Background: Based on ACS data, nearly 217,730 men will be diagnosed

with CaP in 2010. Over 32,050 men will die of this disease in 2010. Over 2 million men are alive today in US with CaP. The 5-yr survival rate is now almost 100% & 10-yr rate

91%. The ACS attributes this to “modern detection & treatment”

techniques while they have not supported early detection. Survival rates for A.A.’s are 10-15% lower than those of

whites for the most common cancers (other than lung). The incidence of CaP among A.A. men is 73% higher than

for white men.

ACS. Cancer.org / June 30, 2010

Lu-Yao et al. The Prostate Patient Outcomes Research Team. JAMA 1993;269:2633-2636

The Diagnosis and The Diagnosis and Prevention of Prostate Prevention of Prostate

Cancer:Cancer:A Challenge for the 21A Challenge for the 21stst

Century ManCentury Man

Brian A. Stone MD, FACSBaptist Health Systems of

AlabamaJasper Urology Associates

Freedland S, Isaacs W. Prostate. 2005; 62(3):243-252.

Higher incidence of prostate cancer, greater mortality compared with white men

Access to care Attitudes about care

Distrust of medical institutions Less likely to be screened

Socioeconomic, educational differences Knowledge regarding prostate cancer dependent on education and

income Men without health insurance more likely to be diagnosed with

advanced stage disease Relationship between low income and advanced stage at diagnosis

Differences in type and aggressiveness of treatment Less likely to be treated with aggressive therapy

Genetic differences More potent androgen receptor for given androgen concentration Increased androgen receptor expression Slower testosterone deactivation

Dietary differences?

African Americans with advanced prostate cancer exhibited:

Socioeconomic status Under insured Incidence early detection

Biologic differences in disease behaviorEarlier age onsetPathologic, genetic differences (i.e., tumor

volume, androgen receptor pathway)Modifiable factors affecting gene expression (diet,

obesity)

Hoffman R, et al. J Gen Intern Med. 2003;18:845-853.

To Screen or Not to Screen??????Several studies have attempted to answer the

big question.1) The Quebec Trial (Labrie et al) – 46,486 men2) The Tyrol Study (Tyrol, Austria) – 21,079

men3) ERSPC (European Study of Screening for

CaP) – 162,243 men4) PLCO Cancer Screening Trial – 154,942 men

Have They Succeeded????Quebec study criticism: Concerns over the

study design & absence of men of African descent.

Tyrol study criticism: Follow up period not long enough & absence of men of African descent.

ERSPC study criticism: Follow up period inadequate to assess mortality impact & absence of data on men of African descent.

PLCO study criticism: Follow up period not long enough & absence of data analysis in African American men.

Suggestive Benefits of Labrie DataUnscreened men had 41.6% death rate vs.

13.7% in the screened men. (Yields 3.85 odds ration advantage!)

6 deaths out of 7233 screened men vs. 69 deaths out of 14419 controls. (82% fewer deaths; even correcting for the 4 vs 7 yr f/u there were 69% fewer deaths!)

Low stage Ca detection is enhanced.Stage migration is clear.Metastatic disease at Dx is reduced.Suggests survival benefits.

New Findings of ERSPC5990 cancers found in screened men vs 4307

found in controls.Cumulative CaP incidence is 8.2% vs 4.8%.71% more cancers found in screened men!72% of screened men had < G6 vs 55% of

controls.45% of controls had > G7 vs 28% of screened

men.Local disease favored in screened men.20% reduction in cancer deaths in screened

group vs the controls.

US Preventative Services Task Force. Ann Intern Med. 2008;149:185-191.

Current evidence is insufficient to assess the balance of benefits and harmsof prostate cancer screening in men younger than 75 years

USPSTF recommends against screening for prostate cancer in menage 75 years or older

A clinician should not order the PSA test without first discussing with the patient the potential but uncertain benefits and known harms of prostate cancer screening and treatment

Men should be informed of the gaps in the evidence and should be assisted in considering their personalpreferences before deciding whether to be tested

Who in the world should men listen to regarding early detection????

The US Preventative Services Task ForceAmerican College of Preventive MedicineThe National Comprehensive Cancer NetworkAmerican Urological AssociationThe R. Frank Jones Urological SocietyThe American Cancer Society

A thoughtful and broad approach to PSA is important The age for obtaining a baseline PSA has been lowered to 40

years There is no longer a single threshold PSA value that should

prompt prostate biopsy Decision to biopsy should be based:

Primarily on PSA and DRE results Also take into account

Free and total PSA Patient age PSA velocity PSA density

Recent studies suggest that prostate screening leads to overdetection and overtreatment of some patients Men should be informed of the risks and benefits of prostate

cancer screening before biopsy Certain men newly diagnosed with prostate cancer should be

informed of the option of active surveillance instead of immediate treatment

Available at: http://www.auanet.org/content/guidelines-and-quality-care/clinical-guidelines/main-reports/psa09.pdf. Accessed May 2009.

AUA: American Urological Association

– Family history– Ethnicity– Prior biopsy history– Comorbidities

Trial Risk GroupMolecular

TargetResults

PCPT Low Type II 5AR Updated 2008

SELECT Low Oxidative Stress Reported 2008

REDUCE Intermediate Types I and II 5AR Reported 2009

SWOG/Se HighSe-mediated

effects2010

Toremifene High Estrogen Receptor 2010

Andriole G. Urology. 2009;73(S5A):36-43.NCT00030901; NCT00106691. Available at: www.clinicaltrials.gov. Accessed June 2009.

