EURURO-5465; No. of Pages 3 EUROPEAN UROLOGY XXX (2014) XXX–XXX
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening Andrew Vickers a,*, Sigrid Carlsson b,c, Vincent Laudone b, Hans Lilja b,d,e a
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;
b
Department of Surgery, Memorial Sloan-
c
Kettering Cancer Center, New York, NY, USA; Department of Urology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; d Departments Medicine and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; e Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Early detection of prostate cancer by means of prostatespecific antigen (PSA) testing of asymptomatic men remains subject to debate. Commentators discuss the evidence as to whether screening actually reduces prostate cancer mortality and, if so, whether the extent of mortality reductions outweighs the harms of overdiagnosis and overtreatment. The difficulty with this sort of debate is that it appears to assume that PSA is a single intervention. However, estimates for the effects of PSA screening are subject to important variations because PSA screening can be done in different ways in terms of the criteria and procedures for screening, biopsy, and treatment. For instance, it seems reasonable to suppose that PSA screening would do far more harm than good were we to focus on screening men >80 yr of age, have liberal criteria for biopsy, aggressively treat men who have low-risk disease or a short life expectancy, undertreat high-risk disease, and treat predominantly in low-volume settings. ‘‘Screening better’’ means avoiding such an approach. In this paper, we present five golden rules for PSA screening that importantly and favorably will shift the ratio of benefits to harms [1]. 1.
Golden Rule 1. Get consent
Despite guidelines emphasizing shared decision making, many doctors order the PSA test without discussing it with the patient [2]. PSA often appears to be a test added when a doctor orders some blood work as part of a regular health checkup, for example. On straightforward ethical grounds, we believe that doctors should not order a PSA test, perhaps unique among blood tests in terms of its downstream consequences, without, at the very least, informing the
patient about the uncertain balance between the benefits versus harms, providing a rationale in terms of why screening could do more harm than good for that individual patient, and obtaining explicit verbal consent before proceeding to order the PSA test. Golden Rule 2. Don’t screen men who won’t 2. benefit Prostate cancer is generally a slow-growing disease, and the benefits of screening take considerable time, no less than 10–15 yr, to accrue. Currently, men are being screened who are dying from other cancers [3] or who are age 80 and have multiple comorbidities [4]. PSA screening in such men is highly unlikely to have any benefit but may lead to harm. There is some variation as to the criteria for ending screening. Age 75 is used as a stopping point in several recommendations, although statistical modeling has shown that any reductions in mortality associated with screening men in their 70s are offset by reductions in quality of life [5]. There is also evidence that men can stop in their 60s if PSA is 75 yr of age should be screened only in special circumstances and that men with multiple comorbidities and a life expectancy 50% involvement of one core.
urinary symptoms, had no suspicious findings at digital rectal examination, was not in need of urologic care, that PSA screening was not of value in a man of that age, and that a moderately elevated PSA alone was not a strong indication for biopsy in an older man. Or consider if more urologists told prostate cancer patients, ‘‘I have been a urologist for a long time, and I am good at what I do. But you have prostate cancer, and cancer treatment is very specialized. So I am going to refer you to a comprehensive cancer center for your treatment. I’ll keep in contact with them and monitor your progress.’’ In summary, primary care physicians and urologists need to collaborate and take a more active role in ensuring that PSA screening does more good than harm for the individual requesting the PSA test. Following the five golden rules described here is a first step in ensuring that it does. Conflicts of interest: Hans Lilja holds patents for free PSA, hK2, and intact PSA assays, and he is named, along with Andrew Vickers, on a patent application for a statistical method to detect prostate cancer. Funding support: This study was supported by National Cancer Institute (R01CA160816, R01 CA175491, and P50-CA92629), the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program.
