the oncogenic transcription factor ERG. This fusion is found in about half of all prostate tumors, and has been associated with adverse clinical outcomes.

Initially reported at the end of 2005, this fusion was the first specific chromosomal rearrangement identified in prostate tumors, and appears to be “an ideal target for a diagnostic test because of the high specificity for prostate cancer,” according to Jack Groskopf, Ph.D., director of research and development in the cancer diagnostics division of Gen-Probe Inc., the San Diego-based company developing the test.

The test, known as the T2:ERG test, may eventually be useful in determining prognosis and selecting treatment in men diagnosed with prostate cancer, Dr. Groskopf said at a press briefing in advance of the study's presentation at a symposium on genitourinary cancers. He cited the need for a test that can help determine which prostate cancers require aggressive treatment and which could be managed conservatively.

To date, the test has been used on urine specimens collected in 556 men at three medical centers following a digital rectal exam and before prostate biopsy. The test predicted the presence of prostate cancer on biopsy with a specificity of 84%, compared with a specificity of 27% for serum prostate-specific antigen (PSA), with similar results at all three sites, he said.

The gene fusion has been present in about 42% of all positive biopsies to date, an indication that the test is “doing pretty well” in terms of sensitivity, as this correlates to the prevalence of the gene fusion in about half of all prostate cancers, he noted.

In addition, there have been significant correlations between a positive test and indicators of cancer aggressiveness, Gleason score, percent of prostate cancer involvement, and percent positive core, providing preliminary evidence indicating that T2:ERG status correlates with the criteria for aggressive cancers, he said.

The next step is to follow up and confirm these findings, and “perhaps more importantly,” to start studying the correlation between the urine test and pathologic features in prostatectomy tissue, such as tumor volume, stage, and grade, Dr. Groskopf said.

Describing this work as an “important first step,” Dr. Howard Sandler, moderator of the briefing, remarked that it represents “an amazingly short interval between the basic fundamental discovery and potential clinical utility of a diagnostic test.”

If it turns out that gene fusion is related to progression of prostate cancer in half of all men who develop prostate cancer, the molecular change will have major implications for diagnosis and possibly treatment as well, because it may also be a therapeutic target, said Dr. Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles. “There is interest in targeting our diagnostic strategies towards patients who will have cancers that really need to be treated, not those that are overdiagnosed and are never destined to cause clinical harm,” he added.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

A molecular urine test that detects the fusion of two genes associated with more aggressive prostate cancers was highly specific for prostate cancer in a study in men undergoing prostate biopsies, investigators report based on an interim review.

The test, which is not available commercially, detects fusions between TMPRSS2 (T2), an androgen-responsive gene, and the oncogenic transcription factor ERG. This fusion is found in about half of all prostate tumors, and has been associated with adverse clinical outcomes.

Initially reported at the end of 2005, this fusion was the first specific chromosomal rearrangement identified in prostate tumors, and appears to be “an ideal target for a diagnostic test because of the high specificity for prostate cancer,” according to Jack Groskopf, Ph.D., director of research and development in the cancer diagnostics division of Gen-Probe Inc., the San Diego-based company developing the test.

The test, known as the T2:ERG test, may eventually be useful in determining prognosis and selecting treatment in men diagnosed with prostate cancer, Dr. Groskopf said at a press briefing in advance of the study's presentation at a symposium on genitourinary cancers. He cited the need for a test that can help determine which prostate cancers require aggressive treatment and which could be managed conservatively.

To date, the test has been used on urine specimens collected in 556 men at three medical centers following a digital rectal exam and before prostate biopsy. The test predicted the presence of prostate cancer on biopsy with a specificity of 84%, compared with a specificity of 27% for serum prostate-specific antigen (PSA), with similar results at all three sites, he said.

The gene fusion has been present in about 42% of all positive biopsies to date, an indication that the test is “doing pretty well” in terms of sensitivity, as this correlates to the prevalence of the gene fusion in about half of all prostate cancers, he noted.

In addition, there have been significant correlations between a positive test and indicators of cancer aggressiveness, Gleason score, percent of prostate cancer involvement, and percent positive core, providing preliminary evidence indicating that T2:ERG status correlates with the criteria for aggressive cancers, he said.

The next step is to follow up and confirm these findings, and “perhaps more importantly,” to start studying the correlation between the urine test and pathologic features in prostatectomy tissue, such as tumor volume, stage, and grade, Dr. Groskopf said.

Describing this work as an “important first step,” Dr. Howard Sandler, moderator of the briefing, remarked that it represents “an amazingly short interval between the basic fundamental discovery and potential clinical utility of a diagnostic test.”

If it turns out that gene fusion is related to progression of prostate cancer in half of all men who develop prostate cancer, the molecular change will have major implications for diagnosis and possibly treatment as well, because it may also be a therapeutic target, said Dr. Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles. “There is interest in targeting our diagnostic strategies towards patients who will have cancers that really need to be treated, not those that are overdiagnosed and are never destined to cause clinical harm,” he added.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

A molecular urine test that detects the fusion of two genes associated with more aggressive prostate cancers was highly specific for prostate cancer in a study in men undergoing prostate biopsies, investigators report based on an interim review.

