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The differences of re-treatment percentages after 2 yearsare not clear for most parameters. The lines diverge onlyafter 3 or more years, which underlines the necessity forstudies with long-term followup to determine differences intreatment efficacy. From our study we cannot concludewhether the differences in re-treatment rates are caused by adifference in efficacy or side effects. It might well be thatpatients are less compliant or choose another treatment mo-dality based on the experienced side effects.
One may question whether the study groups were identicalat baseline. As patients were not randomized to use 1 of the3 �-blockers, differences in baseline characteristics amongthe 3 groups are expected. Differences in post-void residual,detrusor pressure at maximum flow and prostate volumewere relatively large. Mean post-void residual in the tamsu-losin group was significantly lower than that in the othergroups but the 20 ml. difference was of no clinical relevance.The same holds for the small yet statistically significantdifferences in detrusor pressure at maximum flow and pros-tate volume among the 3 groups. From a clinical point of viewthe difference between a 27, 32 or 34 ml. prostate is irrele-vant as all are in the range of small prostates. For instance,a different distribution of prostate volume at baseline amongthe types of �-blocker also does not imply that the relation ofprostate volume to risk of re-treatment must be differentamong the types of �-blocker.
Since the prevalence of men with lower urinary tract symp-toms is high in the community, there is a need for �-blockers.They are widely prescribed by family practitioners as well asurologists without pretreatment patient selection. In otherwords, one can give an �-blocker on a trial basis to all menwith lower urinary tract symptoms. In this way of prescrib-ing �-blocker, treatment has a substantial macro-economicalimpact. Therefore, improvement in the selection of patientswho will benefit from �-blocker treatment in the long termwill have considerable consequences for health service costs.The results of our study enable us to define patients with ahigh risk of re-treatment, namely the patient with severesymptoms, poor uroflow, large prostate and significant uro-dynamic obstruction. This study also indicates that effective-ness of different �-blockers is variable.
1. Abrams, P.: New words for old: lower urinary tract symptoms for“prostatism.” BMJ, 308: 929, 1994
2. Garraway, W. M., Collins, G. N. and Lee, R. J.: High prevalenceof benign prostatic hypertrophy in the community. Lancet,338: 469, 1991
3. Furuya, S., Kumamoto, Y., Yokoyama, E. et al: Alpha-adrenergicactivity and urethral pressure in prostatic zone in benignprostatic hypertrophy. J Urol, 128: 836, 1982
4. Djavan, B. and Marberger, M.: A meta-analysis on the efficacyand tolerability of alpha1-adrenoceptor antagonists in pa-tients with lower urinary tract symptoms suggestive of benignprostatic obstruction. Eur Urol, 36: 1, 1999
5. Barry, M. J., Fowler, F. J., Jr., O’Leary, M. P. et al: The Amer-ican Urological Association symptom index for benign pros-tatic hyperplasia. The Measurement Committee of the Amer-ican Urological Association. J Urol, 148: 1549, 1992
6. Rollema, H. J. and van Mastrigt, R.: Improved indication andfollowup in transurethral resection of the prostate using thecomputer program CLIM: a prospective study. J Urol, 148:111, 1992
7. Jardin, A., Bensadouin, H., Delauche-Cavallier, M. C. et al:Long-term treatment of benign prostatic hyperplasia with al-fuzosin: a 24–30 month survey. Br J Urol, 74: 579, 1994
8. Lepor, H.: Long-term efficacy and safety of terazosin in patientswith benign prostatic hyperplasia. Terazosin Research Group.Urology, 45: 406, 1995
9. Lepor, H., Kaplan, S. A., Klimberg, I. et al: Doxazosin for benignprostatic hyperplasia: long-term efficacy and safety in hyper-tensive and normotensive patients. The Multicenter StudyGroup. J Urol, 157: 525, 1997
10. Schulman, C. C., Cortvriend, J., Jonas, U. et al: Tamsulosin:3-year long-term efficacy and safety in patients with lowerurinary tract symptoms suggestive of benign prostatic obstruc-tion: analysis of a European, multinational, multicenter, open-label study. European Tamsulosin Study Group. Eur Urol, 36:609, 1999
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The �-blocking agents have become first line therapy for lowerurinary tract symptoms that are significantly bothersome. The long-term fate of these patients and the durability of treatment benefithave not been widely reported. Indeed, many urologists have seenpatients with bladder failure treated with these agents for severalyears manifested by detrusor instability and loss of contractility.Previously, however, it was thought that this group of long-termfailures was small.
