A review of detrusor overactivity and the overactive bladder after radical prostate cancer treatment Nikesh Thiruchelvam, Francesco Cruz†, Mike Kirby‡, Andrea Tubaro§, Christopher R. Chapple¶ and Karl-Dietrich Sievert**††‡‡ Department of Urology, Cambridge University Hospitals NHS Trust, Cambridge, UK, †Faculty of Medicine, Hospital S. Joao, Porto, Portugal, ‡Faculty of Health and Human Sciences, University of Hertfordshire and the Prostate Centre, London, UK, §Department of Urology, La Sapienza, University of Rome, Rome, Italy, ¶Sheffield Teaching Hospital, NHS Foundation Trust, Sheffield, UK, **Department of Urology, Eberhard-Karls-University, Hoppe-Seyler Strasse 3 72076, € beck, Schleswig-Holstein, Ratzeburger Allee 160 23538, Lu € beck, Germany, and Tuebingen, ††Department of Urology, Lu ‡‡ Dept of Urology and Andrology, SALK Clinic/Paracelsus Medical University, Salzburg, Austria

There are various forms of treatment for prostate cancer. In addition to oncologic outcomes, physicians, and increasingly patients, are focusing on functional and adverse outcomes. Symptoms of overactive bladder (OAB), including urinary frequency, urgency and incontinence, can occur regardless of treatment modality. This article examines the prevalence, pathophysiology and options for treating OAB after radical prostate cancer treatment. OAB seems to be more common and severe after radiation therapy than after surgical therapy and even persisted longer with complications, suggesting an advantage for surgery over radiotherapy. Because OAB that occurs after radical prostate surgery or radiotherapy can be

Introduction Treatment of prostate cancer has advanced considerably over the past few decades. Improvements in techniques for radical removal of the prostate, such as nerve-sparing radical prostatectomy (RP), have been made possible by improved visualization of prostate cancer tumour and nerves [1–8]. More recently, the tendency has been to move towards laparoscopic and, subsequently, robotic RP. In radiotherapy, advances have increasingly focused on the delivery of radical treatment for prostate cancer. Furthermore, minimally invasive techniques using heat-producing sources such as ultrasonography and cooling effects with cryotherapy are currently under evaluation. Early evaluation criteria for a successful outcome of treatment for prostate cancer included the trifecta of biochemical cancer-free status (determined by PSA assessment), continence and potency [9]. Subsequent authors added surgical margins and complication rates as criteria for

© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13078 Published by John Wiley & Sons Ltd. www.bjui.org

difficult to treat, it is important that patients are made aware of the potential development of OAB during counselling before decisions regarding treatment choice are made. To ensure a successful outcome of both treatments, it is imperative that clinicians and non-specialists enquire about and document pretreatment urinary symptoms and carefully evaluate post-treatment symptoms.

Keywords prostatectomy, overactive bladder (OAB), radiotherapy, prostate cancer, brachytherapy

evaluation [10]. There is a large body of work examining oncological outcomes of available treatment methods for prostate cancer. Research regarding the effects of radical surgery on LUTS has focused on potency and stress urinary incontinence (SUI) due to sphincter weakness. For radical radiotherapy, interest has focused on urinary and rectal toxicity, although definitions of these toxicities are not disease-specific. Fewer data are available regarding the relationship between treatment and bladder function. Overactive bladder syndrome (OAB) can adversely affect quality of life and satisfaction, especially over the longer term. OAB is a complex of storage symptoms consisting of urgency with or without urgency urinary incontinence, usually with frequency and nocturia [11]. The prevalence of OAB symptoms in men aged >60 years in western populations has been estimated to be 19% for urgency, 11% for frequency, and 2.5% for urgency incontinence [12]. In men, OAB is usually attributable to detrusor overactivity (DO), which is characterized by involuntary contractions of the detrusor