The test, which is not available commercially, detects fusions between TMPRSS2 (T2), an androgen-responsive gene, and the oncogenic transcription factor ERG. This fusion is found in about half of all prostate tumors, and has been associated with adverse clinical outcomes.

Initially reported at the end of 2005, this fusion was the first specific chromosomal rearrangement identified in prostate tumors, and appears to be “an ideal target for a diagnostic test because of the high specificity for prostate cancer,” according to Jack Groskopf, Ph.D., director of research and development in the cancer diagnostics division of Gen-Probe Inc., the San Diego-based company developing the test.

The test, known as the T2:ERG test, may eventually be useful in determining prognosis and selecting treatment in men diagnosed with prostate cancer, Dr. Groskopf said at a press briefing in advance of the study's presentation at a symposium on genitourinary cancers. He cited the need for a test that can help determine which prostate cancers require aggressive treatment and which could be managed conservatively.

To date, the test has been used on urine specimens collected in 556 men at three medical centers following a digital rectal exam and before prostate biopsy. The test predicted the presence of prostate cancer on biopsy with a specificity of 84%, compared with a specificity of 27% for serum prostate-specific antigen (PSA), with similar results at all three sites, he said.

The gene fusion has been present in about 42% of all positive biopsies to date, an indication that the test is “doing pretty well” in terms of sensitivity, as this correlates to the prevalence of the gene fusion in about half of all prostate cancers, he noted.

In addition, there have been significant correlations between a positive test and indicators of cancer aggressiveness, Gleason score, percent of prostate cancer involvement, and percent positive core, providing preliminary evidence indicating that T2:ERG status correlates with the criteria for aggressive cancers, he said.

The next step is to follow up and confirm these findings, and “perhaps more importantly,” to start studying the correlation between the urine test and pathologic features in prostatectomy tissue, such as tumor volume, stage, and grade, Dr. Groskopf said.

Describing this work as an “important first step,” Dr. Howard Sandler, moderator of the briefing, remarked that it represents “an amazingly short interval between the basic fundamental discovery and potential clinical utility of a diagnostic test.”

If it turns out that gene fusion is related to progression of prostate cancer in half of all men who develop prostate cancer, the molecular change will have major implications for diagnosis and possibly treatment as well, because it may also be a therapeutic target, said Dr. Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles. “There is interest in targeting our diagnostic strategies towards patients who will have cancers that really need to be treated, not those that are overdiagnosed and are never destined to cause clinical harm,” he added.

The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

SAN DIEGO — Before you recommend a treatment for erectile dysfunction, make sure to rule out underlying factors that may contribute to the condition.

“Treat the whole person. Try to take care of other medical problems they might have,” Dr. Edward (Lev) Linkner advised at a meeting sponsored by the Scripps Center for Integrative Medicine and the American Board of Integrative Holistic Medicine.

Medical conditions that should be ruled out include arteriosclerosis, diabetes, Syndrome X (cardiometabolic syndrome), hypothyroidism, and hypogonadism. Emotional etiologies such as depression and relationship difficulties should also be investigated, as should stress and lifestyle habits, especially smoking and alcohol consumption.

“Even bicycling can put abnormal pressure on pelvic nerves and result in erectile dysfunction,” said Dr. Linkner, a founder of the American Board of Holistic Medicine and current member of their board of directors. He is in private practice in Ann Arbor, Mich.

If erectile dysfunction is secondary to a treatable disease or condition, treatment of that disease or condition may be all that's necessary. If not, consider one of the following herbs:

▸ Yohimbine. This herb is derived from bark shavings of a West African tree, Pausinystalia yohimbe. “Some studies show positive results, some don't,” Dr. Linkner said. “The major side effects are hypertension, anxiety, nausea, trembling, and insomnia.” Yohimbine is contraindicated for use by those with liver and kidney disease. It is available in tablet form as the prescription drug Yocon (yohimbine hydrochloride), an alpha2-adrenergic blocker that increases blood flow to the penis. “It may be especially helpful for erectile dysfunction induced by the use of selective serotonin reuptake inhibitors,” Dr. Linkner said. He recommends a dose of one-half to one whole 5.4-mg tablet t.i.d.

▸ Ginkgo biloba. A German study showed that this herb increased blood flow to the penis within 8 weeks of starting treatment, and half of the participants regained normal potency (J. Sex Educ. Ther. 1991;17:53–61). The recommended dose is 60–120 mg b.i.d.

▸ Damiana (Turnera diffusa). Although poorly studied, this herb has been used as an aphrodisiac for centuries, especially in Mexico. Its leaves also are used to make a tea. The recommended dose is 300–450 mg once daily.

▸ Ginseng. Panax ginseng appears to works best for erectile dysfunction, but Siberian ginseng also can be used. Ginsenoside, a triterpenoid saponin, increases nitric oxide and “works like a natural Viagra,” Dr. Linkner said. The recommended dose is 200–1,000 mg.

