BPH Importance of prostate volume and urinary flow rate in prediction of bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia

BPH Importance of prostate volume and urinary flow rate in prediction of bladder outlet obstruction in men with symptomatic benign prostatic hyperplasia
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  Central european Journal of urology   2011/64/2 75   Central european Journal of urology   2011/64/2 75 BpH IntroDuCtIon Benin prostatic enlarement (BPE), bladder outlet obstruction (BOO) and lower urinar tract smptoms (LUTS) is the basic triad for clinical dianosis of benin prostatic hperplasia (BPH) [1]. BPH is rare in men ouner than 40, but is present in up to 50% of men over 60 ears of ae and nearl 88% b 80 ears of ae [2, 3]. Mac-roscopic enlarement of the land is found in almost half of men who have microscopic BPH. Smptoms caused b BPH and named LUTS, can be cateo-rized as obstructive (voidin) and irritative (storae). Obstructive smptoms are caused b enlarement of the phsical mass of the land (static component) as well as tone of smooth muscle of the prostatic stroma (dnamic component). Irritative smptoms are associated with the bladder dsfunction caused b BOO [4]. It has been estimated that 25% of men in their sixth decade of life have urinar smptoms and objective sins of BOO [2]. However, the evidence for a direct link between BPE, BOO, and LUTS is far from convincin [4, 5].The aim of surical treatment for BPH is to relieve or eliminate BOO. Most patients with LUTS and an enlared prostate will benet from prostatectom; however, part of them still experience per-sistent storae smptoms [4]. Fifteen to 30% of the patients with BPH do not have a favorable outcome after transurethral resection of the prostate (TURP) if smptoms are considered [6]. One of the main causes of unfavorable results is absence of obstruction before surer. Pressure-ow urodnamic studies remain the most denitive method of objective documentin BOO. It serves as the best instru-ment to nd out if the smptoms are caused b prostatic obstruc-tion or bladder dsfunction [7]. Preoperative investiations with pressure-ow stud has been demonstrated that 20-50% of pa-tients with LUTS had no urodnamic evidence of obstruction [7-9]. However suitabilit of urodnamics in assessin BPH is controver-sial in terms of invasiveness, cost, time consumption, and, both, reproducibilit and variabilit of results [7]. Therefore these studies still are not routinel recommended in BPH.It has been proven that the dianosis of BOO cannot be made b smptomatic assessment alone [8]. Size of prostate and post-void residual (PVR) of urine are important in evaluation of BPH, but not critical for dianosis of obstruction. It has been conrmed b studies that the best sinle predictor of BOO is urinar ow rate. Approximatel 70% of men with peak ow rate (Qmax) less than 15 ml/s are obstructed [10]. Value of other parameters of free ow is more controversial. Recent studies show that ultrasound estimated prostate weiht or prostate transition zone volume can also predict obstruction [11, 12].Better prediction of obstruction usin parameters of non-invasive investiations aimed to improve results of BPH surer is an important topic for more than two decades, but there is no worldwide-accepted model. Some studies show that predictabil-it of conventional tests alone or in combination for BOO is onl 60-70% [13]. The aim of our stud was to look for possibl better simple predictors. key worDs prostate volume »  urinar flow rate »  bladder outlet obstruction »  benin prostatic hperplasia »  pressure/flow stud   aBstraCt objciv.  