Skip to main content

Advertisement

SpringerLink
Log in

Estimating the rate of overdiagnosis with prostate cancer screening: evidence from the Finnish component of the European Randomized Study of Screening for Prostate Cancer

  • Original Paper
  • Published:
Cancer Causes & Control Aims and scope Submit manuscript

Abstract

Purpose

Screening for prostate cancer may have limited impact on decreasing prostate cancer-related mortality. A major disadvantage is overdiagnosis, whereby lesions are identified that would not have become evident during the man’s lifetime if screening had not taken place. The present study aims to estimate the rate of overdiagnosis using Finnish data from the European randomized trial of prostate cancer screening.

Methods

We used data from 80,149 men randomized to a screening or a control group, distinguishing four birth cohorts. We used the “catch-up method” to identify when the difference in the cumulative incidence of prostate cancer between the screening and control groups had stabilized, implying that the screening has no further effect. We define the overdiagnosis rate to be the relative excess cumulative incidence in the screened group at that point. As an independent method, we also examined the diagnosis rates of T1c tumors as an indicator of early tumors detected by PSA.

Results

The estimates of overdiagnosis rates from the catch-up method using the full period of available follow-up ranged between cohorts from 2.3% to 15.4%, and the T1c analysis gave very similar results.

Conclusion

Some overdiagnosis has occurred, but there is uncertainty about its extent. A long follow-up is required to demonstrate the full impact of screening. We evaluated the overdiagnosis rates at a population level, associated with being offered screening, taking account of contamination (screening among the controls). The overall evaluation of screening should incorporate mortality benefit, cost-effectiveness, and quality of life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

Finnish privacy regulations and General Data Protection Regulations of the EU do not allow sharing pseudonymised data with sensitive content such as health information.

Code availability

Not applicable.

References

  1. Culp MB, Soerjomataram I, Efstathiou JA, Bray F, Jemal A (2020) Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol 77:38–52

    Article  Google Scholar 

  2. American Cancer Society (2018) Cancer Facts & Figures 2017. American Cancer Society, Atlanta

    Google Scholar 

  3. Martin RM, Donovan JL, Turner EL et al (2018) Effect of a low-intensity PSA-based screening intervention on prostate cancer mortality: the CAP randomized clinical trial. JAMA 319:883–895

    Article  Google Scholar 

  4. Hoffman RM, Meisner ALW, Arap W, Barry M, Shah SK, Zeliadt SB, Wiggins CL (2016) Trends in United States prostate cancer incidence rates by age and stage, 1995–2012. Cancer Epidemiol Biomar Prev 25:259–263

    Article  Google Scholar 

  5. Andriole GL, et al., PLCO Project Team (2009) Mortality results from a randomized prostate cancer screening trial. New Engl J Med 360: 1310–1319

  6. Hugosson J, Roobol MJ, Mansson M, Tammela TLJ, Zappa M, Nelen V, Kwiatkowski M, Auvinen A (2019) A 16-yr follow-up of the European randomized study of screening for prostate cancer. Eur Urol 76:43–51

    Article  Google Scholar 

  7. Mottet N, Bellmunt J, Briers E et al (2018) EAU-ESTRO-ESUR-SIOG Guidelines on prostate cancer. Eur Urol 73(5):e134–e135

    Article  Google Scholar 

  8. Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R et al (2009) Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst 101:374–383

    Article  Google Scholar 

  9. Etzioni R, Gulati R, Mallinger L, Mandelblatt J (2013) Influence of study features and methods on overdiagnosis estimates in breast and prostate cancer screening. Ann Intern Med 158:831

    Article  Google Scholar 

  10. Draisma G, De Koning H (2003) MISCAN: estimating lead-time and over-detection by simulation. BJUrol Int 92(s2):106–111

    Article  Google Scholar 

  11. Tsodikov A, Szabo A, Wegelin J (2006) A population model of prostate cancer incidence. Stat Med 25:2846–2866

    Article  CAS  Google Scholar 

  12. Etzioni R, Tsodikov A, Mariotto A, Szabo A, Falcon S, Wegelin J, Feuer E (2008) Quantifying the role of PSA screening in the US prostate cancer mortality decline. Cancer Causes Control 19:175–181

