Predictors of short-term overactive bladder symptom improvement after transurethral resection of prostate in men with benign prostatic obstruction

bs_bs_banner International Journal of Urology (2014) 21, 1035 1040 doi: 10.1111/iju.12482 Original Article: Clinical Investigation Predictors of short-term overactive bladder symptom improvement after transurethral resection of prostate in men with benign prostatic obstruction Yao-Rui Zhao, 1 Wen-Zhan Liu, 1 Michael Guralnick, 2 Wen-Jie Niu, 1 Yong Wang, 1 Guang Sun 1 and Yong Xu 1 1 Department of Urology, Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, Tianjin, China; and 2 Department of Urology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA Abbreviations & Acronyms BOO = bladder outlet obstruction BPE = benign prostatic enlargement BPH = benign prostatic hyperplasia BPO = benign prostatic obstruction DC = detrusor contractility DO = detrusor overactivity fqmax = free maximum flow rate ICS = International Continence Society IPSS = International Prostate Symptom Score IPSS-S = summation of frequency, urgency and nocturia scores of International Prostate Symptom Score IPSS-V = subtotal voiding symptom scores of International Prostate Symptom Score LinPURR = linear passive urethral resistance relation LUTS = lower urinary tract symptoms MCC = maximum cystometric capacity N = normal detrusor contractility OAB = overactive bladder OABSS = overactive bladder symptoms score P+ = statistical comparison between baseline and postoperative. Pdet.Qmax = detrusor pressure at maximum flow rate PDO = phasic detrusor overactivity PFS = pressure-flow study Postop. = postoperative Preop. = preoperative PSA = prostate-specific antigen PV = prostate volume PVR = post-void residual volume Qmax = maximum flow rate QOL = quality of life ST = strong detrusor contractility TDO = terminal detrusor overactivity TURP = transurethral resection of the prostate UDS = urodynamic study W = weak detrusor contractility Correspondence: Yao-Rui Zhao M.D., Ph.D., Department of Urology, Second Hospital of Tianjin Medical University, Tianjin Institute of Urology, No. 23, Pingjiang Road, Hexi District, Tianjin 300211, China. Email: zhaoyaorui@sina.com Received 2 November 2013; accepted 6 April 2014. Online publication 13 May 2014 Objectives: To investigate the correlation of preoperative overactive bladder symptoms and urodynamic parameters to the improvement of overactive bladder symptoms after transurethral resection of the prostate. Methods: A retrospective study was carried out in 128 patients with urodynamically proven benign prostatic obstruction that underwent transurethral resection of the prostate. All patients had preoperative urgency symptoms. The patients were divided into groups according to overactive bladder symptom severity and preoperative urodynamic parameters (presence and type of detrusor overactivity, degree of obstruction, bladder contractility). The 3-month postoperative changes in overactive bladder symptoms were then compared between the groups. Results: Overall, there was a statistically significant improvement in mean overactive bladder symptoms score from 9.6 to 2.7 (P < 0.001). However, patients with preoperative mild overactive bladder symptoms had significantly lower postoperative overactive bladder symptoms scores than those with moderate or severe symptoms (P < 0.05). Patients with preoperative terminal detrusor overactivity had significantly higher overactive bladder symptoms scores compared with patients with phasic and no detrusor overactivity (P < 0.05), and were more likely to have persistent urge incontinence. Preoperative detrusor contractility and severity of obstruction did not affect postoperative overactive bladder symptom improvement. Conclusions: Most patients with benign prostatic obstruction and overactive bladder symptoms experience an improvement in their symptoms after transurethral resection of the prostate. The presence of preoperative terminal detrusor overactivity might be negatively associated with this improvement. The preoperative severity of overactive bladder symptoms, detrusor contractility and degree of bladder outlet obstruction do not appear to have an effect. Key words: benign prostatic hyperplasia, overactive bladder, transurethral resection of prostate, urodynamics. Introduction BPH is a common condition affecting older men, with 15 30% having LUTS (storage and voiding). 