To predict bladder outlet obstruction with parameters of non-invasive investiations for patients with smptomatic benin prostatic hperplasia. pi d mhd. A sample of 122 men with moderate to severe lower urinar tract smptoms su-estive of benin prostatic hperplasia was selected. Transrectal prostate ultrasound, free flow measurement, and transabdominal ultrasound for residual urine were carried out toether with diital rectal examination for all patients. All patients underwent urodnamic pres-sure/flow test. Two roups of obstructed (91 patient) and equivocal/unobstructed (31 patient) were analzed. Probabilistic model based on loistic reression was developed for prediction of obstruction. r.  Various parameters were compared in obstruct-ed and non-obstructed/equivocal roups, hihliht-in important parameters for obstruction. Correlation analsis indicates hiher obstruction dependence on averae and peak flow rates and lower dependence on total prostate and transition zone volumes, transition zone index. Binar loistic reression model suests that averae flow rate combined with total prostate vol-ume is the best predictor of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analzed sample. The analzed model suests that peak flow rate could also be almost equall important parameter instead of averae flow rate. Cci.  The stud suests that averae/peak flow rate combined with total prostate volume can be used for prediction of obstruction. The developed probabilistic model helps to determine patients who need invasive urodnamic testin for decision on surical treatment. Imc   vm d i   i dici  bdd  bci i m ih mmic bi ic hi Drius trumbecs  1 , Dimns Milons  1 , Mindus Jievls  1 , aivrs Jons Mjosiis  1 , Mrius kincius  1 , aivrs grybs  1 , Vyis kopusinss  2    1 Clinic of Urolo, Lithuanian Universit of Health Sciences, Kaunas, Lithuania 2 Centre of Statistics, Universit of Vtautas Manus, Kaunas, Lithuania    Central european Journal of urology   2011/64/2  76   DARIUS TRUMBECKAS, DAIMANTAS MILONAS, MINDAUgAS JIEVALTAS, AIVARAS JONAS MATJOSAITIS, MARIUS KINCIUS, AIVARAS gRyBAS, VyTIS KOPUSTINSKAS MaterIal anD MetHoDs There were 122 men aed 45-85 ears with moderate to severe LUTS suestive for BPH involved in this prospective stud durin the period from March 2003 to December 2004. Permission for the stud was obtained from the Reional Ethics Committee. Informed consent was received from all patients. Onl subjects with Interna-tional Prostate Smptom Score (IPSS) ≥ 7 and Qmax in rane 3-20 ml/s in total voided volume of 120 ml or reater were included. Smptoms were measured accordin IPSS toether with qualit of life (QoL) question. All uroow traces were reviewed b a sinle investiator for correction of artifacts.Individuals who had underone previous prostate or lower uri-nar tract surer or who had prostate cancer or PSA level exceed-in 10 n/ml were excluded. Carcinoma of the prostate in case of PSA rane 4 to 10 n/ml had to be excluded b prostate biops. Pa-tients with bladder stones, urinar tract infection, and suprapubic drainae as well as evidence of neuroenic bladder were excluded from the stud. Uroowmetric free urinar ow measurement (Urodn 1000, Medtronic) was performed for ow parameters. Prostate size was measured b transrectal ultrasound (Siemens Sonoline SI-250 with probe of 5-7.5 MHz) evaluatin total prostate volume (TPV) as well as transition zone volume (TZV). For calculation of prostate volume, the ellipsoid formula (0.52 x width x heiht x lenth) was used [14]. Transition zone index (TZI) was calculated b dividin TZV/TPV. Post void residual (PVR) was measured b transabdominal ultrasound usin bladder measurements in transverse and saittal plains im-mediatel after free ow measurement. Eventuall all patients un-derwent urodnamic pressure-ow stud (Duet ®  Loic, Medtronic, software Duet 8.37, 1995-2001 Medtronic Functional Dianostics A/S). Bladder llin with subsequent pressure-ow stud was per-formed in rate of 30 ml/min with 37°C saline via transurethral two-channel 7 F urodnamic catheter. The test was repeated two times and lower deree of obstruction showin data was taken to account. The International Continence Societ (ICS) nomoram was used for obstruction evaluation. Accordin to this nomoram the patients were classied into two roups: obstructed (Abrams-grifths number – Ag >40) and unobstructed/equivocal (Ag ≤ 40).   