▸ Muria puama. In European studies, this extract of a shrub (Ptychopetalum olacoides) from the Amazon has been shown to increase erections and libido. It is listed in the British Herbal Pharmacopoeia as a treatment for erectile dysfunction and dysentery.

▸ Maca (Lepidum meyenii). This radishlike plant native to the Peruvian Andes is thought to increase sexual function and stamina. The recommended dose is 1.5–3 g daily.

Adaptogens—herbs that are restorative or enhance physical performance—also may have a role in the treatment of erectile dysfunction, said Dr. Linkner, also of the University of Michigan, Ann Arbor. They “increase energy and resistance to all types of stress, thereby preventing fatigue, enhancing memory, concentration, and improving work performance.” Some adaptogens are cordyceps, ashwagandha, and rhodiola.

Other herbs with historical use in treating erectile dysfunction include oats, which increase stamina and decrease irritability; rosemary, which may help the adrenal gland produce more sex hormones; and catuba, a Brazilian herb that may increase libido.

Arginine, a biologic precursor to nitric oxide, also is used as a treatment for erectile dysfunction. However, it may reduce blood pressure, so precautions should be taken with patients on antihypertensive medications. The recommended dose of arginine is 500–1,500 mg b.i.d., or 1,000 mg 30 minutes before sex.

Dr. Linkner had no conflicts of interest to disclose.

SAN DIEGO — Before you recommend a treatment for erectile dysfunction, make sure to rule out underlying factors that may contribute to the condition.

“Treat the whole person. Try to take care of other medical problems they might have,” Dr. Edward (Lev) Linkner advised at a meeting sponsored by the Scripps Center for Integrative Medicine and the American Board of Integrative Holistic Medicine.

Medical conditions that should be ruled out include arteriosclerosis, diabetes, Syndrome X (cardiometabolic syndrome), hypothyroidism, and hypogonadism. Emotional etiologies such as depression and relationship difficulties should also be investigated, as should stress and lifestyle habits, especially smoking and alcohol consumption.

“Even bicycling can put abnormal pressure on pelvic nerves and result in erectile dysfunction,” said Dr. Linkner, a founder of the American Board of Holistic Medicine and current member of their board of directors. He is in private practice in Ann Arbor, Mich.

If erectile dysfunction is secondary to a treatable disease or condition, treatment of that disease or condition may be all that's necessary. If not, consider one of the following herbs:

▸ Yohimbine. This herb is derived from bark shavings of a West African tree, Pausinystalia yohimbe. “Some studies show positive results, some don't,” Dr. Linkner said. “The major side effects are hypertension, anxiety, nausea, trembling, and insomnia.” Yohimbine is contraindicated for use by those with liver and kidney disease. It is available in tablet form as the prescription drug Yocon (yohimbine hydrochloride), an alpha2-adrenergic blocker that increases blood flow to the penis. “It may be especially helpful for erectile dysfunction induced by the use of selective serotonin reuptake inhibitors,” Dr. Linkner said. He recommends a dose of one-half to one whole 5.4-mg tablet t.i.d.

▸ Ginkgo biloba. A German study showed that this herb increased blood flow to the penis within 8 weeks of starting treatment, and half of the participants regained normal potency (J. Sex Educ. Ther. 1991;17:53–61). The recommended dose is 60–120 mg b.i.d.

▸ Damiana (Turnera diffusa). Although poorly studied, this herb has been used as an aphrodisiac for centuries, especially in Mexico. Its leaves also are used to make a tea. The recommended dose is 300–450 mg once daily.

▸ Ginseng. Panax ginseng appears to works best for erectile dysfunction, but Siberian ginseng also can be used. Ginsenoside, a triterpenoid saponin, increases nitric oxide and “works like a natural Viagra,” Dr. Linkner said. The recommended dose is 200–1,000 mg.

▸ Muria puama. In European studies, this extract of a shrub (Ptychopetalum olacoides) from the Amazon has been shown to increase erections and libido. It is listed in the British Herbal Pharmacopoeia as a treatment for erectile dysfunction and dysentery.

▸ Maca (Lepidum meyenii). This radishlike plant native to the Peruvian Andes is thought to increase sexual function and stamina. The recommended dose is 1.5–3 g daily.

Adaptogens—herbs that are restorative or enhance physical performance—also may have a role in the treatment of erectile dysfunction, said Dr. Linkner, also of the University of Michigan, Ann Arbor. They “increase energy and resistance to all types of stress, thereby preventing fatigue, enhancing memory, concentration, and improving work performance.” Some adaptogens are cordyceps, ashwagandha, and rhodiola.

Other herbs with historical use in treating erectile dysfunction include oats, which increase stamina and decrease irritability; rosemary, which may help the adrenal gland produce more sex hormones; and catuba, a Brazilian herb that may increase libido.