1 The storage symptoms, in particular, interfere considerably with the activities of daily life, and consequently adversely affect QOL. 2,3 TURP is considered the most effective therapy for LUTS resulting from BOO caused by BPH (i.e. BPO). 4 However, generally, the improvement is greater for voiding symptoms, 5 with a quarter of patients having persistent or worsening storage symptoms. 6 UDS are often used preoperatively to assess LUTS and aid in treatment decisions. There are three important parameters on UDS in patients with LUTS/BPH: the presence of DO, BOO and DC. The role of these parameters in predicting the improvement of OAB symptoms after TURP is controversial, with prior studies yielding mixed results. 7 14 Lower DC appeared to predict less improvement in storage symptoms after TURP in one study; 14 whereas in another study, 60% of patients with weak DC and no BOO still had significant improvement after TURP. 15 2014 The Japanese Urological Association 1035

Y-R ZHAO ET AL. An increasing degree of preoperative BOO has been associated with increased symptomatic efficacy of TURP, 11 although one study found that patients with equivocal BOO did not do significantly worse than those with clear cut BOO. 16 DO, when present preoperatively, does not appear to adversely affect the symptomatic efficacy of TURP if there is concomitant BOO present, but might result in worse outcomes in patients who do not have BOO. 11,16 There are different patterns of DO, PDO and TDO, 17 and Shahab et al. found that 55% of symptomatic patients with BPE and DO on UDS had TDO, whereas 45% had PDO. 18 They also noted higher detrusor contraction pressures in patients with TDO compared with PDO. However, to our knowledge, no one has ever examined whether the pattern of DO influences the improvement of OAB symptoms after TURP. The purpose of the present study was to determine whether preoperative OAB symptom severity, the presence and pattern of DO, and the degree of BOO and DC affect the short-term improvement of OAB symptoms after TURP in patients with LUTS/BPO. This determination might help with managing patients expectations after TURP. Methods A retrospective study was carried out on 128 patients with LUTS as a result of BPO who underwent TURP between November 2009 and January 2013. All patients had urgency symptoms (determined by a symptom questionnaire described later) and all had urodynamically proven BOO (describer later). During this period of time a total of 720 patients underwent TURP, but not all had urgency symptoms or urodynamic testing. The decision for TURP was based on clinical assessment and the patients desire. Before carrying out TURP, all patients were evaluated with symptom assessments including IPSS 19 and QOL index, OABSS, 20 serum PSA, PV (estimated by transrectal ultrasound), PVR measurement by transabdominal ultrasound, and UDS. TURP was carried out with bipolar electrocautery. All patients had BPH on final pathology. OAB symptom severity was assessed using the OABSS. 20 Unlike IPSS, 19 which only assesses the storage symptoms of urgency, frequency and nocturia, OABSS also assesses urge incontinence. Patients were stratified into mild ( 5), moderate (6 11) and severe ( 12) based on the preoperative OABSS, and were also categorized into OAB wet and OAB dry according to the presence/absence of urge incontinence. UDS was carried out following the good urodynamic practice standards of the ICS. 21 Filling cystometry, to evaluate DO, PDO and TDO, was carried out with a transurethral 8-Fr double-lumen catheter in the seated position. The filling rate was 50 ml/min. For the ICS, PDO was defined by a characteristic waveform during the filling phase, that may or may not lead to urinary incontinence. 17 TDO was defined by a single involuntary detrusor contraction occurring at cystometric capacity, which cannot be suppressed, resulting in incontinence, often with bladder emptying. 