29. PSA and Prostate Cancer Screening, the Failed Experiment

Chapter 29. PSA Screening for Prostate Cancer, the Failed Medical Experiment

Jim Smith is a 55 year old athlete and outdoors man, who runs marathons and camps outdoors. He was not worried about prostate cancer until he saw the Larry King Show endorsing PSA screening for prostate cancer.  Larry King showed celebrity endorsements from Colin Powell, Charlton Heston,  Jerry Lewis, Arnold Palmer, Rudy Giuliani, John Kerry, Bob Dole, Norman Schwarzkopf, John McEnroe and Michael Milken all relating personal prostate cancer stories.  Watching all these celebrities urging PSA testing on the Larry King show lured Jim into a local Miami hospital offering free screening for prostate cancer.  Jim's PSA test showed an elevated PSA of 4.7 (normal is less than 4), so Jim was sent over to a local urologist office all set for a needle biopsy of his prostate.

Pioneering Ultrasound Guided Biopsy 

Working as an interventional radiologist in the early days, I actually pioneered ultrasound guided prostate biopsies, and taught many urologists how to do the procedure.  This procedure involves placing an ultrasound probe into the patient to image the prostate, and advance a long needle into the prostate gland for the tissue sample.  Usually 6 samples are obtained.  As uncomfortable as it sounds, it's really all not that bad. 

Seeking a Second Opinion

Thinking the rush to biopsy a bit hasty, Jim declined, and instead came to my office seeking a second opinion.  After a brief chat, Jim complained of recent urinary symptoms.  Sure enough, his urine test indicated a simple infection of the prostate gland which is quite common.

Antibiotics, The Miracle Drug

Inflammation and prostate infection is a common cause of PSA elevation.(27-31)  The plan was to treat Jim with antibiotics for his prostate infection and repeat the PSA test.  After a few weeks of daily antibiotic called Ciprofloxin™, Jim was smiling ear-to-ear because his repeat PSA was back down to 3.8 and his doctors no longer advised prostate biopsy.

PSA Screening, A 20 Year Failed Medical Experiment

PSA is Prostate Specific Antigen, a protein discovered in 1986, and a marker for prostate cancer and inflammation. This article will show you that PSA screening for prostate cancer is, in fact, a 20 year failed medical experiment which provides little or no benefit in saving lives.

New Studies Oppose PSA Screening

Gina Kolata of the New York Times wrote a scathing indictment of PSA screening citing two studies published from March 2009 New England Journal of Medicine, considered the most important studies in the history of men's health. (1) The large US study, the PLCO, showed no mortality benefit from PSA screening.   The European Study, on the other hand, did much better.  Their ERSPC study provided a 20% mortality reduction from PSA screening.  However, this came at a high cost of significant over-diagnosis.  Fifty men were treated for prostate cancer unnecessarily for every life saved. This treatment of surgery, radiation and hormonal castration is associated with erectile dysfunction (ED) and incontinence.(9-12)

One Million Male Victims – Over Diagnosed and Over Treated Since 1986

Dr. Welch reported a very unpleasant finding in the August 2009 issue of the Journal of the National Cancer Institute.(2)  Since the invention of the PSA test in 1986, one million men have been treated for a clinically insignificant prostate cancer that did not require treatment. (3-7) These are 1 million male victims, many suffering from side effects of treatment, such as erectile dysfunction and incontinence.

Sept 2009 BMJ and Archives of Internal Med Papers

Another series of papers just released in the British Medical Journal Sept. 24 2009, again criticizes mass PSA screening, advising against it. (13-16) Another highly critical article from the 2009 Archives of Internal Medicine, by Dr Kirsten Howard from the University of Sydney's School of Public Health, showed that PSA Testing is not a major factor in prostate cancer mortality.  Dr Howard says  “men with PSA-detected cancer may often undergo therapies for clinically insignificant cancers " which does not affect mortality rates from prostate cancer.(115)(116)

Why Doesn't It Work? Where Did We Go Wrong with PSA Screening?

We have known since 1935 with the publication of Arnold Rich's autopsy study that there is a large pool of latent, clinically insignificant prostate cancer in the male population which increases with age.(47)   By the age of fifty, 30-40 per cent of males will harbor a clinically insignificant focus of prostate cancer.  The vast majority succumb to old age before the prostate cancer bothers them.  These prostate cancers are the incidental findings at post mortem exam. 

Prostate cancer is a slow growing indolent disease with a 99 per cent 5 year survival after diagnosis.  The incidence of latent prostate cancer is estimated to be one half of the male population 65 and over (7 million of the 14 million males), yet there are only 30,000 deaths per year.  This means the average male has a 0.5% chance of dying from prostate cancer, (or a 99.5 chance of dying from other causes, not prostate cancer).

PSA screening programs send the screened patients to trans-rectal ultrasound guided biopsy which finds these latent prostate cancers, many of which should not be treated.  Mainstream conventional treatment involves radical prostatectomy, radiation therapy, and hormonal castration.  The first two are associated with adverse effects of incontinence, and erectile dysfunction. Treatment with androgen blockade, (a form of chemical castration) is associated with increased mortality and osteoporosis.(117)

The Buffalo Hunt Factor - Advanced Prostate Cancer Hunted to Extinction

One impact of wide scale PSA screening for prostate cancer is the eradication of advanced cases of prostate cancer over the past two decades.  During my training years in the nuclear medicine department at Rush Medical School in Chicago in the 1970's, the doctors followed dozens of patients with metastatic prostate cancer on serial bone scans.  This is rarely seen today.  The advanced prostate cancer case is a rare bird driven to extinction, now seen only occasionally. 

