Editorial
Screening for Prostate Cancer — The Controversy That Refuses to Die
N Engl J Med 2009; 360:1351-1354March 26, 2009
- Article
In the United States, most men over the age of 50 years have had a prostate-specific–antigen (PSA) test,1 despite the absence of evidence from large, randomized trials of a net benefit. Moreover, about 95% of male urologists and 78% of primary care physicians who are 50 years of age or older report that they have had a PSA test themselves,2 a finding that suggests they are practicing what they preach. And indeed, U.S. death rates from prostate cancer have fallen about 4% per year since 1992, five years after the introduction of PSA testing.3 Perhaps the answer to the PSA controversy is already staring us in the face. At the same time, practice guidelines cite the unproven benefit of PSA screening, as well as the known side effects,4,5 which largely reflect the high risks of overdiagnosis and overtreatment that PSA-based screening engenders.6
The first reports from two large, randomized trials that many observers hoped would settle the controversy appear in this issue of the Journal. In the U.S. Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Andriole et al.7 report no mortality benefit from combined screening with PSA testing and digital rectal examination during a median follow-up of 11 years.8 In the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, Schröder et al.8 report that PSA screening without digital rectal examination was associated with a 20% relative reduction in the death rate from prostate cancer at a median follow-up of 9 years, with an absolute reduction of about 7 prostate cancer deaths per 10,000 men screened.8 The designs of the two trials are different and provide complementary insights.
First, one must ask, “Why were these results published now?” Neither set of findings seems definitive; that is, there was neither a clear declaration of futility in the PLCO trial nor an unambiguous net benefit in the ERSPC trial. Both studies are ongoing, with future updates promised. The report on the ERSPC trial follows a third planned interim analysis, which found a marginally significant decrease in prostate-cancer mortality after adjustment of the P value for the two previous looks in an attempt to avoid a false positive conclusion (yet apparently preserving no alpha for the planned final analysis). On the other hand, the investigators in the PLCO trial made the decision to publish their results now because of concern about the emerging evidence of net harm compared with potential benefits associated with PSA screening. Both decisions to publish now can be criticized as premature, leaving clinicians and patients to deal with the ambiguity.
The ERSPC trial is actually a collection of trials in different countries with different eligibility criteria, randomization schemes, and strategies for screening and follow-up. The report by Schröder et al. is based on a predefined core group of men between 55 and 69 years of age at study entry. Subjects were generally screened every 4 years, and 82% were screened at least once. Contamination of the control group with screening as part of usual care is not described. Biopsies were generally recommended for subjects with PSA levels of more than 3.0 ng per milliliter. It is unclear whether the clinicians and hospitals treating patients with prostate cancer differed between the two study groups.
Adjudications of causes of death were made by committees whose members were unaware of study-group assignments, though not of treatments. This point is important, since previous research has suggested that the cause of death is less likely to be attributed to prostate cancer among men receiving attempted curative treatment.9 Misattribution might then create a bias toward screening, since the diagnosis of more early-stage cancers in the ERSPC trial led to substantially more attempted curative treatments.
The ERSPC interim analysis revealed a 20% reduction in prostate-cancer mortality; the adjusted P value was 0.04. The estimated absolute reduction in prostate-cancer mortality of about 7 deaths per 10,000 men after 9 years of follow-up, if real and not the result of chance or bias, must be weighed against the additional interventions and burdens. The 73,000 men in the screening group underwent more than 17,000 biopsies, undoubtedly many more than did men in the control group, though the latter is not reported. Men had a substantially higher cumulative risk of receiving the diagnosis of prostate cancer in the screening group than in the control group (820 vs. 480 per 10,000 men). Diagnosis led to more treatment, with 277 versus 100 per 10,000 men undergoing radical prostatectomy and 220 versus 123 per 10,000 undergoing radiation therapy with or without hormones, respectively (tentative estimates given the unknown treatments in both groups).
Although estimates of the benefit of screening were somewhat greater for men who actually underwent testing (taking into account noncompliance) than for those who were not tested, the side effects would be proportionately higher as well. Given these trade-offs, the promise of future ERSPC analyses addressing quality of life and cost-effectiveness is welcome indeed. The ERSPC results also reemphasize the need for caution in screening men over the age of 69 years, given an early trend toward higher prostate-cancer mortality with screening in this age subgroup, although this finding may well be due to chance alone.