Arginine, a biologic precursor to nitric oxide, also is used as a treatment for erectile dysfunction. However, it may reduce blood pressure, so precautions should be taken with patients on antihypertensive medications. The recommended dose of arginine is 500–1,500 mg b.i.d., or 1,000 mg 30 minutes before sex.

Dr. Linkner had no conflicts of interest to disclose.

SAN DIEGO — Before you recommend a treatment for erectile dysfunction, make sure to rule out underlying factors that may contribute to the condition.

“Treat the whole person. Try to take care of other medical problems they might have,” Dr. Edward (Lev) Linkner advised at a meeting sponsored by the Scripps Center for Integrative Medicine and the American Board of Integrative Holistic Medicine.

Medical conditions that should be ruled out include arteriosclerosis, diabetes, Syndrome X (cardiometabolic syndrome), hypothyroidism, and hypogonadism. Emotional etiologies such as depression and relationship difficulties should also be investigated, as should stress and lifestyle habits, especially smoking and alcohol consumption.

“Even bicycling can put abnormal pressure on pelvic nerves and result in erectile dysfunction,” said Dr. Linkner, a founder of the American Board of Holistic Medicine and current member of their board of directors. He is in private practice in Ann Arbor, Mich.

If erectile dysfunction is secondary to a treatable disease or condition, treatment of that disease or condition may be all that's necessary. If not, consider one of the following herbs:

▸ Yohimbine. This herb is derived from bark shavings of a West African tree, Pausinystalia yohimbe. “Some studies show positive results, some don't,” Dr. Linkner said. “The major side effects are hypertension, anxiety, nausea, trembling, and insomnia.” Yohimbine is contraindicated for use by those with liver and kidney disease. It is available in tablet form as the prescription drug Yocon (yohimbine hydrochloride), an alpha2-adrenergic blocker that increases blood flow to the penis. “It may be especially helpful for erectile dysfunction induced by the use of selective serotonin reuptake inhibitors,” Dr. Linkner said. He recommends a dose of one-half to one whole 5.4-mg tablet t.i.d.

▸ Ginkgo biloba. A German study showed that this herb increased blood flow to the penis within 8 weeks of starting treatment, and half of the participants regained normal potency (J. Sex Educ. Ther. 1991;17:53–61). The recommended dose is 60–120 mg b.i.d.

▸ Damiana (Turnera diffusa). Although poorly studied, this herb has been used as an aphrodisiac for centuries, especially in Mexico. Its leaves also are used to make a tea. The recommended dose is 300–450 mg once daily.

▸ Ginseng. Panax ginseng appears to works best for erectile dysfunction, but Siberian ginseng also can be used. Ginsenoside, a triterpenoid saponin, increases nitric oxide and “works like a natural Viagra,” Dr. Linkner said. The recommended dose is 200–1,000 mg.

▸ Muria puama. In European studies, this extract of a shrub (Ptychopetalum olacoides) from the Amazon has been shown to increase erections and libido. It is listed in the British Herbal Pharmacopoeia as a treatment for erectile dysfunction and dysentery.

▸ Maca (Lepidum meyenii). This radishlike plant native to the Peruvian Andes is thought to increase sexual function and stamina. The recommended dose is 1.5–3 g daily.

Adaptogens—herbs that are restorative or enhance physical performance—also may have a role in the treatment of erectile dysfunction, said Dr. Linkner, also of the University of Michigan, Ann Arbor. They “increase energy and resistance to all types of stress, thereby preventing fatigue, enhancing memory, concentration, and improving work performance.” Some adaptogens are cordyceps, ashwagandha, and rhodiola.

Other herbs with historical use in treating erectile dysfunction include oats, which increase stamina and decrease irritability; rosemary, which may help the adrenal gland produce more sex hormones; and catuba, a Brazilian herb that may increase libido.

Arginine, a biologic precursor to nitric oxide, also is used as a treatment for erectile dysfunction. However, it may reduce blood pressure, so precautions should be taken with patients on antihypertensive medications. The recommended dose of arginine is 500–1,500 mg b.i.d., or 1,000 mg 30 minutes before sex.

Dr. Linkner had no conflicts of interest to disclose.

A Dutch study of 5,176 men found four factors to be helpful in predicting a man's risk of developing prostate cancer: serum prostate-specific antigen, a previous negative biopsy of the prostate, family history of prostate cancer, and prostate volume.

“PSA assessments combined with the other common predictive factors may offer a personalized assessment of a man's risk of future prostate cancer,” coauthor Monique J. Roobol, Ph.D., said at a briefing before the study's presentation at a symposium on genitourinary cancers.

The men, aged 55–75 years at baseline, were from the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. They were screened every 4 years for prostate cancer.

Using multivariate modeling, with data on factors at baseline and prostate cancer 4 years later, the investigators determined that PSA “is still the most significant predictor … but there are other factors that also contribute to risk estimation,” said Dr. Roobol, an epidemiologist in urologic oncology at Erasmus Medical Center, Rotterdam, the Netherlands.

