It has been estimated that patients suffering from neurogenic lower urinary tract dysfunction have 16- to 28-fold increased risk of bladder cancer compared to the general population, with incidence rates ranging from 0.1 to 10% (the pooled incidence of 0.6%) [1–6]. Studies of those after spinal cord injury (SCI) demonstrated that bladder cancer tends to present at an earlier age (with an average of 18–24 years after initial injury) and in more advanced stages, thus resulting in poor long-term survival [7]. Concurrent findings were shown for patients with spina bifida [8]. Those with multiple sclerosis (but not with Parkinson disease) were also found to have an increased risk of bladder cancer [9, 10]. In the SCI population, 58–100% of new bladder cancers are muscle invasive at presentation compared to 25% in the general population [7, 11]. The mean patient age at bladder cancer diagnosis in a neurogenic population has been calculated as 50 years (in the general population, 73 years with the highest percentage between ages 75 and 84 years) [1]. Furthermore, studies have shown that the standardized mortality ratio due to bladder cancer among SCI individuals is 7- to 70-fold higher than that of the general population [3, 12]. The 1-year overall survival rates after treatment of bladder cancer in neurogenic patients range between 61 and 70% [13, 14]. A recently published systematic review with meta-analysis revealed that transitional cell carcinoma is the most common histological type (46.3%, in the general population 90%) followed by squamous cell carcinoma (36.8%, in the general population 2–7%) and other pathological types (17.1%) [1].

Potential risk factors for bladder cancer among neurogenic individuals include [7, 15]:

It has been demonstrated that bladder management with chronic indwelling catheterization (both transurethral and suprapubic) leads to certain histological changes, including papillary or polypoid cystitis, widespread cystitis glandularis, moderate to severe acute and chronic inflammatory changes in bladder mucosa, follicular cystitis, squamous metaplasia, and urothelial dysplasia [16–18]. However, clinicians should be aware that up to 50% of neurogenic patients diagnosed with bladder cancer have not been managed with an indwelling catheter [6]. This supports the idea that perhaps the neurogenic bladder itself is the primary risk factor for cancer neogenesis. The role of augmentation cystoplasty in the development of bladder cancer is still controversial, as the long-term results are not available [19]. Nevertheless, it seems possible that ileal/colonic bladder augmentation (with the exception of gastrocystoplasty) does not appear to increase the risk of bladder malignancy [20]. Note that these findings refer to the adult population, as bladder cancer is a known complication of bladder augmentation in the pediatric population [19, 21]. The urodynamic type of neurogenic bladder dysfunction seems not to influence the development of bladder neoplasm [22].

Because the exact mechanism of increased risk of bladder cancer in neurogenic patients, particularly in those after SCI, has not been well analyzed, strong recommendations cannot be provided. The bladder cancer screening strategy of this specific population remains a matter of dispute and seems to depend on presenting risk factors.

The majority of neurogenic patients who have developed bladder cancer present with traditional symptoms , such as gross hematuria, suprapubic mass, or hydronephrosis/renal failure [7]. Any episode of gross hematuria should be investigated in the same manner as in the general population. It is important to stress that neurogenic patients may also present with less specific symptoms or signs, including frequent urinary tract infections, bladder calculi, penile discharge, or scrotal infection. These symptoms, although commonly associated with benign causes, should lead to a differential diagnosis of bladder cancer.

Some experts emphasize that routine cystoscopic surveillance is mandatory, as it detects malignant lesions at an early stage [23]. Importantly, studies have shown that endoscopic findings may not significantly differ between symptomatic and asymptomatic groups [24]. Others emphasize that cystoscopy screening does not fulfill the necessary criteria for the screening of bladder cancer in a neurogenic population and cannot be recommended [25–27]. Therefore, different follow-up strategies have been developed. It has been proposed that regular cystoscopic monitoring (with 1-year interval) should be considered in patients who have one or more of the following risk factors: smoking and age >50 years, enterocystoplasty or any augmentation cystoplasty over 10 years, any neurogenic bladder over 15 years [28]. Evaluation should be performed with urethrocystoscopy and biopsy/bladder-washing cytology if suspected lesions have been detected (Figs. 15.1, 15.2, and 15.3) [29]. Other proposals recommend performing surveillance urethrocystoscopy and bladder washing cytology on patients suffering from neurogenic bladder for at least 5 years on a regular short-term basis, that is, every 1–2 years [24, 30]. However, yearly monitoring with cystoscopy and biopsy in patients after SCI (without multiple risk factors for cancer neogenesis) from 5 years after catheter insertion has been found to be a poor screening test, with chronic cystitis and squamous metaplasia being the most common findings [26]. In view of these findings, a careful assessment of patient risk factors may be of utmost importance in choosing a screening strategy for bladder cancer in the neurogenic population. In a recent meta-analysis of neurogenic patients, cystoscopy demonstrated a sensitivity of 64% (95% CI, 49.3–76.5% I² = 37.7%) for detecting bladder cancer [1]. To sum up, cystoscopy alone is not sufficient and biopsy is required to make the final diagnosis because long-standing inflammatory changes or squamous metaplasia may be difficult to distinguish from cancerous lesions. A recently published prospective analysis of 129 neurogenic patients concluded that surveillance urethrocystoscopy might be warranted, although the ideal starting point and frequency remain to be determined in further studies [30].