Comparin to Schafer nomoram these roups were separated b line between cateories two and three. Urodnamic studies were performed and evaluated accordin ICS recommendations b one investiator (DT).Statistical analsis was performed usin SPSS software. Mean, standard deviation (SD), 10-90 percentiles, median, and correlation coefcients (r) were calculated. Sinicant differences in roups were analzed b t-test for independent normall distributed samples and b Mann-Whitne U test for non-normall distributed samples. The binar loistic reression model was developed for obstruction probabilit estimation and identication of the most important predictors. A level of statistical sinicance was chosen to be 95%. results There were 91 obstructed and 31 unobstructed/equivocal out of 122 tested patients. Ae of patients was not statisticall dif-ferent between the roups (p = 0.088). Qmax in rane of 4-15 ml/s was determined in 85.3% of patients. The characteristics of parameters for both roups are summarized in Table 1. A statisti-call sinicant difference between the roups was reached for total IPSS score, score of obstructive smptoms evaluated b ques- tb 1. Characteristics of obstructed and unobstructed/equivocal patients a i,  = 122obcd,  = 91ubcd/qivc,  = 31-vMsD10-90 ciMdiMsD10-90 ciMdiMsD10-90 cimdi Ae (ears)67.68.558.0-77.768.568.48.159.0-79.06965.49.351.5-76.8660.09Duration of smptoms (ears) smptoms (2,4,7 of IPSS) smptoms (1,3,5,6 of IPSS) (n/ml) void residual (ml)76.588.02-21345.087.193.06-23450.045.663.20-12230.00.002Total prostate volume (ml)53.832.124.9-84.945.558.834.228.0-89.850.039.218.317.2- zone volume (ml)28.624.86.5-50.723.632.626.59.4-56.326.816.813.43.5-36.812.00.0001TZI0.480.150.28-0.660.490.510.130.33-0.680.510.380.140.16-0.600.400.0001Qmax free (ml/s) free (ml/s) number67.737.125.0-120.365.682.531.047.3-127.777.824.910.411.7- (cm/H 2 O)85.533.347.3- – International Prostate Smptom Score, QoL – Qualit of Life score, TZI – transition zone index (transition zone volume/total prostate volume), Qmax free – free peak ow rate, Qave free – free averae ow rate, Ag number – obstruction number, if over 40 – obstruction (Ag number = pdetQmax – 2 Qmax), pdetQmax – detrusor pressure at peak ow). p - values were calculated to test sinicant differences between the roups (difference considered statisticall sinicant if p <0.05), SD – standard deviation.   Central european Journal of urology   2011/64/2 77 IMPORTANCE OF PROSTATE VOLUME AND URINARy FLOW RATE IN PREDICTION OF BLADDER OUTLET OBSTRUCTION IN MEN WITH SyMPTOMATIC BENIgN PROSTATIC HyPERPLASIA tions 1, 3, 5, and 7 of IPSS, TPV, TZV, TZI, peak (Qmax) and averae (Qave) ow rates, as well as PVR. These variables correlated with the deree of obstruction evaluated b the Ag number, but hih correlation was observed onl with Qave and Qmax (r respectivel -0.501 and -0.496, p = 0.0001). Ag number correlated with TZI (r = 0.29, p = 0.001), total prostate and transition zone volumes (r = 0.27 for both, p = 0.003) as well. Correlation with residual urine was considerabl lower (r = 0.198, p = 0.03). No statisticall si-nicant correlation between ae of patients and obstruction was observed. Loistic reression model suests that obstruction is best predicted when combination of Qave and TPV are used. Overall pronostic power of this combination for detectin correct results was 83% (with probabilit cut value of 0.6). PPV (positive predictive value) = 92%; NPV (neative predictive value) = 52%. Pronostic power for prediction of obstruction in the rst roup reached 91%. Unobstructed/equivocal subjects were predicted correctl in 61% of cases in the second roup. Analsis of odds ratio (OR) for each variable shows that in case of Qave and TPV it was