The authors review their experience with the use of 3 �-blockersfor the treatment of lower urinary tract symptoms and extendedfollowup of those men requiring re-treatment or other modalitiesbecause of treatment failure or intolerance. Factors at highest risk ofpredicting failure included large prostate volume, severe lower uri-nary tract symptoms, urodynamically documented obstruction andlow urine flow. While the 3 �-blockers were not randomly or blindlyprescribed, the likelihood of failure was highest with terazosin andlowest with tamsulosin.
While the conclusions appear to be valid and the data compelling,there are some issues of which to be aware, including the moderatedoses of some �-blockers with only 5 mg. terazosin and 0.4 mg.tamsulosin. Could some patients have been salvaged with dose es-calation? Indeed, some men classified as nonresponders changed toalternative �-blockers, perhaps because of adverse events and theultimate course may have been satisfactory on the second agent.These cases may not be true re-treatments and skew the data some-what. Finally, the definition of re-treatment in this setting remainsunclear and ultimate outcome of men selecting re-treatment is notavailable. Specifically, what are the risks of these treatment failureson ultimate bladder function and how many men have permanentbladder dysfunction because of the approximately 3-year medicalrather than definitive surgical therapy?
Despite these reservations, this is an important study as it is thefirst to follow men on �-blocking agents and determine re-treatmentrates. Furthermore, the data strongly suggest that re-treatmentrates are least with tamsulosin in men with smaller prostates. Fullevaluation of these men may assist in choosing those best treatedwith finasteride, surgery or watchful waiting.
Culley C. CarsonDivision of UrologyUniversity of North CarolinaChapel Hill, North Carolina
The question addressed by the authors is important. Given theprevalent use of �-blockers for the management of men with lowerurinary tract symptoms secondary to BPH, defining treatment suc-cess with these agents is important. At first glance, the data clearlysuggest baseline proxies that can be used to predict treatment suc-cess. Not surprisingly, the more obstructed, more symptomatic andlarger the prostate, the worse long-term use of these agents. How-ever, there are a number of questions about the interpretation of thedata. Were these selected patients? That is, were these consecutivemen treated or only those for whom records could be obtained? Didthe patients receive concomitant therapy such as phytotherapeuticagents or finasteride?
The authors attempt to explain what their definition of an�-blocker failure. Frankly, I strongly disagree. Failure of a specifictherapy implies that the treatment either does not work or thepatient has an adverse event that precludes him from taking thatmedication. However, if terazosin fails, that is the patient is stillsymptomatic but is switched to tamsulosin and is perfectly content,is this a failure of �-blockers? According to the authors it is. Virtuallyany clinician would disagree. Most importantly, the patient woulddisagree. Finally, one could argue that some patients were treated ata dose that was subtherapeutic (5 mg. terazosin). Why were they nottitrated to 10 mg. if they were not having a response?
In summary, this is an important topic. However, there are several
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major concerns about the interpretation of the data, the appropri-ateness of the analyses at 3 years, and the random and arbitrarytreatment regimens and response categorization. Notwithstanding,many of the subgroups were treated with subtherapeutic doses of�-blockers. Critics could justifiably claim that had the authors usedthe correct dose, the rates of treatment failure would have beenmuch lower. We look forward to the National Institutes of HealthMTOPS study to be released at the upcoming AUA meeting. Thisreport will be the first, long-term study to ascertain the progression
rates, and secondarily response and therapeutic failure rates ofmedical therapies for lower urinary tract symptoms in men second-ary to BPH.
Steven A. KaplanDepartment of UrologyNew York Presbyterian HospitalNew York, New York
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