Bladder cancer (BC) treatment can have a detrimental effect on the sexual organs of patients and yet assessment of sexual health needs has been greatly overlooked for these patients compared to those who have undergone other cancer therapies.
This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines in July 2019. 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) using a list of defined search terms.
15 out of 37 studies included men only, 10 studies women only and 11 both sexes. Most participants were aged 50 to 65 years. Most studies (n = 34) focused on muscle invasive BC and only three on non-muscle invasive BC. Measurements of sexual dysfunction, including erection, ejaculation, firmness and desire, were the most commonly used measurements to report sexual health in men. In women, lubrification/dryness, desire, orgasm and dyspareunia were the most commonly reported. Twenty-one studies evaluated sexual dysfunction based on validated questionnaires, two with a non-validated questionnaire and through interviewing participants.
While recognition of the importance of the inclusion of psychometric measurements to assess sexual health is growing, there is a lack of consistent measures to assess sexual health in BC. With the focus on QoL arising in cancer survivorship, further studies are needed to develop, standardize and implement use of sexual health questionnaires with appropriate psychometrics and social measures to evaluate QoL in BC patients.
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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 . 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 . Therefore, sexual health has to be evaluated holistically due to the complex interactions between biological, psychological, interpersonal and social/cultural factors , as all these factors may effect sexual function and wellbeing .
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 . 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  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%) . 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 .
Current European Association of Urology (EAU 2019) guidelines  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 . Such treatments can induce serious complications and greatly impact the patient’s body image and quality of life (QoL) . 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 . 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.
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.
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).
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).
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 . Regarding mental wellbeing, perception of body image [20, 22, 24], worry about daily life , feeling of anxiety  and depression  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.
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 . Indeed, the need for a robust measure of sexual function in bladder cancer that includes psychometric assessment is well recognised, but not yet developed . Mohamed et al. (2014) identified unmet needs in MIBC patients and sexual function was a significant concern . 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 , 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 , 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 . 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% ; 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.  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.  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 . 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.
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.
Availability of data and materials
Quality of life
Non-muscle invasive bladder cancer
Muscle invasive bladder cancer
Health-related quality of life
European Organisation for Research and Treatment of Cancer
European Organisation for Research and Treatment of Cancer Sexual health questionnaire - 22
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all authors have read and approved the manuscript. Conception and design: AB, RM, MVH. Acquisition of data: AB, RM. Analysis and interpretation of data: AB, RM, MVH. Drafting of the manuscript: AB. Critical revision of the manuscript for important intellectual content: CH, DE, SA, MK, FC, HW, SB, KC, SM, RN, PK, AH, SG, MN, KB, RT, MVH.
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PROTOCOL: Systematic literature review on sexual health for patients with bladder cancer.
AIM: To consolidate an overview of studies that address sexual health in bladder cancer patients
Assess the methodology used to evaluate sexual health in terms of coverage and validation after bladder cancer treatment,
Understand the role of bladder cancer treatment and psychosocial factors of sexual functioning
Reports of current systematic review protocol adhere to the Preferred Items for Systematic Reviews and Meta-Analysis Protocol (PRISMA-P) checklist. The systematic review itself will adhere to the PRISMA.
Criteria for considering studies for this review.
Types of studies.
Any study that investigated sexual function or sexual dysfunction; any study where sexual function/sexual dysfunction/sexual health were measured by self-reports or an interview. Studies were original full text report in English and were published in peer-reviewed journals.
Types of participants.
The population of interest will be bladder cancer patients. Demographic factors are no exclusion criteria except for age (< 18 years of age).
Types of outcomes measures.
For both primary and secondary outcome measures, there will be no exclusion based on length of follow-up.
Sexual function or sexual dysfunction in bladder cancer patients.
Treatment and psychosocial factors of sexual functioning.
SEARCH METHODS FOR IDENTIFICATION OF STUDIES.
The following electronic databases will be searched from inception until the search date: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (using the PubMed interface), Embase (using the embase.com interface) and PsychINFO.
Data collection and analysis.
Selection of studies.
All references found through the search process will be downloaded in a database created by reference management software (Endnote). After removing duplicates in Endnote, all references will be imported into Covidence for screening purposes. Obviously irrelevant studies, based on title and abstract, will independently be excluded by two review authors. After screening the titles and abstracts, two review authors will independently assess full-text reports for eligibility. Discrepancies will be discussed with a third review author. Reasons for exclusion of full-texts will be documented. Studies will be excluded if no full-text is available. Abstracts in any other language than English will be excluded. There will be no language restriction for full texts, and translations will be carried out if necessary. If studies have multiple publications with the same outcome(s) reported, manuscripts with the longest follow-up will be selected for inclusion.
For each included study in the review, at least the following information will be extracted:
- General information: report title, report ID, authors’ names, country, contact address, language of publication and year of publication.
- Population and setting: population description (from which study participants are drawn), setting when applicable (eg, inpatient, outpatient, hospital setting, home setting and combination) and inclusion and exclusion criteria.
- Methods: aim of study, design, start and end date and duration of participation.