respectivel 0.61 (95% CI 0.49-0.76) and 1.04 (95% CI 1.01-1.07). It means that increase of Qave b 1 ml/s decreases obstruction probabilit b 1.6 times and increase of total prostate volume b 1 ml increases it b 1.04.The developed binar loistic model for prediction of obstruc-tion is the followin: ,where P – probabilit of obstruction;z = 2.149 + 0.037   TPV – 0.501 QaveIt can be calculated that in case of total prostate volume 40 ml and Qave 5 ml/s probabilit of obstruction equals to 0.75 (75%). Predictive power of Qmax in combination with TPV was slihtl lower – small difference is seen onl in the roup of unobstruct-ed/equivocal subjects (58% of correct predictions) with the al-most same rate of correct results in total and in the roup with obstruction. Compatibilit of model with the data (Cox Snell and Naelkerke coefcients of determination) was slihtl lower in case of Qmax and TPV. Equation for prediction of obstruction with Qmax in combination with TPV is the followin: ,where z = 1.952 + 0.039 TPV – 0.249 QmaxCombinations of TZV or TZI with Qmax or Qave were not supe-rior in prediction of obstruction compared to TPV. The free ow pattern of a patient with TPV of 51 ml (Fi. 1) and computer based calculation of obstruction probabilities (Fi. 2) are presented. Chanes in obstruction probabilit due to value of parameters are shown in Fis. 3 and 4. Fi. 3 visualizes obstruc-tion probabilit as function of averae ow rate and TPV. Fiure 4 presents isolines of selected obstruction probabilit. Fiure 4 also visualizes the area of obstruction probabilit bein more than 0.9 isoline (upper left corner of the plot). DIsCussIon In face of numerous micro-invasive techniques for BPH treat-ment, transurethral resection is still the main and the best option. TURP is performed in approximatel 95% of surical procedures and open procedures are reserved onl for ver lare prostates [15]. fi. 1.  Uroowmetric trace of a 59-ear-old patient with total prostate volume of 51 ml: peak ow rate 18.4 ml/s, averae ow rate 10 ml/s. fi. 2. Obstruction predicted for the same 59-ear-old patient. Total prostate volume 51 ml, peak ow rate 18.4 ml/s, averae ow rate 10 ml/s. Probabilit of obstruction 27-35%. fi. 3. Bladder outlet obstruction probabilit dependence on total prostate vol-ume (TPV) and averae ow rate (Qave). fi. 4. Bladder outlet obstruction probabilit isolines due to total prostate vol-ume (TPV) and averae ow rate (Qave).  VibtpV (cc) 51Qv (m/) 10Qmx (m/) 18.4Imdi cci-0.97 -0.64pbbii  bci ccdi Qv 0.27pbbii  bci ccdi Qmx 0.35  z  z  ee P  += 1  z  z  ee P  += 1  Central european Journal of urology   2011/64/2  78   DARIUS TRUMBECKAS, DAIMANTAS MILONAS, MINDAUgAS JIEVALTAS, AIVARAS JONAS MATJOSAITIS, MARIUS KINCIUS, AIVARAS gRyBAS, VyTIS KOPUSTINSKAS In the Department of Urolo at Kaunas Medical Universit Hospital, 150-160 prostatectomies due to BPH are performed annuall, TURP comprise 60-70%. Thouh TURP is an effective procedure with ood or excellent results in 80-85% of cases [6, 16, 17], the pos-sibilit of an unfavorable outcome is still hih. One of reasons for unfavorable results is unsatisfactor preoperative selection of pa-tients. Prediction of obstruction in terms of postoperative effect would be of most important value.Accordin to literature, the most valuable parameter for pre-diction of obstruction is peak ow rate (Qmax). In case of Qmax <10 ml/s, likelihood of obstruction is 90%, in rane of Qmax 10-14 ml/s – 67% and in Qmax >15 ml/s – onl 30% [15]. Approximatel 1/3 of patients with Qmax over 10 ml/s are unobstructed. Probabilit of obstruction in case of Qmax >10 ml/s for elderl man (>80 ears) falls to 40% [15]. In some studies, on the basis of uroow alone, 21% of the patients were misclassied [6]. Sinle or combined con-ventional tests can predict correctl just in 60-70% of cases [13]. Accordin to our stud, misclassications in 21-25% is possible if onl a sinle free ow