The PSA screening test for prostate cancer is not perfect. It can indicate cancer when none is present and miss life-threatening tumors. But a new study suggests the test is more reliable in men taking dutasteride (Avodart®), a drug widely prescribed to shrink an enlarged prostate gland.
Dutasteride lowers PSA levels by about half within six months. But the researchers found that even a slight rise in PSA levels among men taking the drug was a stronger indicator of prostate cancer, particularly aggressive tumors that require early diagnosis and treatment, than rising PSA levels in men who took a placebo.
"Dutasteride stabilizes the amount of PSA that comes from enlarged prostates and low-grade cancers," says lead author Gerald Andriole, MD, the Robert Killian Royce, MD, Distinguished Professor and chief of urologic surgery at Washington University School of Medicine in St. Louis. "This enhances a rising PSA's ability to detect high-grade cancers that require early diagnosis and treatment, while reducing the discovery of tumors that are unlikely to cause harm if left untreated."
The study is now available online and will be published in January in the Journal of Urology.
The PSA test measures the amount of prostate-specific antigen in the blood. The larger a man's prostate, the more PSA he produces. Elevated levels can point to cancer. But PSA often rises naturally as men age, mainly due to benign prostatic hyperplasia (BPH), a progressive enlargement of the prostate. This leads to many false positive PSA tests for cancer. Indeed, biopsies only find cancer in about one in four men with an elevated PSA.
In the new study, the researchers looked more closely at data from a four-year trial that evaluated whether dutasteride could reduce the risk of detecting prostate cancer in men with an increased risk of the disease. The study involved 8,231 men ages 50-75 who were randomly assigned to receive a placebo or a daily 0.5 mg dose of dutasteride. The men had elevated PSA levels (2.5 ng/ml-10 ng/ml) but no evidence of cancer on biopsies performed within six months of enrolling in the trial.
Results published earlier this year in the New England Journal of Medicine showed that dutasteride reduced the risk of a prostate cancer diagnosis by 23 percent. Dutasteride appears to keep tumors small or shrink them to the point that they are less likely to be detected by a biopsy, says Andriole, who led the steering committee that oversaw the earlier trial.
In the current analysis, the researchers looked at the performance of PSA as a marker for prostate cancer, particularly for aggressive cancer. Among men taking dutasteride, the investigators found that any subsequent rise in PSA levels over the course of the study was more likely to be linked to aggressive, high-grade tumors (Gleason score 7-10), compared to rising PSA levels in men on a placebo.
The Gleason scoring system measures tumor aggressiveness based on biopsy results and can range from 2-10, with 10 being the most aggressive.
"If a man is taking dutastride and his PSA level starts to rise, he has a higher chance of having an aggressive cancer," Andriole says. "This makes PSA a more effective screening tool for prostate cancer but even more importantly for aggressive cancer."
Over four years, PSA levels increased in 72 percent of men taking a placebo and only 29 percent of men taking dutasteride, the data show. However, there was no significant difference in high-grade tumors between the two groups.
Men taking dutasteride were almost twice as likely to have aggressive prostate cancer if their PSA levels rose, compared to men whose PSA levels went up while taking a placebo. In men with any increase in PSA, aggressive, high-grade tumors were diagnosed in 13.2 percent of those on dutasteride and 7.7 percent of those taking a placebo.
Even a slight rise in PSA levels was a more accurate predictor of aggressive tumors. Among men whose PSA levels increased one point or less, 10.3 percent of those taking dutasteride had aggressive cancer, compared with 5.4 percent taking a placebo.
That trend also held for larger increases in PSA levels. Among men whose PSA levels rose two points or more, nearly 20.9 percent of those taking dutasteride had aggressive cancer, compared with 9.8 percent taking a placebo.
In contrast, PSA levels tended to decrease or remain stable in men taking dutasteride who either had low-grade tumors or no cancer at all.
The study's authors do not suggest that men take dutasteride just to get a more accurate readout of PSA levels attributable to cancer. "However, men who are taking dutasteride can be confident that the drug does not weaken the ability of PSA to find cancer if it develops," Andriole says. "Rather, the drug enhances the ability to find cancer if PSA levels are rising."
Washington University School of Medicine
Showing posts with label Prostate Cancer Detection. Show all posts
Showing posts with label Prostate Cancer Detection. Show all posts
Thursday, December 16, 2010
Thursday, December 2, 2010
Genetic mutations associated with increased PSA and prostate cancer
Austrian researchers have uncovered mutations throughout the mitochondrial genome that are associated with prostate cancer. An exciting aspect of the study, published by Cell Press on December 2 in the American Journal of Human Genetics, is the association of tRNA mutations with elevated levels of prostate-specific antigen (PSA) in Austrian men diagnosed with various stages of prostate cancer.
Prostate cancer is among the most prevalent cancers diagnosed in the United States and Europe. The most common and noninvasive way to detect prostate cancer is to check PSA levels. This is a routine part of men's health checks starting around the age of 50. Elevated PSA levels indicate the possibility of prostate cancer. Prostate biopsies are used for verification of PSA results and cancer diagnosis. Treatment may include surgery, radiation, or chemotherapy. "Identifying genetic variants associated with prostate cancer and its primary biomarker is an exciting accomplishment," says Dr. Anita Kloss-Brandstätter, the lead author of this study.
Recognizing the important role mtDNA mutations have been found to play in development and progression of many types of cancer, Dr. Kloss-Brandstätter and colleagues set out to sequence the entire mitochondrial genome in 30 prostate cancer patients. "The influence of mtDNA on the origin and progression of prostate cancer is still not understood, leaving much to be discovered," says Dr. Kloss-Brandstätter. The group used a high-quality sequencing approach to detect differences in mtDNA sequence between cancerous and noncancerous tissue from the same 30 men. "It is the first study targeting the entire mitochondrial genome in prostate cancer and benign tissue from the same patient with a superior sequencing strategy," notes Dr. Kloss-Brandstätter.
By examining both the frequency and types of somatic mtDNA mutations in prostate cancer patients, Dr. Kloss-Brandstätter and colleagues were able to identify several genetic changes having clinical significance. They suggest that, "sequencing of selected mitochondrial regions will likely result in a mutation spectrum useful for prognosis." Perhaps the most striking finding of the study is the association between somatic tRNA mutations and PSA levels at diagnosis. "Patients with a somatic tRNA mutation had a significantly higher PSA value at diagnosis than did patients without a somatic tRNA mutation," explains Dr. Kloss-Brandstätter. "These findings will potentially help others monitor malignant transformation, tumor progression, and metastasis," she says.
Cell Press
Prostate cancer is among the most prevalent cancers diagnosed in the United States and Europe. The most common and noninvasive way to detect prostate cancer is to check PSA levels. This is a routine part of men's health checks starting around the age of 50. Elevated PSA levels indicate the possibility of prostate cancer. Prostate biopsies are used for verification of PSA results and cancer diagnosis. Treatment may include surgery, radiation, or chemotherapy. "Identifying genetic variants associated with prostate cancer and its primary biomarker is an exciting accomplishment," says Dr. Anita Kloss-Brandstätter, the lead author of this study.
Recognizing the important role mtDNA mutations have been found to play in development and progression of many types of cancer, Dr. Kloss-Brandstätter and colleagues set out to sequence the entire mitochondrial genome in 30 prostate cancer patients. "The influence of mtDNA on the origin and progression of prostate cancer is still not understood, leaving much to be discovered," says Dr. Kloss-Brandstätter. The group used a high-quality sequencing approach to detect differences in mtDNA sequence between cancerous and noncancerous tissue from the same 30 men. "It is the first study targeting the entire mitochondrial genome in prostate cancer and benign tissue from the same patient with a superior sequencing strategy," notes Dr. Kloss-Brandstätter.
By examining both the frequency and types of somatic mtDNA mutations in prostate cancer patients, Dr. Kloss-Brandstätter and colleagues were able to identify several genetic changes having clinical significance. They suggest that, "sequencing of selected mitochondrial regions will likely result in a mutation spectrum useful for prognosis." Perhaps the most striking finding of the study is the association between somatic tRNA mutations and PSA levels at diagnosis. "Patients with a somatic tRNA mutation had a significantly higher PSA value at diagnosis than did patients without a somatic tRNA mutation," explains Dr. Kloss-Brandstätter. "These findings will potentially help others monitor malignant transformation, tumor progression, and metastasis," she says.
Cell Press
'Watchful waiting' has a new set of eyes
A UCSF research collaboration with GE Healthcare has produced the first results in humans of a new technology that promises to rapidly assess the presence and aggressiveness of prostate tumors in real time, by imaging the tumor's metabolism.
This is the first time researchers have used this technology to conduct real-time metabolic imaging in human patients and represents a revolutionary approach to assessing the precise outlines of a tumor, its response to treatment and how quickly it is growing.
Data on the first four patients are being presented today at the Radiology Society of North America's weeklong annual conference.
The initial results validate extensive preclinical research that has linked the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.
So far, the technology has produced the same response in human patients' tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of Radiology and Biomedical Imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF.
"This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors," Nelson said. "We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for."
For an oncologist, that means immediate feedback on whether a patient should continue in "watchful waiting" or pursue treatment, and also whether a therapy is working, either during standard treatment or in a clinical trial.
"If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient's outcome and quality of life," said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.
