Phenotyping Overactive Bladder—Part 1: Are There Different Types of Urgency and Can They be Translated to Clinical, Urodynamic and Radiological Phenotyping? ICI‐RS 2025

ABSTRACT

Introduction

Overactive bladder (OAB) is defined as urinary urgency, usually accompanied by increased daytime frequency and/or nocturia, with urgency urinary incontinence (OAB‐wet) or without (OAB‐dry), in the absence of urinary tract infection or other detectable disease. The key symptom of OAB, urinary urgency, is defined as a complaint of sudden, compelling desire to pass urine which is difficult to defer. However, patients report a range of individual experiences and sensations associated with urgency and studies have identified different types of urgency. Patients with OAB not only differ in clinical presentation, but also have different urodynamic and radiological findings. These variations may explain why OAB treatments work well for some individuals but not others. This paper investigates how knowledge can be advanced by phenotyping OAB by urgency symptom variation, and clinical, urodynamic measurements and radiological features.

Methods

A Think Tank at the International Consultation on Incontinence‐Research Society (ICI‐RS) 2025 discussed the question, “Can OAB management be improved by phenotyping if there are different types of urgency?” The group discussed the current literature on this topic and developed a list of research questions to help shape the future of the field.

Results

Clinical, urodynamic and radiological phenotyping of urgency were discussed and research studies to phenotype urgency were proposed.

Conclusion

Further research to phenotype OAB beyond the presence or absence of urgency and urgency urinary incontinence, using clinical, urodynamic measurements and radiological features, is needed. High priority research questions and strategies were defined. Advanced OAB phenotyping may guide tailored management beyond a stepwise approach, with the aim to improve therapeutic outcomes. This would validate phenotyping and is explored in Part 2 of the topic.

1. Introduction

Overactive bladder (OAB) syndrome is defined by the International Continence Society (ICS) as “urinary urgency, usually accompanied by frequency and nocturia, with or without urgency urinary incontinence (UUI), in the absence of urinary tract infection or other detectable disease.” [1, 2] Urinary urgency is the chief symptom of OAB and is defined by the ICS as “complaint of sudden, compelling desire to pass urine which is difficult to defer.” [1, 3] A Think Tank at the International Consultation on Incontinence‐Research Society (ICI‐RS) 2025 meeting discussed the question “Can OAB management be improved by phenotyping if there are different types of urgency?”. More specifically, the group discussed whether there are different types of urgency and whether they can be translated to clinical, urodynamic and radiological phenotyping of OAB. The group reviewed the current literature on this topic and developed a list of high priority research questions and strategies to help shape the future of the field and advance patient care.

1.1. Urgency

Urgency is not a single symptom, as patients report different individual experiences/sensations involving a sudden compelling desire to pass urine. There are many expert opinions about the definition of urgency and debate whether specific experiences meet the definition of urgency or OAB. The psychological aspects of urgency response conforms to the axiom, “once bitten is twice shy,” as a previous definition of urgency included “fear of leakage,” [4] and some experts feel that “fear of leakage” is an important aspect to define urgency and OAB [5]. The Think Tank discussed the definition of urgency, and specifically whether “fear of leakage” should again be included in the definition, without reaching consensus. The Think Tank recommends that the ICS Standardization Steering Committee consider this topic.

Several studies have investigated bladder sensations and urgency in patients with lower urinary tract dysfunction (LUTD) [5, 6]. For example, studies in patients with OAB have found that the sensation of bladder filling is different and varied, and includes tingling, pressure, tension and/or pain [7, 8]. There may also be more than one type of urgency: “a sudden absolute need to void” and “a slowly developing absolute need to void” have been reported [8]. Another study found that some individuals experience urgency as an intensification of the normal sensations of bladder filling, while others identify urgency as a different sensation [9]. Furthermore, one study showed that urgency events and detrusor overactivity (DO) can be triggered by personalized cues in some individuals [10], while another study found seasonal variations in OAB symptoms [11].