The average risk of developing biopsy-detectable prostate cancer over 4 years was 5.1% at an average PSA level of 1.5 ng/mL in the study, so men with a serum PSA level above 1.5 ng/mL are at an above-average risk of developing prostate cancer over 4 years—and are at a sevenfold greater risk than are those with levels below this level, Dr. Roobol said.

Other risk factors were found to modify this threshold level: The risk of prostate cancer increases if there is a positive family history of prostate cancer, but decreases with an increasing prostate volume at the same PSA level. Risk also decreases if a man ever had a negative prostate biopsy, she said.

For example, a man with a high serum PSA, a positive family history, a small prostate, and no previous negative biopsy was at a higher than average risk, while a man with a low serum PSA and no additional risk factors was at a very low risk, which increased if he had a positive family history, she explained.

To illustrate the effect of prostate volume on PSA level (with a volume under 40 cc considered a small prostate), she said a man with a high PSA, no previous negative biopsy, and a small prostate was at a higher than average risk, which would decrease if he had a larger prostate.

Based on these findings, she and her associates concluded that a man with a PSA of 1.3 ng/mL, with no previous negative biopsy, a positive family history, and a prostate volume under 40 cc has a 5% risk of developing prostate cancer within 4 years. However, a man with a previous negative biopsy, no family history, and a large prostate can have a PSA up to 4 ng/mL “before reaching the similar threshold of a 5% risk of prostate cancer within 4 years,” Dr. Roobol added.

Using these individualized predictive factors to identify men above certain risk thresholds could make it possible to identify men who “may warrant more frequent screening and vice versa,” she said, adding that “active risk-reduction strategies can be applied, if available.”

The moderator of the press briefing, Dr. Howard Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, described this approach as “a very sensible method of integrating other factors besides PSA into the complex problem of prostate cancer screening and detection.”

The study is in press at the Journal of Urology. Dr. Roobol had no disclosures to report. The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

A Dutch study of 5,176 men found four factors to be helpful in predicting a man's risk of developing prostate cancer: serum prostate-specific antigen, a previous negative biopsy of the prostate, family history of prostate cancer, and prostate volume.

“PSA assessments combined with the other common predictive factors may offer a personalized assessment of a man's risk of future prostate cancer,” coauthor Monique J. Roobol, Ph.D., said at a briefing before the study's presentation at a symposium on genitourinary cancers.

The men, aged 55–75 years at baseline, were from the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. They were screened every 4 years for prostate cancer.

Using multivariate modeling, with data on factors at baseline and prostate cancer 4 years later, the investigators determined that PSA “is still the most significant predictor … but there are other factors that also contribute to risk estimation,” said Dr. Roobol, an epidemiologist in urologic oncology at Erasmus Medical Center, Rotterdam, the Netherlands.

The average risk of developing biopsy-detectable prostate cancer over 4 years was 5.1% at an average PSA level of 1.5 ng/mL in the study, so men with a serum PSA level above 1.5 ng/mL are at an above-average risk of developing prostate cancer over 4 years—and are at a sevenfold greater risk than are those with levels below this level, Dr. Roobol said.

Other risk factors were found to modify this threshold level: The risk of prostate cancer increases if there is a positive family history of prostate cancer, but decreases with an increasing prostate volume at the same PSA level. Risk also decreases if a man ever had a negative prostate biopsy, she said.

For example, a man with a high serum PSA, a positive family history, a small prostate, and no previous negative biopsy was at a higher than average risk, while a man with a low serum PSA and no additional risk factors was at a very low risk, which increased if he had a positive family history, she explained.

To illustrate the effect of prostate volume on PSA level (with a volume under 40 cc considered a small prostate), she said a man with a high PSA, no previous negative biopsy, and a small prostate was at a higher than average risk, which would decrease if he had a larger prostate.

Based on these findings, she and her associates concluded that a man with a PSA of 1.3 ng/mL, with no previous negative biopsy, a positive family history, and a prostate volume under 40 cc has a 5% risk of developing prostate cancer within 4 years. However, a man with a previous negative biopsy, no family history, and a large prostate can have a PSA up to 4 ng/mL “before reaching the similar threshold of a 5% risk of prostate cancer within 4 years,” Dr. Roobol added.

Using these individualized predictive factors to identify men above certain risk thresholds could make it possible to identify men who “may warrant more frequent screening and vice versa,” she said, adding that “active risk-reduction strategies can be applied, if available.”

The moderator of the press briefing, Dr. Howard Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, described this approach as “a very sensible method of integrating other factors besides PSA into the complex problem of prostate cancer screening and detection.”

The study is in press at the Journal of Urology. Dr. Roobol had no disclosures to report. The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

A Dutch study of 5,176 men found four factors to be helpful in predicting a man's risk of developing prostate cancer: serum prostate-specific antigen, a previous negative biopsy of the prostate, family history of prostate cancer, and prostate volume.

“PSA assessments combined with the other common predictive factors may offer a personalized assessment of a man's risk of future prostate cancer,” coauthor Monique J. Roobol, Ph.D., said at a briefing before the study's presentation at a symposium on genitourinary cancers.

