Statins could boost prostate health, studies show

Medical Tribune July 2009 P4

David Brill

Evidence is growing to suggest that statins could help to maintain a healthy prostate – protecting against both benign and malignant disease.

Recent studies have found that statins lowered the risk of developing prostate cancer, reduced the aggressiveness of cancers, and reduced the risk of cancer recurrence after surgery.

Other reports have suggested that the drugs can protect against lower urinary tract (LUT) symptoms, benign prostatic hyperplasia (BPH) and even erectile dysfunction.

Researchers, however, are urging caution, saying that further studies are needed before firm conclusions can be drawn.

Six key studies were presented recently at the annual meeting of the American Urological Association (AUA) in Chicago, US. Three come from a single cohort of 2,447 men aged 40 to 79, who have been followed since 1990 by researchers at the Mayo Clinic, Minnesota, US.

The first study found that men who were taking statins were three times less likely to develop prostate cancer than non-users. Just 6 percent of statin users developed cancer over a median of 14.1 years of follow-up – a considerable reduction compared to the US national average, which sees around 17 percent of all men diagnosed with prostate cancer in their lifetime.

The second study, which included only 1,480 of the men, found that statins reduced the risk of erectile dysfunction in those aged over 60. This apparent protective effect increased over time – men who had been taking statins for 9 years or more were 64 percent less likely to develop the condition than men not taking statins, whereas those taking statins for less than 3 years were equally as likely.

A third analysis of the Mayo Clinic cohort, meanwhile, reported that statin users had a 57 percent reduction in risk of developing BPH, and a 63 percent risk reduction for developing LUT problems.

"If you are taking a statin for a heart condition or to lower cholesterol, these studies suggest that statins could have other benefits," said one of the study authors Dr. Jennifer St. Sauver, an epidemiologist at the Mayo Clinic. "However, it's very clear we need more information before men are advised to start taking statins for their urological health."

The fourth study presented at the AUA meeting found that men taking statins at the time of radical prostatectomy for prostate cancer were 30 percent less likely to have a recurrence. They also had lower prostate-specific antigen levels than non-users, and were more likely to have T1-stage disease. The study included 1,325 men, of whom 237 were taking statins at the time of surgery.

“Our findings suggest that statins may slow prostate cancer progression after radical prostatectomy," said study author Dr. Robert Hamilton, of the University of Toronto, Canada.

“Although the results of these studies are exciting, they need to be confirmed,” he added. “At this point we cannot say with confidence that statins reduce the risk of prostate cancer recurrence after radical prostatectomy."

The fifth study, led by Johns Hopkins University, US, found that prostate cancer was less aggressive in statin users than non-users. Of 1,282 men who underwent radical prostatectomy over 5 years, the 418 who were taking statins had lower tumor volume, lower prevalence of positive surgical margins, and lower percentage of cancer in their prostatectomy specimens.

The final study, meanwhile, suggests that statins might exert their beneficial effects by reducing inflammation within prostate tumors. Researchers from Duke University Medical Center, US, examined specimens from 254 men who had undergone radical prostatectomy, and found that inflammation was reduced by 72 percent in statin users compared to non-users.

Despite the positive results presented at the AUA, not all studies have shown benefits of statins of prostate cancer outcomes. One paper published earlier this year found that statin usage had no effect on progression-free survival after radiotherapy for prostate cancer. [Urology 2009 Jan;73(1):158-62. Epub 2008 Aug 22]

Some researchers have even suggested that statins could actually increase prostate cancer, and have called for further attention to be given to the issue. [Cancer Epidemiol Biomarkers Prev 2008 Feb;17(2):459]

Rifts widen in prostate screening debate

Medical Tribune June 2009 P1&9
David Brill

American and European experts have diverged in their stances on prostate cancer screening, as debate intensifies over the benefits of prostate-specific antigen (PSA) testing.

The subject has held center stage since the publication of two major studies in March: one showed that PSA testing every 4 years reduced mortality by 20 percent but carried a high risk of overdiagnosis; the other showed that annual screening had no impact on death rates.

