Review question

What are the differential toxicities and outcomes of abiraterone acetate versus enzalutamide therapy for prostate cancer, and how do these relate to patient risk factors?

Protocol design

This scoping review follows the framework outlined by the Joanna Briggs Institute Manual for Evidence Synthesis (JBIMES), incorporating protocols established by Arksey and O’Malley along with revisions from Levac et al and Peters et al [10–14]. This review will include the following six steps: defining the research question; identifying relevant studies; study selection; charting the data; collating, summarizing, and reporting the results; and consultation. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines utilizing the extension for scoping reviews (PRISMA-ScR) [15]. The PRISMA-ScR checklist is attached (S1 Checklist). This protocol has been registered at https://doi.org/10.6084/m9.figshare.19149227 [16].

Identifying relevant studies

The review will primarily evaluate outcomes utilizing data regarding drug-associated toxicities, mortality, hospitalizations, and patient co-morbidities. Data on monitoring or mitigating drug-induced toxicities will also be gathered. Outcomes have been purposefully left broad to capture as much information as possible. All outcome data will be categorized in the “collating, summarizing, and reporting the results” stage.

Search strategy

The search strategy for this scoping review is informed by prior research in prostate cancer therapy, as well as recommendations by Tawfik et al to adapt searches to the database being utilized [17]. An experienced search librarian was also consulted. We will conduct a search of PubMed, Cochrane Library, CINAHL, and Scopus.

We will conduct a search using the following keywords: “prostate cancer”, “prostatic neoplasms”, “abiraterone acetate”, “enzalutamide”, “toxicities”, “outcomes”, and associated MeSH terms. These terms will be combined with the Boolean operators “AND” and “OR”.

The initial search will be in PubMed. A similar search will be used for Cochrane Library and CINAHL, which also utilize MeSH terms. Only keywords will be used for Scopus.

The search string for the PubMed database is as follows:

("Prostatic Neoplasms"[MeSH Terms] OR "Prostatic Neoplasms"[All Fields] OR "prostate cancer"[All Fields]) AND ("Abiraterone Acetate"[MeSH Terms] OR "Abiraterone Acetate"[All Fields]) AND ("enzalutamide"[All Fields] OR "Androgen signaling inhibitor"[All Fields]) AND ("Drug-Related Side Effects and Adverse Reactions"[MeSH Terms] OR "Treatment Outcome"[MeSH Terms] OR "Hospitalization"[MeSH Terms] OR "Mortality"[MeSH Terms] OR "Comorbidity"[Mesh]).

Types of participants

This scoping review will only include patients being treated with abiraterone acetate or enzalutamide for PCa.

Concept

This review will focus on full-length peer-reviewed publications that elucidate and compare the observed outcomes and toxicities of abiraterone or enzalutamide and their possible associations with patient co-morbidities.

Context

This review will focus on population-based studies from institutional and community care settings.

Types of sources

All peer-reviewed publications through January 31, 2022.

Exclusion criteria

The search will be restricted to articles and reports published in English. Free-standing abstracts, opinion pieces, and letters to the editor will be excluded. Studies investigating only one of either abiraterone or enzalutamide will be excluded. If further information is required, we will contact authors of the publications as appropriate.

Study selection

Studies identified by the above search strategy which satisfy the initial inclusion criteria will be considered for title and abstract screening. The search strategy will be adapted for other databases as required. The reference lists of all included articles will be searched for additional studies. As required by good practice, the completed strings for each database will be included in the published scoping review.

Endnote 20 (Clarivate, Philadelphia, PA) will be employed for imported reference management and duplication removal. The title, abstracts, and keywords will be screened by two independent reviewers to determine whether they satisfy the inclusion criteria (S1 File). Articles satisfying initial screening will undergo full-text screening by two independent researchers. Disagreements of study eligibility will be resolved through discussion with a senior member of the research team.

Charting the data

Collating, summarizing, and reporting the results

Search results will be presented in a PRISMA flowchart and an appended PRISMA-Scr checklist (S1 Checklist). The extracted data will be presented under the following headings: author, year of publication, study type, study population, primary objective(s), and outcome(s).

A full summary of evidence, including an overview of concepts and types of evidence available, as well as a discussion of limitations and study conclusions, will follow. The research team will identify gaps in the literature and highlight implications for future research.

Stage 6: Consultation

This protocol has purposefully included researchers from multiple disciplines (pharmacy, medicine, and epidemiology) within the research team. The diversity of the group brings unique views and broad experience to the literature analysis. At the end of the study, a final consultation will allow researchers to insert the context of clinical practice knowledge to the study results.

Ethics and dissemination

As indicated earlier, the scoping review is based upon openly accessible published material and is therefore not subject to an ethical review board. The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on patient-specific factors influencing risk assessment and treatment choice for abiraterone and enzalutamide.