Together, these studies and discussions highlight the multifaceted nature of the symptom “urgency”, which is inherent to a sensation symptom as it is subjective, and many different aspects come into play that drive the experience. The current definition may be too limited as it does not cover the range of sensations which are experienced by individuals with urgency and OAB. Further investigation is needed to allow phenotyping of the symptom urgency by patient experience, clinical characteristics, and by investigational findings relating to these different sensations. Eventually, this spectrum of the symptom urgency, and its subsequent phenotyping, may guide treatment choices to improve outcomes, which is discussed in Part 2 of the topic.

1.2. Clinical Phenotyping

Clinical phenotyping of OAB implies sorting patients based on observable characteristics, in a manner that is clinically relevant [12]. This might imply etiopathological grouping, defining narrower cohorts that might respond (better) to specific therapies, or identifying patients more prone to adverse events. Such phenotyping is challenged by difficulties in capturing the subjective symptom of urgency [13]. The challenges range from differentiating the need to void urine in normal individuals from the abnormal sensations of “urgency” that are experienced by patients with OAB, to the sociocultural and linguistic differences that impact the description of its experience. Notwithstanding these limitations, characteristic features of the symptom urgency, clinical epidemiology of patients, and noninvasive investigations, can potentially be used as a first step to phenotype patients with OAB symptoms.

Urgency in its current definition is regarded as an on‐off binary symptom, whereas gradations of an abnormal need to void ranging from an increased to an intense sensation that is difficult to postpone have been defined [8, 9]. Urgency has also been recognized as multi‐dimensional with several different components including sensory intensity, perceived difficulty in ‘holding on’, suddenness, and unpleasantness [13, 14]. Of note, normal individuals seldom rate these components as ‘zero’ suggesting a range of normal sensations. Individuals with OAB may also chart different locations for their perceived sensation of urgency and this can differ between both different individuals but also on different occasions in the same individual [14]. It is unclear whether UUI should be regarded as one end of the spectrum of urgency or as an entirely different entity and whether patients with UUI (or OAB‐wet) might respond differently to therapy [15]. Urgency can also accompany voiding difficulty, especially in men. De‐obstructing prostate surgery can resolve storage LUT symptoms (LUTS) in about two‐thirds of men but it remains unclear whether this is due to relief of obstruction, or due to denervation of the prostatic urethra, or some other mechanism [16]. Pain is not uncommon in patients with urgency and has been regarded as the end of the spectrum of abnormal sensation, but patients often report a mix of urgency and pain [17, 18]. The prevalence of pain in OAB is likely to depend on whether patients are classified as bladder pain syndrome or as OAB with pain symptoms [17]. “Letting urine go”, that is a deliberate act to allow a small void that may result in relief in specific situations, especially when pain is involved, has to be distinguished from UUI [19]. The presence of pain may also influence the location of where pain or urgency are felt: suprapubic or urethral [20].

OAB may be influenced by age (child, adolescent, adult, geriatric or transition between) as well as gender [21]. Prostatic disease in men, and child‐bearing, menopause, or prolapse in women, can imply potential for different sensations and mechanisms, and differences in response [22, 23, 24]. This is important since a vast majority of patients in clinical trials are women [25]. Frailty, comorbidities, metabolic syndrome and obesity/overweight, smoking, diet, and other lifestyle aspects might all help to phenotype patients [12, 26]. Mental health, constipation, sexual dysfunction, pelvic floor dysfunction, and prior surgery (such as female and male stress UI or benign prostate surgery), and underlying neurogenic causes (outside the scope of this review) can influence the development, severity, and responsiveness of OAB [12, 23, 27, 28, 29, 30, 31, 32]. Finally, the urinary tract microbiome may influence OAB in as yet unknown ways [33].

Several biomarkers, including urinary nerve growth factor, nerve growth factor/creatinine ratio, and brain‐derived neurotrophic factor/creatinine ratio, have been studied in OAB patients [34]. Several metabolites, particularly increased serotonin level and decreased 3‐hydroxypropionic acid and 3‐indoleacetonitrile levels have been associated with nocturia and could be further studied as biomarkers of OAB‐related nocturia [35]. However, the potential in the use of urinary biomarkers in phenotyping OAB patients is currently restrained by the lack of randomized studies, concerns regarding variations in the testing kits and their accuracy, remain important limitations [34]. Questions have been also raised about the rationale for creatinine normalization of nerve growth factor and brain‐derived neurotrophic factors thought to be released from the bladder into urine by recent findings concerning adenosine triphosphate (ATP) levels in urine of normal and OAB subjects [36, 37].