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muscle during the filling phase, as observed during urodynamic studies [13]. Whether the presence of LUTS is a predictor of prostate cancer is unclear [14,15]. In patients with prostate cancer, the relationship between the presence of pretreatment LUTS and the outcome after cancer treatment also needs to be clarified [16]. On the one hand, the symptoms can be lower in patients who undergo radical surgery [5], radiotherapy [17] or hormonal therapy [18] than in those who undergo nonoperative surveillance. On the other hand, LUTS could be exacerbated or occur de novo as a result of prostate cancer treatment, regardless of the treatment method [19–22]. Male SUI is a well recognized complication after surgical treatment of prostate cancer. Clearly, urinary urgency and frequency are also highly bothersome symptoms [23]. Yet there are few data documenting the onset and progression of bladder dysfunction and OAB resulting from the treatment of prostate cancer, as evidenced by the failure to mention specific measures of bladder dysfunction, such as urodynamic data, in several excellent reviews of oncological and functional outcomes after RP [5,24–27]. Likewise, reviews of radiotherapy for prostate cancer include clearly defined classifications of acute and chronic urinary toxicity, but with only minimal specific recording of specific measures of OAB [19,28–31].

possible articles. Any question with regard to the inclusion of a particular article, such as concern of bias or selective reporting, was resolved by discussion between the primary and senior authors. Only articles published in English and related to human subjects were considered. As subject number in clinical studies was low and therefore, inherently, quality of evidence, bias was minimized by inclusion of all possible studies. This review was constructed by summarizing findings with the presentation of results under thematic headings. The discussion was determined by expert consensus.

Results The search resulted in 1 236 papers (see Fig. 1). After all abstracts were assessed and after relevant exclusion due to non-relevance, 117 full papers were accessed and reviewed. A further 18 papers were accessed after manual inspection of the reference lists of the 117 articles. A further review of the identified 135 articles led to the exclusion of 13 papers. Those papers were excluded if they did not answer the primary research question. In all, 122 full-text articles were assessed and summarized for this review. A summary of the interpretable results is shown in Table 1.

To provide a basis for counselling patients regarding management and potential impact of these symptoms after radical surgery, the present review examines the relationship between OAB and prostate cancer treatment in greater detail. We therefore examined the urodynamic evidence regarding prevalence of OAB after surgery or radiotherapy, the relationship between pre-and post-treatment LUTS, the factors predictive of achieving continence, including surgical technique, and options for the management of LUTS.

Radical Prostatectomy

Review Methods

In patients with either urinary incontinence or LUTS after RP who underwent urodynamic testing after RP, Chung et al. [34] reported DO in 27% of the total (71/264): 25% of patients with postoperative incontinence (59/238) and 46% of continent patients (12/26). Interestingly, these authors also found detrusor underactivity in 41% of all patients (108/264); of these, 48% used abdominal straining to void. In 110 patients who underwent urodynamic studies before and after laparoscopic RP, Matsukawa et al. [35] reported detrusor underactivity in only 9% and postoperative DO in 33% (including de novo DO in 21%) of patients after laparoscopic RP. By contrast, Chao and Mayo [36] found that only 4% of 74 patients with incontinence after prostatectomy had DO alone, while 39% had mixed bladder and sphincter dysfunction. In a prospective study of 29 patients undergoing RP, Constantinou and Freiha [37] reported that urodynamic studies showed pretreatment DO in 16 (55%). After surgery,

This review was conducted in accordance with the systematic review guidelines provided by the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The authors undertook a PubMed search using the following terms in combination: ‘prostate cancer outcomes’, ‘prostate cancer/overactive bladder’, ‘radiotherapy/overactive bladder’ and ‘prostate cancer/LUTS’ from January 1995 through to December 2013. Among the identified citations, clinical articles relevant to the prevalence and management of OAB after surgery and radiotherapy for prostate cancer were selected. Because the number of relevant references was limited, manual inspection of the reference list of each selected article was performed to further identify studies that were not captured by the online search but that might be potentially relevant for the review. The authors also undertook a repeated search to ensure inclusion of all