More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancers in men nationwide and also one of the leading causes of cancer death in men, according to the Centers for Disease Control.
Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.
"This test could give both physicians and patients the information they need to make that decision," said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumor's production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.
The method uses compounds involved in normal tissue function – in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid – and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.
That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272O C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state.
The result is a highly defined and clear image of the tumor's outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.
The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice. As the birthplace of the field of clinical pharmacy and one of only a handful of schools nationwide with drug production expertise, the UCSF School of Pharmacy and contributions of Marcus Ferrone, PharmD, and his colleagues in the Drug Products Services Laboratory were integral to this process.
The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.
"All of that insight is why we moved this technology to Northern California," said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. "This is a huge accomplishment UCSF and QB3 have achieved. They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical center. We are delighted with the speed of progress of this collaboration. The science is very exciting."
The first trial involves men with prostate cancer involved in the "watchful waiting" phase of treatment, Nelson said. Future studies will directly compare these data with the results from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.
The project's funding through the National Institute of Biomedical Imaging and Bioengineering, in the National Institutes of Health, was critical in adapting this technology for humans and developing new ways to obtain the MR metabolic imaging data. The project received further support from the American Recovery & Reinvestment Act and the UC Discovery Program.
Initial development of this instrumentation and its demonstration of proof of principle was conducted by Jan Henrik Ardenkjaer-Larsen, Klaes Golman and other colleagues from across GE. UCSF customized that principle and obtained the Investigational New Drug (IND) approval from the Food and Drug Administration to use the hyperpolarized pyruvate in humans.
These concepts are still investigational and not being offered for sale, nor have they been cleared or approved by the FDA for commercial availability.
University of California - San Francisco
This is the first time researchers have used this technology to conduct real-time metabolic imaging in human patients and represents a revolutionary approach to assessing the precise outlines of a tumor, its response to treatment and how quickly it is growing.
Data on the first four patients are being presented today at the Radiology Society of North America's weeklong annual conference.
The initial results validate extensive preclinical research that has linked the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.
So far, the technology has produced the same response in human patients' tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of Radiology and Biomedical Imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF.
"This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors," Nelson said. "We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for."
For an oncologist, that means immediate feedback on whether a patient should continue in "watchful waiting" or pursue treatment, and also whether a therapy is working, either during standard treatment or in a clinical trial.
"If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient's outcome and quality of life," said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.
More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancers in men nationwide and also one of the leading causes of cancer death in men, according to the Centers for Disease Control.
Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.
"This test could give both physicians and patients the information they need to make that decision," said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumor's production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.
The method uses compounds involved in normal tissue function – in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid – and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.
That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272O C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state.
The result is a highly defined and clear image of the tumor's outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.
The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice. As the birthplace of the field of clinical pharmacy and one of only a handful of schools nationwide with drug production expertise, the UCSF School of Pharmacy and contributions of Marcus Ferrone, PharmD, and his colleagues in the Drug Products Services Laboratory were integral to this process.
The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.
"All of that insight is why we moved this technology to Northern California," said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. "This is a huge accomplishment UCSF and QB3 have achieved. They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical center. We are delighted with the speed of progress of this collaboration. The science is very exciting."
The first trial involves men with prostate cancer involved in the "watchful waiting" phase of treatment, Nelson said. Future studies will directly compare these data with the results from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.
The project's funding through the National Institute of Biomedical Imaging and Bioengineering, in the National Institutes of Health, was critical in adapting this technology for humans and developing new ways to obtain the MR metabolic imaging data. The project received further support from the American Recovery & Reinvestment Act and the UC Discovery Program.
Initial development of this instrumentation and its demonstration of proof of principle was conducted by Jan Henrik Ardenkjaer-Larsen, Klaes Golman and other colleagues from across GE. UCSF customized that principle and obtained the Investigational New Drug (IND) approval from the Food and Drug Administration to use the hyperpolarized pyruvate in humans.
These concepts are still investigational and not being offered for sale, nor have they been cleared or approved by the FDA for commercial availability.
University of California - San Francisco
Monday, November 29, 2010
New prostate cancer imaging shows real-time tumor metabolism
A UCSF research collaboration with GE Healthcare has produced the first results in humans of a new technology that promises to rapidly assess the presence and aggressiveness of prostate tumors in real time, by imaging the tumor's metabolism.
This is the first time researchers have used this technology to conduct real-time metabolic imaging in a human patient and represents a revolutionary approach to assessing the precise outlines of a tumor, its response to treatment and how quickly it is growing.
Data on the first four patients will be presented on Dec. 2 at the Radiology Society of North America's weeklong annual conference.
The initial results validate extensive preclinical research that has linked the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.
So far, the technology has produced the same response in human patients' tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of Radiology and Biomedical Imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF.
"This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors," Nelson said. "We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for."
For an oncologist, that means immediate feedback on whether a patient's therapy is working, either during standard treatment or in a clinical trial.
"If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient's outcome and quality of life," said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.
More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancer in men nationwide and also one of the leading causes of cancer death in men, according to the Centers for Disease Control.
Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.
"This test could give both physicians and patients the information they need to make that decision," said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumor's production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.
The method uses compounds involved in normal tissue function – in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid – and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.
That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272O C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state.
The result is a highly defined and clear image of the tumor's outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.
The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice. As the birthplace of the field of clinical pharmacy and one of only a handful of schools nationwide with drug production expertise, the UCSF School of Pharmacy and contributions of Marcus Ferrone, PharmD, and his colleagues in the Drug Products Services Laboratory were integral to this process.
The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.
"All of that insight is why we moved this technology to Northern California," said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. "This is a huge accomplishment UCSF and QB3 have achieved. They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical center. We are delighted with the speed of progress of this collaboration. The science is very exciting."
The first trial involves men with prostate cancer involved in the "watchful waiting" phase of treatment, Nelson said. Future studies will directly compare these data with the results from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.
The project's funding through the National Institute of Biomedical Imaging and Bioengineering, in the National Institutes of Health, was critical in adapting this technology for humans and developing new ways to obtain the MR metabolic imaging data. The project received further support from the American Recovery & Reinvestment Act and the UC Discovery Program.
Initial development of this instrumentation and its demonstration of proof of principle was conducted by Jan Henrik Ardenkjaer-Larsen, Klaes Golman and other colleagues from across GE. UCSF customized that principle and obtained the Investigational New Drug (IND) approval from the Food and Drug Administration to use the hyperpolarized pyruvate in humans.
University of California - San Francisco
This is the first time researchers have used this technology to conduct real-time metabolic imaging in a human patient and represents a revolutionary approach to assessing the precise outlines of a tumor, its response to treatment and how quickly it is growing.
Data on the first four patients will be presented on Dec. 2 at the Radiology Society of North America's weeklong annual conference.
The initial results validate extensive preclinical research that has linked the speed at which tumors metabolize nutrients to the aggressiveness of their growth. The new imaging technique also has been used to show early biochemical changes in animal tumors in real time as they respond to medication therapy, long before a physical change occurs.
So far, the technology has produced the same response in human patients' tumors as it did in laboratory studies, even at the lowest dose, according to Sarah Nelson, PhD, a professor of Radiology and Biomedical Imaging and a member of the California Institute for Quantitative Biosciences (QB3) at UCSF.
"This is a key milestone that could dramatically change clinical treatment for prostate cancer and many other tumors," Nelson said. "We had shown this worked in animal models and tissues samples. Now, in men, we are seeing exactly the type of results we had hoped for."
For an oncologist, that means immediate feedback on whether a patient's therapy is working, either during standard treatment or in a clinical trial.
"If we can see whether a therapy is effective in real time, we may be able to make early changes in that treatment that could have a very real impact on a patient's outcome and quality of life," said Andrea Harzstark, MD, an oncologist with the UCSF Helen Diller Family Comprehensive Cancer Center who is leading the clinical aspects of the current study.
More than 200,000 men are diagnosed with prostate cancer each year and 28,000 die from it, making it one of the most common cancer in men nationwide and also one of the leading causes of cancer death in men, according to the Centers for Disease Control.
Yet the disease ranges widely in its rate of growth and aggressiveness, according to John Kurhanewicz, PhD, a UCSF expert in prostate cancer imaging. As a result, there is great debate over the ideal strategy for treating the disease, he said, leaving patients with a difficult and potentially life-changing decision over how aggressively to respond to the disease.
"This test could give both physicians and patients the information they need to make that decision," said Kurhanewicz, whose work with Dan Vigneron, PhD, and their colleagues from the UCSF Department of Radiology and Biomedical Imaging first linked a prostate tumor's production of lactate to tumor aggressiveness. Other researchers also have linked that lactate production to tumor aggressiveness and response to therapy in other cancers.
The method uses compounds involved in normal tissue function – in this case, pyruvate, which is a naturally occurring by-product of glucose, and lactate, also known as lactic acid – and uses newly developed equipment to increase the visibility of those compounds by a factor of 50,000 in a magnetic resonance imaging (MRI) scanner.
That process requires pyruvate to be prepared in a strong magnetic field at a temperature of minus 272O C, then rapidly warmed to body temperature and transferred to the patient in an MRI scanner before the polarization decays back to its native state.
The result is a highly defined and clear image of the tumor's outline, as well as a graph of the amount of pyruvate in the tumor and the rate at which the tumor converts the pyruvate into lactate.