Thompson I, et al. N Engl J Med. 2003;349:215-224.

Annual DRE, PSAfor 7 years

End of Study Biopsy

End of Study Biopsy

Enrollment

Placebo Finasteride (5 mg daily)

Randomization

N = 18,882 men > 55 years, normal DRE, PSA < 3.0 ng/mL

Primary endpoint: prevalence of prostate cancer during 7 years of study

Prostate cancer @ 7 years Placebo: 24.4% Finasteride: 18.4% 24.8% reduction P < 0.001

Tumors ~ Gleason Score 7–10 Placebo: 237/1068 tumors (22%) Finasteride: 280/757 tumors (37%) P < 0.001 May be due to sampling artifact and not drug-induced

high grade disease

Safety Sexual side effects (gynecomastia, loss of libido,

impotence, decreased ejaculate) more common in finasteride-treated patients; urinary symptoms more common in placebo-treated patients

Thompson I, et al. N Engl J Med. 2003;349:215-224.

4 year, multicenter, international, randomized, double-blind, placebo-controlled trial

Dual 5-α reductase inhibitor dutasteride (0.5 mg/day) vs placebo

Looking at patients with higher risk for prostate cancer (PSA 2.5-10 ng/mL for men 50-60 years; 3.0-10 ng/mL for men > 60 years)

Single negative biopsy within 6 months of enrollment at baseline

Primary endpoint: biopsy-detectable prostate cancer at 2 and 4 years of treatment

Andriole GL. Urology. 2009;73(S5A):36-43.

Prostate cancer @ 4 years Placebo: 11.8% Dutasteride: 9.1% 23% reduction P < 0.001

Tumors ~ Gleason Score 7–10 Placebo: 233/3406 (6.8%) Dutasteride: 220/3298 (6.7%) P = 0.81

Safety Sexual side effects (gynecomastia, loss of libido, erectile

dysfunction) more common in dutasteride-treated patients

Andriole G, et al. American Urological Association Annual Meeting, Chicago, IL. April 28, 2009. LBA1.

Man who is 55 years old or olderProstate volume > 40 mLSymptomatic: AUA score > 10 or soRisk factor for prostate cancer: AA, family historyElevated PSA with prior negative biopsyMale pattern baldnessWants to prevent prostate cancerAlready on Alpha-Blocker

Thompson IM, et al. N Engl J Med. 2003;349:215-224. Andriole GL, et al. Urology. 2004;64:537-543.

• Men with a prostate-specific antigen (PSA) score of 3.0 or below who are screened regularly (or plan to get yearly PSA tests) and currently show no signs of prostate cancer are encouraged to talk with their doctor about the risks and benefits of taking a 5-alpha reductase inhibitor (5-ARI) to further prevent their likelihood of getting prostate cancer

• Men who are already taking a 5-ARI for other conditions should talk with their doctor about continuing to use this drug for the prevention of prostate cancer

ASCO: American Society of Clinical Oncology

Strength of evidence: The systematic review completed for this guideline identified 15 randomized clinical trials that met the inclusion criteria, nine of which reported prostate cancer period-prevalence.

Kramer B, et al. J Clin Oncol. 2009;27:1502-1516.

Randomized

Pre-Randomization

Period

Calendar Year

2001 - 2013

Placebo +

Selenium

Placebo +

Placebo

Vitamin E +

Placebo

Follow - upProstate cancer, other cancer, death

Vitamin E +

Selenium

Calendar Year

2001 – 2004(Planned 2001 – 2006)

SELECT Study Design(Selenium and Vitamin E)

Klein E. Ann NY Acad Sci. 2004;1031:234-241. Selenium: 200 mcg/day; Vitamin E: 400 International Units/day

SELECT: Prostate Cancer Incidence

Placebo Vitamin E Selenium Vitamin E + selenium

Lippman S, et al. JAMA. 2009;301(1):39-51. Data as of October 23, 2008; median follow-up 5.46 years

Hazard Ratios for Prostate Cancer(compared with placebo)Vitamin E: 1.13 (P = 0.06)Selenium + Vitamin E: 1.05 (P = 0.52)Selenium: 1.04 (P = 0.62)

When to refer to a urologist:Significant risk based on “risk calculator” Abnormal PSA velocity (> 0.75 ng/mL/year)Abnormality detected on DREFailure of medical management for BPHPatients with hematuria (> 3 RBCs/HPF)

BPH: benign prostatic hyperplasia; RBCs: red blood cells; HPF: high powered field

Age, race/ethnicity, and family history are significant risk factors for prostate cancer

Prostate cancer screening Clinician and patient dialog regarding DRE, PSA Thoughtful and broad approach to PSA Discuss risks and benefits of testing in advance of tests AUA now recommends a baseline PSA at 40 years of age for

healthy, well-informed men who wish to be tested

Chemoprevention Promising results from PCPT and REDUCE with 5-alpha-

reductase inhibitors finasteride, dutasteride; significant reduction in prostate cancer incidence at study endpoints (25 and 23%, respectively)

ASCO/AUA practice guideline Selenium or vitamin E alone or in combination did not prevent

prostate cancer in the SELECT trial