Resident Editors: Scott Goldberg, MD, Marcus Dahlstrom, MD

Faculty Editor: Jeffrey A. Tice, MD

Background

• Estimated 233,000 new cases of prostate cancer and 29,480 deaths from PC in the U.S. each year
• 2^nd most common cancer in men and 2^nd leading cause of cancer death in men
• Lifetime risk of developing PC is 15.3%
• Three percent of men die from prostate cancer even though 40% of men > age 50 and 67% > age 80 have prostate cancer at autopsy
• Risk factors are increased age, black ancestry, family history (first-degree relatives diagnosed before age 65)

Who to Screen

• In 2012, the USPSTF recommended against screening for prostate cancer with PSA (Grade D recommendation); concluding with moderate certainty that the benefits of PSA-based screening do not outweigh the harms
• In 2018, the USPSTF changed their recommendation to a Grade C – stating that the decision to screen men ages 55-69 is an individual one based on the patient’s understanding of potential benefits and harms and their values and preferences
  • They note that screening offers a small potential benefit of reducing the chance of dying of prostate cancer; however, many men will experience potential harms of screening including false-positive results that require additional workup, overdiagnosis and overtreatment, and treatment complications such as incontinence and impotence
• Screening should not be offered to men >70 years old (Grade D recommendation)
• The American Urological Association (AUA), European Association of Urology (EAU), and American Cancer Society (ACS) recommend or suggest offering screening with an informed consent and shared decision-making process for men at increased risk: men aged 50-69 years, men aged >40 years with risk factors (black race or family history in first-degree relative)

Evidence for Screening

• Two main trials that form the evidence base for screening
• Prostate, Lung, Colorectal and Ovarian (PLCO) screening trial
  • Randomized 76,693 men to annual PSA for 6 years (>4 ng/mL considered positive) plus digital rectal exam (DRE) for four years versus “usual care”
  • Demonstrated an increase in cancer incidence in the screening group but no cancer-specific mortality benefit to PSA screening after 13-year follow-up (RR, 1.09, 95% CI, 0.87-1.36)
  • Study had high quality but 40-52% contamination (screening) of control group

• European Randomized Study of Screening for Prostate Cancers (ERSPC)
  • 182,160 men ages 50-74 in eight European countries
  • PSA at least once every four years (>3 ng/mL considered positive) vs. no screening
  • Demonstrated an increase in cancer incidence with screening and an improvement in the risk of prostate cancer-specific death after 11 years (RR, 0.79; 95% CI, 0.68-0.91)
  •  Screening 1,410 men aged 55-69 years with mean 1.7 screenings over 9 years may detect 48 additional cancers and prevent 1 PC death

Shared Decision-Making

• There are many online decision aids to help guide discussion with patients about the risks/benefits of screening
• Discussion is like “informed consent” and should highlight:
  • Prostate cancer is a common disease but in many cases is not aggressive and can be something a man dies with rather than from. About 15 in every 100 men in the U.S. will develop prostate cancer in their lifetime.
  • 30 in every 100 men with a high PSA level will have prostate cancer. Inflammation and infection also cause high PSA levels.
  • About 15 in every 100 men with a normal PSA level have prostate cancer.
  • Screening may reduce the chance of dying from prostate cancer, but the evidence is mixed and the benefit is small. Studies have shown that the test may prevent 1 in every 1,000 men (0.1%) from dying of prostate cancer.
  • 33 in every 100 prostate cancers are aggressive and benefit from early treatment. The rest do not. Most men will never experience problems from their prostate cancer.
  • If you have a high PSA level, you may receive further testing such as transrectal ultrasound and biopsy.
  • There are risks associated with biopsy (i.e. infection) and with treatment (about 30 in every 100 men treated have long-standing problems with erections and 20 in 100 will leak urine).

How to Screen

• Use PSA as the primary screening method although no cutoff level appears to have both high sensitivity and high specificity for detection of PC

• Consider a DRE as a complementary screening method but should not be performed alone
• DRE causes transient minimal (0.26 – 0.4 ng/mL) elevations in PSA (controversial)
• PSA elevation can be caused by ejaculation, biopsy, prostatitis, and urinary retention.
• Five alpha reductase inhibitors (finasteride and dutasteride) cut PSA values in half so many recommend doubling the value prior to interpretation.
• Consider biopsy if the PSA > 4 ng/mL (or possibly if >3) or if there is an abnormal DRE
  • DRE includes palpation for prostate nodules, induration, or asymmetry. Only the lateral and posterior portions of gland can be examined.
• If initial screening is negative, recommendations for screening frequency are inconsistent.
  • Consider no further screening or a risk-adjusted frequency such as every 1-2 years if the PSA is >2.5 and every 2-8 years if <2.5.
• PSA velocity (> 0.4 ng/mL/year), determined by 3 or more separate PSA values calculated over at least 18-monht period, may be greater in men eventually diagnosed with PC than in men not diagnosed with disease
  • May have limited role in patients with low PSA levels
  • PSA slope may have greater accuracy than velocity for predicting PC on biopsy

References

Andriole GL, Crawford ED, Grubb III RL, et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine. 2009;360(13):1310–1319.

DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. 113802, Prostate cancer screening; [updated 2018 Feb 28, cited 1 April 2018]; [about 36 screens]. Available from http://www.dynamed.com/login.aspx?direct=true&site=DynaMed&id=113802. Registration and login required.

Hayes JH, Barry MJ. Screening for prostate cancer with the prostate-specific antigen test: a review of current evidence. JAMA. 2014 Mar 19;311(11):1143-9

Holmström, Benny, Mattias Johansson, Anders Bergh, Ulf-Håkan Stenman, Göran Hallmans, and Pär Stattin. “Prostate Specific Antigen for Early Detection of Prostate Cancer: Longitudinal Study.” BMJ 339 (September 24, 2009): b3537. https://doi.org/10.1136/bmj.b3537.

Moyer VA. Screening for Prostate Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine. 120AD;157(2).

Schröder FH, Hugosson J, Roobol MJ, et al. Prostate-cancer mortality at 11 years of follow-up. New England Journal of Medicine. 2012;366(11):981–990.

U.S. Preventive Services Task Force. Screening for prostate cancer: draft recommendation statement. https://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementDraft/prostate-cancer-screening1. Accessed April 30, 2018.