Tag Archive | "PSA"

The Importance of Knowing Your Baseline PSA For Prostate Health

If you have been recently diagnosed with prostate cancer, then your urologist most likely provided you with a PSA score. The PSA baseline score is your prostate specific antigen at the time of your first measurement of the antigen. This baseline is important because subsequent PSA values that are higher than the baseline may indicate a disease of the prostate, such as prostate cancer or benign prostatic hyperplasia. Further, your oncologist or urologist may consider your PSA before treatment has been administered.

One of the first questions patients who have been diagnosed, or re-diagnosed, with metastatic prostate cancer ask is, “How long do I have to live?” The answer to this question has changed over the years. While in the 1980s and early 1990s men were given an estimated 18 to 36 months from the time of diagnosis to live, the current understanding and estimation of survival is 5 to 6 years, maybe longer. The difference in survival rates is, in part, due to treatments; however, the major factor is the inclusion of PSA scores, velocity numbers, etc. These numbers allow researchers to form a clearer picture of the individual cancer and a closer estimation of survival.

And for those who have already been diagnosed with prostate cancer and have been treated, recurrence is a reality. According to the Prostate Cancer Foundation, out of those who have undergone treatment for prostate cancer, 20-30% will relapse after the five-year mark and begin to show signs of disease recurrence.
But survival for recurrence has also been extended. Many men in the United States are actually diagnosed at an earlier stage of the disease because of wide-spread PSA testing. Further, we now have a better understanding of cancer therapies, including hormone manipulation and taxane chemotherapy.

According to Duke University Medical Center researchers, men with a baseline PSA value of 10 or higher are up to 11 times more likely to die from prostate cancer than are men with lower initial values. In the study conducted by Duke University, 4,568 men over the past 20 years who have had PSA tests and were eventually diagnosed with prostate cancer were followed. With age and race taken into account, the risk of death from prostate cancer was calculated.

The study released showed a median age for their study as 65 years. The median baseline PSA was 4.5. Nearly 3.5% of the men died from prostate cancer during the study period, while more than 20 percent died from other causes. The analysis showed that men with a baseline PSA of less than 4 had a very low risk of death from prostate cancer, but those with 4 to 9.9 baselines were three times more likely to die from prostate cancer. And men with a baseline PSA value of greater than 10 were 11 times more likely to die than were men with PSAs under 2.5.

Given these results, it is evident that early diagnosis of prostate cancer, when the baseline PSA is lower, will decrease the mortality rate from prostate cancer. With PSA screenings and digital rectal exams, men may be saved from early, unnecessary death.

Baseline PSA scores are important in determining predicted survival rates for men who have been diagnosed with prostate cancer. Ping Tang, MD, a member of the Duke Prostate Center and the department of urology at Guangzhou First Municipal People’s Hospital, Guangdong, China comments, “It’s commonly held that men over the age of 75 don’t need to bother with PSA screening any longer, but [this study] tells us that chronological age alone may not be enough. Patients need to take into account their initial baseline value, and if it’s over 4, continuous screening may be beneficial.”

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Brisk Walking Slows Down Prostate Cancer Progression

A recent study at the University of California, San Francisco (UCSF) and the Harvard School of Public Health found that an association between brisk walking and lowered risk of prostate cancer progression in a study of 1,455 men in the U.S. diagnosed with early-stage prostate cancer.

The research team found that men who walked briskly at least at three miles per hour for at least three hours each week after diagnosis were about sixty percent less likely to develop biochemical markers of cancer recurrence or less likely to need a second round of prostate cancer treatment.  The study was published in the journal Cancer Research.

This new finding complements an earlier study published by UCSF’s June Chan, ScD, and collaborators at the Harvard School of Public Health showing that physical activity after diagnosis could reduce disease-related mortality in a distinct population of men with prostate cancer.  The recent study by Erin Richman, ScD, a postdoctoral fellow at UCSF is the first to focus on the effect of physical activity after diagnosis on early indications of disease progression, such as rise in prostate-specific antigen (PSA) blood levels.

An advantage of this study is the focus on early recurrence of prostate cancer, which occurs before men may experience painful symptoms of prostate cancer metastases, a frequent cause for men to decrease their usual physical activity. Additionally, the researchers reported that the benefit of physical activity was independent of the participants’ age at diagnosis, type of treatment and clinical features.  This work was funded by the Department of Defense, the Prostate Cancer Foundation, Abbott Labs, and through a National Institutes of Health training grant.

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No Relationship Between Small Prostate Size and High Grade Cancer

Previously, radical prostatectomy series have shown an inverse relationship between prostate size and high grade cancer.  It was suggested that smaller sized prostates arise in a low androgen environment, which enables development of more aggressive cancer.  A recent study by a team of authors from Stanford University School of Medicine in the Journal of Urology, however, shows that small prostate size is not associated with high grade cancer.  The authors argue that previous observations are the result of ascertainment bias driven by prostate specific antigen performance.