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Urodynamic Studies After RP Varied urodynamic changes have been observed in patients with LUTS, particularly in those with incontinence, after radical prostate surgery, regardless of the surgical approach. Ventimiglia et al. [32] undertook a urodynamic analysis of 51 patients with urinary incontinence 8–24 months after nervesparing RP. DO was present in 32 patients (63%). Leach et al. [33] concluded that bladder dysfunction contributed to incontinence in 60% of 215 patients.

Detrusor overactivity and OAB after radical prostate cancer treatment

(presented according to PRISMA guidelines for

Included

Eligibility

Screening

systematic review).

Identification

Fig. 1 Results of PubMed literature review

the maximum DO pressure did not decrease significantly. In a study of 66 patients who were incontinent after radical retropubic prostatectomy, Dubbelman et al. [38] found DO before surgery in 26% and after surgery in 21%. In consecutive patients undergoing radical retropubic prostatectomy, Giannantoni et al. [39] found pretreatment DO in 61% (33/54, three of whom complained of urgency with urge incontinence). At 8 months after surgery, DO had disappeared in three patients and had developed de novo in eight. After 3 years of follow-up in 32 patients, DO was detected in 56% (de novo in five patients, pre-existing in 13). DO was associated with impaired detrusor contractility in 22%. These authors concluded that altered detrusor function becomes established over time but is masked because patients develop new voiding behaviours. Recently, Barniou et al. [40] noted that de novo DO had developed in 25% of 32 consecutive patients 3 months after robotic RP. Whereas Ventimiglia et al. [32] considered incontinence to be purely due to DO in 35% of 51 patients, Huckabay et al. [41] found that incontinence was due to DO in 13% of 60 patients. Groutz et al. [42] concluded from their research series of 83 patients experiencing incontinence after RP that sphincteric incontinence (SUI) was the most common urodynamic finding and that detrusor instability was the main cause of incontinence in 7.2%. Kielb and Clemens [43]

Records identified through database searching (n = 1236)

Full-text articles assessed (n = 117)

Full-text articles assessed for eligibility (n = 135)

Records excluded (n = 1119)

Additional records identified through reference sources (n = 18)

Records excluded (n = 13)

Full-text articles assessed for synthesis (n = 122)

found that 95% of patients with incontinence after prostatectomy had sphincteric weakness and only 2% had DO alone. Majoros et al. [44] found DO alone in 3.2% of 63 patients with incontinence after radical retropubic prostatectomy. Winters et al. [45] found DO to be the sole cause of incontinence in 3.3% of 92 patients. From all of these observations, it is clear that DO, as measured by urodynamic analysis, is infrequently the sole cause of incontinence after prostatectomy. Bladder dysfunction could also coexist with sphincteric weakness. Nevertheless, unlike the transient early DO seen after TURP, DO after prostatectomy remains an important clinical consideration. Because of the wide variation in the prevalence of DO after radical prostate surgery and its association with other disorders, urodynamic studies are essential to identify the exact cause(s) of incontinence in patients with LUTS after RP. Pre-Existing LUTS It is unclear whether the presence of LUTS before radical surgery affects postoperative urinary symptoms and by how much. One problem in investigating this issue is that, instead of urodynamic testing, many studies measure bladder dysfunction using questionnaires such as the AUA Symptom Score (AUA-SS)/IPSS [46] or similar symptom scores. © 2015 The Authors BJU International © 2015 BJU International

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Table 1 A summary of detrusor overactivity and overactive bladder after radical prostate cancer treatment. After RP

Percentage of patients with urodynamic DO after surgery

Ventimiglia et al. [32] Leach et al. [33] Giannantoni et al. [39] Matsukawa et al. [35] Chung et al. [34] Barnoiu et al. [40] Dubbelman et al. [38] Huckabay et al. [41] Groutz et al. [42] Majoros et al. [44] Winters et al. [45] Kielb and Clemens [43]

