Skip to main content

Main menu

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022
    • CHEST 2021
    • IDWeek 2021
    • IAS 2021
    • ADA 2021
    • ATS 2021
    • ACC 2021
    • ACP 2021
    • AAN 2021
  • Other Publications
    • www.clevelandclinic.org

User menu

  • Register
  • Log in

Search

  • Advanced search
Cleveland Clinic Journal of Medicine
  • Other Publications
    • www.clevelandclinic.org
  • Register
  • Log in
Cleveland Clinic Journal of Medicine

Advanced Search

  • Home
  • Content
    • Current Issue
    • Ahead of Print
    • Past Issues
    • Supplements
    • Article Type
  • Specialty
    • Articles by Specialty
  • CME/MOC
    • Articles
    • Calendar
  • Info For
    • Manuscript Submission
    • Authors & Reviewers
    • Subscriptions
    • About CCJM
    • Contact Us
    • Media Kit
  • Conversations with Leaders
  • Conference Coverage
    • ACC / WCC 2023
    • AAAAI Meeting 2023
    • ACR Convergence 2022
    • Kidney Week 2022
    • AIDS 2022
    • CHEST 2021
    • IDWeek 2021
    • IAS 2021
    • ADA 2021
    • ATS 2021
    • ACC 2021
    • ACP 2021
    • AAN 2021
Commentary

Prostate cancer screening and the role of PSA: A UK perspective

Prasanna Sooriakumaran, MD, PhD, FRCSUrol, FEBU
Cleveland Clinic Journal of Medicine January 2021, 88 (1) 14-16; DOI: https://doi.org/10.3949/ccjm.88a.20164
Prasanna Sooriakumaran
Lead for Urology, Urology Service, Digestive Diseases & Surgery Institute, Cleveland Clinic London, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: psoori@santishealth.org
  • Article
  • Info & Metrics
  • PDF
Loading

Prostate cancer is the most common solid-organ cancer and the second-leading cause of cancer death in Western men.1 Nearly 50,000 men are diagnosed with prostate cancer each year in the United Kingdom, and more than 11,000 die of it.2 Prostate cancer is therefore a significant killer of men. And it is usually a silent killer, asymptomatic in its curable stages. Hence, to save lives from prostate cancer, we must diagnose it early, before symptoms appear.

See related editorial, page 17

Fortunately, the serum biomarker prostate-specific antigen (PSA) has become widely used over the last 40 years.3 True, it is an imperfect test. PSA is prostate-specific, not cancer-specific. Conditions such as benign prostatic hyperplasia, prostatitis, recent instrumentation of the urinary tract, urinary tract infection, and even ejaculation can cause a rise. But temporal trends in PSA can provide better accuracy than single readings in determining risk of prostate cancer, and can signal the need for subsequent investigation.

RATIONALE FOR SCREENING

We believe that PSA screening should be offered to all middle-aged men, especially if they have prostate cancer risk factors:

  • Age > 50

  • Black ethnicity

  • A first-degree relative with prostate cancer.

The European Randomised Study of Screening for Prostate Cancer (ERSPC)

This multinational European trial randomized 182,160 men to undergo screening for prostate cancer (intervention) or not (control).3 Screened men had PSA tests every 2 to 4 years and a prostate biopsy if their PSA concentration was greater than 3 ng/mL. At 16 years of follow-up,3 20% fewer men had died of prostate cancer in the intervention group than in the control group. The number needed to be screened to diagnose 1 case of prostate cancer was 18 in this latest follow-up of the study, a significant lowering compared with the prior study report.

The study investigators concluded3 correctly that PSA screening significantly reduces prostate cancer mortality, with a larger absolute benefit with longer follow-up. Hence, my view is that for men with a long life expectancy (ie, most middle-aged men), screening for prostate cancer with PSA is warranted.

The PLCO study provides no useful information over the ERSPC

The US Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO),4 which included a prostate-screening arm, found more cancers in screened men but no survival advantage.

However, the PLCO study was smaller than the ERSPC and was heavily contaminated, as 44% of men in the control group (assigned to no-screening) had PSA tests anyway, so really it was a study of screening vs less screening. Further, the assigned interventions and subsequent investigations were not well adhered to: some men allocated to having their PSA checked did not get tested, 44% of men allocated to no-PSA testing got tested anyway, and only about a third of patients with a PSA level higher than 4 ng/mL had a prostate biopsy.4 All in all, this study does not really provide any useful information over ERSPC.