References [1] Carlsson S, Vickers AJ, Roobol M, et al. Prostate cancer screening: facts, statistics, and interpretation in response to the US Preventive Services Task Force Review. J Clin Oncol 2012;30:2581–4. [2] Volk RJ, Linder SK, Kallen MA, et al. Primary care physicians’ use of an informed decision-making process for prostate cancer screening. Ann Fam Med 2013;11:67–74. [3] Sima CS, Panageas KS, Schrag D. Cancer screening among patients with advanced cancer. JAMA 2010;304:1584–91.
Golden Rule 5. If you have to treat, do so at a 5. high-volume center
[4] Drazer MW, Huo D, Schonberg MA, Razmaria A, Eggener SE. Population-based patterns and predictors of prostate-specific antigen screening among older men in the United States. J Clin Oncol 2011;29:1736–43.
Convincing evidence indicates that experienced surgeons have higher cure rates, lower complication rates, and better outcomes for urinary and erectile function [16]. There is also convincing evidence that many patients are treated by lowvolume surgeons. The learning curve for radical prostatectomy has been estimated to be at least 250 procedures [17]. Yet among urologists who treat prostate cancer, the median annual volume is three, with more than a quarter conducting only a single radical prostatectomy per year [18].
[5] Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012;367: 595–605. [6] Vickers AJ, Cronin AM, Bjork T, et al. Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study. BMJ 2010;341:c4521. [7] van Leeuwen PJ, Connolly D, Tammela TL, et al. Balancing the harms and benefits of early detection of prostate cancer. Cancer 2010;116: 4857–65. [8] Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med 2004;350:2239–46.
6.
Conclusions
[9] Eastham JA, Riedel E, Scardino PT, et al. Variation of serum prostatespecific antigen levels: an evaluation of year-to-year fluctuations.
PSA screening is often thought to be a problem for primary care providers. Yet urologists are the gatekeepers for all downstream effects of PSA testing. Consider a 83-year-old man referred to the local urologist due to a finding of an elevated PSA test (5 ng/ml) where the urologist recommended not to conduct a biopsy, sending a note back to the primary care physician explaining that the patient had no
JAMA 2003;289:2695–700. [10] Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS, Free PSA Study Group. A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 2006;67:762–8. [11] Gosselaar C, Roobol MJ, Roemeling S, Schro¨der FH. The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam. Eur Urol 2008;54:581–8.
Please cite this article in press as: Vickers A, et al. It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2013.12.049
EURURO-5465; No. of Pages 3 EUROPEAN UROLOGY XXX (2014) XXX–XXX
[12] Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical
3
[15] Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus
evaluation of guidelines on prostate-specific antigen velocity in
observation for localized prostate cancer. N Engl J Med 2012;367:
prostate cancer detection. J Natl Cancer Inst 2011;103:462–9.
203–13.
[13] Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010;28:126–31. [14] Reese AC, Landis P, Han M, Epstein JI, Carter HB. Expanded criteria to identify men eligible for active surveillance of low risk prostate cancer at Johns Hopkins: a preliminary analysis. J Urol 2013;190: 2033–8.
[16] Eastham JA. Do high-volume hospitals and surgeons provide better care in urologic oncology? Urol Oncol 2009;27:417–21. [17] Vickers AJ, Bianco FJ, Serio AM, et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst 2007;99:1171–7. [18] Savage CJ, Vickers AJ. Low annual caseloads of United States surgeons conducting radical prostatectomy. J Urol 2009;182:2677–9.