parameter, Qmax or Qave, is used.Traces of uroow often have peaks and reistered Qmax is not reliable. Such artifacts need to be corrected. Averae ow rate is a quite stead parameter and should be important in case of con-tinuous ow without terminal dribblin [3]. Our stud shows, that Qave predicted obstruction even better than Qmax, but the differ-ence compare to Qmax was not pronounced. Combination of Qave and TPV had the best predictive power in our sample. Combinations of Qmax – TPV or Qmax – TZV were not superior. As has been shown in man of studies PVR is not important predictor of obstruction. Our data also conrm that post-void re-sidual volume is not of paramount importance in terms of obstruc-tion. Thouh we found statisticall sinicant difference for PVR between the roups, correlation of PVR with obstruction was weak. Predictive models usuall use PVR as one of important parameters (Clinical Prostate score model developed b Rosier et al. as well as models developed b Van Venrooij et al. and Madersbacher S. et al.), but we did not nd its importance for prediction [8]. A bi volume of residual urine indicates bad detrusor contractilit rather than obstruction [10]. From the other hand, bad contractilit shows terminal phase of obstructive process. Transition zone volume more than total prostate volume repre-sents processes of benin hperplasia. Therefore, measurement of transition zone volume is essential, especiall in terms of treatment options [12]. Transition zone volume correlates well with resected volume of the prostate [12]. It was shown b studies of Kaplan that transition zone volume is directl associated with urodnamic ob-struction of the bladder and this correlation is mostl reliable when transition zone index is over 0.5 [11]. Thouh it was shown that transition zone index is important on prediction of outcome after TURP [17], recent stud did not conrm superiorit of TZV or TZI for prediction of urodnamic obstruction compare to TPV.There are less correct predictors in the roup of unobstructed/equivocal subjects, which directl worsens total rate of correct pre-dictions. Better prediction in this roup would be ver important because it would let us improve surical results. Unfortunatel there are no clear parameters for prediction of bad contractilit/unobstructed. We uess that in case of calculated probabilit of obstruction 0.4-0.8, an invasive urodnamic pressure/ow stud would be benecial, especiall if surical treatment is considered (Table 2). Thouh combination of Qmax and TPV was not superior, the predictive power of it was almost the same as Qave combined with TPV. Considerin ow pattern either Qave or Qmax should be used. Probabilities should be calculated usin both models and results compared. We suppose that similar results show reliable pronosis. In case of difference, uroowmetr should be repeated and prob-abilities re-evaluated. Pronounced difference and/or probabilit around 0.5 would be indicative for invasive pressure ow stud. In case of hih probabilit of obstruction, urodnamic pressure ow stud could be spared. Our stud shows that Qave is as ood as Qmax and can be used more often. ConClusIons A binar loistic reression model was developed, which su-ests that averae ow rate and total prostate volume are the best predictors of obstruction (83% of correct predictions; PPV = 92%; NPV = 52%) in the analzed sample. The analzed model suests that peak ow rate could also be an almost equall important pa-rameter instead of averae ow rate. The above parameters could be obtained from simple ultrasound and free ow measurements. The developed probabilistic model also provides information that is useful to select patients who need invasive urodnamic testin for decision on surical treatment. It is suested to perform invasive urodnamic testin in case obstruction probabilit is in the rane of 0.4-0.8. referenCes 1. Pesce F, Rubilotta E, Rihetti R et al: Results in 522 patients assessed in a ‘ow-clinic’.  