Urine cytology is another possible method of bladder cancer screening. A retrospective study of 208 SCI patients monitored for more than 5 years demonstrated that positive cytology has a sensitivity of 71% and a specificity of 97% [31]. Authors recommended a minimum of annual cytology in all patients with chronic indwelling catheters or other risk factors, followed by biopsy when the cytology was positive or if any suspicious findings have been detected. Another proposal includes annual urine cytology in neurogenic patients after 10 years of injury or diagnosis of underlying neurological disorder [16]. If the cytology is positive or doubtful (because of the difficulty in interpreting the results due to chronic bacteriuria and hematuria from catheter use), cystoscopy and cold cup biopsy should be performed randomly if no suspicious lesion is found. Although urine cytology may be of benefit in monitoring patients with additional risk factors for bladder cancer, one must remember that cytology is generally normal in patients with low grade transitional cell carcinoma and in those with non-transitional types of bladder cancer [32]. Moreover, several authors have found cytology to have a very low diagnostic yield [33–36]. This has been supported by results of a recent meta-analysis that estimated the sensitivity of cytology as 36.3% (95% CI, 21.5–54.3%, I² = 40.2%) [1]. As intra-observer variations exist, the usefulness of cytology also likely depends on the ability of the cytopathologist to interpret samples with background inflammation [31]. To conclude, cytology alone may be a poor screening test in neurogenic patients.

A screening strategy with abdominal imaging in the form of ultrasound has been found inferior to cystoscopy and should not be considered a substitute for urethrocystoscopy and bladder washing cytology (Fig. 15.4) [37]. Contrast computed tomography as a screening method has not been well studied (Figs. 15.5 and 15.6).

As presented above, the gold standard screening test has not been established and available methods do not fill the criteria of proper screening test for effective cancer surveillance. These criteria are [38]:

It is noteworthy that bladder cancer can occur rapidly, making annual screening less likely to detect the disease at an earlier stage [7]. The cost, use of resources, and the possibility of morbidity associated with different screening procedures along with the lack of evidence for benefit make proposed screening strategies for bladder cancer in neurogenic patients less appealing [8].

Comprehensive guidelines for the diagnosis and treatment of bladder cancer have been developed and they can be directly applied to management of patients with neurogenic lower urinary tract dysfunction [39]. These include Guidelines of the European Association of Urology (EAU) [40, 41], the American Urological Association (AUA) [42, 43], and the Canadian Urological Association (CUA) [44].

SD among patients suffering from neurogenic lower urinary tract dysfunction is a serious concern. Although variations in definition, methodology, and study populations exist, it has been demonstrated that the prevalence of SD is high in the neurogenic population. Up to 40% of male patients after SCI report dissatisfaction with their sexual life [46, 47] and 25% of SCI females report decreased sexual satisfaction [48–50]. Estimated rates of successful intercourse in men with SCI range from 5 to 75% [51]. Only 12% of complete and 33% of incomplete SCI males can ejaculate during intercourse or masturbation without the aid of medication or devices [52]. Orgasm can be achieved by up to 50% of SCI patients [46]. Different degrees of SD may occur, depending on the level of SCI, extent of lesion, and timing from injury. Interestingly, lower lesions (particularly affecting sacral segments) are associated with more frequent and more severe SD compared to higher injuries, as they lead to impairment of reflex activity and maintain only psychogenic potential, which, however, lacks the muscular component to maximize sexual function [53]. The overall prevalence of SD among females suffering from multiple sclerosis has been estimated as 82.5%, and 45% reported worsening of their sexual functioning after the onset of the disease [54]. In male patients, SD related to multiple sclerosis is generally understudied in spite of its apparent high prevalence [45]. One of the few studies demonstrated that in males with multiple sclerosis erectile dysfunction, ejaculatory dysfunction, and decreased libido can be observed in approximately 63%, 50%, and 40%, respectively [55]. Once the diagnosis of multiple sclerosis has been established, up to 60% of men and 25% of women complain of SD. Stroke-related SD is also fairly frequent and affects up to 75% of stroke patients [56]. SD prevalence of 50–70% is documented in sufferers of Parkinson disease [57–61]. Similar findings have been shown for those affected by multiple system atrophy [62, 63]. It is estimated that 50–75% of adult patients with myelomeningocele are unable to have sexual intercourse [64–67]. As shown, SD is very common in neurogenic patients but still often overlooked and underestimated by medical staff, not only by urologists [54, 68].