63 60 56 33 27 25 21 13 7 3 3 2

After radiotherapy

Percentage of post-treatment patients

Boettcher et al. [19], post–brachytherapy

30% severe urgency on symptom scores (vs 11% post-RP) 85% urodynamic DO 17% >grade 2 GU toxicity 40% suffered urgency (non-pelvic radiation-matched controls 30%)

Blaivas et al. [60], post-brachytherapy Buckstein et al. [28], post-brachytherapy Olsson et al. [78], post-brachytherapy and/or post-EBRT GU, genitourinary.

Although it is clearly easier to administer a questionnaire than to perform a urodynamic evaluation, such questionnaires do not adequately discriminate between storage and voiding symptoms. Choi et al. [47] reviewed data from 183 patients with available AUA-SS scores before and after robotic RP. Based on their AUA-SS scores, preoperative urinary symptoms were classified as mild in 94 (5.14%), moderate in 70 (38.2%) and severe in 19 (10.4%). Patients with severe preoperative LUTS showed a non-significant decrease in urinary function subscales after surgery (P = 0.056) and had significantly higher postoperative urinary bother scores than did patients with fewer preoperative symptoms (P < 0.01). However, several studies found improvement in LUTS or DO after RP. Kleinhans et al. [48] found that DO was present before surgery in 44% (16/44) of the patients. In 14 of these 16 patients, DO disappeared after surgery. Although Matsukawa et al. [35] found de novo DO after surgery in 21% of 110 patients who underwent prostatectomy, DO disappeared in 54% of 28 patients with preoperative DO. Similar results were found by Slova and Lepor [49], who reported that storage symptoms were significantly improved after open RP and this improvement was maintained 4 years after the operation. Masters and Rice [50] found moderate-tosevere IPSS symptom score values in 56% of 125 patients before surgery, but in only 14% at 2 years after open RP. Schwartz and Lepor [51] found that AUA-SS scores were significantly reduced after 1 year in 104 patients with moderate-to-severe scores before undergoing open RP. In a

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study of 117 patients, Matsubara et al. [52] found a reduction in IPSS values in patients with moderate-to-severe LUTS at 1 year after perineal RP. Interestingly, the group with no or only mild preoperative symptoms (based on IPSS symptom scores) was the only group in which adverse effects (e.g. worsening symptom scores) were found after surgery. Boettcher et al. [19] found that in 66 patients treated with RP for localized prostate cancer, the frequency of OAB increased slightly after open RP (from 12% before surgery to 15% at 6 months) but decreased within the first postoperative year and was below the initial level at 3 years. These studies show that bothersome symptoms exist before treatment of prostate cancer and that RP can provide major benefits for patients with these pre-existing bothersome LUTS. Pathophysiology of Postoperative Bladder Dysfunction Various attempts have been made to better understand the factors predictive of achieving continence, but these have focused on discovering causes and reducing rates of stress incontinence. Theories on the development of OAB symptoms include: partial decentralization of the bladder as a result of its mobilization during prostatectomy [42], combined with somatic denervation (because the branches of the pudendal nerves innervating the pelvic floor muscles and the striated urethral sphincter split before reaching the urogenital diaphragm) [53]; and postoperative decentralization of the bladder, inflammation or infection, and geometric bladder wall alteration associated with preexisting hypoxemia with or without neuroplasticity (Porena et al. [54]).

