Epidemiologist suggests discouraging PSA testing

Virginia McMillan
vmcmillan@clear.net.nz

DAILY NEWS: PSA testing may need to be discouraged, an epidemiologist says [image: RCPA]

Epidemiologist Brian Cox is not only promoting caution around PSA screening but also suggests such testing should be discouraged.

Dr Cox says population screening for prostate cancer would be unwise, and suggests PSA (prostate-specific antigen) testing on asymptomatic men should be specialist-ordered only.

Director of the Hugh Adam Cancer Epidemiology unit at Otago University, Dr Cox was commenting on an editorial he wrote with colleague Mary Jane Sneyd in today’s New Zealand Medical Journal.

Dr Cox acknowledges high public concern about prostate cancer and widespread belief that early detection must be good.

Patients being ‘sold a pup’

“If you have had prostate cancer detected and treated, you will naturally believe your life has been saved. But 50 per cent of these people have been ‘sold a pup’,” he says.

The problem is, “we don’t know which 50 per cent”.

Thirty per cent of men aged over 50 have a small tumour in the prostate gland. Under a microscope, these tumours are indistinguishable from cancer but, Dr Cox says, “the vast majority” will never cause symptoms, and may or may not grow.

He also says 50 per cent of men diagnosed via the PSA test would never experience symptoms if left untreated.

Benefits small, if any

Having analysed the two major controlled trials reported in the US and Europe recently, he has concluded that at present, the benefits of PSA testing in asymptomatic men are small, “if they exist at all”.

Even if the at-best 20 per cent mortality reduction suggested by the European randomised study is correct, there are still “major issues” in the harm of over-diagnosis and over-treatment, Dr Cox says.

It’s estimated that 12 to 14 per cent of men who undergo radical prostatectomy develop incontinence and 5 per cent become impotent; 3 to 4 per cent of those undergoing radiotherapy become faecally incontinent and 5 to 10 per cent, impotent.

Screening not only leads to treatment of well men who have no symptoms, it also soaks up resources that could be used on others in the health system, Dr Cox points out.

Although he anticipates opposition to the idea of specialist-ordered PSA tests for asymptomatic men, Dr Cox says it should be considered.

“That’s the only technical way I can see this being manageable.”

Live in the real world

But Peter Foley, chair of the NZMA, says doctors must live in the real world, and public expectations have already been created.

Most men will interact with their GP and he considers this the right place for working through the information on, and uncertainties around, prostate cancer.

Some may decide against getting a PSA test, he says.

Not enough education

Jim Tucker, who blogs about his own prostate surgery and prostate cancer issues says resources must be provided for a public education campaign.

Men often don’t recognise symptoms and need to be encouraged to talk to their doctors about whether tests (PSA and digital) are advisable in their individual case, he says.

The idea of discouraging PSA tests is “extraordinary”, says Mr Tucker.

Minister considering blogger’s letter

He has written to health minister Tony Ryall asking what the Government will do to bring down prostate cancer rates, noted by Mr Ryall earlier this year as a priority.

Jackie Maher, of the minister’s office, says only that the matter is “under consideration”.

Mr Tucker says he was advised of an update to be issued by the health ministry next week.

“There is no imminent announcement on prostate screening,” a ministry spokesperson told New Zealand Doctor today.
source: www.nzdoctor.co.nz

Gene Test May Predict Prostate Cancer Study Shows Experimental Blood Test May Be More Accurate Than PSA Test

By Charlene Laino
WebMD Health News
Reviewed by Louise Chang, MD

June 2, 2009 (Orlando, Fla.) -- A blood test that characterizes each prostate tumor by its unique genetic fingerprint may help pinpoint which men actually have prostate cancer, researchers say.

In a new study, the powerful genetic tool beat out standard PSA testing in discriminating between men who had cancer and those who did not, says Robert Ross, MD, of the Dana-Farber Cancer Institute in Boston.

PSA levels are a measure of a protein called prostate-specific antigen, which is produced by cells in the prostate. High PSA levels can signal cancer.

