Background

It is well known that the diagnosis and treatment of cancer causes significant physical, psychological, and social effects that interfere with a person’s sexual health. Indeed, it has been estimated that between 40 and 100% of cancer patients will experience a degree of sexual dysfunction [1]. Sexual dysfunction is characterized by disturbances in sexual desire and in the psychophysiological changes associated with the sexual response cycle in men and women or pain during intercourse [2, 3]. The degree to which sexual dysfunction has been studied in different cancer types varies, with most studies performed in patients with prostate, breast or gynaecological cancers. The World Health Organization (WHO) defines sexual health as a state of physical, emotional, mental, and social wellbeing related to sexuality, and is not merely the absence of disease, dysfunction or infirmity [4]. Therefore, sexual health has to be evaluated holistically due to the complex interactions between biological, psychological, interpersonal and social/cultural factors [5], as all these factors may effect sexual function and wellbeing [6].

Bladder cancer (BC) treatments are known to have a potential detrimental effect on both the genitals and the internal sexual organs of patients and yet it has been greatly overlooked compared to other cancer therapies [7]. Research of the treatment impact on sexual health has been widely identified as an unmet need in bladder cancer patients [8, 9].

Non-muscle invasive bladder cancer (NMIBC) accounts for about 70% of all bladder cancers [10] and those are mostly treated with transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy (22%) or immunotherapy with bacillus CalmetteGuerin (BCG, 29%) [11]. Muscle invasive bladder cancer (MIBC) are commonly treated with cystectomy [11, 12]. The vast majority of studies currently available for bladder cancer focus on those who have undergone a radical cystectomy. Among those, many studies evaluate sexual-sparing radical cystectomy with the goal of reaching definitive oncologic control while attempting preservation of sexual function [13].

Current European Association of Urology (EAU 2019) guidelines [14] recommend that a standard radical cystectomy in men should include removal of the bladder, prostate, seminal vesical, distal ureters and regional lymph nodes, while in women removal of the bladder, entire urethra and adjacent vagina, uterus, distal ureters and regional lymph nodes is recommended. The guidelines also stated that a prostate-sparing radical cystectomy could be considered in carefully selected patients if oncologically safe. However, a sexual organ preserving operation in women is not advised, largely due to a paucity of available evidence [14]. Such treatments can induce serious complications and greatly impact the patient’s body image and quality of life (QoL) [11]. Health-related QoL (HRQoL) can be formally defined as the extent to which one’s usual or expected physical, emotional, and social wellbeing are affected by a medical condition or its treatment [15]. HRQoL issues of special concern to patients with BC include, among others, threats to body image and sexuality [16, 17].

With the focus on HRQoL arising in cancer survivorship, it is needed to closely address and evaluate post-treatment sexual dysfunction and offer goal-directed treatment. To date no detailed assessment of the overall burden of sexual health in bladder cancer patients has been made. This systematic literature review aimed to provide a consolidated overview of studies that address sexual health in bladder cancer patients. We specifically aimed to assess the methodology used to evaluate sexual health in terms of coverage and validation after BC treatment, which may provide a basis for future studies.

Methods

This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines in July 2019. A detailed overview of the protocol is provided in Appendix 1.

Search strategy and inclusion criteria

Studies were identified by conducting searches for Medline (using the PubMed interface), the Cochrane Central Register of Controlled Trials (CENTRAL) and Ovid Gateway (Embase and Ovid) between May and July 2019 using a list of defined search terms (see Appendix 2). To be included in the analysis, the studies must have met the following criteria: study on the impact of bladder cancer treatment on sexual health/dysfunction and reported outcomes specifically for sexual health/dysfunction (e.g. erection, ejaculation, dryness).

Data collection and analysis

Initially, the titles of the studies were screened to identify the relevant studies. The abstracts and subsequently full texts were then carefully read to identify those which met the inclusion criteria. Two independent reviewers (AB and RM) used the exact same search strategy and inclusion criteria and after each screening phase, a discussion was conducted with a third party (MVH) to match and decide on the included studies. Information on patient characteristics, number of study participants and type of treatment, as well as sexual health outcomes and mental wellbeing information was extracted from each study. The latter data was collected as sexual dysfunction may also have an impact on HRQoL through effects on mental wellbeing (4). The references of the included studies were also reviewed to ensure no relevant citation was missed.

