4.1 Introduction

This chapter introduces the scope of evaluations used to reinforce the evaluation derived from clinical history and examination. These may include relevant tests if there is suspicion that all may not be as it seems, i.e., that the presentation with LUTS could actually reflect something serious, the ‘red flag’ scenarios; here the professional needs to be willing to divert care along an entirely different path and potentially refer to colleagues to pin down the exact nature of the situation.

Many questionnaires are now available of particular interest and developmental quality for the broad assessment of LUTS, the impact of LUTS on HRQL and those that target specific urological conditions. Factors which should be considered when choosing a PRO include its context of use (the condition and population to be measured), its measurement properties, the logistics surrounding its administration and other recommendations from regulatory bodies. However, there is no substitute for the location of the instrument from the developer and the careful review of its content, for an informed decision when selecting a PRO measure for research or clinical practice.

In clinical practice, a rough estimate of prostate volume can be made by DRE. This may influence choice of treatment (for medication and operation). However, the method generally underestimates the true size of the gland, and it is best suited to identify large prostates. Serum PSA value correlates well with prostate volume, and in theory, the marker provides an easy estimate of prostate volume. However, PSA has important implications in prostate cancer detection, which complicates its use in LUTS. This means that ultrasound is the modality of choice when measuring prostate volume. In this regard, the transrectal approach is more precise than transabdominal ultrasound. MRI provides an even more precise measurement of the prostate volume, but it is not routinely used in benign prostatic hyperplasia.

Free flow rate (FFR) testing is an important tool in the initial assessment of patients with lower urinary tract symptoms (LUTS). Due to the noninvasive nature of the test and the relatively low-cost equipment required for it, FFR testing is one of the simplest urodynamic tests. Although FFR or urine flow rates are rarely diagnostic, they can provide valuable information pertaining to patients’ voiding and storage symptoms.

Urodynamic assessment can identify dysfunction of the lower urinary tract in both the storage and voiding phases. It is the only way of accurately differentiating voiding symptoms due to bladder outflow obstruction (BOO) from those due to detrusor failure. Various guidelines are in place to help identify those who warrant urodynamic assessment. Urodynamics should be performed by an individual trained in interpretation of the urodynamic trace, and with a clear question to answer in mind. Test conditions should be kept as close to normal for the patient as possible in order to gain optimal study results. Free flow, filling cystometry and pressure flow studies should all be assessed. On occasion, they are done with the addition of special tests such as video studies and urethral pressure profiling. For some patients, the urodynamic question cannot be answered with standard cystometry—either the symptoms were not reproduced, or extra information is required. In these cases, special urodynamic tests can be undertaken, notably ambulatory testing. Artefacts may be experienced during the trace, which can alter the interpretation, and therefore they need to be accurately identified and noted at the time. Noninvasive urodynamic techniques have been developed, mainly concerned with attempts to diagnose bladder outlet obstruction noninvasively. The overall message about the value of noninvasive urodynamics remains unclear.

4.2 ‘Red Flags’

4.3 Symptom Assessment Tools

The overlap of symptoms from different lower urinary tract and voiding disorders can present a challenge for clinicians to ascertain a clinical hypothesis by history taking alone. However, there are a few ways by which a clinician may objectively capture a patient’s experience in order to formulate treatment strategies. The urinary diary (includes the frequency volume chart and bladder diary) allows a patient to record and self-report their symptoms as they occur and is accepted as an integral tool in the initial assessment of LUTS. When completing a bladder diary , the patient records information such as fluid intake, voided volume, the time of micturition and other symptoms for a few days before their visit to their clinician [3]. Clinician-completed questionnaires are available [4, 5]; however, these are not widely used, as it has been shown that interviewer administration can introduce potential bias when assessing patient responses [6, 7]. Patient-centered questionnaires are increasingly recognised as the most important way of reviewing symptoms and their impact from the patient perspective [8, 9]. A patient reported outcome (PRO) is defined by the U.S. Food and Drug Administration (FDA) as ‘any report of the status of the status of a patient’s health condition that comes directly from the patient, without interpretation of the patient’s response by a clinician or anyone else’ [10]. Over the last 20 years, there has been a large growth in the number and scope of available PRO measures for the assessment of LUTS, and their impact on health-related quality of life (HRQL). The following chapter will give an overview of the design and validation of PROs, discuss the choice of appropriate instrument and review some of the important instruments that are available for use in research and clinical practice.

PROs, or the synonymously termed patient-reported outcome measures (PROMs), enable the capture of the subjective patient experience in an objective and measurable way. They are recognised as providing valuable information of symptoms, signs and impact on quality of life and to allow assessment of change during ongoing clinical evaluation, research or as outcome measures in clinical trials. PRO measures tend to be structured as a series of simple questions (or items) with fixed responses which patients are able to understand and answer quickly and easily. The patient is asked to remember information about perceived severity of symptoms or impact on quality of life over a recent period of time known as a ‘recall period’. The questions include a series of possible answers (response options) which allow the patient to indicate the frequency or severity by which they experience a particular symptom or impact on quality of life. These response options are usually assigned points from low to high severity, which allows the calculation of an overall symptom score. Through multiple administrations of the measure, it is therefore possible to monitor the ongoing progress of a patient, to formulate clinical hypotheses and manage treatment accordingly.