Radical Radiotherapy Because radiotherapy carries a risk of ischaemia and induces an inflammatory response mediated by oxygen reactive species, both temporary and permanent irritative symptoms from any of the pelvic organs are common, including urinary symptoms in addition to proctitis, reduced penile size and erectile dysfunction. Only with the slowly growing interest in the surgical field have oncologists defined toxicity (e.g. complications) by using Radiation Toxicity Oncology Group criteria [55]. Unfortunately, these criteria have not been easy to interpret, especially regarding the OAB. OAB after radiotherapy could be due to BOO (bladder neck stenosis, urethral stricture disease), bladder stones or mucosal inflammation. Hence, clinical correlation of toxicity and symptoms is not straightforward. Radiation therapy – whether external beam radiotherapy (EBRT) or brachytherapy – can be a cause of voiding dysfunction and incontinence [31,56]. This can be a direct effect of the radiation, or it could be related to other sequelae

Detrusor overactivity and OAB after radical prostate cancer treatment

such as urinary retention. The initial response is primarily oedema and then gradually degeneration, fibrosis and disorganization of the bladder musculature. While radiation is primarily delivered to the prostate, it also affects the bladder neck. Perivascular fibrosis of blood vessels might then cause vascular occlusion followed by ischaemia of the bladder wall, which can then progress to fibrosis within 6–12 months [57,58]. In addition, the innervation of the trigone is affected, which primarily affects bladder sensation [59].

found in 2–30% of patients after brachytherapy [66–70]. Most patients with retention have resolution of the obstruction within weeks, whereas others require surgery. A retrospective review of over 2 100 patients aged ≥65 years who underwent brachytherapy for prostate cancer found that 8.3% required a surgical procedure to relieve BOO after brachytherapy [71]. Others report lower rates of obstruction, e.g., 2% [72] to 3.1% [73]. External Beam Radiotherapy

Brachytherapy Boettcher et al. [19] found that rates of OAB were significantly higher after brachytherapy than after RP, even after 3 years. Approximately 12% of patients in each group had pretreatment OAB symptoms, but the rate almost quadrupled within the first 6 months after brachytherapy and remained at three times the pretreatment rate after 3 years, whereas after prostatectomy the rate of OAB had increased only slightly at 6 months and returned to pretreatment rates at 12 months [20]. These authors also found that the presence of LUTS before brachytherapy was significantly associated with higher rates of OAB. Interestingly, OAB symptoms persisted longer in patients who underwent brachytherapy than in those who underwent RP (30% vs 11% at 3 years). OAB symptoms were also more severe after brachytherapy. Blaivas et al. [60] evaluated patients with symptomatic LUTS 6 months or more after brachytherapy for localized prostate cancer: 71% (31/44) were incontinent, 79% had OAB symptoms (37/47), and 85% (28/33) had DO. In a comparison between their brachytherapy patients and 541 patients with LUTS from an unselected patient population, the authors found that, after brachytherapy, patients had a higher rate of DO (85% vs 47%) and higher rates of urethral strictures and prostatic urethral stones [19]. In a long-term study of 131 patients treated with brachytherapy, Buckstein et al. [28] reported that 17% of patients had grade 2 or greater genitourinary toxicities, with 4.5% persisting with symptoms after 10 years. In general, scores for OAB during the first 3–6 months after brachytherapy are elevated, returning to pretreatment baseline by 12 or 18 months [61–64]. Okaneya et al. [61] reported that the time needed to return to the initial level was longer for storage symptoms than for voiding symptoms [20]. Kelly et al. [64] found that large pretreatment prostate volume and high IPSS values were related to greater severity of urinary symptoms in the first few months. However, ongoing total urinary incontinence and other severe urinary symptoms are rare after brachytherapy [31,65]. Other common problems after brachytherapy include urinary retention and increased obstructive LUTS. Retention has been