Urgency is typically assessed using questionnaires, such as the International Consultation on Incontinence Questionnaire on OAB (ICIQ‐OAB) [38], that quantify the frequency of urgency episodes, the bother associated with these episodes, and the presence or absence of UUI. More detailed questionnaires [39] and other tools [7] have been developed to assess sensation and urgency.

A list of high‐priority research questions and strategies to advance clinical phenotyping of urgency/OAB are listed in Table 1.

Table 1.

High‐priority research questions and strategies to advance OAB/urgency phenotyping.

Topic	Research question	Research strategy
Clinical phenotyping	Should fear of leakage define a type of urgency and does it correlate with DO?	Qualitative research to explore whether fear of leakage should define urgency or a type of urgency and the correlation with the UDS finding of DO
	Can biomarkers effectively phenotype OAB?	Additional clinical studies to correlate potential biomarkers with UDS findings and identify range and cut‐off levels in various OAB phenotypes. Gender‐specific research is also needed.
	Can the types and locations of urgency sensations be used to phenotype OAB?	Clinical study to correlate the types/descriptions (tingling vs pressure vs pain; intensification of normal sensation or a different sensation) and locations (suprapubic vs urethral) of urgency sensations with UDS parameters (DO, terminal vs phasic) and treatment outcomes
Urodynamic phenotyping	Can new UDS analysis tools be developed to improve phenotyping of OAB?	Evaluate new, existing and combinations of UDS parameters such as timing, patterns and kinetics of DO events and area under the detrusor pressure curve, to develop OAB phenotypes
	Why does ambulatory UDS identify DO more efficiently than office based UDS and can continuous UDS assessment methods provide improved OAB phenotyping?	Use a wireless implanted pressure monitoring system [40] for ambulatory UDS studies and compare with conventional UDS. Specifically investigate the relationship between bladder fill rate and DO
Radiological phenotyping	Can brain imaging quantify subconscious and conscious sensory information related to bladder filling to reveal distinct bladder phenotypes?	Recruit middle aged individuals likely to develop OAB for a longitudinal brain MRI every two years to potentially identify brain MRI signatures of OAB at naturalistic bladder filling rates without catheterization.
	Are structural and functional changes in the brain of OAB patients secondary to structural changes in bladder?	Perform a longitudinal study combining brain MRI and bladder ultrasound imaging in individuals likely to develop OAB
	Can brain fMRI during episodes of urgency be combined with a FLASH MRI scan of the bladder to detect DO without catheterization?	Use brain fMRI and FLASH MRI scan of the bladder to probe the potential role of ureter jets in triggering DO
	Can the correlation between MRI measurements of neurodegeneration and OAB severity scores be used to identify clinically useful OAB phenotypes?	Use longitudinal DTI studies to confirm whether the observed correlation between ARWMHs and OAB severity scores indicates causation

Abbreviations: ARWMHs, age‐related white matter hyperintensities; DO, detrusor overactivity; DTI, diffusion tensor imaging; FLASH, fast low‐angle shot; fMRI, functional magnetic resonance imaging; MRI, magnetic resonance imaging; OAB, overactive bladder; UDS, urodynamics.

1.3. Urodynamic Phenotyping

Urodynamic studies are a valuable tool to further phenotype OAB, and potentially allow treatment to be tailored in a patient‐centered manner. To accurately phenotype OAB with urodynamics, it is essential to consider urodynamic test conditions, as well as both storage and voiding findings.

