Prostate Cancer Screening Guidelines in 2017

Pocharapong Jenjitranant, M.D. Division of Urology, Department of Surgery,

Faculty of Medicine, Ramathibodi Hospital

Prostate Specific Antigen (PSA)

Prostate Specific Antigen (PSA)

• Androgen-regulated protease enzyme

• Function : liquefy semen

Bloodborne biomolecular markers in prostate cancer development and progression. Nat Rev Cancer 2002;2(12):918–26. 33.

Prostate Specific Antigen (PSA) • Normally found in low concentration in serum (ng/mL)

• Within serum, PSA circulates in bound (complexed PSA) and unbound (free PSA [fPSA]) forms

Christensson A, Laurell CB, Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem 1990;194:755–63.

Prostate Specific Antigen (PSA)

• PSA produced from malignant cells serum

↑complexed PSA escape proteolytic processing

↓ free PSA

Woodrum DL, Brawer MK, Partin AW, et al. Interpretation of free prostate specific antigen clinical research studies for the detection of prostate cancer. J Urol 1998;159:5–12.

Prostate Specific Antigen (PSA)

• Highly organ specific

• Primarily produced by prostatic luminal cells

• Not cancer specific

Catalona WJ, Smith DS, Ratliff TL, et al. Measurement of prostate-specific antigen in serum as a screening test for prostate cancer. N Engl J Med 1991;324:1156–61.

Elevated serum PSA

Disruption of cellular architecture within the

prostate gland

• Barrier loss (prostate disease): BPH, prostatitis, prostate cancer

• Prostate manipulation: prostate massage,

long distance bicycle riding

• Urinary retention

• Prostatic trauma: prostate biopsy

Mejak SL, Bayliss J, Hanks SD. Long distance bicycle riding causes prostatespecific antigen to increase in men aged 50 years and over. PLoS One 2013;8:e56030.

Stamey TA, Yang N, Hay AR, et al. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med 1987;317: 909–16.

Prostate Specific Antigen (PSA)

• The 5α-reductase inhibitors (5ARI), such as finasteride and dutasteride, lower PSA levels 50% after 12 months of treatment

• Doubling rule

• May overestimate PSA values in the first 6 months of treatment and underestimate PSA levels after several years of treatment

Marks LS, Andriole GL, Fitzpatrick JM, et al. The interpretation of serum prostate specific antigen in men

receiving 5alpha-reductase inhibitors: a review and clinical recommendations. J Urol 2006;176:868–74.

Guess HA, Heyse JF, Gormley GJ. The effect of finasteride on prostate-specific antigen in men with benign prostatic hyperplasia. Prostate 1993;22: 31–7.

Early Detection and Screening

Early Detection and Screening

• Detection of disease at an early, pre-symptomatic stage when a man would have no reason to seek medical care

• An intervention referred to as secondary prevention

• In the US, early detection by PSA-based screening followed by prostate biopsy for diagnostic confirmation

Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol. 2013;190:419-426.

Benefits of PSA Screening

Benefits of PSA Screening

• Lower stage and grade of cancer at diagnosis

• Reduction in prostate cancer specific mortality rates

Aus G, Bergdahl S, Lodding P et al: Prostate cancer screening decreases the absolute risk of being diagnosed with advanced prostate cancer—results from a prospective, population based randomized controlled trial. Eur Urol 2007; 51: 659.

Schröder FH, Hugosson J, Carlsson S et al: Screening for prostate cancer decreases the risk of developing metastatic disease: findings from the European Randomized Study of Screening for Prostate Cancer (ERSPC). Eur Urol 2012; 62: 745. Labrie F, Canda sB, Cusan L et al: Screening decreases prostate cancer mortality: 11-year follow up of the 1988 Quebec prospective randomized controlled trial. Prostate 2004; 59: 311.

Why the recommendation against screening for prostate cancer?

Why the recommendation against screening for prostate cancer?

Screening and consequent treatment, as currently practiced, are often harmful:

• Too much screening of elderly men with a short life expectancy

• Too liberal criteria for biopsy

• Too aggressive treatment of low risk cancers

• Inadequate treatment of high risk cancers

• Treatment largely administered by low volume providers (higher risks of side effects and lower risks of cure)

Vickers AJ, Lilja H. Time for another rethink on prostate cancer screening. Nat Rev Clin Oncol. 2011; 9:7-8.

Overdiagnosis

• The detection of a prostate cancer that would have remained undetected during life in the absence of screening

Overdiagnosis

Of all screen-detected cancers, an estimated 10-56% would not have become apparent or caused symptoms in the patients’ lifetimes.

Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012;367:595–605.

Draisma G, Etzioni R ,Tsodikov et al. Lead Time and Overdiagnosis in Prostate-Specific Antigen Screening: Importance of Methods and Context . J Natl Cancer Inst 2009;101:374–83.

Harms: Prostate biopsy

Study population

30-day hospitalization

rate (%) Infection Bleeding

Urinary

obstruction

30-day mortality

rate (%)

5% random sample of Medicare

participants, 1991-2007 (n = 17,472) 6.9 0.38 Not

reported

Not

reported

0.31

All men receiving an initial prostate

biopsy not resulting in diagnosis of

cancer in Ontario, Canada, 1996-2005

(n=41,682)

1.9 1.36 0.37 0.17 0.11

Consecutive patients at a single

academic medical center, 2001-2010

(n = 1,000)

2.5 1.2 0.4 0.8 —

Loeb S, Carter HB, Berndt SI, Ricker W, Schaeffer EM. Complications after prostate biopsy: data from SEER-Medicare. J Urol 2011;186:1830-1834.

Nam RK, Saskin R, Lee Y, Liu Y, Law C, Klotz LH, Loblaw DA, Trachtenberg J, Stanimirovic A, Simor AE, Seth A, Urbach DR, Narod SA. Increasing hospital

admission rates for urological complications after transrectal ultrasound guided prostate biopsy. J Urol 2010;183:963-968.

Pinkhasov GI, Lin YK, Palmerola R, Smith P, Mahon F, Kaag MG, Dagen JE, Harpster LE, Reese CT, Raman JD. Complications following prostate needle

biopsy requiring hospital admission or emergency department visits - experience from 1000 consecutive cases. BJU Int 2012;110:369-374.

Harms

• Psychological impact of prostate cancer screening

• Distress involved in the decision making process, the biopsy and deciding among treatment options

• Severe psychological stress with one study showing an increased rate of suicide and cardiovascular events in newly diagnosed men

Fang F et al: Immediate Risk of Suicide and Cardiovascular Death After a Prostate Cancer Diagnosis: Cohort Study in the United States. JNCI 2010; 102: 307.

Roobol, M.J.; Carlsson, S.V. Risk stratification in prostate cancer screening. Nat. Rev. Urol. 2013, 10, 38–48.

Claire L. Tonry et al. The role of proteomics in biomarker development for improved patient diagnosis and clinical decision making in prostate cancer. Diagnostics 2016, 6, 27.

PSA Screening and Overdiagnosis

Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostatespecific antigen screening. N Engl J Med 2012;367:595–605.

PSA Screening Guidelines

PSA Screening Guidelines

• AUA

• EAU

• NCCN

PSA Screening Guidelines

• AUA

• EAU

• NCCN

Early Detection Guidelines: AUA 2013

• For men ages 55 to 69 years

• Weighing the benefits of preventing prostate cancer mortality in 1 man for every 1,000 men screened over a decade against the known potential harms associated with screening and treatment

Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol. 2013;190:419-426.

Early Detection Guidelines: AUA 2013

1. Recommends against PSA screening in men under age 40 years

2. Does not recommend routine screening for men 40-54 years at

average risk (Family History, African-American)

3. Strongly recommends shared decision making

for men 55-69 years

4. Screening interval should be ≥ 2 years

5. Does not recommend routine screening for men ≥ 70 years or

those with ≤10-15 year life expectancy

Carter HB, Albertsen PC, Barry MJ, et al. Early detection of prostate cancer: AUA guideline. J Urol. 2013;190:419-426.

PSA Screening Guidelines

• AUA

• EAU

• NCCN

PSA Screening Guidelines

• AUA

• EAU

• NCCN

45-75 years

NCCN Guidelines 1.2017

Percent free PSA<10%, PHI>35 or 4K score Multiparametric MRI

Conclusion How to Increase the Benefits and Reduce the Risks

of Screening for Prostate Cancer

• Risk-adjust screening by age and PSA (reduce false positives)

• Reduce false positive PSA results by repeating (verifying) positives and by adding additional markers (4Kpanel or

-2(pro)PSA) (reduce indications for biopsy)

• Active surveillance for low-risk cancers

(reduce harms of unnecessary therapy)

• Refer patients who need treatment to high-volume physicians or centers (reduce harm of necessary therapy)

Vickers A, Roobol M, Lilja H. Annu. Rev. Med. 2012. 63:161–70.

Thank You