Few topics in medicine stimulate the same level of controversy and emotionally charged debate as questions related to screening for cancer. The word 'cancer' frequently invokes vivid images of pain and suffering that threaten to subvert a rational discussion founded in facts. At the same time, questions of screening are among the most complex to fully comprehend, requiring decision-makers to have a solid understanding of methodological issues relating to common validity threats to clinical trials (e.g. selection bias, length time bias, lead time bias) as well as an understanding of baseline risks and downstream harms through additional diagnostic testing and subsequent treatments.
It is for these challenging topics that the contributions of The Cochrane Collaboration are most important in helping to shape the public debate by providing unbiased summaries of the underlying evidence upon which decision-making should be founded. As the Collaboration celebrates its 20th Anniversary, it's an opportunity to recall how the Cochrane Prostatic Diseases and Urologic Cancers (PDUC) Group (prostate.cochrane.org) has been and continues to be a loud and clear voice in the debate over the benefits and harms of prostate-specific antigen (PSA)-based prostate cancer screening.
In 2004, when PSA screening was widely utilised in many countries, in particular the United States, a team of authors led by Dragan Ilic from Monash University in Australia developed the first Cochrane Protocol on screening for prostate cancer. The first version of the Cochrane Review found no robust evidence from randomised controlled trials (RCTs) regarding the impact of screening on quality of life, harms of screening, or economic value. These screening-related harms not only include complications directly related to subsequent prostate biopsies, such as pain, haematuria, and infectious complications, but also the anxiety related to a potential cancer diagnosis and the downstream side effects of treatment, which include urinary incontinence and erectile dysfunction, among others. The authors recommended awaiting the results of two large, on-going RCTs, which were published in 2009.[3,4] Once those RCTs were published, the authors updated their Cochrane Review, finding that "prostate cancer screening did not significantly decrease all-cause or prostate cancer-specific mortality in a combined meta-analysis of five RCTs". Based on these findings, the authors recommended that men with a life expectancy of less than 15 years be told that prostate cancer screening is unlikely to be beneficial.
Publication of this updated Cochrane Review in 2010 was timely as it coincided with the work of the US Preventive Services Task Force to update its recommendations on screening for prostate cancer. The Cochrane Review was subsequently one of the two high-quality systematic reviews that found consideration in the Task Force's deliberation about the benefits and risks of prostate cancer screening,[5,7] which ultimately led to a Grade D recommendation against routine population-based efforts to screen for prostate cancer. It is also cited in the recent American Urological Association guideline document on the early detection of prostate cancer, which takes a much more nuanced approach to prostate cancer screening than the Best Practice Statement that it replaces for this clinical question.[8,9]
In line with the Cochrane principle to update systematic reviews as new evidence becomes available, the review on prostate cancer screening was updated this year to include extended follow-up information that had become available for the two major trials. While the main conclusions remained largely unchanged, the updated review placed greater emphasis on the discussion of screening-related overdiagnosis and overtreatment. These results have been given an additional forum for discussion at the first-of-its-kind conference on preventing overdiagnosis, hosted by the Dartmouth Institute for Health Policy and Clinical Practice in partnership with BMJ, Consumer Reports, and Bond University.
The 2013 update of the Cochrane Review also accounts for The Cochrane Collaboration's interval endorsement of efforts by the Cochrane Applicability and Recommendations Methods Group (armg.cochrane.org) and contributions by the GRADE Working Group by incorporating a summary of findings (SoF) table to provide a concise and transparent summary of the key findings of the review (Table 1). This includes an outcome-by-outcome rating of the confidence in the estimates of effect (quality of evidence) as well as relative and absolute effect size estimates. The updated review is finding consideration in on-going efforts by Canadian Task Force on Preventive Health Care and other organisations to update their guidelines on prostate cancer screening.
Table 1: Summary of findings from Cochrane Review of prostate cancer screening (dx.doi.org/10.1002/14651858.CD004720.pub3)
These three Cochrane Reviews are emblematic of the important work that Cochrane authors do on a day-to-day basis: providing unbiased summaries, untainted by conflicts of interest, of the totality of evidence for a given clinical question to guide individual patient and provider as well as health policy decision-making. Cochrane Reviews focus on patient-important outcomes of both benefit and harm and provide a critical assessment of our confidence in the estimates of the effect, which is the bedrock for informed decision-making.