A final point to make about the ERSPC trial is that to the extent that the diagnosis and treatment of prostate cancer in the screening group differed from those in the control group, it becomes difficult to dissect out the benefit attributable to screening versus improved treatment once prostate cancer was suspected or diagnosed. A similar distribution of treatments among seemingly similar patients with cancer is only partially reassuring in this regard.
Despite a longer median follow-up, the PLCO trial was smaller and therefore less mature than the ERSPC trial, with 174 prostate-cancer deaths driving the power of the study, as compared with 540 such deaths in the ERSPC trial. The screening protocol was homogeneous across sites with an enrollment age of 55 to 74 years and annual PSA tests for 6 years and digital rectal examinations for 4 years, with about 85% compliance. Subjects in the screening group who had a suspicious digital rectal examination or a PSA level of more than 4.0 ng per milliliter received a recommendation for further evaluation. This strategy helped to ensure that any difference in outcome was attributable to screening, rather than downstream management. The effectiveness of screening, of course, will be determined by the effectiveness of subsequent “usual care,” but this is the same usual care that many practitioners assume has been responsible for the falling U.S. death rate from prostate cancer. Adjudication of causes of death was similar to that in the ERSPC trial.
Though the PLCO trial has shown no significant effect on prostate-cancer mortality to date, the relatively low number of end points begets a wide confidence interval, which includes at its lower margin the point estimate of effect from the ERSPC trial. Other likely explanations for the negative findings are high levels of prescreening in the PLCO population and contamination of the control group. Contamination was assessed by periodic cross-sectional surveys, with about half the subjects in the control group undergoing PSA testing by year 5. It is unclear whether these estimates reflect testing that year or since trial inception; if the former, the cumulative incidence may be even higher. The smaller difference in screening intensity between the two study groups in the PLCO trial, as compared with the ERSPC trial, is reflected in a smaller risk of overdiagnosis (23% vs. more than 70%) and a less impressive shift in cancer stage and grade distributions. Given that study-group contamination from the use of digital rectal examination was less problematic (only about 25%), ongoing results from both of these trials may necessitate rethinking the role of digital rectal examination in cancer screening.
After digesting these reports, where do we stand regarding the PSA controversy? Serial PSA screening has at best a modest effect on prostate-cancer mortality during the first decade of follow-up. This benefit comes at the cost of substantial overdiagnosis and overtreatment. It is important to remember that the key question is not whether PSA screening is effective but whether it does more good than harm. For this reason, comparisons of the ERSPC estimates of the effectiveness of PSA screening with, for example, the similarly modest effectiveness of breast-cancer screening cannot be made without simultaneously appreciating the much higher risks of overdiagnosis and overtreatment associated with PSA screening.
The report on the ERSPC trial appropriately notes that 1410 men would need to be offered screening and an additional 48 would need to be treated to prevent one prostate-cancer death during a 10-year period, assuming the point estimate is correct. And although the PLCO trial may not have the power as yet to detect a similarly modest benefit of screening, its power is already more than adequate to detect important harm through overdiagnosis. However, the implications of the trade-offs reflected in these data, like beauty, will be in the eye of the beholder. Some well-informed clinicians and patients will still see these trade-offs as favorable; others will see them as unfavorable. As a result, a shared decision-making approach to PSA screening, as recommended by most guidelines, seems more appropriate than ever.
Finally, despite these critiques, both groups of investigators deserve high praise for their persistence and perseverance: to manage such monstrous trials is a herculean task, made no easier when so many observers think the results are self-evident. Further analyses will be needed from these trials, as well as from others — such as the Prostate Cancer Intervention Versus Observation Trial (PIVOT) in the United States (ClinicalTrials.gov number, NCT00007644)10 and the Prostate Testing for Cancer and Treatment (PROTECT) trial in the United Kingdom (Current Controlled Trials number, ISRCTN20141297)11 — if the PSA controversy is finally to sleep the big sleep.
No potential conflict of interest relevant to this article was reported.