The study’s authors analyzed 1,404 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (723) and T2 (681) disease who had surgery between 1988 and 2002 and underwent detailed morphommetric mapping by a single pathologist.  They used multivariate linear regression to analyze the effects of age, prostate weight and prostate specific antigen on total and high grade cancer volume and percentage of high grade disease.

Patients who underwent biopsy due to abnormal prostate specific antigen (stage T1c had a prostate weight that was negatively associated with total cancer volume, which is the volume of high grade disease and percentage of high grade disease.  For patients who underwent biopsy based on abnormal rectal examination (stage T2), these relationships were not present.

The authors conclude that improved prostate specific antigen performance for high grade disease results in ascertainment bias in patients with T1c disease.  For this reason, the relationship between prostate size and high grade disease may be a result of grade dependent performance of prostate specific antigen rather than true tumor biology.

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Urine Test Can Help Detect and Sort Prostate Cancer

Researchers report that an investigational urine test can detect and stratify prostate cancer in men with elevated prostate specific antigen (PSA).  According to Arul Chinnaiyan, MD, PhD, of the University of Michigan Medical School in Ann Arbor and colleagues, the test is based on the detection of a gene fusion that is specific to prostate cancer combined with another marker.  Stratifying patients by the combined marker identified groups with markedly different risks of cancer, high-grade cancer, and clinically significant cancer on biopsy.

This noninvasive test may allow some men with elevated PSA to avoid a needle biopsy.  Although many more men have elevated PSA than actually have cancer, the test could be an intermediate step before getting a biopsy.

The fusion that doctors look for in the test involves the genes transmembrane protease, serine 2 (TMPRSS2), and v-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG).  This fusion appears in roughly half of all prostate cancers, but when it does appear, it is almost 100% specific for malignancy.  Through a series of experiments, the research team showed that the fusion gene was associated with indicators of clinically significant cancer at biopsy and prostatectomy.  The indicators included tumor size, high Gleason score at prostatectomy, and upgrading of Gleason grade at prostatectomy.

Because this fusion gene is not always present, the team created a model that combined it and the prostate cancer antigen 3 (PCA3) gene.

The researchers use the model to stratify 1,065 men who underwent biopsy into three groups – lowest, intermediate, and highest levels of the combined genes.

These tests, however, remain investigational.  Additionally, the researchers note that most of the men studied thus far have been Caucasian.  More studies are needed to see if the results can be generalized.

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Mortality Rate for Prostate Cancer Higher in UK than US

According to researchers in the United Kingdom, prostate cancer is the cause of half of the deaths of men diagnosed with the disease, challenging the notion that prostate caner patients die with rather than of the disease.  Their data show that the number of deaths specifically from prostate cancer was around 20 percent.  In contrast, about 15 percent of men diagnosed with prostate cancer die from this disease in the United States.

Experts attribute this difference to the high uptake of testing for prostate-specific antigen (PSA) in asymptomatic men in the United States and the low uptake in the United Kingdom.

While British researchers say that routine PSA testing in the United States is picking up disease that might be clinically insignificant, thus leading to over-diagnosis and over-treatment of prostate cancer, American researchers argue that PSA testing detects prostate cancer at an earlier stage when it is still treatable and curable, leading to lower mortality rates in the United States.

The new data from the United Kingdom are from an analysis of 50,066 men diagnosed with prostate cancer between 1997 and 2006 from the Thames Cancer Registry.  Patients were followed until the end of 2007.  This registry covers a population of 12 million in Southeast England.  During the study period, 20,181 of the men died.  Prostate cancer was the cause of death in 49.7% of the men who had died.  These results held after researchers controlled for age, cancer stage, and first treatment.  Other causes of death included cardiovascular disease, other cancers, and pneumonia.

Prostate cancer was the cause of death in 74.3% of men who had stage IV cancer at diagnosis, in 46.4% of all men 75 years and older, and in 31% of all men who underwent radical prostatectomy.

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Recent Increase in Unnecessary Prostate Biopsy

With an increase in attention given to PSA (prostate specific antigen) levels in men in the United States comes an increase in referrals for prostate biopsy. Oftentimes, these biopsies are recommended even when doctors have no other indications of prostate cancer besides the PSA level. A new study, however, finds that such prostate biopsies are unnecessary if men have a normal clinical exam and their total PSA levels are not yet high.

“If a man’s PSA has risen rapidly in recent years, there is no cause for concern if his total PSA level is still low and his clinical exam is normal,” said Andrew Vickers, PhD, the lead author of the new study from Memorial Sloan-Kettering Cancer Center.