17 Patients were grouped into categories based on the presence/absence of preoperative DO: DO (PDO + TDO), non-do, PDO (only), TDO and non-tdo (non- DO + PDO). Mixed PDO and TDO were categorized as TDO. Table 1 Baseline urodynamic characteristics of the 128 patients fqmax (ml/s) 5.5 ± 2.9 PVR (ml) 79.4 ± 87.3 DO (n) 43 (33.6%) PDO (n) 25 (19.5%) TDO (n) 18 (14.1%) MCC (ml) 228.9 ± 102.4 Pdet.Qmax (cmh 2O) 91.5 ± 33.4 BOO 4 (3,5) BOO II III/IV VI (n) 36/92 DC 4 (3,5) W/N/ST (n) 43/80/5 Presented as mean ± SD or median (25%,75%) unless specified. BOO was determined using the LinPURR on PFS according to Schäfer. 22 All patients had a LinPURR of at least II, and were divided into mild obstruction (II III) and severe obstruction (IV VI) groups. DC was quantified using the Schäfer nomogram (very weak to weak, normal, strong), and patients were divided into weak (VW, W, W+) and normal/strong (N, N+, ST) groups. The grades of DC were converted to corresponding numerical grades of 1 6 (e.g. VW = 1, W- = 2, W +=3 etc.) for data analysis. Reassessment was carried out at 3 months post-turp with the patients repeating the symptom scores, uroflowmetry and PVR. Symptom scores were compared pre- and postoperatively. Overall treatment success with respect to OAB symptoms was defined as a reduction of 50% in the OABSS. Persistent OAB was defined as postoperative urgency score of OABSS 2. The exclusion criteria included: (i) age <50 years; (ii) PV <20 ml or >150 ml; (iii) urgency score <2 (OABSS); (iv) lack of urodynamic BOO or presence of BOO not as a result of BPH; (v) prostate carcinoma; (vi) history of prostatic and/or urethral surgery; (vii) bladder neoplasm and/or stones; (viii) urinary tract infection or chronic prostatitis; (ix) neurogenic bladder dysfunction; and (x) use of anticholinergics and/or sympathomimetics within 2 weeks before evaluation. Statistical comparisons between group means were carried out using paired and unpaired t-tests. Differences among grades of OAB symptoms were analyzed by one-factor ANOVA. Nonparametric Mann Whitney U-test and Kruskal Wallis rank tests were used for differences in proportions; the χ 2 -test was used for categorical variables. P < 0.05 was considered statistically significant. A multiple logistic regression analysis using forward stepwise regression was carried out to select a set of variables. The odds ratios with a significance level of 0.05 were calculated to include or remove any factor at each step. Results Patient characteristics and follow-up data The mean age of patients was 70.0 years (range 50 88 years). The median (25%, 75%) PV was 60.2 ml (43.0, 80.1). The median (25%, 75%) weight of resected prostate tissue was 30.2 g (20.2, 38.4). The mean PSA was 7.34 ± 7.35 ng/ml. Table 1 shows the baseline urodynamic characteristics of the 128 patients. Table 2 shows baseline, and 3 months postoperative subjective and objective results. Both subjective symptoms 1036 2014 The Japanese Urological Association

OAB symptom improvement post-turp Table 2 Baseline and follow-up values for each outcome variable Parameter Preop. Postop. P Patients (n = 128) IPSS 25.3 ± 5.9 3.7 ± 3.8 <0.001 IPSS-S 11.1 ± 2.9 2.9 ± 2.2 <0.001 IPSS-V 14.2 ± 4.0 0.8 ± 2.1 <0.001 QOL 5 (3,6) 1 (0,5) <0.001 OABSS 9.6 ± 2.4 2.7 ± 2.0 <0.001 fqmax (ml/s) 5.5 ± 2.9 16.0 ± 2.0 <0.001 PVR 79.4 ± 87.3 19.2 ± 17.5 <0.001 Postop. persistent OAB (n = 29) OABSS 10.1 ± 2.1 5.2 ± 2.5 <0.001 Postop. OAB-wet (n = 12) OABSS 10.8 ± 2.0 7.2 ± 2.1 0.001 Presented as mean ± SD or median (25%,75%). Table 3 Preoperative parameters and postoperative changes in OAB symptoms stratified by severity of preoperative OAB symptoms Parameter Mild OAB Moderate OAB Severe OAB (n = 11) (n = 89) (n = 28) Age (years) 67.6 ± 6.8 70.6 ± 7.6 69.1 ± 8.6 BOO 4.0 (3.0,5.0) 4.0 (4.0,5.0) 4.5 (3.0,6.0) DC 5.0 (4.0,5.0) 4.0 (3.0,5.0) 3.5 (3.0,5.0) DO 4 (36.4%) 30 (33.7%) 9 (32.1%) TDO 0 14 (15.7%) 4 (14.3%) OABSS Baseline 4.7 ± 0.5 9.0 ± 1.4 12.9 ± 0.7 Postop. 