Stephen Strum, MD, an oncologist from Oregon writes in the comment section of a March 2009 NEJM article, "The nature of the patient diagnosed with Prostate Cancer has dramatically changed since the introduction of PSA in 1987.  Almost gone are men presenting with advanced local or distant Prostate Cancer."  (20)  

Like the vanishing American Buffalo, these advanced metastatic prostate cancer cases have been hunted to the point of near extinction by the PSA Screening Test.

The Vanishing Buffalo- Hunted to Extinction

Stanford's Dr. Thomas Stamey, the first to advocate PSA screening in 1987, has come full circle, and no longer recommends PSA screening. Stamey found the abundance of advanced cases from the early years of PSA Screening are gone, and the PSA test has become useless. Stamey declares, "The prostate specific antigen era in the United States is over for prostate cancer".  Stamey's data shows there was a substantial decrease in correlation between PSA levels and the amount of prostate cancer - from 43 percent predictive ability in the first five-year group down to 2 percent in the most recent one.  "Our job now is to stop removing every man’s prostate who has prostate cancer," said Stamey. "We originally thought we were doing the right thing, but we are now figuring out how we went wrong." (61)(66)

Organizations Opposed to Routine PSA Screening

In 1997, the American Cancer Society changed its position and no longer recommends screening.  Their chief Medical Officer, Otis Brawley MD declined PSA screening for himself.  Otis Brawley, MD says in a Jan 2000 interview, "twenty-three organizations of experts from the Canadian Urology Association to the American College of Physicians to the U.S. Preventive Services Task Force recommend against screening...the predominance of professional expert opinion is that (PSA screening) is unproven and should not be done." (119)

What is the Clinical Utility of PSA Test?

According Dr Bicker in an article in the August 2009 Anticancer Research, the PSA test is now commonly regarded as an indicator of prostate volume, and is not independently diagnostic or prognostic of prostate cancer. (34)  Even though mass screening of asymptomatic men with the PSA test is no longer recommended, the PSA tests remains a very useful tool in the diagnosis and follow up of prostate cancer. For example, the PSA is useful as a cancer marker to follow cancer recurrence, progression or regression after treatment.(45)

Can We Tell Dangerous Prostate Cancers Apart from Insignificant Ones?

What is the Gleason Score? Gleason Score can help separate the aggressive cancers from the non-aggressive cancers. Gleason Score is a histology grading pattern used to grade the biopsy sample.  Lower scores (one and two) are associated with better prognosis.  Higher scores (4 and 5) are associated with worse prognosis with more aggressive behavior of the tumor.

How to Treat the Aggressive Cancers and Ignore the Others - Watchful Waiting vs. Active Surveillance

One of the major problems with prostate cancer screening with PSA, is the inability of this test to differentiate the clinically insignificant cancers that don't require treatment from the dangerous cancers that do.  Various authors have suggested refinements by using parameters such as PSA velocity(23-24)(33)(65-67), Free PSA ratio (21),  and of course, the Gleason score (74-76), a form of histology grading, applied to prostate biopsy sample to provide this discrimination.  Using these refinements, some doctors such as Laurence Klotz have advocated Active Surveillance based on PSA velocity.(120)  Dr Klotz offers treatment for cases having a PSA Doubling Time of 3 years or less (based on a minimum of three determinations over 6 months).  Others, such as Mark Soloway MD, feel that Gleason score upgrade or histological evidence of tumor aggression is the most important parameter, and have offered radical treatment if this is found at repeat biopsy. (98-99) The obvious goal is to identify and treat aggressive tumors before they invade the prostatic capsule and beyond.  This is not so simple and may require discovery of new biomarkers.

A new bio-marker in prostate cancer cells called Hsp-27 protein indicates an aggressive type of prostate cancer that requires treatment.  The absence of the Hsp-27 protein suggests a silent type of cancer that does not require immediate treatment. (35) Do these new protocols and tools work any better than the old ones?  We don't know yet. It may take another ten years to find out.

Preventing Prostate Cancer -Diet and LifeStyle Modification

Given the reality that PSA screening for early detection for prostate cancer is a misguided adventure which leads to overdiagnosis and does more harm than good, perhaps another approach to prevention is warranted. Such an approach is suggested by urologist Ronald Wheeler at the Sarosota Prostate Center. (105)  Dr Wheeler advocates a nutritional program for prostate cancer prevention with Vitamins C, B6, E, zinc, selenium, Saw palmetto, Pygeum africanum, stinging nettle, pumpkin seed, Echinacea purpurea, garlic, ginkgo biloba, Amino acids–L-glycine, L-alanine, L-glutamic acid and Modified Mediterranean Diet.(105)

Results of Diet and Nutrition Program on PSA

In 20 patients with biopsy proven prostate cancer who had declined radical treatment, Dr Wheeler's herbal-nutritional supplement program reduced mean PSA from 6.8 ng/ml to 3.4 ng/ml over three years of follow-up.(105) (121)  I would also add digestive enzymes, and optimizing vitamin D level with testing and supplementation, as well as optimizing Iodine levels with Iodoral would also be included in a typical prostate cancer prevention program. 