Active surveillance is now preferred in most men with low-risk prostate cancer

Plenty of evidence from several studies shows that low-risk prostate cancers (PSA < 10 ng/mL, Gleason grade 6, and unilateral cancer) usually grow slowly and are safe to monitor, with active treatment advised if surveillance tests show progression.

The world’s largest comparative-effectiveness randomized study of PSA-screened interventions (ProtecT) showed no survival benefit from surgery or radiation therapy compared with active surveillance at a median of 10 years.5

Prostate biopsy is no longer always the next step for men with elevated PSA

In my opinion, multiparametric magnetic resonance imaging (MRI) should be the next step in the investigation of men who have an elevated PSA. This allows men with a normal scan to be monitored, since MRI will detect most clinically significant prostate cancers (negative predictive value 80%–90%).6 Men with suspicious findings on MRI can proceed to prostate biopsy.

While this has become widespread practice in the United Kingdom, in the United States many insurance companies will not reimburse for prebiopsy MRI, and thus, alternatives such as blood-based biomarkers are often used. There are no head-to-head studies comparing prebiopsy biomarkers and MRI; however, MRI can be used to guide the locations of any subsequent biopsy (see below), whereas biomarkers cannot. I prefer to use MRI.

Prostate biopsy is more accurate and has fewer side effects than ever before

Many prostate cancer experts have replaced transrectal prostate biopsy with MRI-targeted transperineal template biopsy, performed as an outpatient procedure with the patient under general anesthetic. As well as enhancing the prostate cancer detection rate, this technique also reduces the risk of biopsy-related infections and thus decreases antibiotic resistance. Further, fusing the prebiopsy MRI images onto the biopsy platform improves the accuracy of targeting suspicious lesions on MRI; these “fusion” biopsies improve detection of clinically significant cancer while decreasing detection of indolent disease.7

Again, although this technique is gaining in popularity in the United Kingdom, it is significantly more expensive than prostate biopsy under local anesthesia, and thus has had limited uptake so far in the United States.

PSA level before age 50 accurately predicts future risk of prostate cancer

Several studies have shown that the PSA level before age 50 is a stronger predictor of prostate cancer risk than race or family history.8 This information could be used to guide the frequency of future PSA testing: “smart” screening.9 A 45-year-old man with a PSA level less than 1 ng/mL would be advised that his next PSA test should be done in 5 years’ time, whereas a man of the same age and race with the same family history with a PSA of 1.5 ng/mL would be advised to have it rechecked in a year.

Further, incorporating novel biomarker panels such as the 4K score, PSA derivatives like PSA density, and polygenic risk scores can improve the accuracy of prostate cancer screening and give more confidence in determining which men to investigate further, which to monitor and at what frequency, and which to safely discharge.

KEY POINTS
  • Prostate cancer is a significant killer of men.

  • Prostate cancer is asymptomatic during its curable stages.

  • PSA screening saves lives.

  • Patients with low-risk prostate cancer do not generally need treatment, whereas those with intermediate- and high-risk cancers usually benefit from curative therapy.

  • Not all men with a raised PSA need a prostate biopsy, thanks to MRI scanning.

  • Prostate biopsy is now more accurate, safer, and more comfortable for patients when informed by an MRI.

  • PSA levels before age 50 accurately predict future risk of developing prostate cancer.

DISCLOSURES

The author reports no relevant financial relationships which, in the context of their contributions, could be perceived as a potential conflict of interest.

  • Copyright © 2021 The Cleveland Clinic Foundation. All Rights Reserved.