Choo et al. [74] found that urodynamic bladder capacity decreased by a mean of 54 mL for the upright position in 17 patients studied 18 months after EBRT, although there were no changes in urodynamic tests, bladder compliance, bladder instability or BOO. Although the primary complaints of patients undergoing EBRT are bowel symptoms (bleeding, frequency and urgency, pain) rather than urinary symptoms [31], questionnaire scores illustrate marked toxicity due to EBRT. Some, if not all, patients have a noticeable increase in OAB symptoms throughout the 7 weeks of treatment with EBRT. These results are also mirrored by physician-reported outcomes of toxicity during treatment, which seem unaffected by the addition of adjuvant hormone therapy [75]. Sanda et al. [22] reported that urinary incontinence and urinary irritation or obstruction occurring after both EBRT and brachytherapy returned to baseline at 1 year, and further improvement was seen in urinary irritation or obstruction at 2 years. Intensitymodulated radiotherapy has been used with some success [76]. However, even this technique can lead to marked deterioration in mental health, energy levels and quality of life in addition to urinary and bowel symptoms [77]. Olsson et al. [78] examined patients with prostate cancer who underwent primary or salvage EBRT and those who underwent EBRT and brachytherapy, compared with nonpelvic-irradiated matched controls from the general Swedish population. Significantly higher prevalence rates were found in the EBRT groups compared with controls for various symptoms, persisting for up to 9 years of follow-up. Prevalence was higher for nocturia and lower for daytime frequency in the combined radiation group than for EBRT only. Significantly higher prevalence was noted for urinary urgency and urge incontinence for all the radiation groups as compared with controls. Such variation in symptoms could be related to the development of radiation-induced injury or to the adverse effect of ageing. In addition to the strong possibility of urinary and bowel toxicity with radiation therapy, there is also concern regarding development of new secondary cancers as a consequence of treating the primary cancer with radiation. This has been observed in children [79] and in the treatment of prostate

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cancer [80]. EBRT and brachytherapy increased the risk of low-mortality bladder and rectal cancer (in the radiation field) and skin cancers (outside the radiation field); at 10 years the risk of development of a secondary cancer was as high as 25% for EBRT and 15% for brachytherapy. Younger patients are undergoing radiation therapy and, given that fact that patients are living longer [81], this is a worrying figure.

Management of LUTS The medical management of urinary symptoms after radical treatment for prostate cancer typically uses alpha-blockers. Ishizaka et al. [82] found that the alpha1-blocker naftopidil improved storage (and voiding) symptoms in a 5-week study of 29 patients who had persistent symptoms at least 1 year after RP. Similarly, alpha-blockers have been reported to improve IPSS scores after radiotherapy: Tsumura et al. [83] found that urinary symptoms after brachytherapy in 212 patients improved with use of alpha-blockers, regardless of type (silodosin, naftopidil, or tamsulosin). Previously, Zelefsky et al. [84] also found a similar improvement in symptoms in 743 patients after radiotherapy with terazosin. Merrick et al. [67] found that prophylactic use of alpha-blockers resulted in significantly less urinary morbidity than either the absence or therapeutic use of alpha-blockers. In patients receiving prophylactic alpha-blockers, the IPSS normalized significantly faster than in those with no alpha-blockers, but there was no effect on urinary retention or on the ultimate need for postimplant surgical intervention. In a retrospective study in 2008, Bittner et al. [29] reported that trospium chloride improved irritative urinary symptoms after brachytherapy in 80% of 69 patients treated. The mean time from brachytherapy to commencement of trospium chloride treatment was just under 2 years, much later than in reports showing a return of urinary symptoms to baseline by 18 months after brachytherapy. Gandaglia et al. [85] also noted an improvement in continence rates in patients who took phosphodiesterase inhibitors after radical surgery, as compared with those who did not require the additional use of this drug. The authors postulated that there could be an improvement in blood flow to the pelvic floor or urinary tract with phosphodiesterase inhibitors and that this could lead to improved continence. Although there is a lack of data on the use of antimuscarinic agents in radically treated patients with prostate cancer, these drugs are widely used in clinical practice in patients with LUTS, so there should be no concern in using these drugs as therapy for patients with OAB after prostate cancer treatment. If medical therapy fails, standard second-line therapy such as botulinum toxin A, sacral nerve stimulation, and, as a last resort, urinary diversion should be considered. Controversial options include hyperbaric oxygen [86], oral pentosan polysulphate sodium or intravesical hyaluronic acid.