1.5 ± 1.0 2.6 ± 1.9 3.4 ± 2.4 P+ <0.001 <0.001 <0.001 Presented as mean ± SD or median (25%,75%) unless specified. Symbols represent statistically significant differences (P < 0.05) between the groups: mild OAB groups compared with moderate OAB groups; mild OAB groups compared with severe OAB groups; moderate OAB groups compared with severe OAB groups. (IPSS, OABSS, QOL index) and objective parameters, such as fqmax and PVR, were significantly improved. A total of 88 patients (68.8%) had OAB wet preoperatively. Postoperatively, 13.6% (12/88) patients had persistent OAB wet, but the OAB symptoms were improved compared with baseline (OABSS 10.8 ± 2.0 vs 7.2 ± 2.1, P = 0.001). Using a 50% improvement in OABSS as criteria for success, the success rate for improvement of OAB symptoms was 87.5% for the entire group. Although 22.7% (29/128) of patients still had OAB symptoms after TURP (based on OABSS), their OAB symptoms were significantly improved compared with baseline. There was no difference between the groups of improved and unimproved patients in pre- and postoperative fqmax and PVR. Subgroup analysis according to preoperative OAB symptom severity Table 3 groups patients according to the severity of OAB symptoms (based on OABSS) and shows several UDS variables between the groups, as well as symptom score outcomes. There were no significant differences in age, grade of BOO, DC, or percentages of patients with DO or TDO. As well, the overall OAB treatment success was not significantly different between the three groups (90.9%, 88.8% and 82.1% respectively). However, patients with mild OAB symptoms preoperatively had a significantly lower postoperative OABSS than those with moderate or severe preoperative OAB symptoms (P < 0.05). Subgroup analysis according to the presence and pattern of preoperative detrusor overactivity On preoperative UDS, 43 of 128 (33.6%) patients had DO, which comprised of PDO in 25 of 128 (19.5%) cases and TDO in 18 of 128 (14.1%) cases. Sensory volume markers, such as first sensation of bladder filling, strong desire to void and maximum cystometric capacity, were significantly lower in the DO patients than the non-do patients, and in TDO patients compared with non-tdo patients (Table S1). There were no differences in age, degree of BOO or DC between any of these subgroups (Table 4). Table 4 compares the pre- and postoperative symptom scores between the groups. There was no significant difference in the pre- and postoperative OABSS between the DO and non-do patients. As well, there was no significant difference between the preoperative and postoperative OABSS between non-do patients and PDO patients. However, the OABSS of TDO patients was significantly higher than PDO patients before and after TURP (P < 0.01), and non-tdo patients after TURP (P < 0.05). There was no significant difference in the degree of OAB symptom improvement (change from baseline in OABSS) between the subgroups. There was no significant difference in the PV or resected weight between the different groups stratified by the type of preoperative detrusor overactivity. Overall OAB treatment success (i.e. 50% improvement in OABSS) was lower in DO patients (79.1%) than non-do patients (91.8%), and lower in TDO patients (66.7%) than non- TDO patients (90.9%) (P < 0.05). In patients with OAB wet preoperatively, seven of 27 (25.9%) patients with DO and five of 61 (8.2%) patients without DO had persistent OAB wet postoperatively (P = 0.025). As well, six of 14 (42.9%) patients with preoperative TDO and one of 13 (7.7%) patients with PDO had persistent OAB wet postoperatively (P = 0.037). Subgroup analysis according to severity of BOO and detrusor contractility Table 5 shows the change in OAB symptoms when patients were grouped according to severity of BOO and DC. There was no significant difference in OABSS between mild obstruction 2014 The Japanese Urological Association 1037