    Article  Google Scholar 

  13. Gulati R, Inoue LY, Gore JL, Katcher J, Etzioni R (2014) Individualized estimates of overdiagnosis in screen-detected prostate cancer. J Natl Cancer Inst 106(2):djt67

    Article  Google Scholar 

  14. Biesheuvel C, Barratt A, Howard K, Houssami N, Irwig L (2007) Effects of study methods and biases on estimates of invasive breast cancer over-detection with mammography screening: a systematic review. Lancet Oncol 8:1129–1138

    Article  Google Scholar 

  15. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Zappa M, Nelen V, ERSPC Investigators (2014) Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. Lancet 384:2027–2035

    Article  Google Scholar 

  16. Gulati R, Feuer EJ, Etzioni R (2016) Conditions for valid empirical estimates of cancer overdiagnosis in randomized trials and population studies. Am J Epidemiol 184(2):140–147

    Article  Google Scholar 

  17. Telesca D, Etzioni R, Gulati R (2008) Estimating lead time and overdiagnosis associated with PSA screening from prostate cancer incidence trends. Biometrics 64:10–19

    Article  Google Scholar 

  18. Finne P, Fallah M, Hakama M, Ciatto S, Hugosson J, Koning HD, Auvinen A (2010) Lead-time in the European randomised study of screening for prostate cancer. Eur J Cancer 46(17):3102–3108

    Article  Google Scholar 

  19. Bell K, Del Mar C, Wright G, Dickinson J, Glasziou P (2015) Prevalence of incidental prostate cancer: a systematic review of autopsy studies. Int J Cancer 137(7):1749–1757

    Article  CAS  Google Scholar 

  20. Krzywinski M, Altman N (2014) Visualizing samples with box plots. Nat Methods 11:119–120

    Article  CAS  Google Scholar 

  21. Auvinen A, Määttänen L, Stenman U, Tammela T, Rannikko S, Aro J, Juusela H, Hakama M (2002) Lead-time in prostate cancer screening (Finland). Cancer Cause Control 13:279–285

    Article  Google Scholar 

  22. Etzioni R, Penson DF, Legler JM, Di Tommaso D, Boer R, Gann PH, Feuer EJ (2002) Overdiagnosis due to prostate-specific antigen screening: lessons from US prostate cancer incidence trends. J Natl Cancer Inst 94(13):981–990

    Article  Google Scholar 

  23. Wu GHM, Auvinen A, Maattanen L, Tammela TLJ, Stenman UH, Hakama M et al (2012) Number of screens for over-detection as an indicator of absolute risk of overdiagnosis in prostate cancer screening. Int J Cancer 131:1367–1375

    Article  CAS  Google Scholar 

  24. Pathirana T, Hayen A, Doust J et al (2019) Lifetime risk of prostate cancer overdiagnosis in Australia: quantifying the risk of overdiagnosis associated with prostate cancer screening in using a novel lifetime risk approach. BMJ Open 9:e022457

    Article  Google Scholar 

  25. Gulati R, Morgan TM, A’mar T, Psutka SP, Tosoian JJ, Etzioni R (2020) Overdiagnosis and lives saved by reflex testing men with intermediate prostate-specific antigen levels. J Natl Cancer Inst 112:384–390

    Article  CAS  Google Scholar 

  26. Gulati R, Psutka SP, Etzioni R (2019) Personalized risks of overdiagnosis for screen-detected prostate cancer incorporating patient comorbidities: estimation and communication. J Urol 202(5):936–943

    Article  Google Scholar 

  27. Zappa M, Ciatto S, Bonardi R, Mazzotta A (1998) Overdiagnosis of prostate carcinoma by screening: an estimate based on the results of the florence screening pilot study. Ann Oncol 9(12):1297–1300

    Article  CAS  Google Scholar 

  28. Schröder F, Hugosson J, Roobol M, Tammela T, Ciatto S, Nelen V et al (2009) Screening and prostate-cancer mortality in a randomized European study. New Engl J Med 360(13):1320–1328