In conclusion, PSA screening for prostate cancer has been a failed medical experiment leaving behind 1 million male victims unnecessarily treated for a type of prostate cancer that was clinically insignificant, providing little or no benefit in terms of lives saved.  Leaders in the field are now alerting us to the pitfalls, harms and limitations involved in PSA cancer screening.  Recognizing that there are 30,000 prostate cancer deaths per year, the urgent challenge is to identify and treat the aggressive cancers destined to kill the host, and avoid harming the other 7 million men representing a silent reservoir of biologically insignificant disease.  Hopefully, this will be the subject of future NIH funded research, so that another one million men in the future will be spared needless over diagnosis and overtreatment.

For references and links, see my web site: www.bioidenticalhormones101.com

References for Chapter 29. PSA Screening for Cancer, the Failed Medical Experiment

(1) http://www.nytimes.com/2009/03/19/health/19cancer.html Prostate Test Found to Save Few Lives By GINA KOLATA  NY Times Published: March 18, 2009.

(2) http://jnci.oxfordjournals.org/cgi/content/abstract/djp278v1 Prostate Cancer Diagnosis and Treatment After the Introduction of Prostate-Specific Antigen Screening: 1986–2005. H. Gilbert Welch, Peter C. Albertsen. J Nat Cancer Inst. August 31, 2009

(3) http://www.medicinenet.com/script/main/art.asp?articlekey=105197 PSA Test: More Harm Than Good? Study: 1 Million Men Suffered Needless Treatment After Prostate Cancer Test By Daniel J. DeNoon WebMD Health News  Aug. 31, 2009 -- The PSA prostate cancer screening test does more harm than good, a new study suggests. Medicine.net.

(4) http://www.cnn.com/2009/HEALTH/09/01/prostate.cancer.screening/index.html Study: Prostate cancer test leads to needless diagnoses . CNN News. Tue September 1, 2009 By Denise Mann 

(5) http://www.modernmedicine.com/modernmedicine/Enews/Prostate-cancer-overdiagnosis-attributed-to-PSA-te/ArticleStandard/Article/detail/624305?contextCategoryId=40237&ref=25
Prostate cancer overdiagnosis attributed to PSA test - Sep 10, 2009 Urology Times E-News

(6) http://www.webmd.com/prostate-cancer/news/20090831/psa-test-more-harm-than-good PSA Test: More Harm Than Good? Study: 1 Million Men Suffered Needless Treatment After Prostate Cancer Test By Daniel J. DeNoon WebMD Health News - Aug. 31, 2009

(7) http://www.baltimoresun.com/health/bal-md.hs.psa01sep01,0,7710170.story Doubt cast on value of PSA test By Kelly Brewington- Baltimore Sun September 1, 2009.

(8) http://www.foundationforurologicalresearch.com/downloads/PSA%20Best%20Practice%20Statement.pdf Adult Urology Prostate Specific Antigen Best Practice Statement: 2009 Update Kirsten L. Greene.  

(9) http://synapse.ucsf.edu/articles/2009/March/26/prostate.html Studies Cast Doubt on Value of Prostate Screenings Synapse Staff Report UCSF .

(10) http://content.nejm.org/cgi/content/full/NEJMoa0810696 Gerald L. Andriole, M.D.,et al . NEJM. Vol 360:1310-1319  March 26, 2009  N 13. Mortality Results from a Randomized Prostate-Cancer Screening Trial.

(11) http://content.nejm.org/cgi/content/full/NEJMoa0810084  NEJM. Volume 360:1320-1328  March 26, 2009  Number 13, Screening and Prostate-Cancer Mortality in a Randomized European Study
Fritz H. Schröder, M.D., Jonas Hugosson, M.D.,

(12) http://www.ncbi.nlm.nih.gov/pubmed/19660851 Eur Urol. 2009 Jul 28. Prostate Cancer Mortality Reduction by Prostate-Specific Antigen-Based Screening Adjusted for Nonattendance and Contamination in the European Randomised Study of Screening for Prostate Cancer (ERSPC). Roobol MJ et al.

(13) http://blog.lib.umn.edu/schwitz/healthnews/2009/09/bmj-papers-conc-1.html BMJ papers conclude not enough evidence to support widespread PSA screening - Gary Schwitzer Sept24, 2009.

(14) http://www.bmj.com/cgi/content/abstract/339/sep24_1/b3537 24 September 2009,  BMJ 2009;339:b3537 . Prostate specific antigen for early detection of prostate cancer: longitudinal study.
Benny Holmström et al.

(15) http://www.bmj.com/cgi/content/extract/339/sep24_1/b3601 24 September 2009,  BMJ 2009;339:b3601. Analysis Screening for prostate cancer remains controversial. Jennifer R Stark,

(16) http://www.bmj.com/cgi/content/extract/339/sep24_1/b3572 24 September 2009,  BMJ 2009;339:b3572 . Editorials  Prostate specific antigen for detecting early prostate cancer
Evidence is inconclusive, so patient education and shared decision making are essential.