This article (10.1056/NEJMe0901166) was published at NEJM.org on March 18, 2009.
Source Information
From Massachusetts General Hospital and Harvard Medical School, Boston.
- References
References
1
Ross LE ,Berkowitz Z ,Ekwueme DU . Use of the prostate-specific antigen test among U.S. men: findings from the 2005 National Health Interview Survey. Cancer Epidemiol Biomarkers Prev 2008;17:636-644
CrossRef | Web of Science | Medline2
Chan EC ,Barry MJ ,Vernon SW ,Ahn C . Brief report: physicians and their personal prostate cancer-screening practices with prostate-specific antigen: a national survey. J Gen Intern Med 2006;21:257-259
CrossRef | Web of Science | Medline3
Ries LAG, Melbert D, Krapcho M, et al. SEER cancer statistics review, 1975–2005. Bethesda, MD: National Cancer Institute, 2008. (Accessed March 6, 2009 at http://seer.cancer.gov/csr/1975_2005/.)
4
Smith RA ,Cokkinides V ,Brawley OW . Cancer screening in the United States, 2008: a review of current American Cancer Society guidelines and cancer screening issues. CA Cancer J Clin 2008;58:161-179
CrossRef | Web of Science | Medline5
US. Preventive Services Task Force. Screening for prostate cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:185-191
Web of Science | Medline6
Barry MJ. Why are a high overdiagnosis probability and a long lead time for prostate cancer screening so important? J Natl Cancer Inst (in press).
7
Andriole GL ,Grubb RL III ,Buys SS , et al. Mortality results from a randomized prostate-cancer screening trial. N Engl J Med 2009;360:1310-1319
Full Text | Web of Science | Medline8
Schroder FH ,Hugosson J ,Roobol MJ , et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med 2009;360:1320-1328
Full Text | Web of Science | Medline9
Newschaffer CJ ,Otani K ,McDonald MK ,Penberthy LT . Causes of death in elderly prostate cancer patients and in a comparison nonprostate cancer cohort. J Natl Cancer Inst 2000;92:613-621
CrossRef | Web of Science | Medline10
Wilt TJ ,Brawer MK ,Barry MJ , et al. The Prostate cancer Intervention Versus Observation Trial: VA/NCI/AHRQ Cooperative Studies Program #407 (PIVOT): design and baseline results of a randomized controlled trial comparing radical prostatectomy to watchful waiting for men with clinically localized prostate cancer. Contemp Clin Trials 2009;30:81-87
CrossRef | Web of Science | Medline11
Donovan J ,Hamdy F ,Neal D , et al. Prostate Testing for Cancer and Treatment (ProtecT) feasibility study. Health Technol Assess 2003;7:1-88
Medline
- Citing Articles (77)
Citing Articles
1
Muin J. Khoury, Marta L. Gwinn, Russell E. Glasgow, Barnett S. Kramer. (2012) A Population Approach to Precision Medicine. American Journal of Preventive Medicine 42:6, 639-645
CrossRef2
John Concato. (2012) When to randomize, or ‘Evidence-based medicine needs Medicine-based evidence’. Pharmacoepidemiology and Drug Safety 21, 6-12
CrossRef3
Edward Ottley, Elspeth Gold. (2012) Insensitivity to the growth inhibitory effects of activin A: An acquired capability in prostate cancer progression. Cytokine & Growth Factor Reviews
CrossRef4
Daniela B. Friedman, Kim M. Johnson, Otis L. Owens, Tracey L. Thomas, DeLisa S. Dawkins, Lucy Gansauer, Sharon Bartelt, Nancy M. Waddell, Pastor J. Talley, James D. Bearden, James R. Hébert. (2012) Developing Partnerships and Recruiting Dyads for a Prostate Cancer Informed Decision Making Program: Lessons Learned From a Community-Academic-Clinical Team. Journal of Cancer Education
CrossRef5
Donna F. Timm, Daniel E. Banks, Jerry McLarty. (2012) Critical Appraisal Process. Southern Medical Journal 105:3, 144-148
CrossRef6