The men, aged 55–75 years at baseline, were from the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. They were screened every 4 years for prostate cancer.

Using multivariate modeling, with data on factors at baseline and prostate cancer 4 years later, the investigators determined that PSA “is still the most significant predictor … but there are other factors that also contribute to risk estimation,” said Dr. Roobol, an epidemiologist in urologic oncology at Erasmus Medical Center, Rotterdam, the Netherlands.

The average risk of developing biopsy-detectable prostate cancer over 4 years was 5.1% at an average PSA level of 1.5 ng/mL in the study, so men with a serum PSA level above 1.5 ng/mL are at an above-average risk of developing prostate cancer over 4 years—and are at a sevenfold greater risk than are those with levels below this level, Dr. Roobol said.

Other risk factors were found to modify this threshold level: The risk of prostate cancer increases if there is a positive family history of prostate cancer, but decreases with an increasing prostate volume at the same PSA level. Risk also decreases if a man ever had a negative prostate biopsy, she said.

For example, a man with a high serum PSA, a positive family history, a small prostate, and no previous negative biopsy was at a higher than average risk, while a man with a low serum PSA and no additional risk factors was at a very low risk, which increased if he had a positive family history, she explained.

To illustrate the effect of prostate volume on PSA level (with a volume under 40 cc considered a small prostate), she said a man with a high PSA, no previous negative biopsy, and a small prostate was at a higher than average risk, which would decrease if he had a larger prostate.

Based on these findings, she and her associates concluded that a man with a PSA of 1.3 ng/mL, with no previous negative biopsy, a positive family history, and a prostate volume under 40 cc has a 5% risk of developing prostate cancer within 4 years. However, a man with a previous negative biopsy, no family history, and a large prostate can have a PSA up to 4 ng/mL “before reaching the similar threshold of a 5% risk of prostate cancer within 4 years,” Dr. Roobol added.

Using these individualized predictive factors to identify men above certain risk thresholds could make it possible to identify men who “may warrant more frequent screening and vice versa,” she said, adding that “active risk-reduction strategies can be applied, if available.”

The moderator of the press briefing, Dr. Howard Sandler, chairman of radiation oncology at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, described this approach as “a very sensible method of integrating other factors besides PSA into the complex problem of prostate cancer screening and detection.”

The study is in press at the Journal of Urology. Dr. Roobol had no disclosures to report. The annual Genitourinary Cancers Symposium is sponsored by the American Society of Clinical Oncology, American Society for Therapeutic Radiology and Oncology, and Society of Urologic Oncology.

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

VANCOUVER, B.C. — Chronic kidney disease and heart failure often go hand in hand, and the treatment strategy is similar for both. But there are some finer points to treating patients who have both conditions, according to Dr. Michael Copland, a nephrologist at Vancouver General Hospital.

In patients with cardiorenal syndrome, cardiac and renal dysfunction synergistically amplify each other. The end result is a sharply elevated rate of cardiovascular events. In general, 44% of deaths among patients with chronic kidney disease are due to cardiovascular causes, Dr. Copland said at the annual Canadian Hospitalist Conference.

For patients with kidney disease and heart failure, focus on diet and lifestyle changes, and control of hypertension, diabetes, and lipids. “These are all very cardiovascular-sounding items, but each of these items carries with it a survival benefit in terms of kidney protection for this group of people,” he said.

Renoprotective measures include angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers (ARBs). “We should be doing our best to get all of our patients on ACE inhibitors and ARBs if they have impaired renal function—particularly if they are diabetic, particularly if they have protein in their urine—because that … is associated with preservation of their renal function,” Dr. Copland said at the meeting, which was sponsored by the University of British Columbia.

Renal function should be monitored closely after starting these agents. “We will accept a 25% loss of renal function up front,” he noted, because this short-term trade-off is acceptable for the long-term gain in renal protection. But “if renal function continues to worsen, that's the one group of people in whom I would have to say I would abandon the therapy.”

Development of hyperkalemia is not a reason to discontinue ACE inhibitors and ARBs. “I add on other therapies for their hyperkalemia,” Dr. Copland said. Calcium resonium is typically preferred over sodium polystyrene, because the sodium in the latter will worsen heart failure.

In treating blood pressure, “our initial target would be 130/80 mm Hg, particularly for people who have protein in their urine,” he said. If they still have proteinuria at that target, “we would just keep going as low as they tolerate.”

Recent studies of epoetin alfa have found no cardiovascular benefit for patients with chronic kidney disease, and a trend toward an increased risk of death. “People do feel better, so they stay off of dialysis for longer. So from a cost point of view, which is not a clinical parameter, we use this therapy,” Dr. Copland said.

“Sometimes treating the heart failure actually treats the kidney disease,” he noted. For challenging patients who have both high cardiac output and volume overload, treatments include loop diuretics, nitrates, positive airway pressure, nesiritide, and possibly ultrafiltration, which may offer an alternative to diuresis.