The sterile production process requires a dedicated clinical pharmacist with the knowledge of both quality control and of clinical practice. As the birthplace of the field of clinical pharmacy and one of only a handful of schools nationwide with drug production expertise, the UCSF School of Pharmacy and contributions of Marcus Ferrone, PharmD, and his colleagues in the Drug Products Services Laboratory were integral to this process.
The procedure must take place within minutes, which meant integrating a clean room into the scanning facility. QB3 also worked with GE Healthcare in designing Byers Hall, in which the Surbeck Laboratory of Advanced Imaging is housed, to accommodate the extremely strong magnetic field of the MRI scanner and enable time-sensitive experiments.
"All of that insight is why we moved this technology to Northern California," said Jonathan Murray, general manager, Metabolic Imaging at GE Healthcare. "This is a huge accomplishment UCSF and QB3 have achieved. They brought together the best engineering from UC Berkeley and the best bioscience and pharmacy knowledge from UCSF, and are now demonstrating the technology in a world-renowned academic medical center. We are delighted with the speed of progress of this collaboration. The science is very exciting."
The first trial involves men with prostate cancer involved in the "watchful waiting" phase of treatment, Nelson said. Future studies will directly compare these data with the results from surgically removed tumors and will look at how specific therapies change tumor metabolism. UCSF also will be studying the process for use in brain tumor patients.
The project's funding through the National Institute of Biomedical Imaging and Bioengineering, in the National Institutes of Health, was critical in adapting this technology for humans and developing new ways to obtain the MR metabolic imaging data. The project received further support from the American Recovery & Reinvestment Act and the UC Discovery Program.
Initial development of this instrumentation and its demonstration of proof of principle was conducted by Jan Henrik Ardenkjaer-Larsen, Klaes Golman and other colleagues from across GE. UCSF customized that principle and obtained the Investigational New Drug (IND) approval from the Food and Drug Administration to use the hyperpolarized pyruvate in humans.
University of California - San Francisco
Friday, October 15, 2010
Urine Test For Prostate Cancer Hopeful
New research led by UK scientists has shown that a protein in urine could be a reliable marker for prostate cancer risk, and although there is still a lot of work to be done to move it from the laboratory to the clinic, the finding is raising hopes that an easy and reliable clinical test for prostate cancer is now much closer.
The study, led by scientists from the Cancer Research UK (CRUK) Cambridge Research Institute and The Institute of Cancer Research (ICR), was published online on 13 October in PLoS ONE, an open access scientific journal from the Public Library of Science. Scientists from other research centres in the UK, Australia, Spain and the US were also involved in the study.
Read more at Medical News Today.
The study, led by scientists from the Cancer Research UK (CRUK) Cambridge Research Institute and The Institute of Cancer Research (ICR), was published online on 13 October in PLoS ONE, an open access scientific journal from the Public Library of Science. Scientists from other research centres in the UK, Australia, Spain and the US were also involved in the study.
Read more at Medical News Today.
Thursday, September 30, 2010
New Prostate Cancer Test Could Be 90 Per Cent Accurate
According to early findings of a pilot study presented at a conference in the US this week, the controversy surrounding prostate cancer screening could be about to change: a UK company has developed a panel of biomarkers that appears to distinguish samples of prostate cancer from samples of benign prostate disease and healthy prostate tissue 90 per cent of the time, considerably higher than current diagnostic tests.
Oxford Gene Technology (OGT) said in their pilot study involving 73 prostate cancer and 60 control samples, they identified a set of biomarkers that differentiated prostate cancer from control samples with both "sensitivity and specificity above 90 per cent."
Read more at Medical News Today.
Oxford Gene Technology (OGT) said in their pilot study involving 73 prostate cancer and 60 control samples, they identified a set of biomarkers that differentiated prostate cancer from control samples with both "sensitivity and specificity above 90 per cent."
Read more at Medical News Today.
Wednesday, September 29, 2010
Novel Test Following Prostate Surgery Could Detect Cancer Recurrence Earlier
• Earlier PSA detection could affirm that cancer is “cured” or needs earlier treatment.
• Test is 1,000 to 10,000 times more sensitive than leading PSA tests.
• Able to measure PSA in all blood samples previously categorized as “below detection levels.”
A new test could reliably detect early increases in prostate specific antigen (PSA) levels — a biomarker commonly used to measure the recurrence of prostate cancer — in men who have undergone prostate cancer-treating surgery. Earlier detection of these rising levels would allow men with cancer recurrence to undergo earlier, more effective treatment for potentially better outcomes.
Data measuring the efficacy of this new test were presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.
“AccuPSA is a simple blood test that can tell a physician important information about prostate specific antigen levels after radical prostatectomy,” said David Wilson, Ph.D., senior director of product development at Quanterix Corporation, the manufacturer of the test. “AccuPSA has the potential to eliminate unnecessary treatments and enable earlier detection of recurrence, which may lead to earlier treatment, better outcomes and have a positive impact on health care costs.”
After undergoing radical prostatectomy, many men remain at a significant risk for cancer recurrence. Because of this, patients are monitored very closely for rapid increases in PSA, which may signal cancer recurrence.
Standard PSA tests are primarily used to screen asymptomatic men for prostate cancer. However, once the prostate is surgically removed, PSA levels are usually undetectable using standard tests, according to Wilson. AccuPSA, which uses Quanterix’s proprietary Single Molecule Array (SiMoA™) technology, is able to detect PSA with unprecedented sensitivity, and at much lower levels than standard PSA tests because it can selectively capture and measure individual PSA molecules.
To determine the accuracy of the novel blood test, PSA levels were measured in blood taken from 60 men who had undergone radical prostatectomy. These specimens had all been categorized as being below the detection limit of standard PSA tests. However, using AccuPSA, researchers were able to measure PSA in all of the samples.
“After radical prostatectomy, many important questions remain for the physician and the patient,” Wilson said. “AccuPSA is designed to help the physician and patients to become better informed by measuring PSA after radical prostatectomy and establishing if the cancer is gone or has metastasized or recurred.”
The next step in this research is to conduct a large retrospective clinical study to formally establish the utility of this test.
“We hope to be able to establish with our clinical study that nadir values — the lowest value of PSA that occurs post-surgery — are predictive of prostate cancer recurrence,” he said. “What this might mean for a post-radical prostatectomy patient is that a nadir PSA level below an established threshold could indicate if the patient is effectively considered ‘cured.’”
American Association for Cancer Research
• Test is 1,000 to 10,000 times more sensitive than leading PSA tests.
• Able to measure PSA in all blood samples previously categorized as “below detection levels.”
A new test could reliably detect early increases in prostate specific antigen (PSA) levels — a biomarker commonly used to measure the recurrence of prostate cancer — in men who have undergone prostate cancer-treating surgery. Earlier detection of these rising levels would allow men with cancer recurrence to undergo earlier, more effective treatment for potentially better outcomes.
Data measuring the efficacy of this new test were presented at the Fourth AACR International Conference on Molecular Diagnostics in Cancer Therapeutic Development.
“AccuPSA is a simple blood test that can tell a physician important information about prostate specific antigen levels after radical prostatectomy,” said David Wilson, Ph.D., senior director of product development at Quanterix Corporation, the manufacturer of the test. “AccuPSA has the potential to eliminate unnecessary treatments and enable earlier detection of recurrence, which may lead to earlier treatment, better outcomes and have a positive impact on health care costs.”
After undergoing radical prostatectomy, many men remain at a significant risk for cancer recurrence. Because of this, patients are monitored very closely for rapid increases in PSA, which may signal cancer recurrence.
Standard PSA tests are primarily used to screen asymptomatic men for prostate cancer. However, once the prostate is surgically removed, PSA levels are usually undetectable using standard tests, according to Wilson. AccuPSA, which uses Quanterix’s proprietary Single Molecule Array (SiMoA™) technology, is able to detect PSA with unprecedented sensitivity, and at much lower levels than standard PSA tests because it can selectively capture and measure individual PSA molecules.
To determine the accuracy of the novel blood test, PSA levels were measured in blood taken from 60 men who had undergone radical prostatectomy. These specimens had all been categorized as being below the detection limit of standard PSA tests. However, using AccuPSA, researchers were able to measure PSA in all of the samples.
“After radical prostatectomy, many important questions remain for the physician and the patient,” Wilson said. “AccuPSA is designed to help the physician and patients to become better informed by measuring PSA after radical prostatectomy and establishing if the cancer is gone or has metastasized or recurred.”
The next step in this research is to conduct a large retrospective clinical study to formally establish the utility of this test.
“We hope to be able to establish with our clinical study that nadir values — the lowest value of PSA that occurs post-surgery — are predictive of prostate cancer recurrence,” he said. “What this might mean for a post-radical prostatectomy patient is that a nadir PSA level below an established threshold could indicate if the patient is effectively considered ‘cured.’”
American Association for Cancer Research
Monday, September 13, 2010
Early prostate cancer detection, screening: No benefit for men with low baseline PSA value
Men aged 55 to 74 years who have low baseline blood levels of prostate specific antigen (PSA) are not likely to benefit from further screening and treatment. That is the conclusion of a new study published early online in Cancer, a peer-reviewed journal of the American Cancer Society. The aim of the study is to help physicians and patients weigh the pros and cons of prostate cancer screening and early detection.
Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of death from cancer in men in Western countries. While a man in the United State has about a one in six chance of being diagnosed with prostate cancer during his lifetime, his risk of dying from the disease is relatively low (about one in 36).
Pim van Leeuwen, MD, of the Erasmus University Medical Centre in Rotterdam, the Netherlands, led a team that tried to identify if the baseline PSA can predict which men have most benefit from additional screening. The investigators compared the incidence of prostate cancer with deaths from prostate cancer as related to PSA levels in 43,987 men aged 55 to 74 years who were enrolled between 1993 and 1999 in the European Randomized Study of Screening for Prostate Cancer (ERSPC) study in the Netherlands, Sweden, and Finland. An additional 42,503 men in the same age range from Northern Ireland who had their PSA levels measured between 1994 and 1999 were also included. All men had PSA levels that were under 20 ng/ml at the start of the study, and were followed for prostate cancer incidence and causes of death through 2006.
A total of 5,861 prostate cancer cases arose during the study period, and prostate cancer death rates were highest in men with high PSA levels at the start of the study. The researchers found that for men with PSA levels between zero and 1.9 ng/ml, a total of 24,642 men would need to be screened and 724 cases of prostate cancer would need to be treated to prevent just one death from prostate cancer. For men with PSA levels between 10 and 19.9 ng/ml, the benefits of screening and treatment were more favorable: a total of 133 men would need to be screened to prevent one death from prostate cancer.
This study indicates that a man's PSA level before diagnosis is a strong predictor for his risk of dying from prostate cancer. For men aged 55 to 74 years who have low PSA levels, the benefits of aggressive follow-up testing and treatment seem limited. Without providing benefits, they may increase prostate cancer diagnoses and lead to overtreatment and increased costs.
"The greatest benefits of early detection programs may be when men, aged 55-74 years, are diagnosed and treated when their serum PSA is in the range 4.0-9.9 ng/ml or 10.0-19.9 ng/ml. Furthermore, following research efforts that recommend more intensive PSA based screening by lowering the PSA cut-off may greatly increase the number of men that need additional investigations and treatment, whilst having little effect on the reduction of prostate cancer mortality," the authors wrote.
Dr. van Leeuwen cautioned that,"the results presented in the current study are limited due to the relatively short follow-up. Consequently the pros of early detection and screening may increase with longer the follow-up while the cons may relatively decrease."
Wiley-Blackwell
Prostate cancer is the most commonly diagnosed malignancy and the third leading cause of death from cancer in men in Western countries. While a man in the United State has about a one in six chance of being diagnosed with prostate cancer during his lifetime, his risk of dying from the disease is relatively low (about one in 36).
Pim van Leeuwen, MD, of the Erasmus University Medical Centre in Rotterdam, the Netherlands, led a team that tried to identify if the baseline PSA can predict which men have most benefit from additional screening. The investigators compared the incidence of prostate cancer with deaths from prostate cancer as related to PSA levels in 43,987 men aged 55 to 74 years who were enrolled between 1993 and 1999 in the European Randomized Study of Screening for Prostate Cancer (ERSPC) study in the Netherlands, Sweden, and Finland. An additional 42,503 men in the same age range from Northern Ireland who had their PSA levels measured between 1994 and 1999 were also included. All men had PSA levels that were under 20 ng/ml at the start of the study, and were followed for prostate cancer incidence and causes of death through 2006.
A total of 5,861 prostate cancer cases arose during the study period, and prostate cancer death rates were highest in men with high PSA levels at the start of the study. The researchers found that for men with PSA levels between zero and 1.9 ng/ml, a total of 24,642 men would need to be screened and 724 cases of prostate cancer would need to be treated to prevent just one death from prostate cancer. For men with PSA levels between 10 and 19.9 ng/ml, the benefits of screening and treatment were more favorable: a total of 133 men would need to be screened to prevent one death from prostate cancer.
This study indicates that a man's PSA level before diagnosis is a strong predictor for his risk of dying from prostate cancer. For men aged 55 to 74 years who have low PSA levels, the benefits of aggressive follow-up testing and treatment seem limited. Without providing benefits, they may increase prostate cancer diagnoses and lead to overtreatment and increased costs.
"The greatest benefits of early detection programs may be when men, aged 55-74 years, are diagnosed and treated when their serum PSA is in the range 4.0-9.9 ng/ml or 10.0-19.9 ng/ml. Furthermore, following research efforts that recommend more intensive PSA based screening by lowering the PSA cut-off may greatly increase the number of men that need additional investigations and treatment, whilst having little effect on the reduction of prostate cancer mortality," the authors wrote.
Dr. van Leeuwen cautioned that,"the results presented in the current study are limited due to the relatively short follow-up. Consequently the pros of early detection and screening may increase with longer the follow-up while the cons may relatively decrease."
Wiley-Blackwell
Wednesday, July 28, 2010
Don't Blame The PSA Test For The 'Overtreatment' Of Prostate Cancer
A new report published in the July 26 issue of Archives of Internal Medicine claims many men who are diagnosed with prostate cancer undergo aggressive therapy, even when they have low PSA scores and low-risk disease, saying "these results underscore the fact that PSA level, the current biomarker, is not a sufficient basis for treatment decisions."
"When it comes to 'overtreatment,' the PSA test is not to blame it's what happens next," said Skip Lockwood, ZERO's CEO.
Read more at Medical News Today.
"When it comes to 'overtreatment,' the PSA test is not to blame it's what happens next," said Skip Lockwood, ZERO's CEO.
Read more at Medical News Today.
Saturday, July 24, 2010
Proenzyme Prostate Specific Antigen Is More Accurate Than Total And Free Prostate Specific Antigen In Differentiating
Prostate Specific Antigen (PSA), the primary means of diagnosing prostate cancer in the modern era, lacks specificity in differentiating benign from malignant disease. Thus clinical decisions based on PSA may lead to unnecessary biopsies in some while overlooking biopsies in others. p2PSA has emerged from studies looking at archived serum samples over the past several years as a better screening tool for detecting prostate cancer.
Read more at Medical News Today.
Read more at Medical News Today.
Saturday, June 19, 2010
Study: Dogs Can Detect Prostate Cancer
A study presented earlier this month at a meeting of the American Urological Association by a team of French researchers found that a particular dog breed, Belgian Malinois shepherd dogs, can be trained to detect prostate cancer.
Doctors at Paris's Hospital Tenon trained the dogs to distinguish between the smell of urine from men with prostate cancer and those without it. At the end of the training and study the dogs correctly identified 63 out of 66 samples.
Read more at Yahoo News.
Doctors at Paris's Hospital Tenon trained the dogs to distinguish between the smell of urine from men with prostate cancer and those without it. At the end of the training and study the dogs correctly identified 63 out of 66 samples.
Read more at Yahoo News.
Sunday, June 13, 2010
Are periodontal disease and prostatitis linked?
Researchers from Case Western Reserve University School of Dental Medicine and University Hospitals Case Medical Center report initial results from a small sample that inflammation from gum disease and prostate problems just might be linked. They discuss their new evidence in the Journal of Periodontology, the official journal of the American Academy of Periodontology.
The researchers compared two markers: the prostate-specific antigen (PSA) used to measure inflammation levels in prostate disease, and clinical attachment level (CAL) of the gums and teeth, which can be an indicator for periodontitis.
A PSA elevation of 4.0 ng/ml in the blood can be a sign of inflammation or malignancy. Patients with healthy prostate glands have lower than 4.0ng/ml levels. A CAL number greater than 2.7 mm indicates periodontitis.
Like prostatitis, periodontitis also produces high inflammation levels.
"Subjects with both high CAL levels and moderate to severe prostatitis have higher levels of PSA or inflammation," stated Nabil Bissada, chair of the department of periodontics in the dental school.
Bissada added that this might explain why PSA levels can be high in prostatitis, but sometimes cannot be explained by what is happening in the prostate glands.
"It is something outside the prostate gland that is causing an inflammatory reaction," he said.
Because periodontitis has been linked to heart disease, diabetes and rheumatoid arthritis, the researchers felt a link might exist to prostate disease.
Thirty-five men from a sample of 150 patients qualified for the study, funded by the department of periodontology at the dental school. The participants were selected from patients at the University Hospitals Case Medical Center with mild to severe prostatitis, who had undergone needle biopsies and were found to have inflammation and in some patients, malignancies.
The participants were divided into two groups: those with high PSA levels for moderate or severe prostatitis or a malignancy and those with PSA levels below 4 ng/ml. All had not had dental work done for at least three months and were given an examination to measure the gum health.
Looking at the results, the researchers from the dental school and the department of urology and the Institute of Pathology at the hospital found those with the most severe form of the prostatitis also showed signs for periodontitis.
Case Western Reserve University
The researchers compared two markers: the prostate-specific antigen (PSA) used to measure inflammation levels in prostate disease, and clinical attachment level (CAL) of the gums and teeth, which can be an indicator for periodontitis.
A PSA elevation of 4.0 ng/ml in the blood can be a sign of inflammation or malignancy. Patients with healthy prostate glands have lower than 4.0ng/ml levels. A CAL number greater than 2.7 mm indicates periodontitis.
Like prostatitis, periodontitis also produces high inflammation levels.