Andrew J. Vickers, Monique J. Roobol, Hans Lilja. (2012) Screening for Prostate Cancer: Early Detection or Overdetection?. Annual Review of Medicine 63:1, 161-170
CrossRef7
Khurshid R. Ghani, Quoc-Dien Trinh, Mani Menon. (2012) THE PHANTOM MENACE OF PROSTATE CANCER SCREENING. BJU International 109:3, 324-326
CrossRef8
Pamela Hartzband, Jerome Groopman. (2012) The New Language of Medicine. Obstetrics & Gynecology 119:2, Part 1, 369-370
CrossRef9
Tao Liu, Mahmud Hossain, Athena A. Schepmoes, Thomas L. Fillmore, Lori J. Sokoll, Scott R. Kronewitter, Grant Izmirlian, Tujin Shi, Wei-Jun Qian, Robin J. Leach, Ian M. Thompson, Daniel W. Chan, Richard D. Smith, Jacob Kagan, Sudhir Srivastava, Karin D. Rodland, David G. Camp. (2012) Analysis of Serum Total and Free PSA Using Immunoaffinity Depletion Coupled to SRM: Correlation with Clinical Immunoassay Tests. Journal of Proteomics
CrossRef10
M T King, R Viney, D P Smith, I Hossain, D Street, E Savage, S Fowler, M P Berry, M Stockler, P Cozzi, P Stricker, J Ward, B K Armstrong. (2012) Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer. British Journal of Cancer
CrossRef11
Stacy Loeb, H. Ballentine Carter, William J. Catalona, Judd W. Moul, Fritz H. Schroder. (2012) Baseline Prostate-Specific Antigen Testing at a Young Age. European Urology 61:1, 1-7
CrossRef12
F. Eisinger. (2012) Gènes prédictions et cancers. Oncologie 14:1, 21-23
CrossRef13
Glen B. Taksler, Nancy L. Keating, David M. Cutler. (2012) Explaining racial differences in prostate cancer mortality. Cancern/a-n/a
CrossRef14
Stacy Loeb, Herbert Ballentine Carter. 2012. Early Detection, Diagnosis, and Staging of Prostate Cancer. , 2763-2770.
CrossRef15
2011. Role of Disease Prevention in Health Care Reform. , 57-72.
CrossRef16
Ken Sikaris. (2011) Prostate cancer screening. Pathology1
CrossRef17
J Maddams, M Utley, H Møller. (2011) A person-time analysis of hospital activity among cancer survivors in England. British Journal of Cancer 105, S38-S45
CrossRef18
Heather Payne, Philip Cornford. (2011) Prostate-specific antigen: An evolving role in diagnosis, monitoring, and treatment evaluation in prostate cancer. Urologic Oncology: Seminars and Original Investigations 29:6, 593-601
CrossRef19
Hartzband, Pamela, Groopman, Jerome, . (2011) The New Language of Medicine. New England Journal of Medicine 365:15, 1372-1373
Full Text20
Nathan Lawrentschuk, Nikhil Daljeet, Greg Trottier, Phillip Crawley, Neil E. Fleshner. (2011) An analysis of world media reporting of two recent large randomized prospective trials investigating screening for prostate cancer. BJU International 108:8b, E190-E195
CrossRef21
Bruce J. Trock. (2011) Application of metabolomics to prostate cancer. Urologic Oncology: Seminars and Original Investigations 29:5, 572-581
CrossRef22
Vibe Hjelholt Pedersen, Jo Armes, Emma Ream. (2011) Perceptions of prostate cancer in Black African and Black Caribbean men: a systematic review of the literature. Psycho-Oncologyn/a-n/a
CrossRef23
Evelyn C.Y. Chan, Stephanie L. McFall, Theresa L. Byrd, Patricia Dolan Mullen, Robert J. Volk, John Ureda, Jessica Calderon-Mora, Pat Morales, Adriana Valdes, L. Kay Bartholomew. (2011) A community-based intervention to promote informed decision making for prostate cancer screening among Hispanic American men changed knowledge and role preferences: A cluster RCT. Patient Education and Counseling 84:2, e44-e51
CrossRef24
Raul Garrido-Medina, Jose Carlos Díez-Masa, Mercedes de Frutos. (2011) CE methods for analysis of isoforms of prostate-specific antigen compatible with online derivatization for LIF detection. ELECTROPHORESIS 32:15, 2036-2043
