Psychological management of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): a systematic review

Database sources and searches

The review was registered in the International Prospective Register of Systematic Review (PROSPERO; CRD4201912746). The design, conduct and reporting of studies were based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA 2020) [22] statement. Six databases were searched. Medline and Embase were searched because they are the most comprehensive sources of reported control trials [23]. Web of Science, Scopus, PsycINFO and CINAHL were also searched because they are subject-specific databases that provide valuable information about various psychological interventions. Each phrase of the search strategy was searched in the categories “title” and “abstract” and, where possible, in the controlled vocabulary or thesaurus (e.g., MeSH, Emtree, CINHAL headings, and PsychINFO thesaurus) of the particular database. Adaptations of the search strategy were made for databases that do not have subject headings and/or limitations in the composition of search terms. Hand searching was also performed on reference lists of full-text articles in order to capture publications that may be overlooked in the online search.

To detect as many relevant studies as possible, the search terms focused on a set of words that are: (1) synonyms for the pain condition, (2) synonyms for the psychotherapy, (3) synonyms for the treatment modality and (4) synonyms for multimodal or non-pharmacological treatment. As the phrase “persistent pelvic pain” only captures studies with female participants, which was not included in the search terms. Synonyms for each group were connected using the Boolean operator OR and the groups between pain conditions and treatment-related terms were connected with AND. The full search strategy is provided in the Supplementary Appendix.

Study selection

Inclusion criteria were developed to capture all relevant studies regarding psychotherapy for CP/CPPS, and these were based on five domains: (a) study type – any primary research with quantitative study type, e.g., retrospective or prospective studies; (b) population – males who were over 18 years of age and were claimed to have CP/CPPS or prostatitis-liked symptoms by the study authors; (c) intervention – modalities of psychotherapy were specified as either active or passive treatment and delivery as either individual- or group-based treatment; (d) outcome – pain reduction, improvement in the QoL and/or improvement in psychological symptoms as primary outcome parameters; and (e) publication – studies written in English or Chinese; studies written in other languages were excluded. Studies were only eligible if they were original work published in peer-reviewed journals; other types of publication such as congress-presentation or posters were excluded.

Screening and data collection

Two independent researchers (AL, LVN) scanned titles and abstracts of yielded articles for inclusion in the present review. The full texts of eligible studies were retrieved for further screening. A third researcher (AW) were involved in the screening process for studies written in Chinese. To minimise errors and subjective judgements, researchers conducted the screening independently. Where consensus among the first three researchers cannot be reached, a fourth researcher (MM) made the final determination. Any inconsistencies were resolved by discussion.

Assessment of quality of studies and risk of bias

Studies were ranked in hierarchical order according to the study type using the Oxford Levels of Evidence created by OCEBM Levels of Evidence Working Group [24]. A study with a higher ranking (from level 1 to 4) has more methodological strengths in its study design than those with a lower ranking [25]. Assessments of study quality were performed using the Quality Assessment Tool for Quantitative Studies developed by Effective Public Health Practice Project (EPHPP) [26, 27]. This tool assesses eight domains of risk of bias, including (A) selection bias, (B) allocation bias, (C) confounders, (D) blinding, (E) data collection methods, (F) withdrawals and dropouts, (G) intervention integrity, and (H) analysis. Each domain can be rated using the criteria of “strong”, “moderate” and “weak” to indicate quality and “low”, “moderate” and “high” to indicate risk of bias. For the determination of overall study quality, a study was assessed as “strong” if no weak ratings from (A) to (F) were obtained, “moderate” if one weak rating was obtained and “weak” when two or more weak ratings were obtained.

The first two researchers (AL, LVN) assessed the risk of bias and study quality using the assessment tool, and the third researcher (AW) involved in the assessment for studies written in Chinese. The full consensus was reached among the first three authors.

Data synthesis and analysis

Narrative data synthesis was conducted using Guidance on the Conduct of Narrative Synthesis in Systematic Reviews [28]. This type of analysis was conducted given the heterogeneous nature of the studies included in the review.

Search results

The Covidence software was employed in the process of screening and articles identification. The initial search returned 4,503 potential studies. After the removal of duplicates, 3,518 studies were screened by title and abstract. 3,475 studies were excluded according to the selection criteria, resulting in 43 studies being eligible for full-text screening with 100% inter-rater agreement. Of the 43 eligible studies, only 40 of them were able to retrieve the full-text articles. After assessing the full-text articles, 34 studies were further excluded because of: study type (e.g., treatment protocol, phenotype directed therapy, 14 studies), population (e.g., female patients or missing information of pain condition or patients’ characteristics, three studies), intervention (e.g., no psychological interventions used, four studies), publication (e.g., written in Russian and German, conference paper, six studies), and others (e.g., duplicates, same population, six studies). An additional study was identified by citation searching. In total, seven studies met the selection criteria and were included in the narrative review. The search was extended through November 2021 to ensure relevant studies were included at the time of publication, and no additional studies were identified. The PRISMA 2020 flow diagram is shown in Figure 1 that summarises the screening process and final search results.

Figure 1:

PRISMA 2020 flowchart illustrating search and screening process of the systematic review.

Overview of study characteristics

The seven studies included research from America, Canada and China, published from 2006 to 2018. Six studies included male participants with a diagnosis of either NIH Type IIIa/IIIb prostatitis, and one study recruited male and female participants with urological chronic pelvic pain syndrome (UCPPS) diagnosis. These studies were heterogeneous in terms of design, intervention evaluated, and outcome measurements. The information of characteristics for each study (including country, population, study type, number of participants, age, symptom duration and setting/context) is shown in Table 1.