Urodinamica   2002; 12: 144-145. tb 2.  Approximate probabilities of bladder outlet obstruction Qv (m/)t  vm (m)2030405060708090100 20.870.910.930.950.970.980.980.990.9930.8*0.850.890.920.950.960.970.980.9940.71*0.78*0.840.880.910.940.960.970.9850.59*0.68*0.75*0.820.870.90.930.950.9760.47*0.56*0.65*0.73*0.8*0.850.890.920.9470.350.44*0.53*0.62*0.7*0.77*0.830.880.9180.250.320.41*0.5*0.59*0.68*0.75*0.810.8690.*0.56*0.65*0.73*0.79**0.52*0.62*0.7**suested indication for pressure/ow stud; Qave – averae ow rate   Central european Journal of urology   2011/64/2 79 IMPORTANCE OF PROSTATE VOLUME AND URINARy FLOW RATE IN PREDICTION OF BLADDER OUTLET OBSTRUCTION IN MEN WITH SyMPTOMATIC BENIgN PROSTATIC HyPERPLASIA 2. Lepor H, Lowe FC: Evaluation and nonsurical manaement of benin prostatic hyperplasia  . In: Walsh PC, Retik AB, Vauhan ED, Wein AJ, eds, Campbell’s Urolo CD-ROM, 8 edn, Vol. 2. Chapt 39. Philadelphia: Saun-ders, 2003.3. Chaple CR, MacDiarmid SA. Voidin difculty  . In: Chaple C, MacDiarmid S, eds, Urodnamics. Made eas, 2 edn, Vol. 1. Chapt 4. London: WB Saunders, Harcourt Publishers Limited 2000, pp. 75-76.4. Andersson KE: Storae and voidin symptoms: pathophysioloic aspects  . Urolo 2003; 62 (5 Suppl. 2): 3-10.5. Shapiro E, Lepor H: Pathophysioloy of clinical benin prostatic hyperpla- sia  . Urol   Clin   North   Am 1995; 22 (2): 285-290.6. Rollema HJ, Van Mastrit R: Improved indication and follow-up in tran- surethral resection of the prostate usin the computer proram CLIM: a prospective study  . J Urol 1992; 148 (1):111-115.7. Te AE, Kaplan SA: Urodynamics and benin prostatic hyperplasia  . In: Kirb R, McConnell J, Fitzpatrick J, Roehrborn C, Bole P, eds, Textbook of Be-nin Prostatic Hperplasia Vol. 1. Oxford: Isis Medical Media LTD 1996, pp. 187-198.8. Madersbacher S, Klinler HC, Djavan B et al: Is obstruction predictable by clinical evaluation in patients with lower urinary tract symptoms?   Br J Urol 1997; 80 (1): 72-77.9. Rodriues P, Lucon AM, Freire gC, Arap S: Urodynamic pressure ow studies can predict the clinical outcome after transurethral prostatic resection  . J Urol 2001; 165 (2): 499-502.10. Jepsen JV, Bruskewitz RC: Comprehensive patient evaluation for benin prostatic hyperplasia  . Urolo 1998; 51 (Suppl. 4A): 13-18.11. Kaplan SA, Te AE, Pressler LB, Olsson CA: Transition zone index as a method of assessin benin prostatic hyperplasia: correlation with symptoms, urine ow and detrusor pressure  . J Urol 1995; 154 (5):1764-1769.12. Milonas D, Trumbeckas D, Juska P: The importance of prostatic measur- in by transrectal ultrasound in surical manaement of patients with clinically benin prostatic hyperplasia  . Medicina (Kaunas) 2003; 39 (9): 860-866.13. Homma y, gotoh M, Takei M, Kawabe K, yamauchi T: Predictability of con- ventional tests for the assessment of bladder outlet obstruction in benin prostatic hyperplasia  . Int J Urol 1998; 5 (1): 61-66.14. Proto Wg: Protocols for the evaluation of therapies in BPO. Other assessments: prostate size and prostate specic antien  . Br J Urol 2000; 85 (Suppl 1): 31-35. 15. de la Rosette JJ, Perachino M, Thomas D et al: guidelines on Benin Pros- tatic Hyperplasia  . European Association of Uroloy / Conference Proceed- in   2001: 1-63. 16. Milonas D: The inuence of clinical factors on the outcome of surical treatment of benin prostatic hyperplasia  . Thesis/Dissertation, Kaunas Universit of Medicine, 2004: 97-98. 17. Milonas D, Jievaltas M, Trumbeckas D: Transition zone index – the most im- portant preoperative parameter on prediction outcome after transurethral resection of the prostate  . Eur   Urol   Suppl 2005; 4 (3): 257-257. Cdc Darius TrumbeckasClinic of UroloHospital of Lithuanian Universit of Health Scienes Kaunas ClinicsEiveniu 2LT-50009, Kaunas, Lithuaniaphone: +37 037 326 090trumbeckas@
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