Patient position affects the likelihood of DO; cystometry performed in the lying position is less likely to reveal DO, and sensations of bladder filling are usually delayed [41]. The bladder filling rate (BFR) also plays a role in bladder sensations: Faster filling is associated with greater ATP release in the lumen [36, 37]. Faster sensation of bladder filling to the brain and spinal centers elicits sympathetic nerve discharge [14] to increase bladder compliance that may obscure DO diagnosis during office urodynamics [42, 43]. While constant BFR from 20 mL/min to 100 mL/min through a transurethral catheter do not seem to influence the occurrence of DO in office urodynamics of multiple sclerosis (MS) patients [44], the significance of naturalistic BFR ≤ 6 mL/min by pulsatile bilateral jets emanating from ureters is underscored by ambulatory urodynamics confirming 80% of inconclusive DO in office urodynamics [42]. Finally, fluid temperature can also impact findings: cold water leads to earlier bladder sensations, DO onset, and potentially reduced voiding efficiency [44]. As test conditions may influence (induce or block) potential urodynamic findings, it remains essential to evaluate whether the urodynamic investigation has reproduced daily‐life symptoms, and whether these symptoms can be correlated to the urodynamic findings [42].

The ICS recommends using at least three descriptors for sensations of bladder filling: first sensation, first desire to void, and strong desire to void. No normative values exist for sensations of bladder filling, as the ranges vary widely and overlap among healthy individuals [45]. Beyond the volume at which sensations occur, the kinetics of their appearance in patients with OAB have been discussed, introducing the concept of “warning volume” referring to the volume between the first sensation and the sensation of urgency. Therefore, a reduced warning volume was associated with a reduced number of sensations reported during urodynamics [41], and a higher severity of OAB on the Urgency Perception Score and Urinary Symptom Profile [43, 46].

An initial classification of DO patterns into phasic and terminal was introduced by ICS in 2002 [47]. Subsequently, three new patterns were described: compound, high and sustained, and detrusor after contraction (DAC). The former two are reported exclusively in patients with neurogenic LUTD [48]. DAC has a prevalence of approximately 13% and is more frequently observed in women. Although it is a post‐void phenomenon, DAC has been positively associated with the presence of DO [49]. Terminal DO is associated with older age, stroke, and Benign Prostatic Obstruction (BPO). In contrast, phasic DO is more common in younger patients with idiopathic DO [50]. A correlation has been described between severity of nocturia and the first phasic DO and the number of DO events; however, its clinical relevance is unclear [50]. The role of DO patterns in predicting treatment outcomes remains uncertain [51]. A recent study observed a trend toward better response to Botulinum Toxin A (BTX‐A) in patients with documented DO [52]. Another study found that DO pressures exceeding 110 cm‐H₂O were linked to poorer outcomes, suggesting that an increased BTX‐A dose might be considered in such cases to tailor treatment [51]. These findings highlight the potential value of DO characteristics in guiding individualized therapy, though further research is needed.

Urethral pressure variations (UPVs) are associated with detrusor contractions via an uncontrolled micturition reflex, where a fall in urethral pressure is the prelude to an uninhibited detrusor contraction [53]. They are significantly linked to DO, particularly in females. A contributing factor is high basal urethral tension, likely resulting from sympathetic overactivity. Therefore, treatment with β₃‐adrenergic agonists and alpha‐blockers has been used. The former has shown a significant reduction in UPVs [54]. Similarly, sacral nerve stimulation, by altering pudendal and sympathetic neural pathways, may reduce the frequency and severity of UPVs [55]. These findings suggest that UPVs may serve as a marker representing a specific DO phenotype.

Low compliance is a predictor of poor response to BTX‐A [56], reinforcing the idea that it may constitute a separate subgroup requiring different treatment strategies. However, compliance is affected by the rate of bladder filling [37], thus complicating phenotyping using compliance measurements, unless filling rate is standardized.

DO associated with voiding dysfunction may represent a distinct pathophysiological phenotype, possibly linked by shared degenerative pathways, particularly with ageing. While bladder outlet obstruction (BOO) has been associated with DO [57], no definitive pathophysiological study has yet confirmed a direct cause‐and‐effect. In some patients, DO persists after BOO surgery. Identified predictive factors include age over 65, a low maximum cystometric capacity (< 250 mL), DO amplitude greater than 40 cm H₂O, and an early onset of the first DO contraction [58]. These factors may reflect the extent of detrusor injury and suggest irreversible functional changes. However, a retrospective study showed that males with BOO had a similar therapeutic response to BTX‐A [52]. This indicates that despite potential differences in pathophysiology, patients still respond to standard DO treatments.