CrossRef25
Stacy Loeb. (2011) Editorial Comment. Urology 78:2, 248-249
CrossRef26
J. A. Hanley. (2011) Measuring Mortality Reductions in Cancer Screening Trials. Epidemiologic Reviews 33:1, 36-45
CrossRef27
Nancy L. Keating, A. James O'Malley, Joanne M. Murabito, Kirsten P. Smith, Nicholas A Christakis. (2011) Minimal social network effects evident in cancer screening behavior. Cancer 117:13, 3045-3052
CrossRef28
Isabelle Vedel, Martine T.E. Puts, Michele Monette, Johanne Monette, Howard Bergman. (2011) The decision-making process in prostate cancer screening in primary care with a prostate-specific antigen: A systematic review. Journal of Geriatric Oncology 2:3, 161-176
CrossRef29
Shabbir M.H. Alibhai, Anne M. Horgan. (2011) Cancer screening in older adults: What to do when we don't know. Journal of Geriatric Oncology 2:3, 149-160
CrossRef30
Michael Nasterlack. (2011) Role of Medical Surveillance in Risk Management. Journal of Occupational and Environmental Medicine 53, S18-S21
CrossRef31
Meelan Bul, Fritz H. Schröder. (2011) Screening for prostate cancer – The controversy continues, but can it be resolved?. Acta Oncologica 50:S1, 4-11
CrossRef32
S.-L. Yao, G. L. Lu-Yao. (2011) The Science and Art of Prostate Cancer Screening. JNCI Journal of the National Cancer Institute 103:6, 450-451
CrossRef33
Stephen J. Freedland. (2011) Screening, risk assessment, and the approach to therapy in patients with prostate cancer. Cancer 117:6, 1123-1135
CrossRef34
Daniela B. Friedman, Alexis Koskan, India D. Rose. (2011) Prostate Cancer Guidelines on Web 2.0-Based Sites: The Screening Dilemma Continues Online. Journal of Cancer Education 26:1, 188-193
CrossRef35
Mones S. Abu-Asab, Mohamed Chaouchi, Salvatore Alesci, Susana Galli, Majid Laassri, Amrita K. Cheema, Fouad Atouf, John VanMeter, Hakima Amri. (2011) Biomarkers in the Age of Omics: Time for a Systems Biology Approach. OMICS: A Journal of Integrative Biology 15:3, 105-112
CrossRef36
Joanna Marie Marroquin. (2011) To Screen or Not to Screen: Ongoing Debate in the Early Detection of Prostate Cancer. Clinical Journal of Oncology Nursing 15:1, 97-98
CrossRef37
Michaela Strobelberger, Angela Kaminski, Gerald Gartlehner. (2011) Österreichische Patienteninformationsmaterialien zu PSA-Screening entsprechen nicht internationalen evidenzbasierten Standards. Wiener Medizinische Wochenschrift 161:3-4, 89-98
CrossRef38
Matthew J. Roberts, Horst J. Schirra, Martin F. Lavin, Robert A. Gardiner. (2011) Metabolomics: A Novel Approach to Early and Noninvasive Prostate Cancer Detection. Korean Journal of Urology 52:2, 79
CrossRef39
E. Siemers. (2011) Designing clinical trials for early (pre-dementia) Alzheimer’s disease: Determining the appropriate population for treatment. The journal of nutrition, health & aging 15:1, 22-24
CrossRef40
Kathrine Røe, Manish Kakar, Therese Seierstad, Anne H Ree, Dag R Olsen. (2011) Early prediction of response to radiotherapy and androgen-deprivation therapy in prostate cancer by repeated functional MRI: a preclinical study. Radiation Oncology 6:1, 65
CrossRef41
Gerald Gartlehner. (2011) Nutzen-Schaden Abwägung von bevölkerungsbezogenen Interventionen am Beispiel von Krebs-Screening. Zeitschrift für Evidenz, Fortbildung und Qualität im Gesundheitswesen 105:3, 176-182
CrossRef42
Ye Hu, Daniel H. Fine, Ennio Tasciotti, Ali Bouamrani, Mauro Ferrari. (2011) Nanodevices in diagnostics. Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology 3:1, 11-32
CrossRef43
2011. References and Readings. , 832-841.
CrossRef44
Alvin M. Matsumoto, William J. Bremner. 2011. Testicular Disorders. , 688-777.