Results

Quantity of evidence identified

The selection process for records to be included in the review was carried out according to PRISMA protocol, and this is demonstrated in a PRISMA flowchart in Fig. 1. A total of 667 records were collected from the literature search and 108 duplicates were removed. All titles were initially screened and 226 remained for abstracts screening. Of those, 71 remained for full text analysis. After the full text was read, 37 studies matched the inclusion and exclusion criteria and were included in this systematic review (Table 1, Appendix 3).

Fig. 1
figure 1

PRISMA Flow diagram for selection of studies in systematic review

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Table 1 Characteristics of the patient profile included in the studies
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Characteristics of the patient profiles

Of the 37 studies included in the systematic review, 15 studies (40.5%) included men only, 10 studies (27.0%), women only and 12 studies (32.4%) included both sexes. The exact number of women and men in the studies that included both sexes is not clearly described for all studies. With respect to age, in 28 studies (75.6%) participants were aged between 50 to 65 years, in five studies (13.5%) 26 to 49 years, in four studies (10.8%) 66 to 80 years and none included participants above 80 years old. The vast majority of studies [n = 34 (91.9%)] included MIBC and only three (8.10%) focused on NMIBC. Patient profiles for each study are described in Table 1.

Measurement of sexual health by sex

Measurements of sexual dysfunction, including erection (73.0%), ejaculation (35.1%), firmness (8.10%) and desire (18.9%), were the most commonly used measurements to report sexual health in men. In women, lubrification/dryness (27.0%), desire (24.3%), orgasm (27.0%) and dyspareunia (29.7%) were the most commonly reported (Table 2).

Table 2 Measures of reported sexual dysfunction by sex
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Comparison of sexual dysfunction outcome by treatments and measurements

Thirty-three (89.2%) studies addressed sexual dysfunction following radical cystectomy, one (2.7%) following radical radiotherapy, one (2.7%) after cystoscopy, and two (5.4%) after other treatments for bladder cancer. There are no studies looking at TURBT only. In four studies (10.8%), participants were treated with drug therapy for their sexual dysfunction. Twenty-one studies (56.8%) evaluated sexual dysfunction based on validated questionnaires, two (5.4%) with a non-validated questionnaire and 14 (37.8%) through interviewing participants.

Patient and partners sexual satisfaction and mental wellbeing

Seven studies evaluated patient sexual satisfaction and mental wellbeing (Table 3). None of those included both patient and partner satisfaction and mental wellbeing. One study included sexual satisfaction for both patients and partners, but did not report on mental wellbeing [18]. Regarding mental wellbeing, perception of body image [20, 22, 24], worry about daily life [19], feeling of anxiety [23] and depression [22] were the most commonly reported outcomes. Six of those studies included patients with MIBC and one NMIBC. Six studies included patients in the age range of 50–65 years and two included patients 66–80 years old. Overall, radical cystectomy was found to be associated with negative feelings regarding patient’s body image and consequently a negative effect in sexual satisfaction. Patients who underwent a bladder sparing technique had a better perception of their body and a better sexual satisfaction. There is no consistency in the measurements used for sexual satisfaction and/or mental wellbeing: interviews and semi-structured interviews, sexual function index questionnaire, QoL questionnaire (SHIM and IFSF) and a functional assessment of cancer therapy questionnaire.

Table 3 Patient and partner sexual satisfaction and mental wellbeing
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Discussion

Sexual dysfunction is a common phenomenon after bladder cancer treatment and yet sexual health is frequently overlooked. Of the 37 included studies included in our review, 15 studies included men only, 10 studies included women only and 12 studies included both sexes. Most studies included participants aged between 50 to 65 years. The majority of studies focused on patients with MIBC. The main outcomes measured in men were erection, ejaculation and desire and in women, lubrification/dryness, orgasm and dyspareunia. A broad range of measures were used in the studies including validated patient reported outcome tools, such as the SHIM and the IFSF questionnaire and interview-based studies.