4.3.1 Development and Validation of PRO Measures

The development of a PRO questionnaire is a detailed and lengthy process involving numerous substudies, designed to demonstrate that the PRO is measuring what it is intended to measure [11–14]. Figure 4.1 gives an overview of the main steps involved. There are three main measurement (psychometric) properties a questionnaire must demonstrate in order that users may have confidence in the measurements that are made: [14, 15]

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  Validity—does the instrument measure what it claims to measure in the population of interest?

  
  
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  Reliability—does the instrument measure concepts over time in a consistent and reproducible manner?

  
  
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  Responsiveness—is the instrument sensitive to treatment outcome following intervention?

The first two, validity and reliability, are traditionally considered the fundamental characteristics that a PRO instrument must possess [14, 16, 17]. The questionnaire must be shown capable of measuring the symptoms or health-related quality of life aspects in an accurate (valid) and stable (reliable) manner [11, 13, 14]. One aspect of validity is content validity. This refers to whether the PRO instrument covers all relevant content, without omitting any important issues, but also excluding any irrelevant items [11, 14, 18]. Content validity is supported by direct patient input from the relevant clinical population using qualitative research methodology when the PRO is being developed, usually by semistructured interviews [19]. Task force reports by the International Society of Pharmacoeconomics and Outcomes Research (ISPOR) provide detailed recommendations for the demonstration of content validity in new instruments, including the development and refinement of new items by cognitive interviews [19, 20]. The third property, responsiveness (or sensitivity to change), is important if a questionnaire is to be used in clinical applications as an outcome measure to detect change in a patient’s condition. Responsiveness to change can be evaluated using percentage change in total score before and after an intervention of known efficacy. A minimally important difference (MID) can also be calculated to describe the smallest change deemed clinically useful as measured by the questionnaire [21].

Selecting PROs for Clinical Practice, Clinical Trials and Research Studies

As there are many PRO measures available for the assessment of LUTS, how does one select which is most appropriate and relevant?

1. 1.
   
   
   

   Use questionnaires that have been rigorously developed and validated.

   
   

   The 6th International Consultation on Incontinence (ICI) 2016 (committee 5B) reviewed the available evidence or the psychometric properties for published self-completion questionnaires [8]. The result was a comprehensive publication and review of the measurement properties and status of validity of the published PROs relating to the assessment and screening of LUTS, and other measures relating to urgency, faecal incontinence and associated sexual function. Each questionnaire reviewed by the committee received a grade A to C based on the documented evidence of the reliability, validity and responsiveness of the questionnaire. The grading of A is given if there is ‘published evidence of validity, reliability and responsiveness to change’ and are ‘highly recommended’. Grade A+ is awarded if there is additional evidence of content validity (i.e., evidence of patient involvement in the item development process). The grading of B and C is given if there is less evidence of validity or reliability and is consequently referred to as ‘recommended’ or ‘have potential’, respectively.

   
   
    
   
   
2. 2.
   
   
   

   Consider who (target population) and what is being assessed.

   
   

   If the intended population is of a particular demographic (e.g., gender, age or cultural origin), this will influence the choice of instrument or mode of administration. A questionnaire may also have to be linguistically validated if translated for a multinational study or for use in multicultural populations [22]. PRO instruments may be generic or condition-specific. Generic measures are designed to measure multidimensional attributes (e.g., emotional, physical and social aspects) which can be applicable to a broad range of populations or conditions [23]. Condition-specific measures have been developed and validated for use in a specific condition and population and are the focus of this chapter. The type of PRO selected is influenced by the population or outcome which is to be measured. However, both types of PROs are often selected for concurrent use in clinical trials or research, to maximize the breadth and depth of the information which is captured.

   
   
    
   
   
3. 3.
   
   
   

   Consider the content and logistics of administration.

   
   

   Familiarity with the content, layout, scoring system and burden on patients is essential to an informed choice. The length of time an instrument takes to complete is particularly important to consider if an instrument is to be completed in a clinical setting, or administered multiple times. Administration using an electronic interface such as an iPad can have several advantages, such as the reduction of data entry workload and accuracy [24, 25], and usually have high patient acceptance [26]. However, while scores from traditional paper-based versions be equivalent, this cannot be assumed [27], so a validated electronic version should be sought from the instrument developer.

   
   
    
   
   
4. 4.
   
   
   

   Has the questionnaire been successfully used and is it recognised by regulatory bodies?

   
   

   There are considerable advantages if the questionnaire has already been successfully used in clinical practice or research studies in the countries where it will be administered. For example, patient-reported symptom assessment tools are recommended in guidelines for initial investigation of patients presenting with LUTS and incontinence by the UK National Institute of Clinical Excellence (NICE). The regulatory requirements for the intended use of the instrument should be also considered. For example, if the PRO measure is to be used in clinical trials, the extent to which their published properties comply with the standards required by the U.S. FDA: ‘Guidance for industry for PRO measures: use in medical product development to support labeling claims’ [10].