"Subjects with both high CAL levels and moderate to severe prostatitis have higher levels of PSA or inflammation," stated Nabil Bissada, chair of the department of periodontics in the dental school.
Bissada added that this might explain why PSA levels can be high in prostatitis, but sometimes cannot be explained by what is happening in the prostate glands.
"It is something outside the prostate gland that is causing an inflammatory reaction," he said.
Because periodontitis has been linked to heart disease, diabetes and rheumatoid arthritis, the researchers felt a link might exist to prostate disease.
Thirty-five men from a sample of 150 patients qualified for the study, funded by the department of periodontology at the dental school. The participants were selected from patients at the University Hospitals Case Medical Center with mild to severe prostatitis, who had undergone needle biopsies and were found to have inflammation and in some patients, malignancies.
The participants were divided into two groups: those with high PSA levels for moderate or severe prostatitis or a malignancy and those with PSA levels below 4 ng/ml. All had not had dental work done for at least three months and were given an examination to measure the gum health.
Looking at the results, the researchers from the dental school and the department of urology and the Institute of Pathology at the hospital found those with the most severe form of the prostatitis also showed signs for periodontitis.
Case Western Reserve University
Tuesday, June 8, 2010
Delay in surgery not likely to worsen tumors in men with low-risk prostate cancer
Johns Hopkins experts have found that men enrolled in an active surveillance program for prostate cancer that eventually needed surgery to remove their prostates fared just as well as men who opted to remove the gland immediately, except if a follow-up biopsy during surveillance showed high-grade cancer.
Active surveillance, or "watchful waiting," is an option open to men whose tumors are considered small, low-grade and at low risk of being lethal. Given the potential complications of prostate surgery and likelihood that certain low-risk tumors do not require treatment, some men opt to enroll in active surveillance programs to monitor PSA levels and receive annual biopsies to detect cellular changes that signal a higher grade, more aggressive cancer for which treatment is recommended. Yet, according to the Johns Hopkins experts, there is concern that delaying surgery in this group until biopsy results worsen may result in cancers that are more lethal and difficult to cure.
Bruce Trock, Ph.D., associate professor at the Johns Hopkins Brady Urological Institute, and his colleagues compared the pathology results of men in an active surveillance group at Johns Hopkins who later had surgery with those who also had low-risk tumors and opted for immediate surgery.
Results initially showed that 116 active surveillance participants who had surgery were more likely to have high-grade, larger tumors than 348 men who had immediate surgery. But Trock says that these results were found only in 43 (37 percent) men in the surveillance group who were recommended for surgery because a follow-up biopsy during surveillance worsened to indicate a high-grade tumor.
"We think that these men had high-grade tumors to begin with that their initial biopsy missed, and this group may be over-represented in men who are recommended for treatment after an initial period of active surveillance," says Trock. He adds that, in general, 15 to 25 percent of men whose initial biopsy shows a low-risk prostate tumor will actually have a high-grade cancer upon further review of the entire prostate once it is removed.
Apart from the 43 men whose pathology results worsened during surveillance, the remaining men in the surveillance group had similar pathology results at surgery to those in the immediate surgery group. "This means that most tumors are not likely to worsen during the period of active surveillance," says Trock.
The researchers calculate that the risk of finding high-grade tumors in the entire group of 801 active surveillance patients is low -- about 4.5 percent per year.
Johns Hopkins Medical Institutions
Active surveillance, or "watchful waiting," is an option open to men whose tumors are considered small, low-grade and at low risk of being lethal. Given the potential complications of prostate surgery and likelihood that certain low-risk tumors do not require treatment, some men opt to enroll in active surveillance programs to monitor PSA levels and receive annual biopsies to detect cellular changes that signal a higher grade, more aggressive cancer for which treatment is recommended. Yet, according to the Johns Hopkins experts, there is concern that delaying surgery in this group until biopsy results worsen may result in cancers that are more lethal and difficult to cure.
Bruce Trock, Ph.D., associate professor at the Johns Hopkins Brady Urological Institute, and his colleagues compared the pathology results of men in an active surveillance group at Johns Hopkins who later had surgery with those who also had low-risk tumors and opted for immediate surgery.
Results initially showed that 116 active surveillance participants who had surgery were more likely to have high-grade, larger tumors than 348 men who had immediate surgery. But Trock says that these results were found only in 43 (37 percent) men in the surveillance group who were recommended for surgery because a follow-up biopsy during surveillance worsened to indicate a high-grade tumor.
"We think that these men had high-grade tumors to begin with that their initial biopsy missed, and this group may be over-represented in men who are recommended for treatment after an initial period of active surveillance," says Trock. He adds that, in general, 15 to 25 percent of men whose initial biopsy shows a low-risk prostate tumor will actually have a high-grade cancer upon further review of the entire prostate once it is removed.
Apart from the 43 men whose pathology results worsened during surveillance, the remaining men in the surveillance group had similar pathology results at surgery to those in the immediate surgery group. "This means that most tumors are not likely to worsen during the period of active surveillance," says Trock.
The researchers calculate that the risk of finding high-grade tumors in the entire group of 801 active surveillance patients is low -- about 4.5 percent per year.
Johns Hopkins Medical Institutions
Monday, June 7, 2010
Molecular imaging detects recurrent prostate cancer
Findings of a clinical trial reported at SNM's 57th Annual Meeting indicate that a new molecular imaging agent could improve diagnosis of recurrent prostate cancer and determine the best possible course of treatment for patients.
"Despite definitive treatment, about 30 percent of prostate cancers recur," said David Schuster, M.D., director of the division of nuclear medicine and molecular imaging and assistant professor of radiology at Emory University School of Medicine, Atlanta, Ga. "This troubling statistic led our research team to diligently work on developing new techniques to more effectively detect and diagnose recurrent prostate tumors and associated cancers that have spread to nearby tissues and organs."
According to the authors, a radiotracer known as anti-18F-FACBC could be used to effectively and non-invasively detect and differentiate tumors recurring in the prostate and metastatic cancers that develop, most notably in the surrounding lymph nodes. "This may lead to custom-tailored treatments for prostate cancer patients that cater to their specific tumor type and progression of disease," added Schuster.
The new imaging agent, developed by Dr. Mark Goodman at Emory University, consists of a fluorine-based radioisotope paired with a synthetic amino-acid analog similar to the naturally-occurring amino acid L-leucine. Amino acids are essentially the building blocks of protein, and many cells have a system that controls the transport of amino acids into the cell in order to facilitate the production of new proteins. Upon injection, anti-18F-FACBC is absorbed by various cells by this transport system, but the "uptake," or admission of the agent, is much higher in aggressively multiplying cancer cells, which need more of these proteins in order to proliferate.
Researchers scanned 83 patients suspected of having recurrent prostate cancer using a hybrid positron emission tomography and computed tomography (PET/CT) system, a molecular imaging technique that displays both anatomical information and physiological processes in the body. Resulting scans were evaluated to determine the presence of recurrent prostate tumors and outlying tumors that had metastasized, or spread, to other tissues, including those of nearby bones and lymph nodes that tend be to a target for cancer metastases. The agent was able to positively identify recurrent carcinomas in the prostate region with 74-percent accuracy, and metastatic cancers with 96-percent accuracy, catching even small tumors within lymph nodes that other imaging agents could not detect. The ability to differentiate tumors recurring in the prostate from metastatic cancers with high accuracy is the most promising aspect of this PET radiotracer.
"Despite definitive treatment, about 30 percent of prostate cancers recur," said David Schuster, M.D., director of the division of nuclear medicine and molecular imaging and assistant professor of radiology at Emory University School of Medicine, Atlanta, Ga. "This troubling statistic led our research team to diligently work on developing new techniques to more effectively detect and diagnose recurrent prostate tumors and associated cancers that have spread to nearby tissues and organs."
According to the authors, a radiotracer known as anti-18F-FACBC could be used to effectively and non-invasively detect and differentiate tumors recurring in the prostate and metastatic cancers that develop, most notably in the surrounding lymph nodes. "This may lead to custom-tailored treatments for prostate cancer patients that cater to their specific tumor type and progression of disease," added Schuster.
The new imaging agent, developed by Dr. Mark Goodman at Emory University, consists of a fluorine-based radioisotope paired with a synthetic amino-acid analog similar to the naturally-occurring amino acid L-leucine. Amino acids are essentially the building blocks of protein, and many cells have a system that controls the transport of amino acids into the cell in order to facilitate the production of new proteins. Upon injection, anti-18F-FACBC is absorbed by various cells by this transport system, but the "uptake," or admission of the agent, is much higher in aggressively multiplying cancer cells, which need more of these proteins in order to proliferate.
Researchers scanned 83 patients suspected of having recurrent prostate cancer using a hybrid positron emission tomography and computed tomography (PET/CT) system, a molecular imaging technique that displays both anatomical information and physiological processes in the body. Resulting scans were evaluated to determine the presence of recurrent prostate tumors and outlying tumors that had metastasized, or spread, to other tissues, including those of nearby bones and lymph nodes that tend be to a target for cancer metastases. The agent was able to positively identify recurrent carcinomas in the prostate region with 74-percent accuracy, and metastatic cancers with 96-percent accuracy, catching even small tumors within lymph nodes that other imaging agents could not detect. The ability to differentiate tumors recurring in the prostate from metastatic cancers with high accuracy is the most promising aspect of this PET radiotracer.
