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Re: Diabetes and benign prostatic hyperplasia progression in Olmsted County, Minnesota
european urology 49 (2006) 1130–1136
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Words of Wisdom
Re: Diabetes and benign prostatic hyperplasia progression in Olmsted County, Minnesota Burke JP, Jacobson DJ, McGree ME, Roberts RO, Girman CJ, Lieber MM, Jacobsen SJ Urology 2006;67:22–5. Expert’s summary: This Olmsted County population-based study has provided a wide range of important information about the prevalence and natural history of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) in males. This study looks into the natural history of the subgroup of 111 men who had a diagnosis of diabetes at the entry into the study. These men had a significantly greater median annual percentage increase in the American Urological Association (AUA) Symptom Index (0.40 versus 0.15, p = 0.04) and a trend towards a greater median annual percentage change in the peak urinary flow rate ( 4.7% versus 2.9%, p = 0.06) compared to those without diabetes. However, no significant difference was found in the annual percentage of change in prostate volume (2.7% versus 2.4%, p = 0.48) and prostate-specific antigen (PSA) (2.8% versus 3.9%). Thus, diabetes is more closely related to the dynamic components of lower urinary tract function than to BPH progression. Expert’s comments: There are two areas of special interest in this paper. The first is the demonstration of increasing LUTS in male patients with diabetes. Although bladder dysfunction in diabetic patients is well known [1], the actual impact on a population with LUTS suggestive of benign prostatic obstruction is largely unknown. In this population of 2,115 males aged 40–79, 5% (111) had diabetes, which corresponds well to the known 0302-2838/$ – see back matter
doi:10.1016/j.eururo.2006.03.045
prevalence in the general population [2]. These males with diabetes developed more LUTS and had a greater decrease in Qmax than males without diabetes; prostatic growth and changes in PSA did not differ between the groups. This seems to be the first good scientific evidence that male patients with LUTS and diabetes deserve a comprehensive evaluation that includes urodynamics before treatment is instituted. Kaplan et al. [1] performed urodynamics in 115 males with LUTS and diabetes, and found that 66 (57%) had infravesical obstruction. Other urodynamic diagnoses were made only for the whole group (including 67 women), but 55% had detrusor overactivity, 23% detrusor underactivity, 10% detrusor areflexia, and 11% had intermediate findings that underlined the importance of a good urodynamic classification before treatment. The other area of special interest is the nomenclature used. The title mentions progression of BPH, which is not defined, but the authors choose to use the AUA symptom score, Qmax, PSA, and prostate volume as parameters. In the Medical Therapy of Prostatic Symptoms study [3], designed in 1991, an increase in the AUA symptom score of 4 or more was defined as BPH progression, so this is probably also the case in this paper. This brings the odd conclusion that patients with diabetes have a higher risk of BPH progression, but not a higher risk of prostatic growth. The authors do not write it this way, but conclude that diabetes is more closely related to the dynamic components of lower urinary tract function than with BPH progression. In 1994 Abrams [4] suggested a new terminology to avoid these mistakes. It would be helpful if the new terminology were applied to papers published today. What do the authors mean, for example, when they state that Swedish researchers found a significant association between metabolic syndrome and BPH? Is it symptoms? Is it prostatic size?
1131
european urology 49 (2006) 1130–1136
References [1] Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol 1995;153:342–4. [2] Fedele D. Therapy insight: sexual and bladder dysfunction associated with diabetes mellitus. Nat Clin Pract Urol 2005;2:282–90. [3] McConnell JD, Roehrborn CG, Bautista OM, et al. The longterm effect of doxazosin, finasteride, and combination
Re: Interchangeability of Measurements of Total and Free Prostate-Specific Antigen in Serum with Five Frequently Used Assay Combinations: An Update Carsten Stephan, Moritz Klaas, Christian Mu¨ller, Dietmar Schnorr, Stefan A. Loening, Klaus Jung Clinical Chemistry 2006;52:59–64 Expert’s comments: Performance of five frequently used commercial assay systems for the determination of total and free prostate-specific antigen (t- and f-PSA) were compared in 596 identical serum samples of untreated men before prostate biopsy. The t-PSA concentrations ranged from 0.49 to 10 mg/l, as measured with Access Hybritech (Beckman Coulter). Considerable differences in analyte concentrations were found for t-PSA, f-PSA, and percent f-PSA depending on the assay system used. Expert’s comments: The clinical impact of PSA interassay variation has become a concern in the last 10 yr. The interpretation of PSA velocity is influencing clinical decisions because many men present today with serial PSA determinations over a period of several years. The study from Stephan et al. shows elegantly that an increase of t-PSA of 0.5 or 0.75 mg/l/yr can be the result of a change in assay systems, rather than reflecting an actual change in PSA concentrations. Further, as recently reviewed [1], the intraindividual biologic variation of t-PSA may well reach 20%. Because of such analytical and biologic variations, PSA changes over time have to be interpreted with great care. Calibration of PSA assays to the World Health Organization (WHO) standard can help reduce interassay variations. Nevertheless, PSA assays incorporate different antibodies and are run on different systems. Therefore, as demonstrated by Stephan
therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387–98. [4] Abrams P. New words for old: lower urinary tract symptoms for ‘‘prostatism’’. BMJ 1994;308:929–30. Jorgen Nordling Herlev Hospital DOI: 10.1016/j.eururo.2006.03.046
et al., PSA assays are not delivering identical results even after WHO standardisation. The term ‘‘harmonisation’’ rather than ‘‘standardisation’’ should be used to avoid the presumption that ‘‘all PSA results are the same.’’ Recalibration to the WHO standard typically results in lower t-PSA concentrations [2,3]. For example, a t-PSA concentration of 4 mg/l may translate into 3.3 mg/l after standardisation. There is a serious risk for misinterpretation of PSA if complete communication on the new cut-off point is not provided after assay recalibration. Indeed, keeping a cut-off point of 4 mg/l after PSA calibration to the WHO standard means that a man may have delayed detection of prostate cancer. We have concerns that not enough attention was paid to inform urologists about the clinical impact of a change to PSA WHO standardisation. To summarise, complete communication is required from the manufacturer about adjusted cut-off values for PSA, f-PSA, and percent f-PSA when assays undergo recalibration to the WHO standard. The time has gone that a sleeping urologist woke up and answered ‘‘four’’ as soon as anyone whispered ‘‘PSA’’ in his ear (B. G. Blijenberg, personal communication, 2005; Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands).
References [1] So¨le´tormos, et al. Clin Chem 2005;51:1342–51. [2] Semjonow, et al. Clin Chem 2001;47:1472–5. [3] Link, et al. J Urol 2004;171:2234–8. Axel Semjonow Prostate Center, Department of Urology, University Clinic, Mu¨nster, Germany DOI: 10.1016/j.eururo.2006.03.047
available at www.sciencedirect.com journal homepage: www.europeanurology.com
Words of Wisdom
Re: Diabetes and benign prostatic hyperplasia progression in Olmsted County, Minnesota Burke JP, Jacobson DJ, McGree ME, Roberts RO, Girman CJ, Lieber MM, Jacobsen SJ Urology 2006;67:22–5. Expert’s summary: This Olmsted County population-based study has provided a wide range of important information about the prevalence and natural history of lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH) in males. This study looks into the natural history of the subgroup of 111 men who had a diagnosis of diabetes at the entry into the study. These men had a significantly greater median annual percentage increase in the American Urological Association (AUA) Symptom Index (0.40 versus 0.15, p = 0.04) and a trend towards a greater median annual percentage change in the peak urinary flow rate ( 4.7% versus 2.9%, p = 0.06) compared to those without diabetes. However, no significant difference was found in the annual percentage of change in prostate volume (2.7% versus 2.4%, p = 0.48) and prostate-specific antigen (PSA) (2.8% versus 3.9%). Thus, diabetes is more closely related to the dynamic components of lower urinary tract function than to BPH progression. Expert’s comments: There are two areas of special interest in this paper. The first is the demonstration of increasing LUTS in male patients with diabetes. Although bladder dysfunction in diabetic patients is well known [1], the actual impact on a population with LUTS suggestive of benign prostatic obstruction is largely unknown. In this population of 2,115 males aged 40–79, 5% (111) had diabetes, which corresponds well to the known 0302-2838/$ – see back matter
doi:10.1016/j.eururo.2006.03.045
prevalence in the general population [2]. These males with diabetes developed more LUTS and had a greater decrease in Qmax than males without diabetes; prostatic growth and changes in PSA did not differ between the groups. This seems to be the first good scientific evidence that male patients with LUTS and diabetes deserve a comprehensive evaluation that includes urodynamics before treatment is instituted. Kaplan et al. [1] performed urodynamics in 115 males with LUTS and diabetes, and found that 66 (57%) had infravesical obstruction. Other urodynamic diagnoses were made only for the whole group (including 67 women), but 55% had detrusor overactivity, 23% detrusor underactivity, 10% detrusor areflexia, and 11% had intermediate findings that underlined the importance of a good urodynamic classification before treatment. The other area of special interest is the nomenclature used. The title mentions progression of BPH, which is not defined, but the authors choose to use the AUA symptom score, Qmax, PSA, and prostate volume as parameters. In the Medical Therapy of Prostatic Symptoms study [3], designed in 1991, an increase in the AUA symptom score of 4 or more was defined as BPH progression, so this is probably also the case in this paper. This brings the odd conclusion that patients with diabetes have a higher risk of BPH progression, but not a higher risk of prostatic growth. The authors do not write it this way, but conclude that diabetes is more closely related to the dynamic components of lower urinary tract function than with BPH progression. In 1994 Abrams [4] suggested a new terminology to avoid these mistakes. It would be helpful if the new terminology were applied to papers published today. What do the authors mean, for example, when they state that Swedish researchers found a significant association between metabolic syndrome and BPH? Is it symptoms? Is it prostatic size?