The new test, which looks at the activity of six genes involved in prostate cancer, was described at the annual meeting of the American Society of Clinical Oncology.

Men whose PSA levels signal a high chance of prostate cancer typically undergo a biopsy, but 60% of these biopsies turn out to be negative, Ross says.

"Each year in the U.S., over 1 million men undergo the anxiety and pain of prostate biopsies at a considerable psychological cost," he tells WebMD.

The hope is that a new genetic test can help men avoid the pain, discomfort, and anxiety of unnecessary biopsies, Ross says.
Six-Gene Test for Prostate Cancer

For the study, which employed a commercially available gene chip, the researchers started with a set of 392 genes that had been associated with cancer.

Using blood samples from 76 men with prostate cancer and 76 healthy men, the researchers homed in on six genes whose activity was significantly associated with prostate cancer. The technique was then validated on blood samples from 128 men with prostate cancer and 84 who didn't have the disease.

"We found that the six-gene test correctly classified 86% of men with the disease," Ross says. In contrast, PSA testing was correct only 70% of the time.

When the gene test and PSA were used in combination, researched achieved the best results of all.

The results are a "significant improvement" over PSA alone, Ross says.

The next step will be to see if the gene test correctly predicts biopsy results in a 1,000-patient study.

Howard Sandler, MD, a prostate cancer specialist at Cedars-Sinai Medical Center in Los Angeles, tells WebMD that PSA testing "is incredibly valuable" for prostate cancer screening.

The gene screen "could be another test that helps to improve early prostate cancer detection," he says.

"But the problem with all these tests is their inability to answer the question we really want to know: Do you have potentially lethal cancer or do you have cancer that will never kill you?" Sandler says.

Sandler is referring to the fact that many prostate tumors grow so slowly that some men are likely to die from other causes long before the tumor itself becomes deadly.

Ross says the test may be able to distinguish between slow and faster growing cancers, but that further testing is needed before that claim can be made.

The study was supported in part by Source MDx, which developed the new test.
source: www.webmd.com

Finasteride Recommended to Prevent Prostate Cancer

Men may benefit from taking Proscar (finasteride), a drug that can reduce their risk of getting prostate cancer, according to new guidelines issued in February by the American Society of Clinical Oncology and the American Urological Association.

“The recommendation is long overdue,” says Eric Klein, MD, chair of the Glickman Urological and Kidney Institute and professor of surgery at Cleveland Clinic Lerner College of Medicine. “We have the highest level of scientific evidence; a phase III randomized control blinded trial that shows finasteride reduces the risk of prostate cancer by 25 percent.”

The new guidelines are based on the latest information emerging from the Prostate Cancer Prevention Trial (PCPT), a study of 18,882 healthy men ages 55 and older that was originally published in 2003. While the PCPT initially reported a 25 percent risk reduction of prostate cancer in men who received 5 milligrams daily of finasteride as compared to the placebo group, it also showed that of the men in the finasteride group who developed prostate cancer, their tumors were more likely to be high-grade.

“As part of the trial findings, it appeared as though some of the men who were diagnosed with prostate cancer actually had worse prostate cancer than expected, and it was worse than in the placebo group,” says Oliver Sartor, MD, professor of cancer research in the department of medicine and urology at Tulane Medical School in New Orleans. “This was a bit of a paradox—that there was an improvement in the overall cancer diagnosis rate but a worsening of some of the cancers in the finasteride-treated group.”

It was previously thought the drug itself was possibly causing the high-grade cancer. But this past year, researchers analyzed biopsy results from PCPT participants and found that the high-grade cancer was simply more detectable in men who took finasteride because the drug shrinks the prostate, making the cancer more visible.

Klein adds, “The secondary analyses show the concern over this drug causing high-grade cancer is not a biologic phenomenon but is related to the fact that it is easier to find high-grade cancer in men on finasteride. Men should not have any hesitation about that issue anymore.”