Tuesday, May 25, 2010
Groundbreaking Study Published In Nature Biotechnology Demonstrates Sensitivity Of Single Molecule Test For Detection Of Prostate Cancer
Quanterix Corporation, the single molecule diagnostics company focused on developing and commercializing high sensitivity tests, announced the publication of a breakthrough study of the company's proprietary technology that demonstrates an unprecedented sensitivity for measuring a biomarker for prostate cancer recurrence. The research article, featured on the cover of the June issue (Volume 28, No. 6) of Nature Biotechnology, describes how researchers developed a simple blood test using Quanterix's Single Molecule Array (SiMoA™) technology to selectively capture and measure individual Prostate Specific Antigen (PSA) molecules in prostate cancer patients. The study showed that SiMoA was 1,700 times more sensitive than standard hospital tests, potentially allowing for detection of prostate cancer recurrence years earlier than current tests.
Read more at Medical News Today.
Read more at Medical News Today.
Wednesday, December 2, 2009
PSA value at 2 years post-treatment can predict long-term survival in prostate cancer patients
Prostate cancer patients who have a prostate-specific antigen (PSA) value of less than or equal to 1.5 at two years after external beam radiation therapy (EBRT) are less likely to have a cancer recurrence and cancer-related death, according to a study in the December 1 issue of the International Journal of Radiation Oncology*Biology*Physics, the official journal of the American Society for Radiation Oncology (ASTRO).
PSA levels in a prostate cancer patient are monitored after a patient's treatments, and after a successful course of EBRT the levels should decline gradually over the following 18 to 24 months. A continued rise in PSA can indicate relapsing disease.
Prior studies have attempted to categorize PSA response patterns after treatment in an effort to identify patients with an increased chance of a relapse earlier; however, most did not use a fixed point after treatment to predict outcomes.
Researchers at the Memorial Sloan-Kettering Cancer Center department of Radiation Oncology and Epidemiology and Biostatistics in New York, sought to determine the significance of a patient's reaching a certain PSA level at a specific point in time after EBRT.
The study authors found that patients with a PSA value of less than or equal to 1.5 at two years had a 2.4 percent incidence of distant metastases at five years after treatment and a 7.9 percent incidence at 10 years after treatment. Patients with a PSA value higher than 1.5 experienced a significantly higher rate of metastases at five and 10 years after treatment (10 percent and 17.5 percent, respectively).
"In the past, patients with a relapsing cancer after receiving radiation were not identified until several years after treatment and at that point it may be too late to effectively salvage their recurrence," Michael Zelefsky, M.D., lead author of the study and a radiation oncologist at Memorial Sloan-Kettering Cancer Center, said. "If we can catch these future instances of cancer recurrence earlier in prostate cancer patients, then we have a much higher chance of reducing the mortality associated with the cancer."
American Society for Radiation Oncology
PSA levels in a prostate cancer patient are monitored after a patient's treatments, and after a successful course of EBRT the levels should decline gradually over the following 18 to 24 months. A continued rise in PSA can indicate relapsing disease.
Prior studies have attempted to categorize PSA response patterns after treatment in an effort to identify patients with an increased chance of a relapse earlier; however, most did not use a fixed point after treatment to predict outcomes.
Researchers at the Memorial Sloan-Kettering Cancer Center department of Radiation Oncology and Epidemiology and Biostatistics in New York, sought to determine the significance of a patient's reaching a certain PSA level at a specific point in time after EBRT.
The study authors found that patients with a PSA value of less than or equal to 1.5 at two years had a 2.4 percent incidence of distant metastases at five years after treatment and a 7.9 percent incidence at 10 years after treatment. Patients with a PSA value higher than 1.5 experienced a significantly higher rate of metastases at five and 10 years after treatment (10 percent and 17.5 percent, respectively).
"In the past, patients with a relapsing cancer after receiving radiation were not identified until several years after treatment and at that point it may be too late to effectively salvage their recurrence," Michael Zelefsky, M.D., lead author of the study and a radiation oncologist at Memorial Sloan-Kettering Cancer Center, said. "If we can catch these future instances of cancer recurrence earlier in prostate cancer patients, then we have a much higher chance of reducing the mortality associated with the cancer."
American Society for Radiation Oncology
Friday, November 6, 2009
New finding suggests prostate biopsy is not always necessary
Researchers at Wake Forest University School of Medicine and the University of Wisconsin-Madison have discovered that some elevated prostate-specific antigen (PSA) levels in men may be caused by a hormone normally occurring in the body, and are not necessarily a predictor of the need for a prostate biopsy.
Elevated levels of PSA have traditionally been seen as a potential sign of prostate cancer, leading to the widespread use of PSA testing. However, the researchers found that parathyroid hormone, a substance the body produces to regulate calcium in the blood, can elevate prostate-specific antigen (PSA) levels in healthy men who do not have prostate cancer. These "non-cancer" elevations in PSA could cause many men to be biopsied unnecessarily, which often leads to unnecessary treatment.
"PSA picks up any prostate activity, not just cancer," said lead investigator Gary G. Schwartz, Ph.D., M.P.H., an associate professor of cancer biology and epidemiology and prevention at the School of Medicine. "Inflammation and other factors can elevate PSA levels. If the levels are elevated, the man is usually sent for a biopsy. The problem is that, as men age, they often develop microscopic cancers in the prostate that are clinically insignificant. If it weren't for the biopsy, these clinically insignificant cancers, which would never develop into fatal prostate cancer, would never be seen."
However, because PSA screening has become so common, more men are being biopsied, Schwartz said. Most men, when told that they have prostate cancer, elect treatment even though it may not be necessary. In reality, Schwartz said, in only one of six cases does a biopsy diagnosis of prostate cancer result in a cancer that would be fatal if untreated.
High rates of prostate biopsy, therefore, lead to the over treatment of prostate cancer, he said, leading to an increased rate of the side effects of treatment, including impotence and urinary incontinence.
The study, coauthored by Halcyon G. Skinner, Ph.D., M.P.H., of the University of Wisconsin-Madison, appears in the current issue of Cancer Epidemiology, Biomarkers & Prevention.
For the study, the researchers analyzed data from 1,273 men who participated in the National Health and Nutrition Examination Survey 2005-2006, and who did not report any current infection or inflammation of the prostate gland, prostate biopsy in the past month, or history of prostate cancer at the time of the survey.
After adjusting for age, race and obesity – because PSA levels increase with age, are higher in black men, and are lower in overweight men – the researchers found that the higher the level of parathyroid hormone in the blood, the higher the PSA level. In men whose parathyroid level was at the high end of normal, the PSA level was increased by 43 percent – putting many in the range for the urologist to recommend a biopsy.
The finding is especially significant for black men, added Skinner. About 20 percent of black men have elevated parathyroid hormone levels, compared with about 10 percent of white men – which means blacks have a greater chance of being recommended for biopsy and over treated, he said.
This finding "could help scientists refine the prostate cancer screening test to better differentiate between those men who need to be biopsied and those who might be spared the procedure," Schwartz said. "It's likely that there are a lot of men out there with elevated PSAs that may be due to elevated parathyroid hormone rather than prostate cancer."
Parathyroid hormone is made by cells of the parathyroid glands, four small glands embedded in the thyroid. Although parathyroid hormone primarily controls calcium levels in the blood, recent research has shown that parathyroid hormone can promote prostate cancer cell growth. The research by Schwartz and Skinner is the first to suggest that parathyroid hormone also promotes prostate cell growth in men without prostate cancer.
Wake Forest University Baptist Medical Center
Elevated levels of PSA have traditionally been seen as a potential sign of prostate cancer, leading to the widespread use of PSA testing. However, the researchers found that parathyroid hormone, a substance the body produces to regulate calcium in the blood, can elevate prostate-specific antigen (PSA) levels in healthy men who do not have prostate cancer. These "non-cancer" elevations in PSA could cause many men to be biopsied unnecessarily, which often leads to unnecessary treatment.
"PSA picks up any prostate activity, not just cancer," said lead investigator Gary G. Schwartz, Ph.D., M.P.H., an associate professor of cancer biology and epidemiology and prevention at the School of Medicine. "Inflammation and other factors can elevate PSA levels. If the levels are elevated, the man is usually sent for a biopsy. The problem is that, as men age, they often develop microscopic cancers in the prostate that are clinically insignificant. If it weren't for the biopsy, these clinically insignificant cancers, which would never develop into fatal prostate cancer, would never be seen."
However, because PSA screening has become so common, more men are being biopsied, Schwartz said. Most men, when told that they have prostate cancer, elect treatment even though it may not be necessary. In reality, Schwartz said, in only one of six cases does a biopsy diagnosis of prostate cancer result in a cancer that would be fatal if untreated.
High rates of prostate biopsy, therefore, lead to the over treatment of prostate cancer, he said, leading to an increased rate of the side effects of treatment, including impotence and urinary incontinence.
The study, coauthored by Halcyon G. Skinner, Ph.D., M.P.H., of the University of Wisconsin-Madison, appears in the current issue of Cancer Epidemiology, Biomarkers & Prevention.
For the study, the researchers analyzed data from 1,273 men who participated in the National Health and Nutrition Examination Survey 2005-2006, and who did not report any current infection or inflammation of the prostate gland, prostate biopsy in the past month, or history of prostate cancer at the time of the survey.
