• Prokar Dasgupta

Fear of cancer recurrence and PSA anxiety in patients with prostate cancer: a systematic review

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Purpose The impact of prostate cancer on the mental wellbeing of patients is increasingly being appreciated. Two important aspects of this include fear of cancer recurrence (FCR) and prostate-specific antigen (PSA) anxiety. However, their prevalence, severity and associating factors remain poorly understood. Therefore, this review aims to evaluate the current evidence for the prevalence, severity and associating features of PSA anxiety and FCR. Methods A systematic search of MEDLINE, EMBASE and PsycINFO databases was conducted by two independent reviewers. Observational studies measuring FCR and PSA anxiety in prostate cancer using validated measures were included. Outcome measures were prevalence of significant levels, mean scores and significant correlations of FCR and PSA anxiety scores with patient, disease, treatment or other mental health and quality of life outcomes. Results One thousand one hundred forty-eight individual records underwent screening with 32 studies included. Median prevalence of significant FCR and PSA anxiety was 16% and 22% respectively across all studies. Longitudinal studies demonstrated severity of both symptoms peaks at diagnosis, with little variability, even several years following this. Evaluating associating factors revealed younger age, generalised quality of life and mental health symptoms to be important factors for both outcomes. Few studies evaluated associations and differences between other patient, disease and treatment characteristics. Conclusion FCR and PSA anxiety are prominent symptoms for prostate cancer patients and importantly when present, are associated with poorer quality of life and mental health symptoms. Screening for these constructs and referral to appropriate services should form part of routine follow-up care.

Background Prostate cancer remains the most commonly diagnosed male cancer in Europe with increasing 10-year survival rates now reaching 80% [1]. Growing global incidences have been attributed to wider utilisation of prostate-specific antigen (PSA) screening resulting in more localised prostate cancer diagnoses. Combining these factors has led to a belief that prostate cancer can often be classified as a chronic condition [2], and as such, issues beyond the pure physical health of the patient are prominent. The psychological impact of prostate cancer is now increasingly recognised [3]. However, it is important to look beyond formal mental health disorders when considering the mental wellbeing of individuals, with other distinct constructs being important for mental wellbeing [4]. Fear of cancer recurrence (FCR) is one of these, being reported as the most common unmet cancer need at 5 years post survival [5]. A common definition describes this as the “Fear, worry, or concern relating to the possibility that cancer will come back or progress” [6]. Despite frequently being neglected during care, FCR is a known significant factor in both physical and mental health for prostate cancer survivors [7]. FCR has already been widely explored in other cancers including breast and testicular cancer where it is not only demonstrated to be present in different levels in 30% of survivors, but has additionally been shown to have a significant correlation with poorer general quality of life and other wellbeing issues such as self-esteem [8]. PSA testing and monitoring poses another distinct source of anxiety for patients [7], with PSA anxiety (previously described as PSAdynia) being a unique problem in prostate cancer. This is commonly seen as the “state of physical or emotional distress due to an elevated PSA level” [9]. It can have a major impact on patients’ overall wellbeing, affecting how they view their symptoms. Both FCR and PSA anxiety are reported as two key factors for distress in patients and due to the usage of PSA testing as an investigation for recurrence have been demonstrated to be closely interlinked [10]. Higher PSA levels lead to higher levels of PSA anxiety and higher levels of generalised cancer-related anxiety [11]. However, despite the importance of FCR and PSA anxiety to mental wellbeing for prostate cancer patients, there remain varied findings in the literature as to their prevalence, severity and progression during the disease process. Furthermore, little is known about which associative factors and modulators are related to these symptoms and the impact they can have on a patient’s health. There are very heterogenous ideas over which factors act as modulators of FCR and PSA anxiety or not. Therefore, this systematic review aims to:

  1. 1.Identify the prevalence, severity and progression of FCR and PSA anxiety symptoms in prostate cancer patients.

  2. 2.Evaluate the evidence for the association between patient, disease or treatment characteristics and FCR and PSA anxiety symptoms.