Finasteride is part of a class of medications called 5-alpha reductase inhibitors (5-ARIs), drugs that work by blocking the production of a hormone that causes the prostate to enlarge. Avodart (dutasteride), another 5-ARI, was recently found to reduce the risk of prostate cancer by 23 percent in men with elevated PSA levels (2.5 to 10 ng/ml) in an international trial entitled Reduction by Dutasteride of Prostate Cancer Events (REDUCE).

Finasteride is also used under the brand name Propecia to treat male pattern baldness and benign prostatic hypertrophy, or enlargement of the prostate gland. Side effects of finasteride include decreased libido, erectile dysfunction, ejaculatory dysfunction, and breast tenderness.

In regards to the side effects, “There was a companion quality of life study that looked at sexual function over the course of seven years in the men on the PCPT that showed, on a 100-point scale, a three point drop in sexual function score, which may be statistically significant but clinically meaningless,” Klein notes. “No one can reasonably argue there are too many side effects with this drug.”

Barnett Kramer, MD, MPH, lead researcher on the new study and associate director for disease prevention at the National Institutes of Health, notes the results of the data are “not thick enough to calculate a cost benefit analysis” yet. However, he called a local pharmacy in Bethesda, Maryland, that estimated the cost of one pill of finasteride around $3, which adds up to $90 a month or $1,080 a year. Kramer says he did not know if insurance would cover the drug since individual health insurance plans vary.

“This still leaves some remaining questions,” Kramer says. “We do not know the impact of 5-ARIs or finasteride on prostate cancer mortality. We also don’t know if we can use lower doses that would lower the risk, and finally, all we know is the efficacy on men being screened for prostate cancer. We cannot see confidence of its effects in men who choose not to be screened.” Researchers hope to continue follow-up studies on PCPT participants.

Sartor says it is important to note how the AUA and ASCO worded the new recommendation. “It’s not a recommendation that people should be on finasteride or not on it. It’s something you should discuss with your physician if you are interested in prostate cancer prevention,” he says.

source: www.curetoday.com

AUA 2009 - The Obstructed Bladder after External Radiation Therapy (XRT) - SUFU Meeting - Session Highlights

CHICAGO, IL, USA (UroToday.com) - Dr. Timothy Boone presented on the obstructed bladder following radiation therapy for prostate cancer. He noted that most men develop urinary retention after external beam radiation therapy (EBRT), after brachytherapy with or without EBRT, and in those who have a combination of EBRT and a RRP. Some of the later develop refractory BNCs. Dr. Boone felt the experience of the person doing brachytherapy affects the incidence of acute urinary retention (AUR) which may be the results of a “learning curve.” He quoted 2 authors who have published their AUR numbers: Keyes, et.al.1 reported overall AUR (n=805) was 12.7%, and prolonged urinary obstruction incidence (> 20 days) was 5%.

He quoted Dr. Landis from the University of Washington who felt that the risk of UR and long-term urinary dysfunction is probably multifactorial and only crudely defined by known clinical variables. But overall, 30 – 50% of men develop “acute” retention symptoms. Bladder outlet obstruction (BOO) beyond 3 months occurs in 2-15% of men who require TURP/dilation.2

Dr. Boone reviewed two large retrospective studies of brachytherapy:

Kollmeier, et al.3, reported on 38 out of 2,050 men (2%) who underwent minimal (channel) TURP due to urinary symptoms or retention.

Chen, et al.4, reported on Medicare claims data from 1991- 1996 that included 5,621 men and indicated that 30% developed BOO within 2 years, with 10% requiring surgery.

Risk factors for developing symptomatic UR following brachytherapy have been identified by Keyes et al and include: older age, use of androgen suppression, large prostate volume (>40 -50 cc), high IPSS (>16) pre-brachy, EBRT before or after, previous TURP and PVR<>3 months) include permanent Urolume Wallstent and there are dissolvable PGA stents for temporary use. Another option is the Mitrofanoff to native bladder or diversion. Dr. Boone concluded that most early BOO occurs following brachytherapy with or without XBRT and that prevention is probably the best medicine. Limited TURP can be successful in many cases but these men have a higher risk of UI (up to 18%) and a higher risk of “non-healing” urothelium, strictures and dystrophic calcification with ongoing necrosis. And there is little published data on the use of Stents post-brachytherapy. But men with PPI and BNC can be successfully managed with a stent and AUS if carefully selected.