After adjusting for age, race and obesity – because PSA levels increase with age, are higher in black men, and are lower in overweight men – the researchers found that the higher the level of parathyroid hormone in the blood, the higher the PSA level. In men whose parathyroid level was at the high end of normal, the PSA level was increased by 43 percent – putting many in the range for the urologist to recommend a biopsy.
The finding is especially significant for black men, added Skinner. About 20 percent of black men have elevated parathyroid hormone levels, compared with about 10 percent of white men – which means blacks have a greater chance of being recommended for biopsy and over treated, he said.
This finding "could help scientists refine the prostate cancer screening test to better differentiate between those men who need to be biopsied and those who might be spared the procedure," Schwartz said. "It's likely that there are a lot of men out there with elevated PSAs that may be due to elevated parathyroid hormone rather than prostate cancer."
Parathyroid hormone is made by cells of the parathyroid glands, four small glands embedded in the thyroid. Although parathyroid hormone primarily controls calcium levels in the blood, recent research has shown that parathyroid hormone can promote prostate cancer cell growth. The research by Schwartz and Skinner is the first to suggest that parathyroid hormone also promotes prostate cell growth in men without prostate cancer.
Wake Forest University Baptist Medical Center
Tuesday, November 3, 2009
Blood vessels might predict prostate cancer behavior
A diagnosis of prostate cancer raises the question for patients and their physicians as to how the tumor will behave. Will it grow quickly and aggressively and require continuous treatment, or slowly, allowing therapy and its risks to be safely delayed?
The answer may lie in the size and shape of the blood vessels that are visible within the cancer, according to research led by investigators at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in collaboration with the Harvard School of Public Health.
The study of 572 men with localized prostate cancer indicates that aggressive or lethal prostate cancers tend to have blood vessels that are small, irregular and primitive in cross-section, while slow-growing or indolent tumors have blood vessels that look more normal.
The findings were published Oct. 26 in the Journal of Clinical Oncology.
"It's as if aggressive prostate cancers are growing faster and their blood vessels never fully mature," says study leader Dr. Steven Clinton, professor of medicine and a medical oncologist and prostate cancer specialist at Ohio State's Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute.
"Prostate cancer is very heterogeneous, and we need better tools to predict whether a patient has a prostate cancer that is aggressive, fairly average or indolent in its behavior so that we can better define a course of treatment – surgery, chemotherapy, radiotherapy, hormonal therapy, or potentially new drugs that target blood vessels – that is specific for each person's type of cancer," Clinton says.
"Similarly, if we can better determine at the time of biopsy or prostatectomy who is going to relapse, we can start treatment earlier, when the chance for a cure may be better."
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in American men.
This study analyzed tumor samples and clinical outcome data from men participating in the Health Professionals Follow-Up Study, which involves 51,529 male North American dentists, optometrists, podiatrists, pharmacists and veterinarians.
After an average follow-up of 10 years, 44 of the 572 men had developed metastatic cancer or died of their cancer.
Men whose tumors had smaller vessel diameters were six times more likely to have aggressive tumors and die of their disease, and those with the most irregularly shaped vessels were 17 times more likely to develop lethal prostate cancer.
The findings were independent of Gleason score, a widely used predictor of prognosis based on a prostate tumor's microscopic appearance, and of prostate specific antigen (PSA) level, a blood test used to identify the presence of prostate cancer.
These findings currently apply to men with local disease, whose PSA is only modestly elevated, and who are younger and more likely to choose surgery.
"If our findings are validated by larger studies, particularly in biopsy specimens, the measurement of tumor blood vessel architecture might help determine the choice of therapy, with the goal of improving long-term survival."
Ohio State University Medical Center
The answer may lie in the size and shape of the blood vessels that are visible within the cancer, according to research led by investigators at The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Richard J. Solove Research Institute in collaboration with the Harvard School of Public Health.
The study of 572 men with localized prostate cancer indicates that aggressive or lethal prostate cancers tend to have blood vessels that are small, irregular and primitive in cross-section, while slow-growing or indolent tumors have blood vessels that look more normal.
The findings were published Oct. 26 in the Journal of Clinical Oncology.
"It's as if aggressive prostate cancers are growing faster and their blood vessels never fully mature," says study leader Dr. Steven Clinton, professor of medicine and a medical oncologist and prostate cancer specialist at Ohio State's Comprehensive Cancer Center-James Cancer Hospital and Solove Research Institute.
"Prostate cancer is very heterogeneous, and we need better tools to predict whether a patient has a prostate cancer that is aggressive, fairly average or indolent in its behavior so that we can better define a course of treatment – surgery, chemotherapy, radiotherapy, hormonal therapy, or potentially new drugs that target blood vessels – that is specific for each person's type of cancer," Clinton says.
"Similarly, if we can better determine at the time of biopsy or prostatectomy who is going to relapse, we can start treatment earlier, when the chance for a cure may be better."
Prostate cancer is the most common cancer in men and the second leading cause of cancer death in American men.
This study analyzed tumor samples and clinical outcome data from men participating in the Health Professionals Follow-Up Study, which involves 51,529 male North American dentists, optometrists, podiatrists, pharmacists and veterinarians.
After an average follow-up of 10 years, 44 of the 572 men had developed metastatic cancer or died of their cancer.
Men whose tumors had smaller vessel diameters were six times more likely to have aggressive tumors and die of their disease, and those with the most irregularly shaped vessels were 17 times more likely to develop lethal prostate cancer.
The findings were independent of Gleason score, a widely used predictor of prognosis based on a prostate tumor's microscopic appearance, and of prostate specific antigen (PSA) level, a blood test used to identify the presence of prostate cancer.
These findings currently apply to men with local disease, whose PSA is only modestly elevated, and who are younger and more likely to choose surgery.
"If our findings are validated by larger studies, particularly in biopsy specimens, the measurement of tumor blood vessel architecture might help determine the choice of therapy, with the goal of improving long-term survival."
Ohio State University Medical Center
Tuesday, October 20, 2009
Experts issue call to reconsider screening for breast cancer and prostate cancer
Twenty years of screening for breast and prostate cancer – the most diagnosed cancer for women and men – have not brought the anticipated decline in deaths from these diseases, argue experts from the University of California, San Francisco and the University of Texas Health Science Center at San Antonio in an opinion piece published in the Journal of the American Medical Association.
Instead, overall cancer rates are higher, many more patients are being treated, and the incidence of aggressive or later-stage disease has not been significantly decreased, the authors conclude. Current screening programs are leading to "potential tumor over-detection and over-treatment," they write in the Oct. 21, 2009 issue of JAMA.
"Screening does provide some benefit, but the problem is that the benefit is not nearly as much as we hoped and comes at the cost of over-diagnosis and over-treatment," said Laura Esserman, MD, MBA, professor of surgery and radiology, director of the UCSF Carol Franc Buck Breast Care Center, and co-leader of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center.
"We need to focus on developing new tools to identify men and women at risk for the most aggressive cancers, to identify at the time of diagnosis those who have indolent or 'idle' tumors that are not life-threatening," she added. "If we can identify groups of patients that don't need much treatment, or don't need to be screened, wouldn't that be great? Screening is by no means perfect. We should want to make it better. For both breast and prostate cancer we need to invest in changing our focus from the cancers that won't kill people to the ones that do."
Breast cancer, the most common cancer in women, is a devastating and costly disease, striking more than 200,000 women annually and killing more than 40,000 women each year, reports the American Cancer Society. Prostate cancer is the most common form of cancer in men and the second most common cause of cancer death after lung cancer. This year, an estimated 192,280 men will be diagnosed with the disease, and 27,360 men will die from it, according to estimates from the American Cancer Society.
The two diseases account for 26 percent of all cancers in the U.S., with an estimated 386,560 patients diagnosed annually.
Because of remarkable survival rates when the diseases are treated before they spread, screening for both cancers has been promoted on the assumption that early detection and treatment is the best way to reduce deaths. In turn, much of the U.S. population undergoes routine screening for the cancers: About half of at-risk men have a routine prostate-specific antigen test and 75 percent have previously had a PSA test, and about 70 percent of women older than 40 report having had a recent mammogram. More than $20 billion is spent annually screening for the two diseases in the U.S.
The screenings have resulted in a "significant increase" in early cancers being detected, according to the article authors. Because of PSA testing, the chances of a man being diagnosed with prostate cancer have nearly doubled: In 1980, a white man's lifetime risk of the cancer was 1 in 11; today it is 1 in 6. Similarly, a woman's lifetime risk of breast cancer was 1 in 12 in 1980; today it is 1 in 8. And, if ductal carcinoma in situ is included, the risk of being diagnosed with breast cancer, like prostate cancer, has nearly doubled as well.
But the authors found that while deaths have dropped for both cancers over the last 20 years, "the contribution from screening is uncertain." They also found that many patients are undergoing treatment from cancers that actually pose minimal risk.
A comparison of prostate cancer incidence rates in the U.S. to the United Kingdom, where PSA screening has not been widely adopted, "did not result in significant differences in mortality," the authors write. For breast cancer the relative reduction in deaths from screening has also been limited.
