The prevalence of the Neglected Sexual Side Effects (NSSEs) after early prostate cancer treatment and the role of a questionnaire in its diagnosis: A Scoping Review Protocol

Background: Early prostate cancer (PCa) treatment interventions may leave men with debilitating sexual side effects. These side effects may remain permanent, often undiagnosed and undermanaged. The objective of this study is to map the evidence about the prevalence, and use of questionnaires, related to the neglected sexual side effects (NSSE) after PCa treatment. Methods: This systematic scoping review's search strategy will involve the following electronic databases: PubMed, Science Direct and Google Scholar. Following title searching, two-independent reviewers will conduct screening of abstracts and full articles. Eligibility criteria will guide the screenings. Data will be extracted from the included studies, and the emerging themes will be analysed. The review team will analyse the implications of the ndings concerning the research question and aim of the study. The Mixed Method Appraisal Tool (MMAT) will be employed for quality appraisal of included studies. Discussion: We anticipate nding a small number of studies about the prevalence and questionnaire use for NSSE after early PCa treatment. The study ndings will be disseminated through publication in a peer-reviewed journal, peer presentations, as well as presentations at relevant conferences.


Background
Prostate cancer (PCa) is a major cause of disease and mortality among men and it is the second most common cancer affecting men on a global scale (1). Early PCa or localized PCa is cancer contained within the prostate described as being stage I or II on the tumour-node-metastasis system (2). Early PCa treatment consisting of surgery or radiotherapy, either through external beam radiotherapy or brachytherapy, results in side effects including sexual dysfunction. Other common side effects could include both pain and incontinence (1). Sexual dysfunction from PCa treatment is common regardless of whether the treatment modality included surgical or non-surgical interventions. Sexual dysfunction was found to increase during each year of follow-up after the initial intervention and it affects an average of 50% of patients within 5 years of receiving treatment (3).
Most men generally recover from pain and incontinence after PCa surgery but sexual dysfunction often remains untreated leaving them with long-lasting and debilitating sexual dysfunction (1). Speci c conditions related to sexual dysfunction are common after PCa treatment. The conditions include orgasm-associated incontinence, urinary incontinence during sexual stimulation, altered perception of orgasm, orgasm associated pain, penile shortening, and penile deformity (1,4,5). These conditions are collectively referred to as the "Neglected Sexual Side Effects" (NSSE) and the symptoms are reportedly prevalent in 20-93% of post prostatectomy patients (1).
Only a fth of the men who had been diagnosed with PCa will ever discuss issues related to sexual dysfunction with their health care practitioners (HCP) (6). A questionnaire may be useful as a non-threatening strategy to initiate such a discussion and allow the patient to indicate their presenting symptoms. Two validated questionnaires, the Expanded Prostate Cancer Index Composite (EPIC) (7) and International Index of Erectile Function (IIEF) (8) were recommended for use in this context in 2015 (9).

Reason for this review
While the EPIC and IIEF both help to stimulate the conversation around general urinary function, they do not address the NSSE after PCa treatment. There is currently a lack of evidence about the availability of a possible questionnaire to speci cally address the NSSE after PCa treatment. It is therefore important to conduct a systematic scoping review to improve our understanding on the prevalence of NSSE and to highlight knowledge gaps on the role of questionnaires in the assessment of the NSSEs.

Methodology
A systematic scoping review will be conducted to map the evidence on A systematic scoping review will be conducted to map the evidence on i. the prevalence of NSSE after early treatment PCa, and ii. summarise literature on the use of questionnaires in the assessment of NSSE after early treatment for PCa.
The scoping review will follow the ve steps described by (10) that included the following; Quality assessment of each of the included primary studies will be done as directed by (11) Identifying the research question This review aims to identify current academic literature on the NSSE after men have undergone early treatment for PCa.
The research questions are as follows: What is the prevalence of NSSE after early treatment for PCa?
Which questionnaires are being used to assess NSSE after early treatment for PCa?