References:

1. Keyes M, Schellenberg D, Moravan V, McKenzie M, Agranovich A, Pickles T, Wu J, Liu M, Bucci J, Morris WJ. Decline in urinary retention incidence in 805 patients after prostate brachytherapy: the effect of learning curve? Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):825-34.
2. Landis, D.,Wallner K, Locke J, Ellis W, Russell K, Cavanagh W, Blasko J. Late urinary function after prostate brachytherapy. Brachytherapy. 2002;1(1):21-6.
3. Kollmeier MA, Stock RG, Cesaretti J, Stone NN. Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy. J Urol. 2005 Mar;173(3):808-12.
4. Chen AB, D'Amico AV, Neville BA, Earle CC. Patient and treatment factors associated with complications after prostate brachytherapy. J Clin Oncol. 2006 Nov 20;24(33):5298-304.
5. Hu K, Wallner K. Urinary incontinence in patients who have a TURP/TUIP following prostate brachytherapy. Int J Radiat Oncol Biol Phys. 1998 Mar 1;40(4):783-6.
6. Kollmeier MA, Stock RG, Cesaretti J, Stone NN. Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy. J Urol. 2005 Mar;173(3):808-12
7. Terk MD, Stock RG, Stone NN. Identification of patients at increased risk for prolonged urinary retention following radioactive seed implantation of the prostate. J Urol. 1998, Oct;160(4):1379-82.
8. Blaivas JG, Weiss JP, Jones M. The pathophysiology of lower urinary tract symptoms after brachytherapy for prostate cancer. BJU Int. 2006 Dec;98(6):1233-7


Presented by Timothy Boone, MD at the Annual Meeting of the American Urological Association (AUA) - April 25 - 30, 2009 - McCormick Place Convention Center - Chicago, Illinois, USA.

source: www.urotoday.com

Associations Between {Alpha}-Tocopherol, {Beta}-Carotene, and Retinol and Prostate Cancer Survival - Abstract

Previous studies suggest that carotenoids and tocopherols (vitamin E compounds) may be inversely associated with prostate cancer risk, yet little is known about how they affect prostate cancer progression and survival. We investigated whether serum alpha-tocopherol, beta-carotene, and retinol concentrations, or the alpha-tocopherol and beta-carotene trial supplementation, affected survival of men diagnosed with prostate cancer during the alpha-Tocopherol, beta-Carotene Cancer Prevention Study, a randomized, double-blind, placebo-controlled primary prevention trial testing the effects of beta-carotene and alpha-tocopherol supplements on cancer incidence in adult male smokers in southwestern Finland (n = 29,133). Prostate cancer survival was examined using the Kaplan-Meier method with deaths from other causes treated as censoring, and using Cox proportional hazards regression models with hazard ratios (HR) and 95% confidence intervals (CI) adjusted for family history of prostate cancer, age at randomization, benign prostatic hyperplasia, age and stage at diagnosis, height, body mass index, and serum cholesterol. As of April 2005, 1,891 men were diagnosed with prostate cancer and 395 died of their disease. Higher serum alpha-tocopherol at baseline was associated with improved prostate cancer survival (HR, 0.67; 95% CI, 0.45-1.00), especially among cases who had received the alpha-tocopherol intervention of the trial and who were in the highest quintile of alpha-tocopherol at baseline (HR, 0.51; 95% CI, 0.20-0.90) or at the 3-year follow-up measurement (HR, 0.26; 95% CI, 0.09-0.71). Serum beta-carotene, serum retinol, and supplemental beta-carotene had no apparent effects on survival. These findings suggest that higher alpha-tocopherol (and not beta-carotene or retinol) status increases overall prostate cancer survival. Further investigations, possibly including randomized studies, are needed to confirm this observation.

Written by:
Watters JL, Gail MH, Weinstein SJ, Virtamo J, Albanes D
source: www.urotoday.com