The American Urological Association (AUA) has since aligned itself with the first study – recommending PSA testing in all well-informed men, and lowering the age for a first test from 50 to 40. It has also adjusted its criteria for proceeding to biopsy.

The European Association of Urology (EAU), meanwhile, has advised against population screening until more data are available – warning of the dangers of overtreatment and calling for urgent development of new diagnostic markers and screening algorithms.

Singapore experts are taking a similar stance to their European counterparts, although they note that the lower incidence of prostate cancer in Asia makes screening less worthwhile than in Western populations.

The Singapore Urological Association (SUA) nonetheless intends to downplay the role of PSA screening in this year’s upcoming Prostate Awareness Month, according to Professor Kesavan Esuvaranathan, SUA president and senior consultant, department of urology, National University Hospital.

“I wouldn’t be in a hurry to recommend screening. We don’t know for sure whether there is a benefit,” he said.

“My feeling is that it’s too early to say that PSA screening is inappropriate, but I also think that it is probably wrong to unconditionally recommend PSA screening. I think we have to wait for the long-term results of these studies.”

Associate Professor Weber Lau, senior consultant, department of urology, Singapore General Hospital, also urged caution in the use of PSA testing, stressing the need to select the right patients.

“We are quite clear that screening is not a goal for Singapore at this juncture. For people who are asking to be tested, the key words are risk stratification,” he said.

“PSA can be used as a tool for early detection of prostate cancer in the right patients. But on the other hand it can be harmful too if used in health screening without understanding the risks of the patient group and the general health of the patient.”

The 20 percent mortality reduction with PSA screening was reported in the European Randomized Study of Screening for Prostate Cancer, which included 162,387 men aged 55 to 69 from seven countries. They were assigned to PSA screening every 4 years on average, or to no screening. [N Engl J Med 2009 Mar 26;360(13):1320-8]

After a median of 9 years’ follow-up, the adjusted rate ratio for prostate cancer death in the screening group was 0.80, as compared to the control group (95 percent CI, 0.65 – 0.98; P=0.04). The absolute risk difference was 0.71 deaths per 1,000 men – meaning that to prevent one death from prostate cancer, 1,410 men would need to be screened and an additional 48 cases would need to be treated.

The second study – the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial – included 76,693 men aged 55 to 74, recruited at 10 US centers. Men were randomized to annual screening – with PSA for 6 years and digital rectal exam for 4 years – or to the control group. [N Engl J Med 2009 Mar 26;360(13):1310-9]

After 7 years’ follow-up, there were 50 prostate cancer deaths in the screening group and 44 in the control group (rate ratio 1.13; 95 percent CI, 0.75 – 1.70). Ten-year data showed similar patterns but follow-up was only complete for 67 percent of patients at the time of publication.

Despite the lack of national recommendations, PSA tests are commonly offered in Singapore as part of executive health screens, according to Kesavan. This situation need not change in light of the studies, he said, but he emphasized the importance of explaining the potential consequences before testing.

“It would place the patient in a quandary if it was not explained properly and then he had an abnormal test. Then to put that worry to rest it would require him to undergo a biopsy.”

Urine test shows promise for prostate cancer detection

Medical Tribune April 2009 P4

David Brill

A prototype urine test has been shown to be highly specific for detecting prostate cancer and could even help to reduce the number of unnecessary biopsies, US researchers suggest.

Moreover the results showed some correlation to disease severity markers, suggesting that the test could be used to distinguish between mild and aggressive forms of cancer.

The urine test detects the presence of a fusion between the TMPRSS2 (T2) and ERG genes, which is found in around 50 percent of prostate cancers.

“Many cancers detected at biopsy are low volume, low grade. There is a real need for tests that can help determine which of those men should receive aggressive treatment such as prostatectomy, and which could potentially be monitored more conservatively,” said lead researcher Dr. Jack Groskopf, who presented the results at the recent Genitourinary Cancers Symposium in Orlando, US.

“The key next steps here are to follow up and confirm the results that we have generated to date and, perhaps more importantly, to start looking at the correlation between the urine test and pathologic features in prostatectomy tissues, such as tumor volume stage and grade,” he said.