REFERENCES

  1. ↵
    1. Siegel RL,
    2. Miller KD,
    3. Jemal A
    . Cancer statistics, 2020. CA Cancer J Clin 2020; 70(1):7–30. doi:10.3322/caac.21590
    OpenUrlCrossRefPubMed
  2. ↵
    1. Prostate Cancer UK
    . About prostate cancer. https://prostatecanceruk.org/prostate-information/about-prostate-cancer. Accessed November 30, 2020.
  3. ↵
    1. Hugosson J,
    2. Roobol MJ,
    3. Mansson M,
    4. et al
    . A 16-yr follow-up of the European Randomised Study of Screening for Prostate Cancer. Eur Urol 2019; 76(1);45–51. doi:10.1016/j.eururo.2019.02.009
    OpenUrlCrossRef
  4. ↵
    1. Pinsky PF,
    2. Prorok PC,
    3. Yu K,
    4. Kramer BS,
    5. Black A
    . Extended mortality results for prostate cancer screening in the PLCO trial with median follow-up of 15 years. Cancer 2017; 123(4):592–599. doi:10.1002/cncr.30474
    OpenUrlCrossRefPubMed
  5. ↵
    1. Hamdy FC,
    2. Donovan JL,
    3. Lane JA,
    4. et al
    . 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med 2016; 375(15):1415–1424. doi:10.1056/NEJMoa1606220
    OpenUrlCrossRefPubMed
  6. ↵
    1. Bryant RJ,
    2. Hobbs CP,
    3. Eyre KS,
    4. et al
    . Comparison of prostate biopsy with or without multiparametric magnetic resonance imaging for prostate cancer detection: an observational cohort study. J Urol 2019; 201(3):510–519. doi:10.1016/j.juro.2018.09.049
    OpenUrlCrossRef
  7. ↵
    1. Kasivisvanathan V,
    2. Stabile A,
    3. Neves JB,
    4. et al
    . Magnetic resonance imaging-targeted biopsy versus systematic biopsy in the detection of prostate cancer: a systematic review and meta-analysis. Eur Urol 2019; 76(3):284–303. doi:10.1016/j.eururo.2019.04.043
    OpenUrlCrossRef
  8. ↵
    1. Lilja H,
    2. Cronin AM,
    3. Dahlin A,
    4. et al
    . Prediction of significant prostate cancer diagnosed 20 to 30 years later with a single measure of prostate-specific antigen at or before age 50. Cancer 2011; 117(6):1210–1219. doi:10.1002/cncr.25568
    OpenUrlCrossRefPubMed
  9. ↵
    1. Sooriakumaran P
    . Smarter screening for prostate cancer: for the few, not the many? A stratified approach based on baseline risk. Expert Rev Anticancer Ther 2011; 11(2):169–172. doi:10.1586/era.10.233
    OpenUrlCrossRefPubMed
PreviousNext
Back to top

In this issue

Cleveland Clinic Journal of Medicine: 88 (1)
Cleveland Clinic Journal of Medicine
Vol. 88, Issue 1
1 Jan 2021
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Complete Issue (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Cleveland Clinic Journal of Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Prostate cancer screening and the role of PSA: A UK perspective
(Your Name) has sent you a message from Cleveland Clinic Journal of Medicine
(Your Name) thought you would like to see the Cleveland Clinic Journal of Medicine web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prostate cancer screening and the role of PSA: A UK perspective
Prasanna Sooriakumaran
Cleveland Clinic Journal of Medicine Jan 2021, 88 (1) 14-16; DOI: 10.3949/ccjm.88a.20164

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Prostate cancer screening and the role of PSA: A UK perspective
Prasanna Sooriakumaran
Cleveland Clinic Journal of Medicine Jan 2021, 88 (1) 14-16; DOI: 10.3949/ccjm.88a.20164
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Linkedin Share Button

Jump to section

  • Article
    • RATIONALE FOR SCREENING
    • DISCLOSURES
    • REFERENCES
  • Info & Metrics
  • PDF

Related Articles

  • Prostate cancer: To screen or not to screen? The question is complicated
  • PubMed
  • Google Scholar

Cited By...

  • Prostate cancer screening
  • Prostate cancer screening
  • Google Scholar

More in this TOC Section

  • The cost of ‘free’: Advising patients about sponsored genetic testing
  • The constellation of vitamin D, the acute-phase response, and inflammation
  • Ignore e-cigarettes at your patient’s peril
Show more Commentary

Similar Articles

Subjects

  • Preventive Care
  • Oncology
  • Men's Health

Navigate

  • Current Issue
  • Past Issues
  • Supplements
  • Article Type
  • Specialty
  • CME/MOC Articles
  • CME/MOC Calendar
  • Media Kit

Authors & Reviewers

  • Manuscript Submission
  • Authors & Reviewers
  • Subscriptions
  • About CCJM
  • Contact Us
  • Cleveland Clinic Center for Continuing Education
  • Consult QD

Share your suggestions!

Copyright © 2023 The Cleveland Clinic Foundation. All rights reserved. The information provided is for educational purposes only. Use of this website is subject to the website terms of use and privacy policy. 

Powered by HighWire