(17) http://health.usnews.com/articles/health/healthday/2009/09/15/watchful-waiting-works-for-older-men-with.html  Watchful Waiting Works for Older Men With Prostate Cancer, But experts stress the same does not hold true for patients under 60. Posted September 15, 2009

(18) http://blogs.consumerreports.org/health/2009/09/
whats-wrong-with-free-prostatecancer-screening-yankees-psa-test-bat-for-the-cure-us-open-john-mcenro.html Consumer Reports. Septr 14, 2009. More What’s wrong with free prostate-cancer screening?

(19) http://medicalconsumers.org/2009/04/16/just-say-no-to-the-psa-prostate-cancer-test/
Just Say No to the PSA Prostate Cancer Test Posted by medconsumers on April 16, 2009

(20) http://www.nejm.org/perspective-roundtable/screening-for-prostate-cancer/ Comment by Stephen Strum, MD, FACP Ashland, Oregon Physician -- Oncologist 03/30/2009.  Also see http://www.nejm.org/doi/full/10.1056/NEJMp0901825 See Comments section. Dr Strum's comments to this article. Perspective Perspective Roundtable. Screening for Prostate Cancer. Thomas H. Lee, M.D., Philip W. Kantoff, M.D., and Mary F. McNaughton-Collins, M.D., M.P.H. N Engl J Med 2009; 360:e18March 26, 2009

(21) http://www.psa-rising.com/prostatecancer/fpsa-flowchart.htm  The "free" PSA test (PSA-f) and how it may spare you a biopsy . PSA Rising Blog.

(22) http://www.sciencedaily.com/releases/2007/05/070525074607.htm Prostate Cancer: High Pretreatment PSA Velocity Predicts Worse Outcome ScienceDaily (May 25, 2007) .

(23) http://www.drcatalona.com/quest/Summer04/quest_summer04_2.asp PSA Velocity: Important New Tool in Fight Against Prostate Cancer - By William J. Catalona, MD 

(24) http://content.nejm.org/cgi/content/abstract/351/2/125 Volume 351:125-135  July 8, 2004  Number 2 Preoperative PSA Velocity and the Risk of Death from Prostate Cancer after Radical Prostatectomy Anthony V. D'Amico, M.D., Ph.D., Ming-Hui Chen, Ph.D., Kimberly A. Roehl, M.P.H., and William J. Catalona, M.D.
 
(25) http://www.ncbi.nlm.nih.gov/pubmed/19682790 Prostate-Specific Antigen Velocity for Early Detection of Prostate Cancer: Result from a Large, Representative, Population-based Cohort .
Andrew J. Vickersa et al.

(26) http://www.ncbi.nlm.nih.gov/pubmed/10096388 Urology. 1999 Mar;53(3):581-9
Serum prostate-specific antigen as a predictor of prostate volume in men with benign prostatic hyperplasia. Roehrborn CG et al. Conclusions.

(27) http://www.ncbi.nlm.nih.gov/pubmed/15947609  J Urol. 2005 Jul;174(1):161-4. Treatment of chronic bacterial prostatitis with levofloxacin and ciprofloxacin lowers serum prostate specific antigen. Schaeffer AJ, Wu SC, Tennenberg AM, Kahn JB. 

(28) http://www.ncbi.nlm.nih.gov/pubmed/15693428 Arch Ital Urol Androl. 2004 Dec;76(4):154-8. PSA decrease after levofloxacin therapy in patients with histological prostatitis. Guercio S et al.

(29) http://www.ncbi.nlm.nih.gov/pubmed/11912396  J Urol. 2002 Apr;167(4):1723-6
Treatment of chronic prostatitis lowers serum prostate specific antigen. Bozeman CB et al.

(30) http://www.ncbi.nlm.nih.gov/pubmed/17695414 Arch Ital Urol Androl. 2007 Jun;79(2):84-92.
Reduction of PSA values by combination pharmacological therapy in patients with chronic prostatitis: implications for prostate cancer detection. Magri V et al,

(31) http://www.ncbi.nlm.nih.gov/pubmed/17637759  Prostate Cancer Prostatic Dis. 2008;11(2):148-52. Epub 2007 Jul 17.  PSA reduction (after antibiotics) permits to avoid or postpone prostate biopsy in selected patients. Serretta V et al.

(32) http://psg-mac43.ucsf.edu/ticr/syllabus/courses/26/2004/03/11/Lecture/readings/psa.pdf
Surrogate End Point for Prostate Cancer–Specific Mortality After Radical Prostatectomy or Radiation Therapy Anthony V. D’Amico, Judd W. Moul, Peter R. Carroll, Leon Sun, Deborah Lubeck,Ming-Hui Chen

(33) http://www.ncbi.nlm.nih.gov/pubmed/17530618  Cancer. 2007 Jul 1;110(1):56-61. Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors. D'Amico AV, Chen MH, Catalona WJ, Sun L, Roehl KA, Moul JW.

(34) http://www.ncbi.nlm.nih.gov/pubmed/19661347 Anticancer Res. 2009 Aug;29(8):3289-98. New molecular biomarkers for the prognosis and management of prostate cancer--the post PSA era. Bickers B, Aukim-Hastie C.

(35) http://www.sciencedaily.com/releases/2009/09/090923102335.htm Two-Thirds Of Prostate Cancer Patients Do Not Need Treatment, Study Reveals. ScienceDaily (Sep. 24, 2009)

(36)  http://www.ncbi.nlm.nih.gov/pubmed/19707199 Br J Cancer. 2009 Aug 25. [Epub ahead of print]
Hsp-27 expression at diagnosis predicts poor clinical outcome in prostate cancer independent of ETS-gene rearrangement. Foster CS et al.