Regarding the concordance of DO with detrusor underactivity (DODU), it is significantly more prevalent in older men while still being present in 9% of those under 40 [59]. Patients with DODU were found to have a thicker bladder wall, lower DO amplitude, and a higher median bladder contractility index compared with those with isolated DU, as well as less BOO [59]. These findings support the concept that DODU is not merely a random overlap of dysfunctions but rather may reflect a distinct clinical and urodynamic profile.

Different urodynamic findings can be found in patients with OAB. Differences in reported sensations of bladder filling, DO presence and patterns, bladder compliance, urethral pressure variations, and maximum cystometric capacity have been reported during filling cystometry in patients with OAB, and some could be related to clinical patient characteristics. The possible relationships between UD features and the different sensations of urgency remains a high priority area of research needed to allow extensive patient profiling. Furthermore, findings during pressure‐flow studies may further complete the profiling as specific voiding dysfunctions have been associated with OAB.

A list of research questions and strategies to advance urodynamic phenotyping of urgency/OAB are listed in Table 1.

1.4. Radiological Phenotyping

A substantial challenge related to bladder sensations is to understand how the continuous afferent traffic sent from the LUT to the spinal cord underpins the intermittent sensations experienced by the individual. The exacerbation of urgency with the progressive demyelination in multiple sclerosis (MS) [60], marked by age‐related white matter hyperintensities (ARWMHs) [61], affirms the role of unmyelinated afferent nerve endings in transmitting the graded sensation of urgency [36, 37] Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a potential tool for objective phenotyping of urgency [62]. The differences in fMRI signatures of urgency evoked by water loading [62] and by a filled bladder during urodynamics [63] underscore the significance of naturalistic BFR < 6 mL/min from bilateral pulsatile ureter jets and constant stream of higher BFR > 50 mL/min from catheter also triggering urethral discomfort alongside urgency in the brain. Given that ambulatory urodynamics relying on naturalistic BFR < 6 mL/min from pulsatile ureter jets can more efficiently detect DO than catheter‐based invasive urodynamics [42], a research question for a cross‐sectional study can be comparing T₁ weighted bladder scan [64] after water loading to probe the role of ureter jets in triggering DO relative to DO observed during office‐based urodynamics. The question is relevant as office‐based urodynamics failed to discern the therapeutic effect of cannabis on urgency of MS patients [60], which foreshadowed the questions over relevance of invasive urodynamics in treatment decision making for OAB patients [51].

A graded rise of urgency in OAB‐dry patients [62] who voided higher urine volume after BOLD‐MRI, exhibited correlation with the increased connectivity of the dorsal attention network to the primary somatosensory cortex, anterior insula, para hippocampal gyrus, and the hippocampus, which is consistent with connectivity patterns recorded at constant BFR of > 50 mL/min with urethral discomfort in UUI patients (OAB‐wet) patients [63]. The thalamus is a central hub for processing and directing sensory information to the cerebral cortex during conscious perception. This represents an enormous amount of information, and salience network of brain prioritizes the relay of afferent information to the cerebral cortex to ensure it is not overwhelmed.

The insula, a deep brain structure located within the lateral sulcus, is the critical hub of the salience network, accountable for shifting the individual's attention from autopilot mode of the default mode network, responsible for the imagination and introspection to the goal‐oriented behavior in response to the most important external and internal stimuli such as a filled bladder propelling the search of nearest toilet. The insula seen in diffusion tensor imaging (DTI) behaves like a movable pivot of a weighing scale that adjusts the afferent signal intensity before the emotional valence (weight) of urgency is registered in the hippocampus, the memory hub [65], after the brain senses the voiding interval [43, 66]. Hence, as a normal bladder gets close to its functional capacity, the increasing sensory information will increase its prioritization. Accordingly, pathophysiological processes affecting the volume of sensory traffic from the LUT could be sufficient to trigger its relay to the cortex, giving rise to the abnormal sensation of urgency (e.g., due to excessive non‐micturition contractions or lower urinary tract inflammation). This process can be referred to as “afferent push”. Alongside this, planning ahead by centers in the cerebral cortex may include consideration of functions such as anticipated need to pass urine after the last voiding event [66]. This would generate a need‐to‐know current state of bladder filling, meaning that the cortex seeks the information which could be considered an “afferent pull”. Decreased activation of the insula correlated with the symptomatic relief from intra‐detrusor injection of BTX‐A [63]. fMRI of OAB patients with UUI revealed weaker connectivity of the default mode network with the salience network and weaker directed connectivity with the fronto‐parietal network which is consistent with longer lag time and higher first sensation of urine volume in controls during office urodynamics [67].