Commenting on the results, Dr. Howard Sandler, chair of radiation oncology at Cedars-Sinai Medical Center, Los Angeles, said: “The fact that this gene fusion is related to the progression and development of prostate cancer in half of all men who develop prostate cancer has major implications for diagnosis but hopefully for therapy as well. This unique fusion protein might become a therapeutic target at some point in the future.”

In a preliminary study of 556 men due to undergo prostate biopsy the urine test was 84 percent specific, reported Groskopf, a senior research scientist at Gen-Probe Incorporated, the San Diego-based company which is developing the test. For serum prostate-specific antigen (PSA) testing this figure is just 27 percent, he said, adding that the other current screening method – digital rectal exam – is also hampered by its low specificity.

“As a result the majority of prostate biopsies are negative, and you could argue that we are doing too many biopsies,” he said.

The sensitivity of the urine test was 42 percent – a favorable result considering that with only half of cancers containing the T2:ERG gene fusion, the theoretical maximum would be 50 percent, Groskopf added.

The urine test showed significant correlations to aggressiveness indicators such as the Gleason Score, the percentage positive prostate cores and the Epstein criteria.

Researchers from the University of Michigan, who are collaborating with Gen-Probe on the test, recently published another research paper linking sarcosine, a glycine derivative, to more aggressive forms of prostate cancer. This metabolite and its pathways could not only serve as a disease severity marker but also as a target for therapeutic intervention in future, they suggest. [Nature 2009 Feb 12;457:910-4]

Singapore doctors urged to raise awareness of prostate disease

Medical Tribune August 2008 SFI
David Brill

Many Singaporean men are suffering prostate problems in silence, according to a recent survey.

While 75 percent of those questioned had experienced symptoms of benign prostatic hyperplasia (BPH), just 56 percent had visited their doctor.

The majority of those who had symptoms had been suffering for at least 6 months, and half of those who did seek medical attention reported that urinary issues had begun to get in the way of their lives.

Nearly all of the men in the study felt that BPH was simply a natural part of growing old rather than a medical condition.

The president of the Singapore Urological Association (SUA) called for more to be done to raise public awareness of prostate disease.

“It is really a shame that here is a disease [BPH] that is eminently treatable, but many men are unaware that this is actually a disease and therefore do not seek treatment,” said Associate Professor Kesavan Esuvaranathan, who is also the clinical director of the National University Hospital Urology Centre.

“In the same way that elderly people will not go to the doctor and say ‘my hair is whitening’, they also don’t go to their doctor and say ‘I’m having difficulty with urination’, because all their buddies are having the same problems.”

GPs should ask their patients about prostate issues but be careful with their choice of approach, he said.

“The question they should not ask is ‘do you have a problem with urination?’ because invariably patients will say no.

“The questions they have to ask are: ‘Do you wake up at night to visit the bathroom? Do you have to wait a long time to finish? Are you bothered by these symptoms?’”

Once this type of dialogue is initiated and problems identified, doctors can go further and begin to provide treatment, Esuvaranathan said, adding that private healthcare doctors tend not to ask these questions so patients are less forthcoming with seeking advice.

Besides BPH, he noted that the incidence of prostate cancer has grown “exponentially” in Singapore and is now in the top ten leading causes of death from cancer.

The survey, which involved 480 Singaporean men, was conducted in July as part of Prostate Awareness Month – a national campaign by the SUA to educate the public about prostate disease and encourage people to seek early treatment.

Over the course of the month various hospitals offered screening to men aged 50 to 75 at a subsidized cost of $8. The campaign began with a free public forum at Kallang Community Centre, which was attended by 920 men.

The most commonly-reported concerns about BPH were physical discomfort caused by the inability to urinate properly, tiredness due to a lack of normal sleep, and the inconvenience and impact that the condition had on relationships and family life.

Treatment options for BPH include medications such as alpha blockers and 5-alpha reductase inhibitors, and surgery. For prostate cancer radiation therapy, hormone therapy, chemotherapy and surgery can be used, depending on the case.