(37) http://www.sciencedaily.com/releases/2008/11/081116142322.htm Men Who Take Aspirin Have Significantly Lower PSA Levels. ScienceDaily (Nov. 17, 2008)

(38) http://www.sciencedaily.com/releases/2008/05/080515072654.htm Low Cholesterol Leads To Lower PSA, Lower Prostate Cancer Risk, Study Suggests. ScienceDaily (May 18, 2008)

(39) http://www.drcatalona.com/quest/Spring04/quest_spring04_1.asp The measurement of PSA, by Dr Catalona.

(40) http://www.themedguru.com/20090926/newsfeature/
studies-highlight-inefficacy-psa-test-86128398.html The Med Guru Blog. Studies highlight inefficacy of PSA test by Jyoti Pal - September 26, 2009 

(41) http://www.medpagetoday.com/Urology/ProstateCancer/16142 No Evidence to Support Routine PSA Screening, By Chris Emery, Contributing Writer, MedPage Today, Published: September 25, 2009

(42) http://caonline.amcancersoc.org/cgi/content/full/59/4/220 Editorial - Prostate Cancer: Current Evidence Weighs Against Population Screening . Peter Boyle, PhD, DSc1 and Otis W. Brawley, MD2 . Published online before print June 29, 2009 CA Cancer J Clin 2009; 59:220-224

(43) http://jama.ama-assn.org/cgi/content/abstract/296/19/2336 PSA Screening Among Elderly Men With Limited Life Expectancies. Louise C. Walter, MD; Daniel Bertenthal, MPH; Karla Lindquist, MS; Badrinath R. Konety, MD JAMA. 2006;296:2336-2342.

(44) http://www.jurology.com/article/S0022-5347(08)03280-1/abstract Volume 181, Issue 4, Pages 1606-1614 (April 2009)  27 of 126. Prostate Specific Antigen Testing Among the Elderly—When To Stop? Edward M. Schaeffera et al.

(45) http://www.bmj.com/cgi/content/extract/339/sep22_1/b3527 Published 22 September 2009, BMJ 2009;339:b3527 . Serum tumour markers: how to order and interpret them, C M Sturgeon.

(46) http://www.ccjm.org/content/76/8/446.full The new data on prostate cancer screening: What should we do now? by Timothy  Gilligan, MD, Cleveland Clinic Journal of Medicine August 2009 vol. 76 8 446-448.

(47) http://caonline.amcancersoc.org/cgi/reprint/29/2/115
http://www.ncbi.nlm.nih.gov/pubmed/108001 Classics in oncology. On the frequency of occurrence of occult carcinoma of the prostate: Arnold Rice Rich, M.D., Journal of Urology 33:3, 1935. 

(48) http://www.ncbi.nlm.nih.gov/pubmed/7803731 In Vivo. 1994 May-Jun;8(3):439-43. High grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma between the ages of 20-69: an autopsy study of 249 cases. Sakr WA et al.

(49) http://www.ncbi.nlm.nih.gov/pubmed/12518329 Prostate. 2003 Feb 15;54(3):238-47. Prevalence of prostate cancer and prostatic intraepithelial neoplasia in Caucasian Mediterranean males: an autopsy study. Sánchez-Chapado M et al.

(50) http://www.ncbi.nlm.nih.gov/pubmed/16203079 Eur Urol. 2005 Nov;48(5):739-44. Epub 2005 Sep 15. The prevalence of prostate carcinoma and its precursor in Hungary: an autopsy study. Soos G, Tsakiris I, Szanto J, Turzo C, Haas PG, Dezso B.

(51) http://www.ncbi.nlm.nih.gov/pubmed/6154966 Scand J Urol Nephrol. 1980;14(1):29-35. Latent prostatic cancer in a consecutive autopsy series. Hølund B.

(52) http://www.ncbi.nlm.nih.gov/pubmed/7107064  Int J Cancer. 1982 Jun 15;29(6):611-6. Geographic pathology of latent prostatic carcinoma. Yatani R et al.

(53) http://www.ncbi.nlm.nih.gov/pubmed/19077395 Urol Int. 2008;81(4):379-82. Epub 2008 Dec 10
Do clinically insignificant tumors of the prostate exist?  Stamatiou K et al.

(54) http://ije.oxfordjournals.org/cgi/content/full/36/2/282  Commentary: Implications of the frequent occurrence of occult carcinoma of the prostate, Anthony B Miller,  13 November 2006.

(55) http://prostate-cancer-questions-and-answers.com/2009/09/miami-urology-psa-test/ 
Miami urology doctors are offering a free PSA Test and DRE exam   September 15th, 2009

(56) http://www.nydailynews.com/lifestyle/health/2009/06/08/2009-06-08
_free_psa_prostate_screening_locations.html Free PSA Prostate Screening Locations  June 8th 2009

(57) http://www.abc15.com/content/living/yourhealth/story/
Free-screening-event-to-fight-deadly-cancer-in-men/vfA8Xj-mr0qgyJMbg3-thg.cspx
Free screening event to fight deadly cancer in men: Eva Bowen  9/23

(58) http://jnci.oxfordjournals.org/cgi/content/full/djp310 Journal of the National Cancer Institute August 31, 2009. Prostate Cancer Screening; Is This a Teachable Moment? Otis W. Brawley

(59) http://blog.lib.umn.edu/schwitz/healthnews/2009/08/powerful-editor.html
The problem with this test is that it tends to create fear and anxiety in many men with no real basis.