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Looking to the future, b3 agonists such as mirabegron, or a combination of medical therapy and stem cell regeneration of urinary sphincter and bladder muscle or nerve tissue, could play a role in such patients.

Discussion Although SUI is more frequently reported in the literature after surgical treatment of prostate cancer than after radiation therapy, it is more severe and far more difficult to treat if intervention is needed after radiation. Clearly, all cases need to be adequately evaluated, and there is a significant potential role for invasive urodynamics as well as endoscopy in assessing cases. Urinary incontinence after RP shows an aetiological diversity, and therefore each case has to be considered on an individual basis [32]. The studies described in the present review outline a wide variation in the severity of OAB and its role in bothersome LUTS after radical prostate cancer treatment. OAB seems to occur after radiation therapy in the early phase but improves rapidly; the combination of brachytherapy and EBRT appears to result in the most severe and long-lasting symptoms. In contrast to SUI after radical surgery, which can be adequately treated by further surgery [87], OAB symptoms after prostate cancer treatment can be very difficult to treat. Patients with a combination of SUI plus OAB before surgery should not be categorically denied male incontinence surgery, such as construction of an artificial urinary sphincter or a male sling. Clearly a judgement needs to be made in each case on the basis of urodynamic studies and careful patient consent. Surgical treatment for prostate cancer appears to be better than radiation therapy in terms of lower rates of mortality and metastatic disease [88]. Because OAB symptoms potentially have a significant impact on quality of life and can be difficult to treat effectively, it is important to counsel patients adequately before selecting treatment of their prostate cancer, to align patient expectations with possible treatment outcomes. The observations reviewed here emphasize the importance of adequate preoperative assessment of LUTS in addition to the patient’s cancer needs when considering radical prostate cancer treatment. Adequate postoperative evaluation, with the use of symptom scores, patient-reported outcome measures and urodynamic evaluation, is also essential.

Acknowledgements The authors would like to thank P.A. Toomey and Kathryn Nelson Emily, ELS, for assisting with preparation of the manuscript.

Conflict of Interest No funding was provided for this body of work. Christopher R. Chapple reports grants and other from

Detrusor overactivity and OAB after radical prostate cancer treatment

Allergan, Astellas and Recordati, outside the submitted work. Francesco Cruz reports personal fees and non-financial support from Astellas, grants and personal fees from Allergan, personal fees from Recordati, personal fees from Ipsen, personal fees from AMS, grants and personal fees from Janssen-Cylag, grants and personal fees from Pfizer, outside the submitted work. Mike Kirby has been paid for work with the pharmaceutical industry, but no payments were received for work on this paper. Karl-Dietrich Sievert reports grants from Medtronics, personal fees from Astellas, personal fees from Allergan, personal fees from American Medical Systems, personal fees from Neotract and grants from Naturin, outside the submitted work. Nikesh Thiruchelvam reports personal fees from Astellas and personal fees from Medtronic, outside the submitted work. Andrea Tubaro reports personal fees from Allergan, personal fees from AMS, grants and personal fees from Astellas, personal fees from GSK, other from Pfizer and other from Pierre Fabre, outside the submitted work.

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Correspondence: Professor Karl-Dietrich Sievert, Department of Urology and Andrology, SALK Universit€atklinikum/ Paracelsus Medizinische, Privatuniversit€at (PMU), M€ ullner Hauptstraße 48, 5020 Salzburg, Austria. e-mails: [email protected]; [email protected] Abbreviations: DO, detrusor overactivity; EBRT, external beam radiotherapy; OAB, overactive bladder; RP, radical prostatectomy; SUI, stress urinary incontinence.

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