Please cite this article in press as: Vickers A, et al. It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2013.12.049
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Platinum Opinion
It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening Andrew Vickers a,*, Sigrid Carlsson b,c, Vincent Laudone b, Hans Lilja b,d,e a
Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA;
b
Department of Surgery, Memorial Sloan-
c
Kettering Cancer Center, New York, NY, USA; Department of Urology, Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden; d Departments Medicine and Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY, USA; e Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Early detection of prostate cancer by means of prostatespecific antigen (PSA) testing of asymptomatic men remains subject to debate. Commentators discuss the evidence as to whether screening actually reduces prostate cancer mortality and, if so, whether the extent of mortality reductions outweighs the harms of overdiagnosis and overtreatment. The difficulty with this sort of debate is that it appears to assume that PSA is a single intervention. However, estimates for the effects of PSA screening are subject to important variations because PSA screening can be done in different ways in terms of the criteria and procedures for screening, biopsy, and treatment. For instance, it seems reasonable to suppose that PSA screening would do far more harm than good were we to focus on screening men >80 yr of age, have liberal criteria for biopsy, aggressively treat men who have low-risk disease or a short life expectancy, undertreat high-risk disease, and treat predominantly in low-volume settings. ‘‘Screening better’’ means avoiding such an approach. In this paper, we present five golden rules for PSA screening that importantly and favorably will shift the ratio of benefits to harms [1]. 1.
Golden Rule 1. Get consent
Despite guidelines emphasizing shared decision making, many doctors order the PSA test without discussing it with the patient [2]. PSA often appears to be a test added when a doctor orders some blood work as part of a regular health checkup, for example. On straightforward ethical grounds, we believe that doctors should not order a PSA test, perhaps unique among blood tests in terms of its downstream consequences, without, at the very least, informing the
patient about the uncertain balance between the benefits versus harms, providing a rationale in terms of why screening could do more harm than good for that individual patient, and obtaining explicit verbal consent before proceeding to order the PSA test. Golden Rule 2. Don’t screen men who won’t 2. benefit Prostate cancer is generally a slow-growing disease, and the benefits of screening take considerable time, no less than 10–15 yr, to accrue. Currently, men are being screened who are dying from other cancers [3] or who are age 80 and have multiple comorbidities [4]. PSA screening in such men is highly unlikely to have any benefit but may lead to harm. There is some variation as to the criteria for ending screening. Age 75 is used as a stopping point in several recommendations, although statistical modeling has shown that any reductions in mortality associated with screening men in their 70s are offset by reductions in quality of life [5]. There is also evidence that men can stop in their 60s if PSA is 75 yr of age should be screened only in special circumstances and that men with multiple comorbidities and a life expectancy 50% involvement of one core.
urinary symptoms, had no suspicious findings at digital rectal examination, was not in need of urologic care, that PSA screening was not of value in a man of that age, and that a moderately elevated PSA alone was not a strong indication for biopsy in an older man. Or consider if more urologists told prostate cancer patients, ‘‘I have been a urologist for a long time, and I am good at what I do. But you have prostate cancer, and cancer treatment is very specialized. So I am going to refer you to a comprehensive cancer center for your treatment. I’ll keep in contact with them and monitor your progress.’’ In summary, primary care physicians and urologists need to collaborate and take a more active role in ensuring that PSA screening does more good than harm for the individual requesting the PSA test. Following the five golden rules described here is a first step in ensuring that it does. Conflicts of interest: Hans Lilja holds patents for free PSA, hK2, and intact PSA assays, and he is named, along with Andrew Vickers, on a patent application for a statistical method to detect prostate cancer. Funding support: This study was supported by National Cancer Institute (R01CA160816, R01 CA175491, and P50-CA92629), the Sidney Kimmel Center for Prostate and Urologic Cancers, and David H. Koch through the Prostate Cancer Foundation, the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre Program.
References [1] Carlsson S, Vickers AJ, Roobol M, et al. Prostate cancer screening: facts, statistics, and interpretation in response to the US Preventive Services Task Force Review. J Clin Oncol 2012;30:2581–4. [2] Volk RJ, Linder SK, Kallen MA, et al. Primary care physicians’ use of an informed decision-making process for prostate cancer screening. Ann Fam Med 2013;11:67–74. [3] Sima CS, Panageas KS, Schrag D. Cancer screening among patients with advanced cancer. JAMA 2010;304:1584–91.
Golden Rule 5. If you have to treat, do so at a 5. high-volume center
[4] Drazer MW, Huo D, Schonberg MA, Razmaria A, Eggener SE. Population-based patterns and predictors of prostate-specific antigen screening among older men in the United States. J Clin Oncol 2011;29:1736–43.