Trials of ultrafiltration have had conflicting results, Dr. Copland said. In the largest one to date—the UNLOAD trial (Ultrafiltration vs. IV Diuretics for Patients Hospitalized for Acute Decompensated CHF)—patients given ultrafiltration had a greater weight loss than patients given diuretics, with a difference of 5 vs. 3 kg (J. Am. Coll. Cardiol. 2007;49:675–83). Subjective dyspnea scores did not differ. But at 90 days, patients given ultrafiltration were less likely to have been rehospitalized for heart failure (18% vs. 32%).

“The problem with all of these trials is that they excluded the sickest groups of people, so I think the jury is still a bit out,” he said.

Dr. Copland said that he sits on the advisory board of Baxter Healthcare.

'Sometimes treating the heart failure actually treats the kidney disease.' DR. COPLAND

PHILADELPHIA — Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, accelerate recovery of renal function, or alter the rate of nonrenal organ failure in the randomized Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study.

Results of previous smaller studies evaluating different strategies of renal support have been inconsistent, and while some studies favored more intensive, higher-dose approaches, such a strategy has not been adopted widely in the United States.

To address the uncertainty as to the optimal approach for acute kidney injury, a large trial was undertaken comparing conventional with intensive renal support. An integrative approach was used, in which hemodynamically stable patients were on standard intermittent therapy and hemodynamically unstable patients were on continuous therapy or sustained low-efficiency dialysis, according to the lead investigator, Dr. Paul M. Palevsky.

“Patients could move between modalities of therapy as their hemodynamic status changed, but they remained within a dosing schedule which was five to six times per week for a total effluent flow rate of 35 mL/kg per hour in the intensive group, and three times per week for a total effluent flow rate of 20 mL/kg per hour in the less-intensive group,” said Dr. Palevsky of the renal section, VA Pittsburgh Healthcare System, and the department of medicine at the University of Pittsburgh.

To be eligible, patients had to be 18 years or older, critically ill, have acute kidney injury consistent with acute tubular necrosis, and have failure of one or more nonrenal organs, or sepsis.

A total of 563 patients were randomized to the intensive group; 561 were randomized to the conventional group.

The populations were well matched at baseline in terms of age, at a mean of 60 years, as well as in race, sex, and ethnicity and in baseline severity of illness and renal function, Dr. Palevsky said at the annual meeting of the American Society of Nephrology.

Mean serum creatinine was 1.1 mg/dL in both groups at baseline. A total of 88% of patients had an estimated glomerular filtration rate of at least 45 mL/min per 1.73 m

Therapy continued for 28 days or until the patient regained renal function, was withdrawn from life-sustaining care, was discharged from the acute care hospital, or died.

Patients in the intensive therapy group received an average of 5.4 sessions per week, with an interval between treatments of 1.1 days, while those in the less-intensive group averaged 3 sessions per week with an interval of 2 days between treatments.

Prescribed and delivered flow rates of venovenous hemodiafiltration were approximately 36 mL/kg per hour for the intensive group and just over 20 mL/kg per hour for the less-intensive group (N. Engl. J. Med. 2008;359:7–20).

“We observed no difference between the two groups on our primary outcome measure of 60-day all-cause mortality, with 53.6% in the intensive arm and 51.5% in the less-intensive arm,” he said.

Complete recovery of kidney function by day 28 was seen in 15% of the intensive therapy group, and in 18% of those in the less-intensive group; there was no difference between the groups in number of days free of organ failure.

“We then looked at 1-year mortality and again there was no difference, with a total mortality of 34% in each group. Among patients who survived to day 60 there was an additional 20% mortality at 1 year,” he said. Not only was mortality not decreased with the intensive therapy, but a greater percentage of patients undergoing intensive therapy experienced treatment-related hypotension and had more hypocalcemia and hypophosphatemia, he noted.

Dr. Palevsky disclosed no conflicts of interest.

PHILADELPHIA — Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, accelerate recovery of renal function, or alter the rate of nonrenal organ failure in the randomized Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study.

Results of previous smaller studies evaluating different strategies of renal support have been inconsistent, and while some studies favored more intensive, higher-dose approaches, such a strategy has not been adopted widely in the United States.

To address the uncertainty as to the optimal approach for acute kidney injury, a large trial was undertaken comparing conventional with intensive renal support. An integrative approach was used, in which hemodynamically stable patients were on standard intermittent therapy and hemodynamically unstable patients were on continuous therapy or sustained low-efficiency dialysis, according to the lead investigator, Dr. Paul M. Palevsky.

“Patients could move between modalities of therapy as their hemodynamic status changed, but they remained within a dosing schedule which was five to six times per week for a total effluent flow rate of 35 mL/kg per hour in the intensive group, and three times per week for a total effluent flow rate of 20 mL/kg per hour in the less-intensive group,” said Dr. Palevsky of the renal section, VA Pittsburgh Healthcare System, and the department of medicine at the University of Pittsburgh.

To be eligible, patients had to be 18 years or older, critically ill, have acute kidney injury consistent with acute tubular necrosis, and have failure of one or more nonrenal organs, or sepsis.