CrossRef45
J. S. Witte. (2010) Personalized Prostate Cancer Screening: Improving PSA Tests with Genomic Information. Science Translational Medicine 2:62, 62ps55-62ps55
CrossRef46
J. Gudmundsson, S. Besenbacher, P. Sulem, D. F. Gudbjartsson, I. Olafsson, S. Arinbjarnarson, B. A. Agnarsson, K. R. Benediktsdottir, H. J. Isaksson, J. P. Kostic, S. A. Gudjonsson, S. N. Stacey, A. Gylfason, A. Sigurdsson, H. Holm, U. S. Bjornsdottir, G. I. Eyjolfsson, S. Navarrete, F. Fuertes, M. D. Garcia-Prats, E. Polo, I. A. Checherita, M. Jinga, P. Badea, K. K. Aben, J. A. Schalken, I. M. van Oort, F. C. Sweep, B. T. Helfand, M. Davis, J. L. Donovan, F. C. Hamdy, K. Kristjansson, J. R. Gulcher, G. Masson, A. Kong, W. J. Catalona, J. I. Mayordomo, G. Geirsson, G. V. Einarsson, R. B. Barkardottir, E. Jonsson, V. Jinga, D. Mates, L. A. Kiemeney, D. E. Neal, U. Thorsteinsdottir, T. Rafnar, K. Stefansson. (2010) Genetic Correction of PSA Values Using Sequence Variants Associated with PSA Levels. Science Translational Medicine 2:62, 62ra92-62ra92
CrossRef47
E. P. Diamandis. (2010) Cancer Biomarkers: Can We Turn Recent Failures into Success?. JNCI Journal of the National Cancer Institute 102:19, 1462-1467
CrossRef48
Jack M. Guralnik, Stephen B. Kritchevsky. (2010) Translating Research to Promote Healthy Aging: The Complementary Role of Longitudinal Studies and Clinical Trials. Journal of the American Geriatrics Society 58, S337-S342
CrossRef49
David E Neal. (2010) PSA testing for prostate cancer improves survival—but can we do better?. The Lancet Oncology 11:8, 702-703
CrossRef50
D. H. Newman. (2010) Screening for Breast and Prostate Cancers: Moving Toward Transparency. JNCI Journal of the National Cancer Institute 102:14, 1008-1011
CrossRef51
Yunjie Song. (2010) Two randomized screening trials with prostate cancer mortality, two interim results. Contemporary Clinical Trials 31:4, 378-380
CrossRef52
Ingrid Metzler. (2010) Biomarkers and their consequences for the biomedical profession: a social science perspective. Personalized Medicine 7:4, 407-420
CrossRef53
William R. Carpenter, Daniel L. Howard, Yhenneko J. Taylor, Louie E. Ross, Sara E. Wobker, Paul A. Godley. (2010) Racial differences in PSA screening interval and stage at diagnosis. Cancer Causes & Control 21:7, 1071-1080
CrossRef54
Fritz H. Schröder, Monique J. Roobol. (2010) ERSPC and PLCO Prostate Cancer Screening Studies: What Are the Differences?. European Urology 58:1, 46-52
CrossRef55
Thomas J. Beckman, Scott C. Litin. (2010) Clinical Pearls in Men's Health. Mayo Clinic Proceedings 85:7, 668-673
CrossRef56
Jennifer M. Croswell, David F. Ransohoff, Barnett S. Kramer. (2010) Principles of Cancer Screening: Lessons From History and Study Design Issues. Seminars in Oncology 37:3, 202-215
CrossRef57
E. Siemers. (2010) Designing clinical trials for early (Pre-Dementia) Alzheimer’s disease: Determining the appropriate population for treatment. The journal of nutrition, health & aging
CrossRef58
Alex Shteynshlyuger, Gerald L. Andriole. (2010) Prostate Cancer: To Screen or Not to Screen?. Urologic Clinics of North America 37:1, 1-9
CrossRef59
Stephen Hearty, Paul Leonard, Richard O'Kennedy. (2010) Nanomedicine: Barcodes check out prostate cancer. Nature Nanotechnology 5:1, 9-10
CrossRef60
D. F. Ransohoff, M. J. Khoury. (2010) Personal genomics: information can be harmful. European Journal of Clinical Investigation 40:1, 64-68
CrossRef61
Imre Boncz, Valentin Brodszky, Márta Péntek, István Ágoston, Zsolt Nagy, Krisztián Kárpáti, Ildikó Kriszbacher, Péter Fuszek, László Gulácsi. (2010) The disease burden of colorectal cancer in Hungary. The European Journal of Health Economics 10:S1, 35-40
CrossRef62
Michael Baum. (2010) Should routine screening by mammography be replaced by a more selective service of risk assessment/risk management?. Women's Health 6:1, 71-76
CrossRef63
Mack Roach, Kent Wallner, I-Chow Joe Hsu, Peter Carroll. 2010. Cancer of the Prostate. , 925-986.