Convincing evidence indicates that experienced surgeons have higher cure rates, lower complication rates, and better outcomes for urinary and erectile function [16]. There is also convincing evidence that many patients are treated by lowvolume surgeons. The learning curve for radical prostatectomy has been estimated to be at least 250 procedures [17]. Yet among urologists who treat prostate cancer, the median annual volume is three, with more than a quarter conducting only a single radical prostatectomy per year [18].
[5] Heijnsdijk EA, Wever EM, Auvinen A, et al. Quality-of-life effects of prostate-specific antigen screening. N Engl J Med 2012;367: 595–605. [6] Vickers AJ, Cronin AM, Bjork T, et al. Prostate specific antigen concentration at age 60 and death or metastasis from prostate cancer: case-control study. BMJ 2010;341:c4521. [7] van Leeuwen PJ, Connolly D, Tammela TL, et al. Balancing the harms and benefits of early detection of prostate cancer. Cancer 2010;116: 4857–65. [8] Thompson IM, Pauler DK, Goodman PJ, et al. Prevalence of prostate cancer among men with a prostate-specific antigen level < or =4.0 ng per milliliter. N Engl J Med 2004;350:2239–46.
6.
Conclusions
[9] Eastham JA, Riedel E, Scardino PT, et al. Variation of serum prostatespecific antigen levels: an evaluation of year-to-year fluctuations.
PSA screening is often thought to be a problem for primary care providers. Yet urologists are the gatekeepers for all downstream effects of PSA testing. Consider a 83-year-old man referred to the local urologist due to a finding of an elevated PSA test (5 ng/ml) where the urologist recommended not to conduct a biopsy, sending a note back to the primary care physician explaining that the patient had no
JAMA 2003;289:2695–700. [10] Lee R, Localio AR, Armstrong K, Malkowicz SB, Schwartz JS, Free PSA Study Group. A meta-analysis of the performance characteristics of the free prostate-specific antigen test. Urology 2006;67:762–8. [11] Gosselaar C, Roobol MJ, Roemeling S, Schro¨der FH. The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam. Eur Urol 2008;54:581–8.
Please cite this article in press as: Vickers A, et al. It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2013.12.049
EURURO-5465; No. of Pages 3 EUROPEAN UROLOGY XXX (2014) XXX–XXX
[12] Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical
3
[15] Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus
evaluation of guidelines on prostate-specific antigen velocity in
observation for localized prostate cancer. N Engl J Med 2012;367:
prostate cancer detection. J Natl Cancer Inst 2011;103:462–9.
203–13.
[13] Klotz L, Zhang L, Lam A, Nam R, Mamedov A, Loblaw A. Clinical results of long-term follow-up of a large, active surveillance cohort with localized prostate cancer. J Clin Oncol 2010;28:126–31. [14] Reese AC, Landis P, Han M, Epstein JI, Carter HB. Expanded criteria to identify men eligible for active surveillance of low risk prostate cancer at Johns Hopkins: a preliminary analysis. J Urol 2013;190: 2033–8.
[16] Eastham JA. Do high-volume hospitals and surgeons provide better care in urologic oncology? Urol Oncol 2009;27:417–21. [17] Vickers AJ, Bianco FJ, Serio AM, et al. The surgical learning curve for prostate cancer control after radical prostatectomy. J Natl Cancer Inst 2007;99:1171–7. [18] Savage CJ, Vickers AJ. Low annual caseloads of United States surgeons conducting radical prostatectomy. J Urol 2009;182:2677–9.
Please cite this article in press as: Vickers A, et al. It Ain’t What You Do, It’s the Way You Do It: Five Golden Rules for Transforming Prostate-Specific Antigen Screening. Eur Urol (2014), http://dx.doi.org/10.1016/j.eururo.2013.12.049