One of the main observations following our systematic review is the heterogeneity in measurements used for sexual health. The SHIM tool is commonly used in prostate cancer and has also been most commonly used in the studies identified here. In female patients the available measurement tools are broader and less commonly implemented in practice. The most commonly used tool we found was the IFSF questionnaire. Both tools have been criticised for their lack of psychometric measures [25]. Indeed, the need for a robust measure of sexual function in bladder cancer that includes psychometric assessment is well recognised, but not yet developed [26]. Mohamed et al. (2014) identified unmet needs in MIBC patients and sexual function was a significant concern [8]. With no evidence of consistent clinical measures from practice, these findings are unsurprising. Patient and public involvement is needed to develop and include appropriate psychometrics measures in sexual health questionnaires. As previously noted by Peter Selby and Galina Velikova [27], patient input is essential, but the process is time consuming, sometimes quite expensive and can involve large numbers of patients or the general population to achieve meaningful results. Therefore, individuals and groups have tended to develop their own questionnaires which led to a lack of general consensus in the field and a confusing number of questionnaires.

Moreover, our systematic review highlights how sexual health may negatively impact on mental wellbeing and HRQoL – and hence indicates the need to address this gap for patients. As suggested by the definition of the WHO [4], sexual health has to be evaluated from a psychosocial perspective and not only the physical and physiological aspects. Although erectile dysfunction in men and physical and physiologic changes associated with cystectomy in women are the dominant factor driving sexual function, other causes of sexual dysfunction, such as depression or anxiety related to changed body image, distress regarding partner reaction to an altered body as well as the degree of problems that patients are experiencing due to their sexual function (bother), should be evaluated and managed.

Currently, HRQOL questionnaires like the Functional Assessment of Cancer Therapy – Bladder Cancer (FACT-BC) do include questions about interest in sex, while the Bladder Cancer Index (BCI) also includes questions about desire, arousal, sensation, and orgasm. Several EORTC questionnaires include a limited number of sexual functioning items. However, there is no single self-reported measure that covers the entire range of sexual health. Recently, the European Organization on Research and Treatment of Cancer (EORTC) developed an EORTC Sexual Health Questionnaire (EORTC SHQ-22) for assessing sexual health in cancer patients [28]. In addition to that, HRQOL assessment should target patient’s current or very recent HRQOL status. This is of interest as (1) it has been suggested that patients overestimate their baseline HRQOL in the sexual function domains by 27% [29]; and (2) it would allow to better understand the degree of problems experienced by patients (measuring “bother”). It is also important to note that function and bother do not necessarily correlate as demonstrated by Letwin et al. [30] and that despite sexual health issues being an important concern to patients, they often experience difficulties in disclosing their complaints with health care providers or their partners. Lastly, as sexual wellbeing is closely correlated with social interactions, patients’ relationship status should also be considered when evaluating sexual wellbeing and its impact on HRQOL.

In our systematic review, most studies addressed sexual health in patients with MIBC who underwent radical cystectomy and only four studies focused on patients with NMIBC. This is potentially affecting the generalisibility of our observations as it is important to note that treatments for NMIBC and MIBC substantially differ, e.g. TURBT vs cystectomy. In a prospective study by Yoshimura et al. [31] on the impact of TURBT on QoL in patients with NMIBC, physical problems were found with the first TURBT, but when the fourth TURBT was performed, patients appeared to have adapted to frequent operations, although their general QoL remained affected. For cystectomy patients, it has been shown that although relationships with friends were unchanged, relationships with spouse or partner were disturbed by sexual problems [32]. Partner response to the presence of an external appliance, such as stoma, may also strain intimate relationships and contribute to a dysfunctional sex life. Nevertheless, these observations highlight that 1) the threat of recurrence, multiple cystoscopies, TURBT, and intravesical instillations make QoL assessment in superficial bladder cancer challenging; 2) the importance of looking at sexual function in patients with bladder cancer in a broader way is needed, i.e. including both the physical perspective as well as the patients’ partner and relationships.

There are limitations of this study that warrant further discussion. The analysis of the included studies was unable to provide an extensive coverage of sexual health in NMIBC patients for which the impact of treatment in sexual health and consequently QoL may also be significative. Due to the nature of the methods used to measure sexual health and the lack of psychometric measures, further research is needed to better understand the role of bladder cancer treatment and psychosocial factors of sexual functioning.

Conclusion

While recognition of the importance of the inclusion of psychometric measurements to assess sexual health is growing, this systematic review highlights the lack of consistent measures to assess sexual health in bladder cancer patients. With the focus on HRQoL arising in cancer survivorship, further studies are needed to develop, standardize and implement the use of sexual health questionnaires with appropriate psychometrics and social measures for bladder cancer patients.