Eligibility criteria
The Population Concept Context (PCC) framework will be used to determine the eligibility of the research question as illustrated in Table 1  This scoping review will include original research of any study design that has been published in peerreviewed papers. To identify the studies an electronic search will be conducted using the Pubmed, Science Direct and Google Scholar databases. We will also include relevant studies found in citations and reference lists of included articles. The search will include publications available in English and published between January 2009 and December 2019.
Boolean terms (AND, OR) and Medical Subject Headings (MeSH) will be used as indicated in Table 2. The search results will be captured on an Excel spreadsheet where the duplicates will be removed. The selected studies will be screened against the eligibility criteria. The study search strategy was piloted to determine the appropriateness and feasibility of conducting this study, and the results are represented in Table 2. The results of all three databases will be combined into one Excel spreadsheet after applying the search parameters. The eligibility criteria were developed to ensure that selected studies contain relevant information to answer the review questions.

The inclusion criteria
Only primary studies that present evidence on: The prevalence of NSSE after 3early stage PCa treatment The use of questionnaires to assess NSSE after early stage PCa treatment Original studies available in English and published between 1 Jan 2009-31 December 2019.

The exclusion criteria
The coping review will exclude:

Review articles
Non-peer reviewed articles (e.g. books, magazines, policy briefs etc.
Commentaries, editorials, programme evaluations and letters.
Literature on sexual dysfunction not relating to the prevalence and questionnaire use after early PCa treatment.
Studies outside the period of interest and studies not available in English.
The primary investigator will conduct a comprehensive search and screening of the study titles from the above-mentioned databases. All the relevant studies with appropriate titles will be extracted and entered into an Excel spreadsheet for processing. All duplicates will be removed before the titles are screened.
The abstracts of the eligible studies will be reviewed by two reviewers. This will be followed by full text screening by both reviewers of the qualifying articles to apply the inclusion and exclusion criteria. Any discrepancies in reviewers' results during the abstract and /or full text screening stage will be resolved by discussion until resolved. If needed, a third reviewer will be used to settle discrepancies. The screening result will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) chart (12).
Charting the data The information will be extracted and organized using a data charting form. Data will be processed so that the relevant information can be summarized to answer the research questions. The data charting tool as illustrated in Table 3 will be used by a second reviewer to validate all the information. An electronic version of the Mixed Method Appraisal Tool (MMAT) (13) will be adapted to assess the quality of the included studies. The study designs included in this scoping review will include qualitative, quantitative descriptive and mixed methods studies. The speci c criteria to determine the appropriateness of each included study is outlined in Appendix 1.
Two reviewers will assign a score to assess each article that will assess the appropriateness of the study aims and its relevance for inclusion on the review. The overall quality for each included study will be calculated according to the following MMAT guidelines (score = number of criteria met/total score in each domain). 1 point will be given for each question and a total score out of 5 will be calculated. This will be represented as a percentage which correlates to the quality of the included studies. (Appendix 1) The results will use the following descriptors.
Very poor quality (20%) where minimal criteria is met Poor quality (40%) where less than half the criteria is not met Fair quality (60%) where just more than half the criteria is met Good quality (80%) where most of the criteria is met Excellent quality (100%) all criteria are met The overall quality of a combination of components cannot be more than its weakest component when it comes to mixed methods studies, making the overall score equal to the lowest scoring component (13).
Collating, summarizing and reporting on the data The ndings of this scoping review will be analysed using a content analysis approach of the themes emerging from the extracted data. The themes will be collated to answer each research question. The review team will discuss ndings, resolve issues and nalise ndings. The review team will analyse the implications of the study ndings in how they relate to the study aims and further research in the eld.

Discussion
PCa constitutes a global public health burden (14) and surgical and non-surgical interventions are routinely administered (15). Men who receive treatment for early stage PCa are often unaware of the debilitating, long-lasting side effects following the treatment (4). Sexual function has been identi ed as the quality of life domain most strongly associated with outcome satisfaction after prostate cancer treatment (16). With most research in the eld of PCa focused around incontinence and erectile dysfunction, the NSSE remain understudied and neglected (1,17). This review will report on the prevalence of the NSSE after early PCa treatment.
Only two studies have been published on the NSSE related to PCa treatment (5,18). There is also no current valid and reliable questionnaire being used in the eld of the NSSE after early PCA treatment. Such a questionnaire would assist health care practitioners to screen for possible NSSEs in patients who had undergone treatment for early PCa.
A review of the literature related to the prevalence and use of questionnaires in the NSSE after PCa treatment may help to inform future clinical practice around the NSSE in PCa survivors.