Clinicians should keep in mind that SD with concomitant neurogenic lower urinary tract dysfunction, especially in young-onset neurological diseases (in particular multiple sclerosis), usually leads to a serious impact on the quality of life. In young-age neurogenic patients sexual relationships are still quite young and their family planning is not always completed [45]. On the other hand, older age might promote eventual comorbidities, for instance, cardiovascular disease, diabetes, impaired mobility, depression, and cognitive dysfunction, thus additionally deteriorating already-impaired sexual activity.

There is universal agreement that identification and recognition of the problem should be the first step in the assessment of SD [45]. As patients are often reluctant to initiate the discussion themselves, the clinician should start the conversation. The presence of the partner in the discussion is recommended, as it helps to assess the impact of SD on the relationship. Privacy and confidentiality of reported SD should be stressed before taking the sexual history. Patients should be questioned about the onset and duration of symptoms, their severity (mild, moderate, severe), and timing (once, always, situational) to help confirm the dysfunction and identify the diagnosis. A complete review of medications is necessary to exclude iatrogenic causes of SD, as a wide variety of antispastics (e.g., baclofen, tizanidine, dantrolene), anticonvulsants (e.g., carbamazepine, phenytoine), antidepressants (e.g., SSRIs, venlafaxine), and anti-fatigue drugs (e.g., amantadine) are recognized causes of SD [69]. In males, physicians should investigate other common causes of erectile dysfunction (e.g., cardiovascular disease, hypertension, hypercholesterolemia, diabetes) or reversible risk factors (e.g., smoking, obesity, alcohol, lack of regular exercises) [70–72]. It is important to establish the presence of erectile dysfunction , often confused with other sexual dysfunctions, including premature ejaculation and inability to reach orgasm. Clinical examination should rule out penile deformities, hypogonadism, or prostatic disease (>50 years). A rectal exam is important to assess rectal tone and reflexes (bulbocavernosal and anal). In female patients, physicians should question about decreased libido, impaired arousal, orgasmic dysfunction, pain from attempted or completed intercourse, difficulty with vaginal entry (due to muscle spasticity), and the awareness of vaginal lubrication. Physical examination should assess sensory function as well as reflexes and muscle tone of the pelvic area. In both sexes, tertiary causes of SD should be carefully evaluated. Additional tests depend on the clinical scenario. These may include hormonal testing (especially in perimenopausal women or those in whom hormonal replacement therapy is considered to treat libido and arousal disorders [73, 74]), metabolic profile, vascular studies, electrophysiological tests, psychodiagnostic testing, and other specialized tests. The majority of such tests are not routinely used and should be reserved for special circumstances [75].

Using validated questionnaires can support evaluation of SD in neurogenic patients, especially when the interviewer is not familiar with the condition and when a measurable clinical response is needed (to assess treatment response and efficacy or disease progression). For those suffering from multiple sclerosis , clinicians can use specific questionnaires including the Functional Assessment of Multiple Sclerosis Quality of Life, or FAMS [76], the Hamburg Quality of Life Questionnaire in Multiple Sclerosis, or HAQUAMS [77], the Multiple Sclerosis Intimacy and Sexuality Questionnaires, or MSISQ-15/MSISQ-19 [78, 79], Multiple Sclerosis Quality of Life Inventory, or MSQLI [80], Multiple Sclerosis Quality of Life-54 Instrument, or MSQoL-54 [81] and RAYS [82]. Patients after SCI can be questioned with SCI specific questionnaires, including the Rick Hansen Spinal Cord Injury Registry, or RHSCIR [83] and Fransceschini [82]. Other questionnaires that have been validated in a neurogenic population and can be widely used among patients with either multiple sclerosis/SCI and other neurological disorders include the Incontinence Quality of Life Questionnaire, or IQOL [84] or Qualiveen/SF-Qualiveen [85, 86]. Patients with SD can also be assessed by other generic questionnaires for either females (the Female Sexual Function Index, or FSFI, the most frequently used female questionnaire; the Derogatis Sexual Functioning Inventory, or DSFI; the Female Sexual Distress Scale, or FSDS; the Sexual Function Questionnaire, or SFQ) and males (the International Index of Erectile Function, or IIEF, the most frequently used male questionnaire ; the Sexual Health Inventory for Men, or SHIM) [87–89]. It is important that the questionnaire of choice be validated in the language in use. Each questionnaire can be used alone or in combination with other questionnaires to improve assessment or monitoring of treatment outcomes.

If the clinician experiences negative emotions and/or difficulties with patient cooperation, it can be beneficial to refer patients and their partners to professional counselors, psychiatrists, psychologists, or sex therapists.