The memory of recent UI episodes can conjure fear of leakage, which heightens urgency, and fear of leakage was mapped to the activity in periaqueductal gray (PAG) and prefrontal cortex [63]. PAG is a midbrain hub for integrating and supposedly modulating sensory information, especially pain. It has a significant contribution in LUT mechanisms so the possibility of PAG modulation of LUT sensation is worth considering [68]. Scientific testing of such processes will be enormously challenging. Nonetheless, early development of an in vivo neuroimaging template of brainstem nuclei for understanding of human brainstem function and pathology has been reported [69]. Hence, the relationship between subconscious sensory information and consciously perceived sensation can foreseeably be evaluated.

At any given time, certain afferent information streams may be prioritized, such that the person becomes consciously aware (“sensation”) of what is otherwise purely subconscious sensory information. This may be a factor in the intermittency of experienced LUT sensations, and potentially could introduce a psychological influence, increasing likelihood that LUT sensations will be experienced. Hence, a psychological factor can influence the likelihood of a person developing OAB.

A DTI study of OAB patients with UUI found a correlate of ARWMHs, lower fractional anisotropy in white matter tracts (anterior thalamic radiations, superior longitudinal fasciculus and corpus callosum) relative to age‐matched controls without UUI [70]. After age and sex adjustment, the study found a modest, inverse correlation between fractional anisotropy in the left inferior fronto‐occipital fasciculus around left insula, left internal capsule, and pons and cerebellum with OAB questionnaire responses. However, longitudinal DTI studies are needed to confirm whether the observed correlation hints at causation between ARWMHs and OAB questionnaire responses [70]. Furthermore, recent innovations in portable ultra‐low field MRI [61] may enable routine clinical phenotyping of OAB and ARWMHs.

The discussion of imaging technologies by this Think Tank focused primarily on fMRI. However, a variety of other imaging‐based approaches may also prove useful for phenotyping OAB [71, 72], including ultrasound measurement of bladder wall thickness [73] and ultrasound bladder vibrometry. For example, ultrasound bladder vibrometry correlates with detrusor pressure and compliance and may detect detrusor overactivity with 70%–75% sensitivity and specificity [74], though current evidence is limited and lacks standardized protocols.

A list of research questions and strategies to advance radiological phenotyping of urgency/OAB are listed in Table 1.

2. Conclusion

The development of OAB phenotypes based on urgency type, patient characteristics, other symptoms, urodynamic findings, and imaging was discussed. This topic produced very interesting debate, with many opinions and hypotheses. These hypotheses require considerable research effort to improve our understanding of OAB and its possible phenotypes. High priority research questions and strategies to improve OAB phenotyping are listed in Table 1. Part 2 of this topic discusses how improved phenotyping may lead to more personalized and effective treatment outcomes.

Author Contributions

All authors contributed to the writing and editing of this manuscript.

Ethics statement

The authors have nothing to report.

Consent

The authors have nothing to report.

Conflicts of Interest

John E. Speich—no relevant disclosures. D. Carolina Ochoa—no relevant disclosures. Pradeep Tyagi—inventor of liposome technology licensed to Lipella Pharmaceuticals and consults for Vensica Therapeutics. Apostolos Apostolidis—consultancy for IPSEN; speaker honoraria by Astellas and Medtronic; educational grants by ARITI SA. and DEMO S.A. Sanjay Sinha—no relevant disclosures. Claire Hentzen—no relevant disclosures. Marcus Drake—trustee of the International Continence Society, speaker/advisory board for Astellas, Viatris. Paul Abrams—no relevant disclosures. Alan J. Wein—no relevant disclosures. Michel Wyndaele—speaker for Astellas, Hollister, Wellspect. Consultant for Coloplast, Medtronic, and Pierre Fabre.

Data Availability Statement

This study did not include data collection or analysis, so there are no data to make available.