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Prostate Testing and Treatment Dilemmas Persist
7/6/2009
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Leading test comes under fire from new studies and top cancer authorities; Men should consult a doctor about their risk factors and the options if cancer is found
by Craig Weatherby


The main screening test for prostate cancer is designed to detect a protein called prostate-specific antigen or PSA.

A PSA blood test reflects the amount of PSA being produced by a man’s prostate cells. If the level of PSA is higher than normal it could be due to a prostate cancer - or it could be caused by an infection, a non-cancerous enlarged prostate, exercise or sexual activity.

Generally speaking, the higher the PSA level, the more likely it is that there is a cancer in the prostate. But in early prostate cancer, PSA levels are usually relatively low. It is not possible to pick out a particular PSA reading as proving the presence of cancer, because “normal” PSA levels varies from man to man and it rises naturally with age.

Having a raised PSA level means you will need to have more medical tests to find the cause.

The American Cancer Society supports screening with a PSA blood test and rectal examination for men over 50, and at age 45 for men believed to be at high risk of prostate cancer (African American men and men with a family history of prostate cancer). The National Comprehensive Cancer Network supports screening for men from the age of 40.

But clinical trials have not yet shown clear evidence that screening reduces deaths from this disease.

Also, many men diagnosed with prostate cancer have very slowly growing cancers that will never cause any symptoms or problems in their lifetime.

In 1985, before PSA screening was available, an American man had an 8.7 percent lifetime risk of being diagnosed with prostate cancer and a 2.5 percent lifetime risk of dying from the disease.

Twenty years later, in 2005, an American man had a 17 percent lifetime risk of being diagnosed with prostate cancer and a three percent risk of dying from the disease (Boyle, P, Brawley OW 2009).

These numbers suggest that the PSA test is worse than useless… except for high-risk men.

Another problem is that prostate cancer treatment can cause side effects such as impotence and incontinence.

There is no clear benefit in diagnosing prostate cancer early, and the UK and other European countries do not recommend PSA testing for these reasons:
  • Some men with prostate cancer do not have a raised PSA level.
  • Two out of three men with a raised PSA do not have prostate cancer.
  • There is uncertainty about the best way to treat early prostate cancer.
  • The treatments can cause unpleasant side effects.
  • If PSA was used as a screening test, some men who did have prostate cancer would be told that they didn’t.
  • Two thirds of men with a raised PSA level go on to have other tests. One of these, called a needle biopsy, can cause infection and/or persistent bleeding.
Two large international trials are looking into the efficacy and safety of universal prostate cancer screening for all men: the large ERSPC trial in Europe and the PLCO trial in the U.S., early results from which were released in March of this year.

The PCLO study divided 76,693 men into two groups:
  • Annual screening with the PSA test and rectal examination.
  • No screening.
As the researchers concluded, “After 7 to 10 years of follow-up, the rate of death from prostate cancer was very low and did not differ significantly between the two study groups” (Andriole GL et al. 2009).

In other words, screening had little or no effect on the risk of death from prostate cancer. But the results are not fully clear, because some men in the “no screening” group got PSA tests from their own doctors.

The ERSPC study involved 182,000 men between the ages of 50 and 74, and compared those who had screening for prostate cancer with a PSA test every four years to men who had no screening.

The early results show that PSA tests can detect very early prostate cancer and may reduce the number of deaths substantially. As the authors wrote, “PSA-based screening reduced the rate of death from prostate cancer by 20% but was associated with a high risk of over-diagnosis” (Schröder FH et al. 2009).

Tellingly, they translated these numbers into terms that put the value of universal screen in a practical perspective: “This means that 1,410 men would need to be screened and 48 additional cases of prostate cancer would need to be treated to prevent one death from prostate cancer” (Schröder FH et al. 2009).

The men in the study will be followed over the next few years to see whether screening reduces the number who die due to prostate cancer.

The combined final results of the PCLO and ERSPC trials are due in 2010.

New analysis undermines PSA test for all
A new evidence review co-authored by Otis Brawley. M.D., Chief Medical Officer of the  American Cancer Society, says because prostate cancer is virtually ubiquitous in men as they age, the goal of “finding more cancers” is not acceptable.

Instead, he and Peter Boyle, Ph.D., President of the International Prevention Research Institute in Lyon, France assert that “…public health principles demand that screening must reduce the risk of death from prostate cancer, reduce the suffering from prostate cancer, or reduce health care costs when compared with a non-screening scenario” (Boyle, P, Brawley OW 2009).

Brawley and Boyle suggest prostate cancer screening has yet to reach one of these standards to date.

Since the mid-1980s, screening with the PSA blood test has more than doubled the risk of a prostate cancer diagnosis.

The Brawley-led review says a decrease in prostate cancer death rates has been observed since that time, but the relative contribution of PSA testing as opposed to other factors, such as improved treatment, has been uncertain.

His team’s report says that more than one in four cancers detected in whites (29 percent) and nearly half of cancers detected in blacks (44 percent) were over-diagnosed cancers.

A similar model using data from Europe estimated a 50 percent over-diagnosis rate.

Dr. Brawley and company say patients who are diagnosed with clinically insignificant tumors are subject to unnecessary diagnostic tests and unneeded treatment and suffer psychosocial harms.

They are also labeled “a cancer patient,” which can have negative economic consequences. Also, say the authors, over-diagnosis significantly affects 5-year survival statistics, making them uninformative in demonstrating progress in cancer control (Boyle, P, Brawley OW 2009).

The report says the future of prostate cancer will include better screening tests, better methods to assess a man's risk of prostate cancer, and prevention strategies.

On that score, see our companion article about green tea's effects on prostate cancer markers, "
Green Tea may Curb Prostate Cancer Progression."


Sources
  • Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, Fouad MN, Gelmann EP, Kvale PA, Reding DJ, Weissfeld JL, Yokochi LA, O'Brien B, Clapp JD, Rathmell JM, Riley TL, Hayes RB, Kramer BS, Izmirlian G, Miller AB, Pinsky PF, Prorok PC, Gohagan JK, Berg CD; PLCO Project Team. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med. 2009 Mar 26;360(13):1310-9. Epub 2009 Mar 18. Erratum in: N Engl J Med. 2009 Apr 23;360(17):1797.
  • Bettuzzi S, Brausi M, Rizzi F, Castagnetti G, Peracchia G, Corti A. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study. Cancer Res. 2006 Jan 15;66(2):1234-40.
  • Boyle, P, Brawley OW. Prostate Cancer: Current Evidence Weighs Against Population Screening [Editorial]. CA Cancer J Clin 2009. doi: 10.3322/caac.20025. Published online before print June 29, 2009. Accessed at http://caonline.amcancersoc.org/cgi/content/full/caac.20025v1
  • Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, Kwiatkowski M, Lujan M, Lilja H, Zappa M, Denis LJ, Recker F, Berenguer A, Määttänen L, Bangma CH, Aus G, Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320-8. Epub 2009 Mar 18.
  • Villers A, Rebillard X, van der Kwast T, Blijenberg BG, Moss SM, de Koning HJ, Auvinen A; ERSPC Investigators. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009 Mar 26;360(13):1320-8. Epub 2009 Mar 18.

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