By Ass. Prof. Malte Rieken (Basel, CH)
This article reflects the highlights of the lecture Ass. Prof. Malte Rieken gave at the EAU20 Virtual Congress on Saturday 18 July. His presentation can be found in the EAU20 Resource Centre.
Lower urinary tract symptoms (LUTS) are highly prevalent in men over 50 years and can be divided into storage, voiding, and post-micturition symptoms. As LUTS can severely impact quality of life, a treatment approach which takes the aetiology of the condition into account seems most promising. While LUTS have traditionally been related to bladder outlet obstruction (BOO) caused by benign prostatic enlargement (BPE), increasing evidence relates LUTS to bladder dysfunction, such as detrusor overactivity (DO) and/or overactive bladder syndrome (OAB). In this context, it is important to explore reasons as well as strategies for the management of patients suffering from persisting OAB symptoms following surgical de-obstruction.
Overactive bladder syndrome is characterised by increased frequency and urinary urgency and can be accompanied by urge urinary incontinence. In contrast, DO is defined as involuntary contractions of the detrusor during the filling phase of the bladder and is observed during urodynamics. Importantly, only around 50% of patients with OAB show DO. In men with BPE, cystometric studies revealed DO in 50-75% of men and a meta-analysis demonstrated DO with a mean prevalence of 60.2%1. The prevalence of DO is associated with grade of obstruction and increases from 51.4% in Schäfer class 0 to 83.3% in Schäfer class VI1. In addition, DO was also associated with increasing age.
OAB symptoms after BPO surgery
When assessing the rate of OAB symptoms after BPO surgery, it is important to adhere to appropriate terminology. Early postoperative storage symptoms, which are often new in onset, are generally summarised under the term ‘dysuria’ and are usually associated with postoperative wound healing, inflammation, and pain2. These are usually short-term (less than 3 months) and self-limiting. In contrast, patients with preoperative OAB and/or DO with persisting symptoms define a distinct clinical entity.
Transurethral resection of the prostate (TURP) is the most studied surgical treatment in men with OAB symptoms. In a study with 46 patients undergoing TURP, DO was present in 26 (56%) men preoperatively. Of those 26 men, 16 (62%) had a resolution of DO while 10 (38%) were suffering from DO at 12 months postoperatively3. Postoperatively, DO did not develop in any patient who did not have DO preoperatively3. Another study on 116 men analysed persisting OAB symptoms six months following TURP and found 33 (28%) men to have persisting symptoms4.
The persistence of DO has also been investigated in patients undergoing HoLEP. In a prospective study in 165 patients, symptoms and urodynamic parameters were analysed prior to and 6 months after HoLEP. The rate of patients with DO decreased from 45% preoperatively to 36% after HoLEP5. In contrast, bladder compliance did not improve. Another study on the effect of HoLEP on patients with DO found that at 6-months follow-up, more patients in the DO group were taking anti-muscarinics compared to patients without preoperative DO (48% vs. 21%)6.
Aetiology of OAB symptoms after BPO surgery
The pathophysiology of DO in men with BPO remains to be fully elucidated. There is a hypothesis involving a three-stage model of BPO-induced bladder remodelling. It consists of:
- hypertrophy, characterised by an increase in collagen production which may play a role in decompensation of bladder function;
- compensation, which is characterised by increased detrusor contractility during the voiding phase and often combined with DO;
- decompensation, which is characterised by detrusor underactivity7.
Neurotrophins may also play a relevant role in DO pathophysiology. Nerve growth factor (NGF) is a signalling protein produced by detrusor smooth muscle cells and bladder urothelial cells8. In a recent study on patients undergoing TURP, urinary NGF was associated with preoperative as well as postoperative OAB symptoms8. In addition, various other mechanisms, such as changes in detrusor muscle calcium-activated chloride channels activity, ischemic-induced variations in response to neurotransmitters of the urothelium and detrusor muscle, and the nitric oxide pathway may play a role in detrusor dysfunction following bladder outlet obstruction2.
“A patient-centred and symptom-focussed approach is crucial for the management of persisting OAB symptoms”
Risk factors behind persisting OAB symptoms
Several studies were able to identify preoperative risk factors behind persisting OAB symptoms after prostate surgery.
In the study of Antunes et al., maximum cystometric capacity (MCC) of less than 250 ml preoperatively was associated with persisting DO. While DO persisted in 64% of patients with MCC less than 250 ml, in patients with MCC greater than 250 ml DO was observed in only 20% of men3. When combining low preoperative MCC with prevalence of DO amplitude > 40 cm H20 and early DO, the chance of persisting DO after TURP was 83.3%3. These results are supported by another study on persisting OAB symptoms after TURP, which found that the preoperative degree of initial storage symptoms on IPSS, small bladder capacity, impaired detrusor contractility, and age were associated with persisting OAB symptoms4. In contrast, a recent systematic review and meta-analysis showed that preoperative DO was not associated with improvement of IPSS, QoL, Qmax and PVR after transurethral BPE surgery9. In a population-based cohort study on 4,887 men who underwent TURP, the association of diabetes mellitus and outcomes of TURP was analysed. Although the data do not contain any information on symptom scores or urodynamic investigations, the higher rate of DM patients with continuing medication of anti-muscarinics or alpha-blockers is suggestive of a detrimental effect of DM on bladder function10.
Treatment strategies persisting OAB symptoms after BPO surgery
Evidence from trials is very limited in patients with persisting OAB symptoms following transurethral BPO-surgery. Ideally, a cohort of patients with preoperative well-defined OAB symptoms or verified DO should be followed for a minimum of 6-12 months to investigate any meaningful and persisting effect of an intervention or medication.
A prospective randomised trial comparing the effect of tamsulosin with the combination of tamsulosin and solifenacin or no additional medication after TURP did not show any additional LUTS improvement during 8 weeks follow-up11. In another prospective randomized trial, tolterodine 2 mg twice daily lead to a significant reduction of storage LUTS (assessed by IPSS subscores) at 4 weeks after TURP compared to placebo12. This could mean that presurgical use of anti-muscarinics is associated with the highest risk of continuing medication following transurethral prostate surgery13. Pelvic floor muscle exercises after TURP lead to a significantly higher reduction in storage LUTS (assessed by IPSS subscores) as compared to TURP alone14.
“In persisting cases of DO, onabotulinum toxin A injections should be taken into consideration.”
Lack of evidence
Given the lack of high-level evidence, a patient-centred and symptom-focussed approach is crucial for the management of persisting OAB symptoms. A thorough clinical assessment as well as urodynamic studies in selected cases are cornerstones in establishing causes of persisting OAB symptoms. Anti-muscarinics and the β-3 agonist mirabegron can be used as oral medication2. Pelvic floor muscle exercises alone or in combination with medication may be of benefit. In persisting cases of DO, onabotulinum toxin A injections should be taken into consideration.
The persistence of OAB symptoms after transurethral prostate surgery is a common clinical scenario. Bladder remodelling from chronic bladder outlet obstruction may lead to persisting bladder dysfunction after adequate de-obstruction. Preoperative predominant OAB symptoms, preoperative DO and older age have been identified as risk factors. In case of persisting OAB symptoms, a thorough clinical investigation, including urodynamics in selected cases, should be performed to identify potential causes and select for adequate treatment. Pharmacotherapy with anti-muscarinics or β-3 agonist, pelvic floor muscle exercises or onabotulinum toxin A injections may be used for treatment. Further studies are necessary to provide high-level evidence on the best treatment approach to improve quality of life in this heavily burdened cohort of patients.
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