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XXIIIrd Congress of the European Association of Urology

Milan, Italy / March 26-29, 2008

The recent International Continence Society definition of overactive bladder (OAB) is based on the presence of urgency, that is, the complaint of a sudden, compelling desire to pass urine which is difficult to defer, with or without urgency incontinence (Abrams et al. Neurourol Urodyn 2002;21:167-78). Urgency is usually but not necessarily associated with frequency and nocturia. As Prof. Paul Abrams, University of Bristol, UK, explained, “This sensation is very different to the sensation of filling and desire to void… it comes suddenly and it varies in intensity.” Although the exact pathophysiological mechanism is not well understood, Prof. Abrams added, “This is a real phenomenon.”

Patient Perspective

From the patient point of view, urgency can have a highly negative impact on quality of life. According to Prof. Piotr Radziszewski, Medical Academy of Warsaw, Poland, patients complain that “I can’t live a normal life anymore, my sex life is ruined, I have lost my job because of frequent urination... or I don’t remember when I slept normally.”

Despite these negative effects, patients often do not consider symptoms worthy of medical attention, partly because they develop gradually. Initial symptoms such as increased frequency and going to the bathroom at night may go largely unnoticed or be seen as part of the aging process. However, “When urgency develops, it is more noticeable and difficult to rationalize and so more unsettling,” explained Prof. Radziszewski. Even when patients recognize they have a problem, however, they may be too embarrassed to discuss it with their physician if he or she is not sufficiently proactive.

Urgency can induce harmful adaptive behaviour in patients such as restricting fluid intake or discontinuing medication associated with incontinence, with the consequent negative effect on health. Social activities may be limited, leading to decreased well-being and increased isolation. Reduced intervals between voiding may lead to lost productivity at work, and sleepless nights due to nocturia may lead to daytime sleepiness. Patients’ sex lives may also be affected—52% of sufferers reported a decreased interest in sex—with consequent personal problems.

Patient Expectations

Patients are generally realistic about the outcomes of treatment—only 17% expect a complete cure whereas 43% expect good improvement. However, only 14% consider that treatment for life is acceptable, perhaps reflecting the fact that patients are unwilling to consider OAB as a life-long condition.

When patients come to the office, Dr. Marc Toglia, Urogynecology Associates of Philadelphia, Pennsylvania, suggested, “It is important to objectively document the symptoms such as urgency, incontinence, nocturia.” Physicians should also recognize and treat contributing factors such as urogenital atrophy, pelvic organ prolapse, urinary tract infections and prostatic obstruction. Given that the drop-out rate for treatment with muscarinic antagonists is relatively high in the first four to 12 weeks, Dr. Toglia asserted that physicians should impress on patients “that this process has been going on for a long time and therefore the correction may be somewhat slow and they should not give up if there is no improvement in the first week or two.” The patient should also understand that treatment is multimodal, and that medication alone is less likely to provide a satisfactory outcome.

Measuring Urgency

Measures of efficacy such as frequency and “all-or-none” type measures such as urgency incontinence are relatively easy to carry out. “Urgency, on the other hand, is harder to determine both in practice and research,” noted Dr. Toglia. It can be determined objectively, for example, from a patient-completed voiding diary or by measuring warning time, or subjectively using instruments that assign subjective grades to urgency.

Although many physicians may be reticent about such tools in clinical practice and prefer patient self-reporting of symptoms, Dr. Toglia pointed out, “The goal is not necessarily a cure but rather symptom reduction... and sometimes a patient may remember the worst symptom and think they are not improving, even though the frequency of symptoms has decreased.” Perhaps the easiest tool to use in clinical practice is the Urgency Perception Scale (UPS), which uses very simple language and contains three categories. In research studies, another tool is the five-category Patient Perception of Intensity of Urgency Scale (PPIUS).

Consolidating Objective and Subjective Measures

VENUS (Vesicare Efficacy and Safety in Patients with Urgency Study)—conducted in 16 centres in the US—used urgency (reduction in urgency episodes/24 h) as the primary outcome measure for comparing the muscarinic antagonist solifenacin (5 mg or 10 mg flexible dosing) and placebo (Serels et al. Urology 2006;68(suppl 1):72 abstr MP-04.11). In the active treatment group, the mean number of urgency episodes decreased from 6.15 at baseline to 2.24 at week 8 compared to a decrease from 6.03 to 3.30 for placebo (P<0.0001). For the subjective measure (UPS), treatment was also effective—the proportion of patients who were able to finish their task upon experiencing urgency increased from 11.7% at baseline to 46.1% after 12 weeks.

Warning time is another important measure, given that a small improvement can make the difference between whether or not a patient can reach the toilet in time. In the VENUS study, treatment with solifenacin increased median and mean warning time by 31.3 sec and 186 sec, respectively. According to market research, 43% of patients considered this an important outcome, 20% noted it would mean a lot and 16% remarked they would have more confidence, so extra warning time is clearly important to patients.

SUNRISE (Solifenacin for Urgency of OAB in a Rising Dose Efficacy Trial) was also based on urgency and compared solifenacin (5 mg or 10 mg) with placebo, with subjective measure (score on PPIUS questionnaire) as the primary study objective (Cardozzo et al. Neurourol Urodyn 2006;25(6):abstr 281). For the active treatment group, the decrease in perceived urgency severity was 60% compared to 33% for placebo (P<0.0001). “So patients are sensitive to differences in severity,” concluded Dr. Matthias Oelke, Department of Urology, Academic Medical Centre, University of Amsterdam, The Netherlands. The reduction in urgency bother on a visual analogue scale was significantly greater with solifenacin than placebo (35.1% vs. 25.4%, P<0.0001). Moreover, “The treatment satisfaction correlated very strongly with the perception of urgency bother, indicating that patients equated reduction in bother with treatment satisfaction,” noted Dr. Oelke.

An important question is whether treatment success can be estimated accurately in clinical practice. The results of the EOS (Evaluation of Solifenacin) study, performed in 50 centres in Belgium with full data from 227 patients, suggest that this is indeed the case. An interesting aspect of this study was that it evaluated changes over time of both patient and physician perception of treatment benefit. At four weeks, 42% of patients thought that treatment was very beneficial compared to 48% of physicians. “So we have a difference between the judgment of the patient and that of the physician, and this difference is statistically significant,” noted Dr. Oelke. However, after eight weeks, no differences were apparent. This suggests that physicians should be prepared to listen to their patients and work with them to achieve success.

Summary

OAB is a distressing problem that negatively affects the health, quality of life and productivity of sufferers. The driving symptom is urgency, and if this can be managed, many of the other associated symptoms will improve. The underlying pathophysiology will usually have been developing over a long period of time, therefore patients should not expect a quick pharmacological cure. Nevertheless, muscarinic antagonists in combination with nonpharmacologic interventions can significantly improve symptoms, particularly if patients manage to adhere to treatment in the long term.