In this most recent study, 5,519 men who participated in the Prostate Cancer Prevention trial were evaluated. All the participants were 55 years or older, had no previous history of prostate cancer, and had normal digital rectal findings and PSA levels of 3.0 ng/mL or less.

The men were randomly assigned to take either finasteride (a medication used to treat BPH) or placebo for seven years. Each year, all the men were screened for PSA levels, and those who had a PSA greater than 4.0 ng/mL were advised to have a prostate biopsy. At the end of the study, men who did not have prostate cancer were asked if they would consent to a biopsy.

The researchers concluded, after reviewing the study’s results, that the main factor that predicted the risk of cancer was a man’s PSA level, not how rapidly the PSA rose. Men with a steady PSA of 5 ng/mL were more likely to have prostate cancer than those whose PSA rose from 2.5 to 3.4 ng/mL. They recommended that a rapidly rising PSA should not be included in screening guidelines for prostate cancer.

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Use Caution When Deciding on HIFU

Normally, high-intensity focused ultrasound (HIFU) is used as a salvage treatment for prostate cancer. Recently, a movement has taken place to push HIFU as a front-line use, but both the US Food and Drug Administration and the European Association of Urology classify the procedure as experimental.

The first case series to report outcomes in men after failed whole-gland HIFU and salvage radical prostatectomy suggests that there is reason for caution.

Researchers report they were alarmed at the pathology results. Morbidity appeared to be higher after salvage prostatectomy than after primary surgery.

Declan G. Murphy, MD, from the Department of Urological Oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, notes, “Whether it is that standard prostate biopsy cannot be relied on to predict final pathological outcome, or that HIFU ‘makes cancer angry,’ patients should be fully counseled about what we know and, importantly, what we do not know about HIFU treatment for localized prostate cancer today.”
“Our own initial experience with HIFU treatment for primary and recurrent prostate cancer unfortunately led us to conclude that the technology is not yet suitable for mainstream clinical practice, and led us to suspend our program,“ Dr. Murphy added.

Dr. Lawrentschuk believes that using radical prostatectomy as salvage treatment after the failure of primary HIFU is feasible; however, he is concerned about the rate of extraprostatic extension.

“HIFU is experimental and should only be done in studies where patients are told of the risks of failure and the poor results of salvage. They need very careful monitoring, follow-up biopsies, etc. I do not advise patients to have HIFU. There may be a problem with HIFU selecting out more aggressive cells, but this warrants further study,” explains Dr. Lawrentschuk.

“Experimental treatments are fraught with danger. I was surprised at the aggressive nature of the disease and the recurrences in this supposedly low-risk group,” he continues. “I think HIFU is inadequate in its current form, perhaps because of poor patient selection for HIFU and a lack of standardized ways of detecting post-HIFU recurrences in a timely fashion.”

Howard Sandler, MD, chair of radiation oncology at Cedars-Sinai Medical Center’s Samuel Oschin Comprehensive Cancer Institute in Los Angeles, California, also reviewed the study.

“I wouldn’t conclude that the high number with extracapsular extension is a result of HIFU. It is more likely that patients who fail HIFU had worse cancers in any case from the start. Additionally, there may have been a bit of a delay after some suspicion of recurrence before salvage surgery was done, given the presurgery PSA [prostate-specific antigen] of 3.8, with the nadir PSA of 1.0. Thus, patients waited on average for their PSA to rise from 1.0 to 3.8 before something was done. During this interval, extracapsular extension may have occurred,” Dr. Sandler explained.

Overall, Dr. Sandler believes that HIFU is a poor choice for whole-gland ablation and focal therapy.

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Research Underway for FDA Approved Investigational Medication for Prostate Cancer

Men naturally produce the male hormone testosterone which stimulates the prostate cancer cells. Constantly suppressing the testosterone can treat prostate cancer however this diminishes quality of life by causing loss of sexual interest, impotence, hot flashes, decreased mental ability, fatigue and even depression. In an effort to turn this around, patients are now being enrolled at Florida Urology Physicians to evaluate the role of a new method of suppressing cancer growth.

The study being conducted by Dr. Barry Blitz evaluates the role of an FDA investigational medicine that has been successfully treating prostate cancer to allow men to live years with fewer side effects than current therapies.

To qualify as a study participant, men must have been treated for prostate cancer and have a rising Prostate Specific Antigen (PSA). Study participants can receive study related exams, lab tests, and study medications at no charge. They are also compensated for their involvement.

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Debunked Prostate Cancer Myths

“As prostate cancer is a major health issue, and not all prostate cancers are the same,” states Dr. Vorstman in his recent article dedicated to correcting patient misunderstandings about prostate cancer and treatment options, “it is vitally important that men and their spouses deal with factual information only.” Dr. Vorstman is concerned about the emerging prostate cancer myths and is working to inform the public in hopes to shed light on the reality of the disorder. He explains over 20 myths and the facts about the topics in his recently published article.

