Posts Tagged ‘psa’

Blood test for ‘nicked’ protein predicts prostate cancer treatment response

The study evaluated two groups of 31 men with prostate cancer that had spread and whose blood levels of prostate-specific antigen (PSA) were still rising despite low testosterone levels. Investigators gave each man either enzalutamide (Xtandi) or abiraterone (Zytiga) and tracked whether their PSA levels continued to rise, an indication that the drugs were not working. In the enzalutamide group, none of 12 patients whose blood samples tested positive for AR-V7 responded to the drug, compared with 10 responders among 19 men who had no AR-V7 detected. In the abiraterone group, none of six AR-V7-positive patients responded, compared with 17 responders among 25 patients lacking AR-V7.

Enzalutamide and abiraterone have been very successful in lengthening the lives of about 80 percent of patients with metastatic prostate cancer, says Emmanuel Antonarakis, M.D., assistant professor of oncology at Johns Hopkins, but the drugs do not work in the remaining 20 percent of patients.

“Until now, we haven’t been able to predict which patients will not respond to these therapies. If our results are confirmed by other researchers, a blood test could use AR-V7 as a biomarker to predict enzalutamide and abiraterone resistance, and let us direct patients who test positive for AR-V7 toward other types of therapy sooner, saving time and money while avoiding futile therapy,” says Antonarakis.

Prostate cancer thrives on male sex hormones (or “androgens”), including testosterone. Enzalutamide and abiraterone target proteins called androgen receptors and block the receptors’ ability to activate prostate cancer cells. AR-V7 is a shortened form of the androgen receptor that lacks a binding spot targeted by enzalutamide and abiraterone. With no binding spot for the two drugs, AR-V7 is free to manipulate prostate cancer cells’ genetic material, which makes the cancer cells grow and spread.

Antonarakis and his colleague Jun Luo, Ph.D., who first identified AR-V7 in 2008, also tracked patients’ progression-free survival (the length of time a patient lives with the disease but does not get worse) and overall survival. They found that, in men receiving enzalutamide, progression-free survival was 2.1 months in AR-V7-positive patients and 6.1 months in AR-V7-negative patients, while overall survival was 5.5 months in AR-V7-positive men and up to 9 months in AR-V7-negative men. Similarly, in men receiving abiraterone, progression-free survival was 2.3 months in AR-V7-positive patients and up to 6 months in AR-V7-negative patients, while overall survival was 10.6 months in AR-V7-positive men and up to 12 months in AR-V7-negative men. The investigators caution that most of the study patients had advanced disease and received multiple prior therapies, so their outcomes may not be generalizable to all men with prostate cancer.

“Patients whose blood samples contained AR-V7 got no benefit from either enzalutamide or abiraterone,” says Antonarakis. He adds that the shortened AR-V7 protein could appear in patients’ blood samples at the very start of therapy or acquired later, after therapy has begun. He says, “This test could be used before starting enzalutamide or abiraterone therapy, and if the test shows the presence of AR-V7, patients may opt for a different therapy. It could also be used to monitor patients receiving enzalutamide or abiraterone for AR-V7, providing an indication these drugs may not work for much longer.”

source : http://www.sciencedaily.com/releases/2014/09/140903203752.htm

Prostate cancer screening reduces deaths by a fifth: Large, long-term European trial

Despite this new evidence for the effectiveness of prostate-specific antigen (PSA) testing to reduce mortality, doubts as to whether the benefits of screening outweigh the harms remain, and routine PSA screening programmes should not be introduced at this time, conclude the authors.

The European Randomised study of Screening for Prostate Cancer (ERSPC) began in 1993 to determine whether screening men for PSA reduces deaths from prostate cancer. It recruited men between the ages of 50 and 74 years from eight countries (Belgium, Finland, France, Italy, Netherlands, Spain, Sweden, and Switzerland) who were randomised to receive either PSA screening every 4 years (2 years in Sweden), or no intervention (control group). Men were referred for biopsy if their PSA concentration was higher than 3·0 ng/ml.

Results showed that screening appeared to reduce prostate cancer deaths by 15% at 9 years, and this improved to 22% at 11 years. Over 13 years follow-up, there was no further improvement in the relative reduction in prostate cancer deaths which decreased by roughly a fifth (21%) in the screening group compared with the control group, although men who were actually screened had a 27% lower chance of dying of prostate cancer.

However, the absolute benefit of screening steadily increased with longer follow-up. The number of men needed to be invited for screening to prevent one death from prostate cancer dropped dramatically from 1410 after 9 years of follow-up to 781 at 13 years. The number needed to be diagnosed and treated to prevent one prostate cancer death also fell from 48 to 27. The risk of advanced prostate cancer was also smaller in the screening group.

According to study leader Professor Fritz Schröder from Erasmus University Medical Center in the Netherlands, “PSA screening delivers a substantial reduction in prostate cancer deaths, similar or greater than that reported in screening for breast cancer. However, over-diagnosis occurs in roughly 40% of cases detected by screening resulting in a high risk of overtreatment and common side-effects such as incontinence and impotence.”