Y-R ZHAO ET AL. Table 4 Preoperative parameters and postoperative changes in OAB symptoms stratified by type of preoperative detrusor overactivity Parameter Non-DO DO PDO Non-TDO TDO (n = 85) (n = 43) (n = 25) (n = 110) (n = 18) Age (years) 69.5 ± 7.8 71.0 ± 7.9 70.4 ± 9.0 69.7 ± 8.0 71.9 ± 6.2 BOO 4 (3,5) 4 (4,5) 4 (4,5) 4 (3,5) 4.5 (3.75,6.0) DC 4 (3,5) 4 (3,5) 5 (4,5) 4 (3,5) 4 (3,5) OABSS Baseline 9.6 ± 2.4 9.5 ± 2.4 8.8 ± 2.4 9.4 ± 2.4 10.6 ± 2.0 Postop. 2.5 ± 1.9 3.1 ± 2.2 2.4 ± 1.8 2.5 ± 1.9 4.0 ± 2.4 P+ <0.001 <0.001 <0.001 <0.001 <0.001 Presented as mean ± SD or median (25%, 75%). Symbols represent statistically significant differences (P < 0.05) between the groups: PDO groups compared with TDO groups; non-tdo groups compared with TDO groups. Table 5 Preoperative parameters and postoperative changes in OAB symptoms stratified by degree of preoperative bladder outlet obstruction and detrusor contractility Parameter BOO DC Mild (n = 36) Severe (n = 92) P Weak (n = 43) Normal/strong (n = 85) P Age (years) 71.0 ± 7.9 69.6 ± 7.7 0.353 70.9 ± 8.6 69.5 ± 7.4 0.364 DO 9 (25%) 34 (37.0%) 0.183 11 (25.6%) 32 (37.6%) 0.162 TDO 4 (11.1%) 14 (15.2%) 0.552 7 (16.3%) 11 (12.9%) 0.611 OABSS Baseline 9.8 ± 2.6 9.5 ± 2.3 0.489 10.3 ± 2.3 9.2 ± 2.4 0.022 Postop. 3.0 ± 2.5 2.6 ± 1.3 0.291 3.1 ± 2.5 2.5 ± 1.8 0.112 P+ <0.001 <0.001 <0.001 <0.001 Presented as mean ± SD unless specified. Table 6 Multiple logistic regression analysis of the parameters influencing improvement of OAB symptoms after TURP OR (95% CI) OABSS-IC DO 0.55 DO/Non-DO 0.64 (0.15 2.72) TDO 0.007 TDO/non-TDO 0.20 (0.062 0.648) BOO 0.58 Severe/mild 1.50 (0.36 6.25) DC 0.84 Normal and strong/weak 0.88 (0.26 2.96) OAB severity 0.63 (0.22 1.81) 0.39 and severe obstruction preoperatively or postoperatively. Detrusor weak patients had higher preoperative OABSS than the detrusor normal/strong patients, but postoperatively there was no difference. Based on univariate analysis, detrusor contractility did not influence the improvement of OAB symptoms after TURP in men with BPO. Analysis of predictive factors influencing improvement of OAB symptoms after TURP Multivariate analysis (Table 6), examining preoperative OAB symptom severity, presence and pattern of DO, severity of BOO, and degree of DC showed that the only variable that P appears to influence the improvement of OAB symptoms after TURP is the presence of TDO (negative influence). Discussion OAB symptoms occur in 52 80% of men with LUTS/BPH. 23 Previous studies have reported that 20 40% of the patients who had undergone prostatectomy have persistent OAB symptoms postoperatively, 24 which is consistent with the present finding of 22.7%. We believe there could be two reasons for this: first, the duration of BOO might have resulted in irreversible changes in bladder structure and function. Second, the cause of preoperative OAB symptoms might not be the BOO, but rather a subtle neurological disorder, diabetes, aging and so on. 25 We found that men with mild OAB symptoms preoperatively had significantly lower OABSS than those with moderate or severe OAB symptoms after TURP, but there was no difference in the overall success rate of OAB symptom improvement. Therefore, patients with different severities of OAB symptoms might experience significant improvement in OAB symptoms after TURP, but those with more mild symptoms preoperatively tend to have more mild symptoms postoperatively. OAB symptoms in men are often associated with urodynamically proven DO, 26,27 leading to the belief that patients with DO have a more severe form of OAB than those without DO. In the present study, DO was urodynamically observed in 33.6% of the BPO patients, and there was no significant difference in the preoperative OAB symptom scores between the presence and absence of DO. Controversy exists 1038 2014 The Japanese Urological Association

OAB symptom improvement post-turp about the relationship between DO and the improvement of LUTS after TURP. Seki et al. 8 found that DO is an independent negative determinant of postoperative symptom improvement, whereas Cho et al. 7 reported that patients with DO had significantly greater improvement in IPSS-S after photoselective vaporization of the prostate than patients without DO. However, other studies reported that preoperative DO does not affect the improvement of postoperative storage symptoms. 