CrossRef64
Franz Porzsolt, Ian Curi Bonotto de Oliveira Costa, Tania Gouvêa Thomaz. (2009) Section Original article. Journal of Public Health 17:6, 425-432
CrossRef65
Simon M. Collin, Chris Metcalfe, Jenny L. Donovan, J. Athene Lane, Michael Davis, David E. Neal, Freddie C. Hamdy, Richard M. Martin. (2009) Associations of sexual dysfunction symptoms with PSA-detected localised and advanced prostate cancer: A case-control study nested within the UK population-based ProtecT (Prostate testing for cancer and Treatment) study. European Journal of Cancer 45:18, 3254-3261
CrossRef66
David E Neal, Jenny L Donovan, Richard M Martin, Freddie C Hamdy. (2009) Screening for prostate cancer remains controversial. The Lancet 374:9700, 1482-1483
CrossRef67
Christian Vutuc, Thomas Waldhoer, Gerhard Lunglmayr, Wolfgang Hoeltl, Gerald Haidinger. (2009) PSA testing in Austria: induced morbidity and saved mortality. European Journal of Cancer Prevention 18:5, 377-380
CrossRef68
Stefania Sciallero, Giuseppe Fornarini. (2009) Prostate cancer screening with PSA: new data, old debate. Oncology Reviews 3:3, 133-135
CrossRef69
Shannon R. Payne, Jűrgen Serth, Martin Schostak, Jőrn Kamradt, Arne Strauss, Paul Thelen, Fabian Model, J. Kevin Day, Volker Liebenberg, Andrew Morotti, Su Yamamura, Joe Lograsso, Andrew Sledziewski, Axel Semjonow. (2009) DNA methylation biomarkers of prostate cancer: Confirmation of candidates and evidence urine is the most sensitive body fluid for non-invasive detection. The Prostate 69:12, 1257-1269
CrossRef70
Matthew W. Gillman. (2009) Childhood Prevention of Hypertensive Cardiovascular Disease. The Journal of Pediatrics 155:2, 159-161
CrossRef71
(2009) Prostate-Cancer Screening. New England Journal of Medicine 361:2, 202-206
Full Text72
Stephan Madersbacher, Christian Vutuc. (2009) Prostatakarzinom-Screening: Sinn oder Unsinn?. Wiener klinische Wochenschrift 121:13-14, 428-430
CrossRef73
Lars Holmberg. (2009) Prostate Cancer Screening: The Need For Problem-Solving that Puts Men's Interests First. European Urology 56:1, 34-37
CrossRef74
Dean Ornish. (2009) Intensive lifestyle changes and health reform. The Lancet Oncology 10:7, 638-639
CrossRef75
P. J. Goodwin, S. S. Sridhar. (2009) Health-Related Quality of Life in Cancer Patients--More Answers but Many Questions Remain. JNCI Journal of the National Cancer Institute 101:12, 838-839
CrossRef76
(2009) More Controversy or Just More Confusion?. BJU International 103:10, i-iv
CrossRef77
Lee, Thomas H., Kantoff, Philip W., McNaughton-Collins, Mary F., . (2009) Screening for Prostate Cancer. New England Journal of Medicine 360:13,
Full Text
- Letters