   
   
    

4.4 Bladder Diaries

Frequency refers to the number of voids observed in a defined time period, and this is most reliably identified by asking the patient to complete a record. The simplest is a micturition time chart, which records only the times of micturitions for at least 24 h [60]. A frequency volume chart (FVC) also records the volumes voided, as well as the time of each micturition, day and night, for at least 24 h. A bladder diary is the most informative, as it records the times of micturitions and voided volumes, and additional information which can be selected to give the most important features for the patient being investigated. The type of information could include fluid intake, incontinence episodes, pad usage, the degree of urgency and social activities. Instructions need to be clear, and patients must be encouraged to write in waking and sleeping times, as these are often overlooked—which makes interpretation difficult.

Interpretation requires a systematic approach, and a checklist of parameters can help (Fig. 4.2). An example of how to derive the values is given in Fig. 4.3.

24-h (or ‘global’) polyuria is th e measured production of more than 2.8 L of urine in 24 h in adults [63]. Nocturnal polyuria (NP) is present when an increased proportion of the 24-h output occurs at night. For the case illustrated in Fig. 4.3, the nocturnal polyuria index was 43%—being above a third (33%), that does indicate this patient had NP. If polyuria or nocturnal polyuria is present, the observation of a high voiding frequency may reflect a cause other than lower urinary tract dysfunction, notably behavioural factors such as a high fluid intake, or a medical condition affecting fluid balance. An example of 24-h polyuria is illustrated in Fig. 4.4; importantly, this patient was not intentionally drinking excessively due to a mistaken impression that high fluid intake is healthy. The patient was actually losing water as a result of diabetes insipidus (DI) , meaning they had to drink a lot to avoid severe dehydration. For this reason, fluid advice to restrict intake must not be given if the patient responds in the affirmative when asked about constant thirst; review is needed beforehand to check for DI.

A diary that includes fluid intake and urine output measurement generally shows the former exceeds the latter each day (the difference is because some water is lost in the breath and some in the faeces, neither of which is measured for the diary). However, on some days, there may be fluid output greater than intake. Such discrepancies generally even out if the diary is completed over a longer time, but it could be a consequence of failure to fill in the diary accurately, or eating foods with a high liquid content (salad, fruit, soup or pasta).

From a bladder diary, abnormalities in the circadian rhythm of urine production may be detected, and psychogenic voiding patterns might be identified. In addition, it has been shown that certain patterns suggest particular types of bladder or urethral pathology (Table 4.3) [64].

Table 4.3

Classifi cation of bladder diaries [60]

4.5 Free Flow Rate Testing

Multiple sources recommend urine flow rates as a baseline assessment for individuals experiencing LUTS [1]. Within the clinical setting, these tests can also be useful in patients for whom pressure flow studies have provided inconclusive or abnormal results—such as unusual flow patterns or incomplete bladder emptying. They may also have a role in the monitoring of patients started on anticholinergic medications, who have a history of difficulties emptying and postvoid residuals. Although fairly universally accepted as a standard assessment for patients with LUTS, the true predictive value of free flow rate tests (FFRs) is still to be debated. Further research into the parameters recorded and their cutoff values are essential for informing practice guidelines.

4.5.2 Parameters Assessed

The most valuable information obtained from urine flow rates comes from comparing multiple, consistent and representative voids. Urine flow rate is usually displayed graphically and described in terms of parameters such as volume voided, maximum flow rate (Q _max), flow time and pattern of flow. A good report is one which accurately describes the observed parameters in conjunction with the clinical history and bladder diary.

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  Voided volume—this is the volume of urine that the patient passes into the flow meter and is commonly presented on a flow rate nomogram.

  
  
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  Maximum flow (Q _max)—normal ranges have been set through the collection of voiding data from large populations of asymptomatic individuals. Maximum flow rates can be presented on nomograms whereby the relationship with voided volume is examined. When Q _max is significantly lower than expected, there are a number of possible explanations; bladder outlet obstruction, poor bladder contractility, low/high voided volume or unrepresentative void.

  
  
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  Nomograms—nomograms display the relationship between two variables; voided volume or bladder volume and maximum flow rate. They are produced to illustrate the likelihood that the recorded maximum flow and voided volume are normal. Nomograms are not diagnostic but, if used correctly, can be a useful screening tool for LUT dysfunction. Patient age and gender will have a bearing on which nomogram should be used.

  
  
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  Pattern of flow—for some patients, the possibility of reaching 150 mL is a daunting and quite frankly an unlikely possibility. For these individuals, the pattern of flow may provide valuable insight. Four of the most common flow patterns seen during FFR clinics are displayed in Figs. 4.5, 4.6, 4.7 and 4.8.

  
  
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  Postvoid residual—this volume is most commonly measured through an ultrasound scan of the bladder and should be conducted as soon after the patient has voided as possible. It refers to the volume of urine left in the bladder following an attempt from the patient to empty their bladder fully. Within the literature, there are various definitions of what is considered to be a chronic PVR, with reported volumes ranging from 100 to 500 mL [66–68].