(60) http://www.drmcdougall.com/misc/2009nl/aug/king.htm Larry King Live on Prostate Cancer Screening (PSA)- Show Sets a New Standard for Disease Mongering. Dr. MacDougal.

(61) http://www.ncbi.nlm.nih.gov/pubmed/15371827 J Urol. 2004 Oct;172(4 Pt 1):1297-301. The prostate specific antigen era in the United States is over for prostate cancer: what happened in the last 20 years? Stamey TA et al.

(62) http://latimesblogs.latimes.com/booster_shots/2008/08/psa-test-dont-d.html PSA test: Don't do it, say angry men August 4, 2008

(63) http://www.bmj.com/cgi/content/full/324/7332/255/a/DC1 Advocates of PSA testing campaign to silence critics, Annabel Ferriman, BMJ 2002;324:255

(64) http://www.bmj.com/cgi/eletters/324/7332/255/a/DC1#19194 Bertrand M.l Bell, Distinguished University Professor Albert Einstein College of medicine . BMJ.letter.

(65) http://jama.ama-assn.org/cgi/content/abstract/279/19/1542 Use of the Percentage of Free Prostate-Specific Antigen to Enhance Differentiation of Prostate Cancer From Benign Prostatic Disease A Prospective Multicenter Clinical Trial . William J. Catalona, MD et al. JAMA. 1998;279:1542-1547.

(66) http://www.innovations-report.com/html/reports/medicine_health/report-33457.html The PSA era is over in the United States," said Thomas Stamey, MD.

(67) http://www.europeanurology.com/article/S0302-2838(05)00449-5/fulltext The PSA Era is not Over for Prostate Cancer- William J. Catalona , Stacy Loeb.   July 2005, pages 541 – 545. European Urology.

(68) http://www.ncbi.nlm.nih.gov/pubmed/19755699 JAMA. 2009 Sep 16;302(11):1202-9. Outcomes of localized prostate cancer following conservative management. Lu-Yao GL at al.

(69) http://www.ncbi.nlm.nih.gov/pubmed/15870412 20-year outcomes following conservative management of clinically localized prostate cancer. Albertsen PC, Hanley JA, Fine J. JAMA. 2005 May 4;293(17):2095-101.

(70) http://jama.ama-assn.org/cgi/content/abstract/274/8/626 Long-term Survival Among Men With Conservatively Treated Localized Prostate Cancer. Peter C. Albertsen, MD; Dennis G. Fryback, PhD; Barry E. Storer, PhD; Thomas F. Kolon, MD; Judith Fine  JAMA. 1995;274(8):626-631.

(71) http://jama.ama-assn.org/cgi/content/abstract/280/11/975 Competing Risk Analysis of Men Aged 55 to 74 Years at Diagnosis Managed Conservatively for Clinically Localized Prostate Cancer . Peter C. Albertsen, MD; James A. Hanley, PhD; Donald F. Gleason, MD, PhD; Michael J. Barry, MD   JAMA. 1998;280:975-980.

(72) http://www.ncbi.nlm.nih.gov/pubmed/12604893 Am J Surg Pathol. 2003 Mar;27(3):365-71. 
Basal cell cocktail (34betaE12 + p63) improves the detection of prostate basal cells. Zhou M et al.

(73) http://www.ncbi.nlm.nih.gov/pubmed/15487448 Am J Clin Pathol. 2004 Oct;122(4):517-23. Usefulness of basal cell cocktail (34betaE12 + p63) in the diagnosis of atypical prostate glandular proliferations. Shah RB et al

(74) http://www.phoenix5.org/Infolink/GleasonGrading.html Understanding Gleason Grading Last Revised May 14, 1997.

(75) http://www.prostate-cancer.org/education/staging/Dowd_GleasonScore.html The Gleason Score: A Significant Biologic Manifestation of Prostate Cancer Aggressiveness On Biopsy By Gerry J. O’Dowd et al. Prostate Cancer Research Institute, Los Angeles, CA Reprinted from PCRI Insights January 2001 v4.1

(76) http://www.yananow.net/Chart-Gleason.htm Gleason Score at Diagnosis

(77) http://jco.ascopubs.org/cgi/content/abstract/23/32/8165 Journal of Clinical Oncology, Vol 23, No 32 (November 10), 2005: pp. 8165-8169. Active Surveillance for Prostate Cancer: For Whom? Laurence Klotz.

(78) http://www.prostatecancerwatchfulwaiting.co.za/ActiveSurveillance.pdf
Actuve surveillance: towards a new paradigm in the management of early prostate cancer
Chris Parker.

(79) http://deb.uthscsa.edu/URORiskCalc/Pages/uroriskcalc.jsp The Cancer Risk Calculator for Prostate Cancer

(80) http://caonline.amcancersoc.org/cgi/content/full/56/2/106  Cancer Statistics, 2006 Ahmedin Jemal

(81) http://www.biomedexperts.com/Abstract.bme/18073376/   Interpreting trends in prostate cancer incidence and mortality in the five Nordic countries. Journal of the National Cancer Institute 2007;99(24):1881-7. Kvåle Rune et al.