A total of 563 patients were randomized to the intensive group; 561 were randomized to the conventional group.

The populations were well matched at baseline in terms of age, at a mean of 60 years, as well as in race, sex, and ethnicity and in baseline severity of illness and renal function, Dr. Palevsky said at the annual meeting of the American Society of Nephrology.

Mean serum creatinine was 1.1 mg/dL in both groups at baseline. A total of 88% of patients had an estimated glomerular filtration rate of at least 45 mL/min per 1.73 m

Therapy continued for 28 days or until the patient regained renal function, was withdrawn from life-sustaining care, was discharged from the acute care hospital, or died.

Patients in the intensive therapy group received an average of 5.4 sessions per week, with an interval between treatments of 1.1 days, while those in the less-intensive group averaged 3 sessions per week with an interval of 2 days between treatments.

Prescribed and delivered flow rates of venovenous hemodiafiltration were approximately 36 mL/kg per hour for the intensive group and just over 20 mL/kg per hour for the less-intensive group (N. Engl. J. Med. 2008;359:7–20).

“We observed no difference between the two groups on our primary outcome measure of 60-day all-cause mortality, with 53.6% in the intensive arm and 51.5% in the less-intensive arm,” he said.

Complete recovery of kidney function by day 28 was seen in 15% of the intensive therapy group, and in 18% of those in the less-intensive group; there was no difference between the groups in number of days free of organ failure.

“We then looked at 1-year mortality and again there was no difference, with a total mortality of 34% in each group. Among patients who survived to day 60 there was an additional 20% mortality at 1 year,” he said. Not only was mortality not decreased with the intensive therapy, but a greater percentage of patients undergoing intensive therapy experienced treatment-related hypotension and had more hypocalcemia and hypophosphatemia, he noted.

Dr. Palevsky disclosed no conflicts of interest.

PHILADELPHIA — Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, accelerate recovery of renal function, or alter the rate of nonrenal organ failure in the randomized Veterans Affairs/National Institutes of Health Acute Renal Failure Trial Network study.

Results of previous smaller studies evaluating different strategies of renal support have been inconsistent, and while some studies favored more intensive, higher-dose approaches, such a strategy has not been adopted widely in the United States.

To address the uncertainty as to the optimal approach for acute kidney injury, a large trial was undertaken comparing conventional with intensive renal support. An integrative approach was used, in which hemodynamically stable patients were on standard intermittent therapy and hemodynamically unstable patients were on continuous therapy or sustained low-efficiency dialysis, according to the lead investigator, Dr. Paul M. Palevsky.

“Patients could move between modalities of therapy as their hemodynamic status changed, but they remained within a dosing schedule which was five to six times per week for a total effluent flow rate of 35 mL/kg per hour in the intensive group, and three times per week for a total effluent flow rate of 20 mL/kg per hour in the less-intensive group,” said Dr. Palevsky of the renal section, VA Pittsburgh Healthcare System, and the department of medicine at the University of Pittsburgh.

To be eligible, patients had to be 18 years or older, critically ill, have acute kidney injury consistent with acute tubular necrosis, and have failure of one or more nonrenal organs, or sepsis.

A total of 563 patients were randomized to the intensive group; 561 were randomized to the conventional group.

The populations were well matched at baseline in terms of age, at a mean of 60 years, as well as in race, sex, and ethnicity and in baseline severity of illness and renal function, Dr. Palevsky said at the annual meeting of the American Society of Nephrology.

Mean serum creatinine was 1.1 mg/dL in both groups at baseline. A total of 88% of patients had an estimated glomerular filtration rate of at least 45 mL/min per 1.73 m

Therapy continued for 28 days or until the patient regained renal function, was withdrawn from life-sustaining care, was discharged from the acute care hospital, or died.

Patients in the intensive therapy group received an average of 5.4 sessions per week, with an interval between treatments of 1.1 days, while those in the less-intensive group averaged 3 sessions per week with an interval of 2 days between treatments.

Prescribed and delivered flow rates of venovenous hemodiafiltration were approximately 36 mL/kg per hour for the intensive group and just over 20 mL/kg per hour for the less-intensive group (N. Engl. J. Med. 2008;359:7–20).

“We observed no difference between the two groups on our primary outcome measure of 60-day all-cause mortality, with 53.6% in the intensive arm and 51.5% in the less-intensive arm,” he said.

Complete recovery of kidney function by day 28 was seen in 15% of the intensive therapy group, and in 18% of those in the less-intensive group; there was no difference between the groups in number of days free of organ failure.

“We then looked at 1-year mortality and again there was no difference, with a total mortality of 34% in each group. Among patients who survived to day 60 there was an additional 20% mortality at 1 year,” he said. Not only was mortality not decreased with the intensive therapy, but a greater percentage of patients undergoing intensive therapy experienced treatment-related hypotension and had more hypocalcemia and hypophosphatemia, he noted.

Dr. Palevsky disclosed no conflicts of interest.