The authors said that breast cancer and prostate cancer screening has not led to a more significant drop in deaths in the U.S. for two primary reasons: Screening increases the detection of slow growing and indolent tumors, and it often misses the most aggressive cancers because many may not be detected early enough for cure.
"In other words, tumor biology dictates and trumps stage, so the basic assumption of these screening programs that finding and treating early stage disease will prevent late stage or metastatic disease may not always be correct," they state.
Periodic screening may find some tumors early, but patients may not be screened often enough for lethal tumors to be detected in time to prevent death, the authors conclude: "Without the ability to distinguish cancers that pose minimal risk from those posing substantial risk and with highly sensitive screening tests, there is an increased risk that the population will be over-treated."
"People will think that we're saying screening is bad, and nothing could be further from the truth," said Ian Thompson, MD, who has authored about 400 scientific articles addressing prevention, early detection, and treatment for prostate, kidney, and bladder cancers. "What we are saying is that if you want to stop suffering and death from these diseases, you can't rely on screening alone."
"The basic assumption that screening programs that find and treat early stage disease will then prevent late-stage disease, or prevent cancer from spreading, may not always be correct," added Thompson. "If a tumor is aggressive, finding it early may not prevent death."
Thompson is professor and chairman of the Department of Urology and holds the Glenda and Gary Woods Distinguished Chair in Genitourinary Oncology at the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio and the Henry B. and the Edna Smith Dielmann Memorial Chair in Urologic Science at the UT Health Science Center. He led the Prostate Cancer Prevention Trial, a study of 18,882 men from around the U.S. that demonstrated that the drug finasteride reduces a man's risk of prostate cancer by 24.8 percent.
In contrast to breast and prostate cancer, screening for cervical and colon cancer -- and the removal of abnormal tissue – has led to a significant drop in invasive cancer. Screening is "most successful when pre-malignant lesions can be detected and eliminated" such as during colonoscopies, said the authors.
The authors suggest that to improve screening, "a new focus is recommended for research and care to identify markers that discriminate minimal-risk from high-risk disease (and) identify less aggressive interventions for minimal-risk disease to reduce treatment burden for patients and society."
The authors list four recommendations in their call to action for early detection and prevention:
1) Develop tests to distinguish between cancers that are lethal and those that are low-risk.
2) Reduce treatment for low-risk disease. Diagnosing cancers that don't kill the patient has led to treatment that may do more harm than good.
3) Develop tools for physicians and patients to help them make informed decisions about prevention, screening, biopsy and treatment. Offer treatments individually tailored to a patient's tumor.
4) Work to identify the people at highest risk for cancer and use proven preventive interventions.
"Over the years we have worked hard to find new treatments and new ways of finding disease and many of these interventions when appropriately assessed have saved lives," said Otis W. Brawley, MD, chief medical officer of the American Cancer Society, and professor of hematology, oncology and epidemiology at Emory University.
"It is very appropriate that we occasionally step back, assess and reflect on what we in medicine are doing," he added. "In the case of some screening for some cancers, modern medicine has overpromised. Some of our successes are not as significant as first thought. Cancer is a complicated disease and too often we have tried to simplify it and simplify messages about it, to the point that we do harm to those we want to help."
University of California - San Francisco
Instead, overall cancer rates are higher, many more patients are being treated, and the incidence of aggressive or later-stage disease has not been significantly decreased, the authors conclude. Current screening programs are leading to "potential tumor over-detection and over-treatment," they write in the Oct. 21, 2009 issue of JAMA.
"Screening does provide some benefit, but the problem is that the benefit is not nearly as much as we hoped and comes at the cost of over-diagnosis and over-treatment," said Laura Esserman, MD, MBA, professor of surgery and radiology, director of the UCSF Carol Franc Buck Breast Care Center, and co-leader of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center.
"We need to focus on developing new tools to identify men and women at risk for the most aggressive cancers, to identify at the time of diagnosis those who have indolent or 'idle' tumors that are not life-threatening," she added. "If we can identify groups of patients that don't need much treatment, or don't need to be screened, wouldn't that be great? Screening is by no means perfect. We should want to make it better. For both breast and prostate cancer we need to invest in changing our focus from the cancers that won't kill people to the ones that do."
Breast cancer, the most common cancer in women, is a devastating and costly disease, striking more than 200,000 women annually and killing more than 40,000 women each year, reports the American Cancer Society. Prostate cancer is the most common form of cancer in men and the second most common cause of cancer death after lung cancer. This year, an estimated 192,280 men will be diagnosed with the disease, and 27,360 men will die from it, according to estimates from the American Cancer Society.
The two diseases account for 26 percent of all cancers in the U.S., with an estimated 386,560 patients diagnosed annually.
Because of remarkable survival rates when the diseases are treated before they spread, screening for both cancers has been promoted on the assumption that early detection and treatment is the best way to reduce deaths. In turn, much of the U.S. population undergoes routine screening for the cancers: About half of at-risk men have a routine prostate-specific antigen test and 75 percent have previously had a PSA test, and about 70 percent of women older than 40 report having had a recent mammogram. More than $20 billion is spent annually screening for the two diseases in the U.S.
The screenings have resulted in a "significant increase" in early cancers being detected, according to the article authors. Because of PSA testing, the chances of a man being diagnosed with prostate cancer have nearly doubled: In 1980, a white man's lifetime risk of the cancer was 1 in 11; today it is 1 in 6. Similarly, a woman's lifetime risk of breast cancer was 1 in 12 in 1980; today it is 1 in 8. And, if ductal carcinoma in situ is included, the risk of being diagnosed with breast cancer, like prostate cancer, has nearly doubled as well.
But the authors found that while deaths have dropped for both cancers over the last 20 years, "the contribution from screening is uncertain." They also found that many patients are undergoing treatment from cancers that actually pose minimal risk.
A comparison of prostate cancer incidence rates in the U.S. to the United Kingdom, where PSA screening has not been widely adopted, "did not result in significant differences in mortality," the authors write. For breast cancer the relative reduction in deaths from screening has also been limited.
The authors said that breast cancer and prostate cancer screening has not led to a more significant drop in deaths in the U.S. for two primary reasons: Screening increases the detection of slow growing and indolent tumors, and it often misses the most aggressive cancers because many may not be detected early enough for cure.
"In other words, tumor biology dictates and trumps stage, so the basic assumption of these screening programs that finding and treating early stage disease will prevent late stage or metastatic disease may not always be correct," they state.
Periodic screening may find some tumors early, but patients may not be screened often enough for lethal tumors to be detected in time to prevent death, the authors conclude: "Without the ability to distinguish cancers that pose minimal risk from those posing substantial risk and with highly sensitive screening tests, there is an increased risk that the population will be over-treated."
"People will think that we're saying screening is bad, and nothing could be further from the truth," said Ian Thompson, MD, who has authored about 400 scientific articles addressing prevention, early detection, and treatment for prostate, kidney, and bladder cancers. "What we are saying is that if you want to stop suffering and death from these diseases, you can't rely on screening alone."
"The basic assumption that screening programs that find and treat early stage disease will then prevent late-stage disease, or prevent cancer from spreading, may not always be correct," added Thompson. "If a tumor is aggressive, finding it early may not prevent death."
Thompson is professor and chairman of the Department of Urology and holds the Glenda and Gary Woods Distinguished Chair in Genitourinary Oncology at the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio and the Henry B. and the Edna Smith Dielmann Memorial Chair in Urologic Science at the UT Health Science Center. He led the Prostate Cancer Prevention Trial, a study of 18,882 men from around the U.S. that demonstrated that the drug finasteride reduces a man's risk of prostate cancer by 24.8 percent.
In contrast to breast and prostate cancer, screening for cervical and colon cancer -- and the removal of abnormal tissue – has led to a significant drop in invasive cancer. Screening is "most successful when pre-malignant lesions can be detected and eliminated" such as during colonoscopies, said the authors.
The authors suggest that to improve screening, "a new focus is recommended for research and care to identify markers that discriminate minimal-risk from high-risk disease (and) identify less aggressive interventions for minimal-risk disease to reduce treatment burden for patients and society."
The authors list four recommendations in their call to action for early detection and prevention:
1) Develop tests to distinguish between cancers that are lethal and those that are low-risk.
2) Reduce treatment for low-risk disease. Diagnosing cancers that don't kill the patient has led to treatment that may do more harm than good.
3) Develop tools for physicians and patients to help them make informed decisions about prevention, screening, biopsy and treatment. Offer treatments individually tailored to a patient's tumor.
4) Work to identify the people at highest risk for cancer and use proven preventive interventions.
"Over the years we have worked hard to find new treatments and new ways of finding disease and many of these interventions when appropriately assessed have saved lives," said Otis W. Brawley, MD, chief medical officer of the American Cancer Society, and professor of hematology, oncology and epidemiology at Emory University.
"It is very appropriate that we occasionally step back, assess and reflect on what we in medicine are doing," he added. "In the case of some screening for some cancers, modern medicine has overpromised. Some of our successes are not as significant as first thought. Cancer is a complicated disease and too often we have tried to simplify it and simplify messages about it, to the point that we do harm to those we want to help."
University of California - San Francisco
Thursday, October 8, 2009
Prostate exams to go hi-tech
Conventional techniques to diagnose and monitor prostate cancer are known to be very reliable, but doctors may soon have a new hi-tech tool in their arsenal.
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