1131
european urology 49 (2006) 1130–1136
References [1] Kaplan SA, Te AE, Blaivas JG. Urodynamic findings in patients with diabetic cystopathy. J Urol 1995;153:342–4. [2] Fedele D. Therapy insight: sexual and bladder dysfunction associated with diabetes mellitus. Nat Clin Pract Urol 2005;2:282–90. [3] McConnell JD, Roehrborn CG, Bautista OM, et al. The longterm effect of doxazosin, finasteride, and combination
Re: Interchangeability of Measurements of Total and Free Prostate-Specific Antigen in Serum with Five Frequently Used Assay Combinations: An Update Carsten Stephan, Moritz Klaas, Christian Mu¨ller, Dietmar Schnorr, Stefan A. Loening, Klaus Jung Clinical Chemistry 2006;52:59–64 Expert’s comments: Performance of five frequently used commercial assay systems for the determination of total and free prostate-specific antigen (t- and f-PSA) were compared in 596 identical serum samples of untreated men before prostate biopsy. The t-PSA concentrations ranged from 0.49 to 10 mg/l, as measured with Access Hybritech (Beckman Coulter). Considerable differences in analyte concentrations were found for t-PSA, f-PSA, and percent f-PSA depending on the assay system used. Expert’s comments: The clinical impact of PSA interassay variation has become a concern in the last 10 yr. The interpretation of PSA velocity is influencing clinical decisions because many men present today with serial PSA determinations over a period of several years. The study from Stephan et al. shows elegantly that an increase of t-PSA of 0.5 or 0.75 mg/l/yr can be the result of a change in assay systems, rather than reflecting an actual change in PSA concentrations. Further, as recently reviewed [1], the intraindividual biologic variation of t-PSA may well reach 20%. Because of such analytical and biologic variations, PSA changes over time have to be interpreted with great care. Calibration of PSA assays to the World Health Organization (WHO) standard can help reduce interassay variations. Nevertheless, PSA assays incorporate different antibodies and are run on different systems. Therefore, as demonstrated by Stephan
therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387–98. [4] Abrams P. New words for old: lower urinary tract symptoms for ‘‘prostatism’’. BMJ 1994;308:929–30. Jorgen Nordling Herlev Hospital DOI: 10.1016/j.eururo.2006.03.046
et al., PSA assays are not delivering identical results even after WHO standardisation. The term ‘‘harmonisation’’ rather than ‘‘standardisation’’ should be used to avoid the presumption that ‘‘all PSA results are the same.’’ Recalibration to the WHO standard typically results in lower t-PSA concentrations [2,3]. For example, a t-PSA concentration of 4 mg/l may translate into 3.3 mg/l after standardisation. There is a serious risk for misinterpretation of PSA if complete communication on the new cut-off point is not provided after assay recalibration. Indeed, keeping a cut-off point of 4 mg/l after PSA calibration to the WHO standard means that a man may have delayed detection of prostate cancer. We have concerns that not enough attention was paid to inform urologists about the clinical impact of a change to PSA WHO standardisation. To summarise, complete communication is required from the manufacturer about adjusted cut-off values for PSA, f-PSA, and percent f-PSA when assays undergo recalibration to the WHO standard. The time has gone that a sleeping urologist woke up and answered ‘‘four’’ as soon as anyone whispered ‘‘PSA’’ in his ear (B. G. Blijenberg, personal communication, 2005; Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, The Netherlands).
References [1] So¨le´tormos, et al. Clin Chem 2005;51:1342–51. [2] Semjonow, et al. Clin Chem 2001;47:1472–5. [3] Link, et al. J Urol 2004;171:2234–8. Axel Semjonow Prostate Center, Department of Urology, University Clinic, Mu¨nster, Germany DOI: 10.1016/j.eururo.2006.03.047