9,10 The presence of actual BOO could be an important variable here, in that some studies have shown poorer results with TURP in patients with DO and no BOO. 11,28 It is possible that some of the patients in the studies showing no adverse effect of DO did not actually have preoperative BOO. The DO of non-boo patients is likely not related to BPH, and this might have confounded the results of those studies. All of the present patients had urodynamically proven BOO, and although the presence/absence of DO did not affect the degree of improvement in OABSS (change from baseline), DO patients did have less overall treatment success ( 50% improvement) compared with non-do patients. It seems that much of this difference comes from the presence of TDO: patients with TDO had worse symptoms preoperatively and poorer symptom improvement postoperatively compared with non-tdo patients. There is limited information on the pathological and physiological differences between PDO and TDO. Valentini et al. studied PDO and TDO in women, and found the occurrence of TDO to be significantly associated with aging and secondary structural changes in the detrusor muscle. 29 We did not identify a significant age difference between PDO and TDO patients, but we did find a significant difference in OAB symptom severity between PDO and TDO patients (higher symptom scores in TDO). Taken together, the present results lead us to speculate that TDO might be a more severe form of OAB. Whether the duration and/or degree of BOO influence the development of the different patterns of DO is unclear and requires further investigation. The degree of BOO has been noted to influence the results of TURP, with Seki et al. noting that obstruction (based on Schäfer s nomogram) was the decisive factor for postoperative IPSS and QOL improvement. 8 Tanaka et al. reported that the overall treatment effect increased as the degree of BOO increased, although there was no significant difference among the different degrees of BOO on single indexes, such as the IPSS or QOL. 11 We found no difference in postoperative improvement in OAB symptoms between patients with severe and mild obstruction preoperatively, and the univariate analysis showed that the degree of BOO did not influence improvement of OAB symptoms after TURP in men with BPO. Preoperative DC has been reported to be a predictor of improvement of LUTS after TURP, 12,13 but there are limited data regarding its effect on the improvement of OAB symptoms. Seki et al., examining the improvement in OAB symptoms (using IPSS) after TURP, noted that the baseline degree of DC was consistently associated with the improvement of each OAB symptom (urgency, frequency and nocturia). 14 We found that preoperative DC was not an independent determinant of the improvement of OAB symptoms after TURP (based on IPSS-S, data not shown). However, the IPSS does not account for urge incontinence. Using OABSS (which factors in urge incontinence), we did not identify a difference postoperatively between the detrusor weak group and the detrusor normal/strong group, although preoperatively detrusor weak patients had higher OABSS. Similarly, the univariate analysis showed that detrusor contractility did not influence improvement of OAB symptoms after TURP in men with BPO. Based on these results, we believe that preoperative DC does not affect the improvement of OAB symptoms after TURP. The present study was limited by its retrospective nature, relatively small sample size and the lack of postoperative pressure-flow urodynamics to confirm the resolution of BOO. However, based on the improvements in fqmax, PVR and IPSS (Table 2), it is reasonable to assume that BOO was indeed relieved by TURP. Our follow up was short, and it is possible that with longer follow up some of the results could change. In conclusion, TURP can improve OAB symptoms in patients with BPO. Patients with preoperative TDO seem to improve less than patients with PDO or no DO, but even TDO patients can have significant improvement. The preoperative severity of OAB symptoms does not appear to influence the degree of improvement in OAB symptoms, although those patients with the mildest symptoms preoperatively tend to have the mildest symptoms postoperatively. 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