One myth has deterred men from seeking medical expertise in regards to their prostates: If no urinary symptoms are present, then you do not have cancer. Dr. Vorstman states that most men who are diagnosed with prostate cancer when it is early enough to be treatable actually have no urinary symptoms at all, nor do they have problems that show up on their examination, but rather are diagnosed entirely through PSA abnormalities.

“This is one of the most damaging myths,” warns the doctor, “as it causes some men to skip the PSA test, and therefore fail to discover their cancer before it is too late for effective treatment.”

While this myth leads to inactivity, other myths over-emphasize PSA numbers. The PSA test is simply an indication that prostate cancer may be present, but elevated PSA numbers combined with the percent of free PSA can point to the need for a prostate biopsy. The biopsy is what determines whether or not the prostate contains cancer. The PSA test itself is simply the first step in the diagnostic process. This means that men with low PSA numbers can still have prostate cancer. In fact, because of this, Dr. Vorstman recommends checking the percent free PSA and doing a digital rectal exam for all patients, regardless of their PSA number.

Yet another common myth comes with strong advertising. This myth suggests that certain supplements will prevent prostate cancer. Although no danger exists for taking vitamins and such supplements may promote overall health, science has not yet proved that supplements or other dietary changes actually lower a man’s risk for cancer.

Finally, Dr. Vorstman warns against myths surrounding prostate cancer treatment. In the past, prostate cancer was often universally treated with surgery. Many believe this is still the case today; however, according to Dr. Vorstman, “This is no longer true with the wide range of minimally invasive prostate cancer treatments on the market. Today’s patient can protect his quality of life while successfully treating prostate cancer without surgery, so it is vital that he and his spouse look at all of the options.”

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Pomegranates and PSA Scores

Recent studies on the effects of pomegranate extract on prostate cancer have yielded mixed results. In one study, which focused on prostate-specific antigen levels, pomegranate extract slowed the PSA doubling time by more than 6 months in a broad population of patients with prostate cancer; however, some evidence suggests that it may accelerate the disease for some individuals.

Overall, the median pretreatment PSA doubling time (PSADT) increased significantly from 11.9 months to 18.5 months post treatment among 92 evaluable men with a rising PSA after primary therapy in the phase II, double-blind, multicenter study.

The increase in median PSADT was similar whether the men were randomized to one capsule daily (from 11.9 to 18 months) or to three capsules daily (from 12.2 to 17.5 months). A negative PSA slope, suggesting declining PSA values, was observed in 13% of patients, reported Dr. Michael Carducci, a professor of oncology and urology at Johns Hopkins University in Baltimore.

Nearly 20% of the population, however, had their PSADTs shortened, leading to treatment discontinuation.
“There is an apparent benefit across all PSA doubling times, although some shortening of PSA doubling time was seen,” stated Dr. Carducci at the Genitourinary Cancers Symposium.

Dr. Michael J. Morris of Memorial Sloan-Kettering Cancer Center in New York indicated that a more prospective evaluation of the study’s results was necessary.

“If you believe that prolonged PSA doubling time is clinically beneficial, what do we say about patients whose disease appears to accelerate as a result of taking the pomegranate extract?” he asked. “Do we say or suggest that a third to 40% of patients might be done some harm, or might have an earlier clinical end point? I don’t know, but I think that’s an issue of concern.”

One limitation of the pomegranate study, acknowledged by Dr. Carducci, is that it lacked a placebo. A number of reports in the literature, including studies of rosiglitazone (Avandia) and atrasentan (Xinlay), have shown that even a placebo can slow PSADT.

“We did not have a placebo, so [these data are not] definitive and could be explained by on-study regression to the mean,” he said, noting that data should be available in the near future from a 200-patient, placebo-controlled trial of pomegranate extract liquid.

Current laboratory data also shows that pomegranate extract is more effective at controlling the growth of prostate cancer than is pomegranate juice in prostate cancer cell lines, but this comparison has not been tested in patients, explained Dr. Carducci.

The 101 men in the intent-to-treat analysis had a medial Gleason score of 7, and about one-third of them had a baseline PSADT of 9 months or less. The men were treated for up to 6 months (92% of patients), 12 months (70%), or 18 months (36%) with capsules containing 1,000 mg of pomegranate juice. In all, 58% of patients completed the 18-month, double-blind portion of the study, and 42% discontinued treatment before progression.

Ultimately, the decision to use pomegranate extract or juice is a matter of discussion between physician and patient, concluded Dr. Carducci.

“I think with two consistent data sets showing slowing PSA doubling time, it would be reasonable for a patient to consider and understand what he’s getting himself into. It’s possible that patients with slower growing disease may have the greater benefit.”

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