Frontiers for the PDUC Group in its third decade of existence as part of The Cochrane Collaboration are to broaden the dissemination and uptake of its reviews among healthcare providers and consumers through close collaboration with other organisations that share the common goal of working together to provide the best evidence for health care. We also hope to work closely with the US Cochrane Center, led by Kay Dickersin, to improve the uptake and impact of Cochrane Reviews in the United States. Given the current challenges of healthcare financing around the globe, there has never been a more important time for Cochrane contributors to take pride in their work and to hold up high the banner for Cochrane Reviews as the standard for high-quality evidence syntheses.
Philipp Dahm1, Molly M Neuberger2, Dragan Ilic3
1Philipp Dahm (email@example.com), Co-ordinating Editor, Cochrane Prostatic Diseases and Urologic Cancers Group, Department of Urology, University of Florida, Gainesville, Florida, USA; 2Molly M Neuberger (firstname.lastname@example.org), Managing Editor, Cochrane Prostatic Diseases and Urologic Cancers Group, Department of Urology, University of Florida, Gainesville, Florida, USA; 3Dragan Ilic (email@example.com), Department of Epidemiology & Preventive Medicine, School of Public Health & Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
How to cite: Dahm P, Neuberger MM, Ilic D. Screening for prostate cancer: shaping the debate on benefits and harms [editorial]. Cochrane Database of Systematic Reviews 2013;7:ED000067. dx.doi.org/10.1002/14651858.ED000067
1. Esserman LJ, Thompson IM Jr, Reid B. Overdiagnosis and overtreatment in cancer: an opportunity for improvement. JAMA 2013 Jul 29. dx.doi.org/10.1001/jama.2013.108415
2. Ilic D, Green S, O'Connor D, Wilt T. Screening for prostatic cancer (Protocol). Cochrane Database of Systematic Reviews 2004;2:CD004720. dx.doi.org/10.1002/14651858.CD004720
3. Andriole GL, Crawford ED, Grubb RL 3rd, Buys SS, Chia D, Church TR, et al. Mortality results from a randomized prostate-cancer screening trial. New England Journal of Medicine 2009;360(13):1310-9. dx.doi.org/10.1056/NEJMoa0810696
4. Schröder FH, Hugosson J, Roobol MJ, Tammela TLJ, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine 2009;360(13):1320-8. dx.doi.org/10.1056/NEJMoa0810084
5. Ilic D, O'Connor D, Green S, Wilt TJ. Screening for prostate cancer: an updated Cochrane systematic review. BJU International 2011;107(6):882-91. dx.doi.org/10.1111/j.1464-410X.2010.10032.x
6. Chou R, Croswell JM, Dana T, Bougatsos C, Blazina I, Fu R, et al. Screening for prostate cancer: a review of the evidence for the U.S. Preventive Services Task Force. Annals of Internal Medicine 2011;155(11):762-71. dx.doi.org/10.7326/0003-4819-155-11-201112060-00375
7. Djulbegovic M, Beyth RJ, Neuberger MM, Stoffs TL, Vieweg J, Djulbegovic B, et al. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ 2010;341:c4543. dx.doi.org/10.1136/bmj.c4543
8. Carter HB, Albertsen PC, Barry MJ, Etzioni R, Freedland SJ, Greene KL, et al. Early detection of prostate cancer: AUA guideline. American Urological Association; 2013. www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer-Detection.pdf (accessed 7 May 2013).
9. Greene KL, Albertsen PC, Babaian RJ, Carter HB, Gann PH, Han M, et al. Prostate specific antigen Best Practice Statement: 2009 update. Journal of Urology 2009;182(5):2232-41. dx.doi.org/10.1016/j.juro.2009.07.093
10. Ilic D, Neuberger MM, Djulbegovic M, Dahm P. Screening for prostate cancer. Cochrane Database of Systematic Reviews 2013;1:CD004720. dx.doi.org/10.1002/14651858.CD004720.pub3
11. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. Journal of Clinical Epidemiology 2013;66(2):158-72. dx.doi.org/10.1016/j.jclinepi.2012.01.012
Competing interests: The authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available upon request) and declare (1) no receipt of payment or support in kind for any aspect of the article; (2) no financial relationships with any entities that have an interest related to the submitted work; (3) that PD has received payments from EnteroMedics Inc (for consultancy) and from Holbrook and Osborn PA (for expert testimony), but there are no other relationships or activities that could be perceived as having influenced, or giving the appearance of potentially influencing, what was written in the submitted work.
Contact the Editor in Chief, Dr David Tovey (firstname.lastname@example.org): Feedback on this editorial and proposals for future editorials are welcome.