BERKELEY, CA (UroToday.com) - Prostate cancer (PCa) is among the most common malignancies and causes of death in men from the Western world, and as a consequence there continues to be a need for improved prediction and classification of PCa risk and mortality. It has recently been shown that a single baseline prostate-specific antigen (PSA) measurement can be used to predict long-term PCa risk and mortality,[1] but it is unclear whether adding long-term prostate-specific antigen velocity (PSAV) further improves prediction and classification. This commentary briefly addresses the two most important differences between the present study and previous studies of PSAV and PCa, and also describes the principal findings of this study.[2]
First, the use of PSAV for PCa risk prediction and diagnosis is recommended in some clinical guidelines,[3, 4] but results from several studies have reported that PSAV does not increase prediction and reclassification of PCa risk and mortality.[5, 6] However, it should be noted that a number of those previous studies were performed using either highly selected participants from randomized controlled trials, or cohorts in which background PSA-based screening was common. The present study benefits from the fact that PSA screening is not currently recommended in Denmark, and PSA was not introduced into general clinical practice until 1995, 14 years after follow-up in this study began.[2] Also, we had repeated PSA measurements over a time span of 20 years and with up to 28 years of follow-up for men selected from the Copenhagen City Heart Study, a prospective general population study. Hence, this study describes results for the use of PSAV in the natural history of the development of PCa and lethal PCa in men representative of the general population.
Second, the majority of previous studies have primarily examined the association between PSAV and PCa. While it is clear that PSAV is associated to PCa, this does not necessarily imply that PSAV adds to prediction and classification of risk, and thereby holds clinical significance. To test this hypothesis, we applied an approach using measures of improvement in model performance, namely Harrel’s C statistic, net reclassification index, and decision curve analysis. These measures allowed us to compare an extended model including long-term PSAV, baseline PSA, and age to a classical model including only baseline PSA and age, and better assess the possible clinical significance of adding long-term PSAV.
The principal finding of this study was that long-term PSAV improves classification of PCa risk and mortality above and beyond that of a single baseline PSA measurement. Importantly, for men without PCa, risk classification was markedly improved, which could lead to fewer biopsies and unnecessary treatments of men with a priori low risk of PCa. In combination with baseline PSA measurement, this may be used to reassure this group of men. Finally, applying long-term PSAV to the entire male Danish population aged between 40-80 years, the ratio of appropriately to inappropriately classified men would, in general, be 5-to-1.
In conclusion, there continues to be scientific debate on the use of PSAV.[7, 8, 9] This study is a contribution to this debate, which in the end will hopefully lead to improved treatment of patients with PCa and the many men concerned with their risk of developing this disease.
References:
- Orsted DD, Nordestgaard BG, Jensen GB, Schnohr P, Bojesen SE. Prostate-specific antigen and long-term prediction of prostate cancer incidence and mortality in the general population. Eur Urol 2012; 61:865-74.
- Orsted DD, Bojesen SE, Kamstrup PR, Nordestgaard BG. Long-term Prostate-specific Antigen Velocity in Improved Classification of Prostate Cancer Risk and Mortality. Eur Urol 2013 (in press).
- National Comprehensive Cancer Network. Prostate cancer detection (version 1.2007). http://www.nccn.org/professionals/physician_gls/pdf/prostate_detection.pdf.
- American Urological Association. Prostate-Specific Antigen Best Practice Statement. http://www.auanet.org/content/media/psa09.pdf.
- Vickers AJ, Till C, Tangen CM, Lilja H, Thompson IM. An empirical evaluation of guidelines on prostate-specific antigen velocity in prostate cancer detection. J Natl Cancer Inst 2011; 103:462-69.
- Ulmert D, Serio AM, O'Brien MF et al. Long-term prediction of prostate cancer: prostate-specific antigen (PSA) velocity is predictive but does not improve the predictive accuracy of a single PSA measurement 15 years or more before cancer diagnosis in a large, representative, unscreened population. J Clin Oncol 2008; 26:835-41.
- Vickers AJ, Pencina MJ. Prostate-specific Antigen Velocity: New Methods, Same Results, Still No Evidence of Clinical Utility. Eur Urol (in press) 2013.
- Orsted DD, Bojesen SE, Kamstrup PR, Nordestgaard BG. Reply from Authors re: Andrew J. Vickers, Michael Pencina. Prostate-specific Antigen Velocity: New Methods, Same Results, Still No Evidence of Clinical Utility. Eur Urol. (in press). Prostate-specific Antigen Velocity: New Unscreened Cohort, Natural History of Prostate Cancer, Room for Different Interpretations. Eur Urol 2013 (in press).
- Vickers AJ. Counterpoint: Prostate-specific antigen velocity is not of value for early detection of cancer. J Natl Compr Canc Netw 2013; 11:286-90.
Written by:
David D. Ørsted, MD, PhD fellowa, b as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
aDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Denmark
bFaculty of Health and Medical Sciences, University of Copenhagen, Denmark
Correspondence:
David D Ørsted, MD
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital
Herlev Ringvej 75, DK-2730 Herlev, Denmark
E-mail:
This work was supported by Herlev Hospital, Copenhagen University Hospital, the Jascha Foundation, and the University of Copenhagen
The author has no conflicts of interest
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