  3. 3.Assess the relationship between FCR and PSA anxiety and other psychological and quality of life outcomes and their impact on mental wellbeing.

Methods This review was conducted adhering to the synthesis without meta-analysis (SWiM), the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and PRISMA-literature search extension (PRISMA-S) guidelines [12,13,14]. A priori protocol was registered on the Prospero database (CRD42020225154). Study eligibility criteria Inclusion criteria were observational studies with data available on FCR or PSA anxiety severity or prevalence in a prostate cancer sample. We included both cross-sectional and longitudinal cohort study (retrospective and prospective) designs. Participants undergoing any management option were included. Studies required the use of a previously validated psychometric tool to measure the outcomes of FCR and PSA anxiety, with prior evidence in a cancer population. We excluded all interventional studies, reviews and opinion articles. Conference abstracts with insufficient information for evaluation of study quality and papers without an English translation were also excluded. Where a study sample included a mixed cancer population, this was excluded if individual results for the prostate cancer population were not available. Duplicate datasets were excluded with the most up to date or comprehensive data selected. Lastly, we excluded studies if non-validated outcome measures were used to record FCR or PSA anxiety or if they measured other constructs of mental wellbeing such as generalised distress or anxiety. Information sources and search A systematic literature search was conducted on the MEDLINE (via Pubmed), EMBASE and PsycINFO (both via OvidSP) databases from inception to 24/08/2021. The search strategy was piloted prior to use and included a mixture of key words, MeSH terms and commonly used abbreviations relating to prostate cancer, FCR and PSA anxiety (online resource 1). Grey literature was searched through conference abstracts on EMBASE and potentially relevant ongoing studies on; however, no relevant ongoing studies were identified. Lastly, we conducted a reference review of included articles. Study selection Studies were independently screened by two reviewers (CJ and OB) through title, abstract and subsequently full-text review against inclusion criteria. Rayyan software was used to manage and screen identified studies [15]. Discrepancies during screening were discussed, until there was 100% agreement. Lastly, studies deemed as high risk of bias according to our study quality assessment were excluded from final inclusion at this stage. All studies excluded at the full-text stage are listed in online resource 2. Data collection and data items Two reviewers (CJ and OB) independently extracted data onto a pre-defined and piloted extraction sheet. Study characteristics extracted from included studies were author, study design, country of study, year of publication, psychometric tool utilised to assess outcome, cut-off used for caseness of outcome and time since diagnosis at data collection. Additionally, we extracted participant characteristics such as age, demographics and treatment received for their prostate cancer. Our outcome measures of interest extracted included data relating to the prevalence of significant levels of FCR or PSA anxiety, raw number of patients meeting cut-off, mean scores of utilised measures for FCR and PSA anxiety, correlations between patient factors and FCR/PSA anxiety as measured by correlation scores. In addition, both the severity and progression over time of each construct were assessed using the most commonly used scale to measure each construct. The full study characteristics are provided in online resource 3. Summary measures and synthesis of results A meta-analysis was found to be unfeasible due to heterogenous designs of studies and reporting of outcomes. Therefore, a structure qualitative synthesis was conducted. Studies were first grouped through the constructs they were measuring (FCR or PSA anxiety) and subsequently through the aim of the review they addressed. Descriptive statistics were utilised to describe some outcomes of interest including prevalence of significant symptoms, mean and median scores. Due to heterogeneity of data, vote counting was used to measure the direction of effect, with study risk of bias rating and size of effect used to measure the clinical significance of findings. Study quality Individual study risk of bias evaluation was conducted using the Joanna Briggs Institute (JBI) checklist (online resource 4) for cross-sectional and cohort studies, depending on study design, by two independent reviewers (CJ and OE) [16]. These were selected as they allowed for evaluation of the internal and external validity of observational studies with varying designs. Total scores were calculated with pre-determined cut-offs based around percentage scores. A total score of 0–4 represented a high risk of bias, 5–6 a moderate and > 7 a low risk of bias. Studies with a high risk of bias were subsequently excluded from the review.

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