- Participants: number of participants, received treatment.
- Outcomes: outcome name, time points measured and reported.
- Results: measurement of sexual function and sexual dysfunction, psychosocial factors measured.
Dealing with missing data.
If essential data are not available in the publication, we will first attempt to contact the study authors. If this is not possible, we will try to back-calculate from the data presented. If data will be obtained from other study authors, this will be reported in the review in a transparent manner. This way, we can keep in mind that these missing data obtained from study authors were not peer reviewed. Studies assessing lifestyle interventions may have issues with compliance. Therefore, reasons for missing data (eg, dropouts, losses to follow-up and withdrawals) will be carefully reported.
The findings from the included studies will be summarised in a table format.
ETHICS AND DISSEMINATION.
Ethics approval is not required, as no primary data will be collected. Results will be disseminated through a peer-reviewed publication.
The results of this systematic review could also have potential limitations in terms of biased results due to the nature of the patient reported outcomes.
“Urinary Bladder Neoplasms”[MESH] OR “Urinary Bladder/abnormalities”[MESH] OR “Urinary bladder/surgery”[MESH] OR “Carcinoma, Transitional Cell”[Mesh] OR “bladder cancer”[TIAB] OR “bladder cancers”[TIAB] OR “bladder carcinoma”[TIAB] OR “bladder carcinomas”[TIAB] OR “bladder malignancy”[TIAB] OR “bladder malignancies”[TIAB] OR “bladder neoplasm”[TIAB] OR “bladder neoplasms”[TIAB] OR “bladder tumor”[TIAB] OR “bladder tumors”[TIAB] OR “bladder tumour”[TIAB] OR “bladder tumours”[TIAB] OR “transitional cell carcinoma”[TIAB] OR “transitional cell carcinomas”[TIAB] OR “transitional cell cancer”[TIAB] OR “transitional cell cancers”[TIAB] OR “transitional cell malignancies”[TIAB] OR “transitional cell tumor”[TIAB] OR “transitional cell tumors”[TIAB] OR “transitional cell tumour”[TIAB] OR “transitional cell tumours”[TIAB]
“Sexual function” OR “sexual dysfunction” OR “wellbeing” OR “intimacy” OR “sexuality” OR “sexual physiology” OR “sexual physiopathology” “sexual heath”
“Cystectomy” OR “radical cystectomy” OR “partial cystectomy” OR “TURBT” OR “Transurethral resection of bladder tumour” OR “BCG” OR “chemotherapy” OR “Radiotherapy” OR “Bacillus Calmette–Guérin vaccine”.
“Urinary Bladder Neoplasms” OR “Urinary Bladder abnormalities” OR “Urinary bladder surgery” OR “Carcinoma, Transitional Cell” OR “bladder cancer” OR “bladder cancers” OR “bladder carcinoma” OR “bladder carcinomas” OR “bladder malignancy” OR “bladder malignancies” OR “bladder neoplasm” OR “bladder neoplasms” OR “bladder tumor” OR “bladder tumors” OR “bladder tumour” OR “bladder tumours” OR “transitional cell carcinoma” OR “transitional cell carcinomas” OR “transitional cell cancer” OR “transitional cell cancers” OR “transitional cell malignancies” OR “transitional cell tumor” OR “transitional cell tumors” OR “transitional cell tumour” OR “transitional cell tumours”
“Sexual function” OR “sexual dysfunction” OR “wellbeing” OR “intimacy” OR “sexuality” OR “sexual physiology” OR “sexual physiopathology”
“Cystectomy” OR “radical cystectomy” OR “partial cystectomy” OR “TURBT” OR “Transurethral resection of bladder tumour” OR “BCG” OR “chemotherapy” OR “Radiotherapy” OR “Bacillus Calmette–Guérin vaccine”.
Urinary Bladder Neoplasms OR Urinary Bladder abnormalities OR Urinary bladder surgery OR Carcinoma, Transitional Cell OR bladder cancer OR bladder cancers OR bladder carcinoma OR bladder carcinomas OR bladder malignancy OR bladder malignancies OR bladder neoplasm OR bladder neoplasms OR bladder tumor OR bladder tumors OR bladder tumour OR bladder tumours OR transitional cell carcinoma OR transitional cell carcinomas OR transitional cell cancer OR transitional cell cancers OR transitional cell malignancies OR transitional cell tumor OR transitional cell tumors OR transitional cell tumour OR transitional cell tumours
Sexual function OR sexual dysfunction OR sexual health OR wellbeing OR intimacy OR sexuality OR sexual physiology OR sexual physiopathology
Cystectomy OR radical cystectomy OR partial cystectomy OR TURBT OR Transurethral resection of bladder tumour OR BCG OR chemotherapy OR Radiotherapy OR Bacillus Calmette Guerin vaccine OR Intravesical therapy OR Systemic immunotherapy.
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Bessa, A., Martin, R., Häggström, C. et al. Unmet needs in sexual health in bladder cancer patients: a systematic review of the evidence.
BMC Urol20, 64 (2020). https://doi.org/10.1186/s12894-020-00634-1