(82) http://jjco.oxfordjournals.org/cgi/content/abstract/39/6/339 Japanese Journal of Clinical Oncology 2009 39(6):339-351  The Japanese Guideline for Prostate Cancer Screening. Chisato Hamashima et al.

(83) http://theoncologist.alphamedpress.org/cgi/content/full/13/3/306 The Oncologist, Vol. 13, No. 3, 306-308, March 2008; doi:10.1634/theoncologist.2008-0008 Commentary: How Serious Is Getting a Diagnosis of Prostate Cancer? Michael J. Barry et al.

(84) http://www.phac-aspc.gc.ca/publicat/cdic-mcc/16-1sup/c_e.html Trends in Incidence and Mortality of Prostate Cancer in Canada . Isra Levy .

(85) http://jnci.oxfordjournals.org/cgi/content/full/99/24/1881 Interpreting Trends in Prostate Cancer Incidence and Mortality in the Five Nordic Countries . Public Health Rep. 2004 Mar–Apr; 119(2): 174–186. 

(86) http://jnci.oxfordjournals.org/cgi/content/full/91/12/1017 Journal of the National Cancer Institute, Vol. 91, No. 12, 1017-1024, June 16, 1999. Cancer Surveillance Series: Interpreting Trends in Prostate Cancer—Part I: Evidence of the Effects of Screening in Recent Prostate Cancer Incidence, Mortality, and Survival Rates. Benjamin F. Hankey et al.

(87) http://jnci.oxfordjournals.org/cgi/content/full/91/12/1025 Journal of the National Cancer Institute, Vol. 91, No. 12, 1025-1032, June 16, 1999. Cancer Surveillance Series: Interpreting Trends in Prostate Cancer—Part II: Cause of Death Misclassification and the Recent Rise and Fall in Prostate Cancer Mortality . Eric J. Feuer, Ray M. Merrill, Benjamin F. Hankey

(88) http://www.eradimaging.com/site/article.cfm?ID=1 Prostate-Specific Antigen Test: Is It a Valid Screening Tool for Prostate Cancer? Pamela C. Cartright.

(89)  http://www.renegadeneurologist.com/prostate-treatment-wasted-40-billion-scientist-says/
Prostate Treatment Wasted $40 Billion, Scientist Says From Bloomberg.com:

(90) http://www.usyd.edu.au/news/84.html?newsstoryid=3911 Testing not a major factor in prostate cancer mortality. 29 September 2009. Renegade Neurologist.

(91) http://archinte.ama-assn.org/cgi/content/full/169/17/1554 Weighing the Benefits and Downsides of Prostate-Specific Antigen Screening. Pignone Arch Intern Med.2009; 169: 1554-1556.

(92) http://www.medicalnewstoday.com/articles/143145.php Otis W. Brawley.

(93) http://www.ncbi.nlm.nih.gov/pubmed/16414494 Active surveillance with selective delayed intervention for favorable risk prostate cancer. Klotz L. Division of Urology, University of Toronto,

(94) http://www.europeanurology.com/article/S0302-2838(07)00713-0/pdf  Prospective Validation of Active Surveillance in Prostate Cancer: The PRIAS Study RCN van den Bergh, S Roemeling, MJ Roobol European Urology, Volume 52, Issue 6, Pages 1560-1563, December 2007

(95) http://www.prostatecancerwatchfulwaiting.co.za/HardieParker2005.pdf Early outcomes of active surveillance for localized prostate cancer C Hardie, C Parker, A Norman, R Eeles, A. BJU international, 2005.

(96) http://www3.interscience.wiley.com/journal/113385414/abstract PSA doubling time predicts the outcome after active surveillance in screening-detected prostate cancer: Results from the European randomized study of screening for prostate cancer, Sweden section Khatami Ali et al.

 (97) http://www3.interscience.wiley.com/cgi-bin/fulltext/118859241/HTMLSTART Cancer. 2008 Jun 15;112(12):2664-70 Active surveillance for the management of prostate cancer in a contemporary cohort. Dall'Era MA et al.

(98) http://www.ncbi.nlm.nih.gov/pubmed/17850361 BJU Int. 2008 Jan;101(2):165-9. Epub 2007 Sep 10. Active surveillance; a reasonable management alternative for patients with prostate cancer: the Miami experience. Soloway MS, Soloway CT et al.

 (99) http://www.ncbi.nlm.nih.gov/pubmed/19233410 J Urol. 2009 Apr;181(4):1635-41;
A multi-institutional evaluation of active surveillance for low risk prostate cancer.
Eggener SE, Mueller A, Berglund RK, Ayyathurai R, Soloway C, Soloway MS et al.

(100) http://www.ncbi.nlm.nih.gov/pubmed/15839912 BJU Int. 2005 May;95(7):956-60.  Early outcomes of active surveillance for localized prostate cancer. Hardie C et al.

 (101) http://www3.interscience.wiley.com/cgi-bin/fulltext/119142464/HTMLSTART Role of repeated biopsy of the prostate in predicting disease progression in patients with prostate cancer on active surveillance . Mohammed Al Otaibi, MD et al.