He adds, “The time for population-based screening has not arrived. Further research is urgently needed on ways to reduce over-diagnosis preferably by avoiding unnecessary biopsy procedures, and reducing the very large number of men who must be screened, biopsied, and treated to help only a few patients. One promising approach is multiparametric MRI technology which may be able to selectively diagnose aggressive prostate cancers and avoid the diagnosis of many inconsequential tumours that generally grow so slowly that most men will die of other causes. But for now, men must to be given well-balanced information including the screening harms of over-diagnosis and overtreatment.”

In a linked Comment, Ian Thompson at the University of Texas HSC, San Antonio, USA and Catherine Tangen at the Fred Hutchinson Cancer Research Center, Seattle, USA, discuss potential ways to mitigate the disadvantages of screening. They conclude, “The new findings from ERSPC are crucially important. In future publications from the study, the distribution of prostate cancer deaths by Gleason score and PSA at diagnosis will be important to understand how to tailor screening and treatment.”

source : http://www.sciencedaily.com/releases/2014/08/140807105049.htm

Skid row cancer study has implications for treatment

In papers published in the American Journal of Public Health and the Bulletin of the History of Medicine, Aronowitz, professor and chair of Penn’s Department of History and Sociology of Science, characterizes the events then and screenings for prostate-specific antigen, or PSA, in more recent years as "part of one continuous story of how medical and lay people came to believe in the efficacy of population screening followed by aggressive treatment without solid supporting scientific evidence."

"This is a call to reflection about how we deal with medical knowledge production and medical technological innovation," Aronowitz said.

In 2012, the U.S. Preventive Services Task Force recommended that healthy men not be screened for prostate cancer with PSA tests. Millions of men, before and after this recommendation, have had screening PSA tests. If an individual’s PSA level is above a certain value, he may be counseled by a doctor to have repeated tests or a tissue biopsy to look for cancer cells. The biopsy is an invasive procedure, and can lead to additional procedures that escalate in their potential for detrimental effects. The recent Task Force decision states that the test has "very small potential benefit and significant potential harms."

Interested in how the PSA test and other prostate cancer screening measures rose in prominence, Aronowitz was researching the history of screening when he came upon a "largely forgotten" story.

In 1951, a young New York urologist began a study to determine whether biopsying the prostate glands of men without signs or symptoms, and then aggressively treating those individuals who had tissue diagnoses of cancer, could reduce deaths from prostate cancer.

Aronowitz details the history of the urologist’s trial, which lasted more than a decade and to which more than 1,200 homeless, alcoholic men from New York’s Bowery neighborhood were recruited. Participants traveled to Francis Delafield Hospital, where they received a physical exam, X-rays, and various invasive tests, including a prostate biopsy that involved the removal of a sizable amount of tissue. Men whose samples were found to contain cancerous cells then underwent aggressive treatment, typically including the removal of the prostate gland and testes and administration of a synthetic estrogen.

Though records are unclear, some men may have given a form of "informed consent" and some may have been aware that they were participating in research, Aronowitz found. But their vulnerable status, as homeless and alcoholic, calls into the question whether they were entering into the research with true free will and understanding, Aronowitz said. Given the state of clinical knowledge, he noted, these largely asymptomatic men clearly were also being exposed to undue risk.

Even though the prostate biopsy procedure today requires the removal of far less tissue and is less dangerous, Aronowitz draws a connection between the vulnerable Bowery population and the millions of men who each year are biopsied for cancer after recording a high level on a PSA screening test.

"Patients today are often not fully informed about risks and benefits of PSA screening," Aronowitz said. "More importantly, and like the Bowery men, many men today, and certainly men in the era before results from good clinical trials were available, have not been informed in the sense of knowing whether the test, and all that it may trigger, is worth it or not."

In the Bulletin of the History of Medicine paper, Aronowitz writes that society’s attitudes toward prostate cancer changed as a result of subsequent medical innovation that modified many aspects of the Bowery series but had similar goals. Where prostate cancer was once only diagnosed in very late stages when it was nearly always fatal, new screening tests enabled many diagnoses at much earlier stages, before patients displayed symptoms.

According to Aronowitz, however, the evidence we now have from randomized controlled trials either does not show that screening saves lives or shows a very small benefit that some men might experience does not outweigh the many known harms from cancer treatments, especially incontinence and impotence. Whether efficacious or not, the mass diffusion of screening and related practices occurred in an "evidence-free" way and transformed prostate cancer as a disease, Aronowitz argued.

"It’s not just costly or a little bit inconvenient to let innovation happen and deal with the ethical and clinical consequences later," he said. "We ended up with not just 1,200 but millions of men who were screened, and maybe a fifth of them go on to get more radical treatment.

"I think when you look back at the Bowery series, those involved were acting in good faith," he added. "So were many people who promoted PSA testing when they thought or continue to think it is only logical to use a test that detects cancer early enough for radical treatments to remove it from the body. But when a medical procedure will be offered at a population level with the potential to transform society and everything we think we know about the targeted disease, we ought to proceed with a very high level of caution, reflection, knowledge production and evaluation."

source : http://www.sciencedaily.com/releases/2013/10/131018203624.htm