    Article  Google Scholar 

  29. Ciatto S, Gervasi G, Bonardi R, Frullini P, Zendron P, Lombardi C, Zappa M (2005) Determining overdiagnosis by screening with DRE/TRUS or PSA (Florence pilot studies, 1991–1994). Eur J Cancer 41(3):411–415

    Article  Google Scholar 

  30. Fenton JJ, Weyrich MS, Durbin S, Liu Y, Bang H, Meinikow J (2018) Prostate-specific antigen–based screening for prostate cancer: evidence report and systematic review for the US preventive services task force. JAMA 319(18):1914–1931

    Article  Google Scholar 

  31. Ciatto S, Zappa M, Villers A, Paez A, Otto SJ, Auvinen A (2004) Contamination by opportunistic screening in the European randomized study of prostate cancer screening. Br J Urol 92(s2):97–100

    Article  Google Scholar 

  32. Nevalainen J, Stenman U, Tammela TL, Roobol M, Carlsson S, Talala K, Auvinen A (2017) What explains the differences between centers in the European screening trial? A simulation study. Cancer Epidemiol 46:14–19

    Article  Google Scholar 

  33. Kilpelainen TP, Pogodin-Hannolainen D, Kemppainen K, Talala K, Raitanen J, Taari K, Kujala P, Tammela TLJ, Auvinen A (2017) Estimate of opportunistic Prostate Specific Antigen testing in the finnish randomized study of screening for prostate cancer. J Urol 198:50–57

    Article  Google Scholar 

  34. Pashayan N, Duffy S, Pharoah P, Greenberg D, Donovan J, Martin R et al (2009) Mean sojourn time, overdiagnosis and reduction in advanced stage prostate cancer due to screening with PSA: implications of sojourn time on screening. Brit J Cancer 100(7):1198–1204

    Article  CAS  Google Scholar 

Download references

Funding

This paper was partially funded by the Natural Sciences and Engineering Research Council, Canada; the Academy of Finland (Grant No. 260931); the Cancer Foundation Finland; and Competitive State Research Funding administered by Pirkanmaa University Hospital special responsibility area (grants 9E089, 9H099, 9F100, 9R002).

Author information

Authors and Affiliations

  1. Department of Health Research Methodology, Evidence, and Impact, McMaster University, Hamilton, ON, Canada

    S. D. Walter

  2. Department of Mathematics & Statistics, McMaster University, Hamilton, ON, Canada

    Jiarui Hu

  3. Finnish Cancer Registry, Helsinki, Finland

    Kirsi Talala

  4. Faculty of Medicine and Health Technology, and Tampere University Hospital, Tampere University, Tampere, Finland

    Teuvo Tammela

  5. Department of Urology, Helsinki University Hospital, University of Helsinki, Helsinki, Finland

    Kimmo Taari

  6. Faculty of Social Sciences, Tampere University, Tampere, Finland

    Anssi Auvinen

Authors
  1. S. D. Walter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jiarui Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kirsi Talala
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Teuvo Tammela
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Kimmo Taari
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anssi Auvinen
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to the study conception and design. Material preparation and data collection were performed by JH, KT, TT, KTa, and AA, and analyses were performed by Hu and Walter. The first draft of the manuscript was written by Walter and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to S. D. Walter.

Ethics declarations

Conflict of interest

All authors declare they have no conflict of interest, with the exception of Dr Auvinen who has received a lecture honorarium from Novartis.

Ethical approval

An ethics committee review was conducted by Tampere University Hospital (tracking no 95077; R10167). All men who participated in screening gave written consent. For the control arm, registry-based follow-up without contact with study participants does not require consent, according to the Finnish regulations.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Walter, S.D., Hu, J., Talala, K. et al. Estimating the rate of overdiagnosis with prostate cancer screening: evidence from the Finnish component of the European Randomized Study of Screening for Prostate Cancer. Cancer Causes Control 32, 1299–1313 (2021). https://doi.org/10.1007/s10552-021-01480-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10552-021-01480-8

Keywords

Search

Navigation