Prostate Cancer Screening: Current Understanding and Management

Adeep Thumar MD

June 11, 2015

What is the Prostate

1. Size and shape of walnut on average

2. Function is the release of fluid to protect and nourish sperm

3. As men age prostate gets bigger and some patients will experience lower urinary tract symptoms

4. As men age likelihood of prostate cancer is higher1. 22-55% by age 50-602. 48-90% by age over 80

Campbell’s Urology 2012

Prostate Cancer Incidence

• 5th most common worldwide cancer

• 2nd most common cancer in men

• 11.7% of new cancers, due to screening 19% of cancers detected in the united states in comparison to 5.3% in developing countries

Prostate cancer and race

• African Americans have incidence 1.6 times white Americans

• Death rates 2.4 times greater than white Americans

Campbell’s Urology 2012

What is PSA

• Prostate Specific Antigen: Protein

Secreted in high concentrations into seminal fluid

Bound and unbound forms

Levels in blood can vary by age, prostate volume, and race

It is influenced by androgen

Prostate disease- bph, prostatitis, prostate manipulation, urinary tract infection and prostate cancer can all elevate psa

What is Screening• The Examination of a group to separate well persons from those who

have an undiagnosed pathologic condition or who are at high risk.

• Benefits of diagnosis at earlier stage of disease to increase better survival and reduce morbidity.

Since the beginning of PSA

• From 1993 to 2008 after the onset of widespread PSA testing, the mortality rate from prostate cancer declined by 40%(Surveillance, Epidemiology, and End Results [SEER] Program),

• 75% reduction in the proportion of advanced-stage disease at diagnosis.

• Compared to United Kingdom screening is only performed in 10% of people

Prostate cancer deaths only decreased by 12% in UK

2 big trials in 1990s• ESPRC- 20% reduction in mortality in screened

population over 9 years. However to prevent one prostate cancer death- 1410 people

need to be screened and 48 people need to be treated

• PLCO trial- Showed no difference in mortality between screened and unscreened population.

Highly controversial trial- contamination of patients

• Bottom line over-treatment risk is high

Interpretation of PSA• Only way to confirm diagnosis is by tissue from prostate biopsy

• Triggers for biopsy: Abnormal digital rectal exam

Traditionally 4 ng/ml was used but 25% of prostate cancers were detected below 4

Now a baseline can be established and reconfirmed depending on age

Rapidly rising psa (psa velocity), elevated psa in comparison to prostate size (psa density) are markers

– PSA density >0.15 for pts with psa between total values of 4 and 10– PSA velocity- >0.75 ng/ml/year for psa 4-10. Some say even lower threshold for lower psa. – % free psa- cancer pts have lower free psa as psa is complexed

What is a biopsy

What is biopsy

• Traditionally performed by transrectal ultrasound

• Performed in office

• Tolerated well

• Main risk is infection which is reduced by antibiotics

• Other risks of bleeding, blood in urine, trouble urinating Risk of hospitalization across the board is low at 4%

Plus and Minus of Biopsy

• Only 26% biopsy will return with cancer diagnosis

• May return with low grade low volume cancer.

• If did not use screening picks up cancers 5-7 years prior to it becoming symptomatic.

Adjunct Markers and Tests

• Alternative blood tests PCA3 Prostate Health Index 4k score

• Prostate MRI May be useful in patients for repeat biopsies May be useful in patients on surveillance No standardization in interpretation at this time

Guidelines- US Preventative Task Force

• 2012- Panel gave PSA screening grade D• Recommends against Prostate Cancer Screening in general population

• They do not have recommendation for people of certain ethnicity known for higher incidence of prostate cancer

• No recommendation for use of psa screening for positive family history

• Prior recommendation was there was insufficient data for general population but definitely no benefit for individuals over age of 75.

• Same task force in 2009 that recommended against mammography screening for breast cancer which was later rescinded

• Conclusions were made based on large trial data that had contamination.

Guidelines- American Cancer Society

• Age 50 and above for average risk• Age 45 for men at high risk• Age 40 for men at even higher risk

• Men screened every 2 years below PSA 2.5

• Men screened annually for PSA > 2.5

Guidelines- National Comprehensive Cancer Network

• Thorough history including family history, previous psa, previous exams and biopsy

• Start discussion risks and benefits for screening

• Age 45-49: obtain baseline psa If > 1 obtain repeat test 1-2 years If < 1 obtain repeat testing at age 50

• Age 50-70 or >70 in specific healthy population 1-2 year testing. Trigger for biopsy is abnormal digital rectal exam or psa

>3

Guidelines- American Urological Association

• The Panel recommends against PSA screening in men under age 40 years.

• The Panel does not recommend routine screening in men between ages 40 to 54 years at average risk.

– This does not include increased risk population such has family history and African Americans

• For men ages 55-69 Recommendation to screen after discussion of weighing benefits of prostate cancer mortality of 1 man for 1000 screened

• Possible to screen PSA every 2 years instead of 1

• No screening in population above 70 unless 10 to 15 year life expectancy

Summary• Societies against screening

US Preventative Task Force

• Societies for screening American Cancer Society National Comprehensive Cancer Network American Urological Association

Conclusions

• In accordance with the American Urological Association

1. PSA screening does yield survival benefit

2. PSA screening picks up cancers 5-7 years prior to symptomatic disease

3. PSA screening may represent over diagnosis in 25% of people

Bottom Line

Each individual is different once the risks of screening are explained and results are individually tailored

• If diagnosis is confirmed, treatment is also custom planned

Guidelines are tools in recommending plan and are not certainly rigid for each individual.

Certainly overtreatment of prostate cancer but if aggressive cancers are caught early, early treatment can be curative rather than palliative

References• Campbell, Meredith F., Wein, Alan J.Kavoussi, Louis R. (Eds.) (2007)

Campbell-Walsh urology /editor-in-chief, Alan J. Wein ; editors, Louis R. Kavoussi ... [et al.]Philadelphia : W.B. Saunders,

• www.auanet.org• www.nccn.org• www.cancer.org• www.uspreventitivetaskforce.org