(102) http://www.ncbi.nlm.nih.gov/pubmed/16713065 Eur Urol. 2006 Sep;50(3):475-82. Epub 2006 May 3.  Management and survival of screen-detected prostate cancer patients who might have been suitable for active surveillance. Roemeling S et al.

(103) http://www.ncbi.nlm.nih.gov/pubmed/18387385 Urology. 2008 Apr;71(4):573-7. Links
Staging saturation biopsy in patients with prostate cancer on active surveillance protocol.
Abouassaly R, Lane BR, Jones JS.

(104) http://www3.interscience.wiley.com/cgi-bin/fulltext/114132008/HTMLSTART Prostate-specific antigen velocity and prostate cancer gleason grade and stage Paul F. Pinsky et al.

(105) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684075/?tool=pubmed Clin Interv Aging. 2007 March; 2(1): 153–161. Is it necessary to cure prostate cancer when it is possible? (Understanding the role of prostate inflammation resolution to prostate cancer evolution) Ronald E Wheeler Prostatitis & Prostate Cancer Center, Sarasota, Fl, USA .

(106) http://www3.interscience.wiley.com/cgi-bin/fulltext/116321833/HTMLSTART Prostate-specific antigen velocity and the detection of gleason score 7 to 10 prostate cancer. Rinaa S. Punglia et al.

(107) http://www.ncbi.nlm.nih.gov/pubmed/18762814 Prostate Cancer Prostatic Dis. 2009;12(2):143-7. Biopsy tissue microarray study of Ki-67 expression in untreated, localized prostate cancer managed by active surveillance. Jhavar S, et al

(108) http://jnci.oxfordjournals.org/cgi/content/abstract/97/17/1248 JNCI Journal of the National Cancer Institute 2005 97(17):1248-1253; Prostate Cancer and the Will Rogers Phenomenon Peter C. Albertsen, James A. Hanley, George H. Barrows, David F.

(109) http://www.forbes.com/2009/08/31/
prostate-cancer-screening-business-healthcare-prostate.html
Medical Tests - The Dark Side Of Prostate Cancer Screening . Robert Langreth, 8.31.09

(110) http://www.cancer.gov/ncicancerbulletin/090809/page2
Study Questions Value of Prostate Cancer Screening.

(111) http://www.ncbi.nlm.nih.gov/pubmed/19720918 J Clin Oncol. 2009 Aug 31. Prospective Study of Determinants and Outcomes of Deferred Treatment or Watchful Waiting Among Men With Prostate Cancer in a Nationwide Cohort. Shappley WV et al.

(112) http://www.cancer.org/docroot/CRI/
content/CRI_2_4_1X_What_are_the_key_statistics_for_prostate_cancer_36.asp The latest American Cancer Society estimates for prostate cancer in the United States are for 2009:  about 192, 280 new cases of prostate cancer will be diagnosed. 27,360 men will die of prostate cancer  According to the most recent data, for all men with prostate cancer, the relative 5-year survival rate is nearly100% and the relative 10-year survival rate is 91%.

(113) http://jama.ama-assn.org/cgi/content/short/302/11/1202 Outcomes of Localized Prostate Cancer Following Conservative Management. Grace L. Lu-Yao et al. JAMA. 2009;302(11):1202-1209.

(114) http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17077805
Br J Cancer. 2006 November 6; 95(9): 1186–1194. Long-term outcome among men with conservatively treated localised prostate cancer J Cuzick et al.

(115) http://www.usyd.edu.au/news/84.html?newsstoryid=3911 "A Model of Prostate-Specific Antigen Screening Outcomes for Low- to High-Risk Men" was published in the Archives on Internal Medicine today. Dr Kirsten Howard from the University of Sydney's School of Public Health was the paper's lead author.

 (116) http://www.ncbi.nlm.nih.gov/pubmed/19786680   Arch Intern Med. 2009 Sep 28;169(17):1603-10. A model of prostate-specific antigen screening outcomes for low- to high-risk men: information to support informed choices. Howard K, Barratt A, Mann GJ, Patel MI. Screening and Test Evaluation Program, School of Public Health, University of Sydney, Sydney, Australia.

(117)  http://jeffreydach.com/2008/10/26/rethinking-testosterone-suppression-for-prostate-cancer-by-jeffrey-dach-md.aspx  Increased Mortality from Androgen Blockade for Prostate Cancer by Jeffrey Dach MD

(118) http://www.medicine.mcgill.ca/mjm/v02n02/psa.html  Prostate Specific Antigen (PSA):The Historical Perspective T. Ming Chu, Ph.D. McGill University.

(119) http://www.psa-rising.com/upfront/otisbrawleyfeb00.htm  Prostate Cancer Planner Never Takes PSA Test, Compares Prostate Screening to Tuskegee Experiment By Jacqueline Strax . Interview with Otis W. Brawley M.D. January 29 and February 1, 2000

(120) http://jco.ascopubs.org/content/23/32/8165.abstract  Journal of Clinical Oncology, Vol 23, No 32 (November 10), 2005: pp. 8165-8169 Active Surveillance for Prostate Cancer: For Whom? Laurence Klotz.

(121) http://www.ronaldwheeler.com/psastats.html PSA stats Dr Ron Wheeler

Author Dr Dach Jeffrey Dach MD