Three modalities of psychological intervention were implemented in these included studies. Two studies [17, 18] included group-based CBT with key strategies including identifying and modifying unhelpful thoughts/behaviours, relaxation techniques, and coping skills training. Two studies [32, 33] included cognitive therapy (CT) that focuses on identifying and changing irrational/anxiety-provoking thoughts. Three studies [29], [30], [31] included paradoxical relaxation training delivered by (clinical) psychologists that aims to modify the habitual tendency to tighten pelvic floor muscle and to reduce anxiety. Of the seven included studies, six studies reported treatment regime combining psychological intervention with physiotherapy and/or drug treatment, e.g., myofascial trigger point release with paradoxical relaxation training, CT with drug-alone treatment and CBT with drug-alone treatment. One study pilot-tested psychological intervention – CBT as an active treatment in the management of CP/CPPS. The detailed information of psychological intervention is shown in Table 2.

Regarding the measurements, there was substantial variability in outcomes and domains measured across the seven studies. All studies employed the National of Institute of Health – Chronic Prostatitis Symptom Index (NIH-CPSI) to assess treatment outcomes, except for one study [31] using a 10-points Likert scale. All studies reported primary outcomes of interests of pain level and urinary symptoms. However, the psychosocial outcomes were only reported in six out of seven studies; these outcomes are QoL impact, anxiety, depression/depressive symptoms, pain catastrophising cognition, sexual function, erectile dysfunction and perceived social support. The outcomes and domains measured in each study can be seen in Table 3 and Figure 2.

Figure 2:

Variability in outcomes and domains measured in included studies. NIH-CPSI, The National Institutes of Health Chronic Prostatitis Symptom Index.

Assessment of quality of studies and risk of bias

The study types included case-series studies (retrospective and prospective), cohort study (prospective), repeated measures study and RCTs. All studies examined the effects of pre-post treatment, and only four studied included randomisation and control groups (but not placebo groups) for comparison with the treatment of interest.

Following the Oxford Level of Evidence [24], three of the seven included studies were RCTs [18, 32, 33] and were ranked as evidence level 2. The cohort [31] and repeated measures studies [17] were ranked as evidence level 3. The remaining two studies were case-series studies [29, 30], with a ranking of evidence level 4.

Figure 3 provide a summary of the risk of bias and quality assessment for all studies. All studies received at least three ratings of “weak” quality or “high” risk of bias using the EPHPP criteria. Confounders bias and the lack of Blinding are main areas of concern. All studies were rated as “weak” or “high” in these two criteria, indicating that all included studies did not conduct adequate measures to manage these procedures.

Figure 3:

Risk of bias and study quality assessment for the eight criteria. Colour green indicated “low” risk of bias and “strong” quality and; Colour yellow indicated “moderate” risk of bias and “moderate” quality; Colour red indicated “high” risk of bias and “low” quality and, colour red. Overall ratings of study quality: study was assessed as “strong” if no weak ratings from (A) to (F) were obtained, “moderate” if one weak rating was obtained and “weak” when two or more weak ratings were obtained.

Study results

The seven studies were grouped according to the modality of psychotherapy implemented as intervention, and the following paragraphs summarise the study results of the different interventions. The results of each study are shown in Table 3.

Evidence of psychological interventions

This systematic review synthesised the available evidence regarding psychological intervention for men with CP/CPPS and their efficacy. A total of seven studies were examined according to the Oxford Level of Evidence [24] – three studies were RCT with a higher ranking of evidence level 2; two studies were the cohort and repeated measures studies and were ranked as evidence level 3; the remaining two studies were case-series studies with evidence level 4. Evidence from all levels demonstrated the potential benefit of integrating psychological interventions in the treatment of CP/CPPS in improving pain, total symptoms and psychological outcomes. Also, preliminary evidence suggests using psychological interaction as an active treatment for CP/CPPS, with significant outcomes on pain reduction and improvements in some aspects of psychosocial symptoms.

A reduction by six points or more in NIH-CPSI total symptoms score has been considered a clinically meaningful change in CP/CPPS condition [34]. The findings in this review indicated that psychological interventions combined with drug treatment produced clinically meaningful outcomes for CP/CPPS (MD in NIH-CPSI total score −7.25 to −14). The effect is comparable to other non-pharmacological approaches and even outweighs the drug-alone treatment [19, 21] Moreover, the findings indicated that combining psychological interventions with drug treatment improves psychosocial outcomes.

Limitations to the evidence: gaps in the literature

Despite some evidence for the utility of psychological components for CP/CPPS, the evidence is subject to a high risk of bias. One striking result was that the overall study quality for all included studies was rated as “weak”. All studies were subject to a high risk of confounding bias; they did not implement adequate measures to control for the possible confounding effects. Most studies considered the combined treatment as one unit for the management of CP/CPPS and did not measure the individual effect of each treatment component. Therefore, the results could not show how much treatment outcomes are accounted for by psychological components. Moreover, most studies did not systematically examine or control for the possible confounders, for instance, engagement in sedentary job [35], alcohol consumption [35], and history of anxiety, depressive and trauma-related disorder [36, 37]. Furthermore, all included studies did not implement the blinding procedure that may inflate the risk of performance bias – participants in the experimental group receive more clinical attention from researchers/practitioners than the other groups. Selection and allocation biases also existed in most studies, which further limit the generalisability of the evidence.

In addition to methodological issues, some practical issues may limit the reliability of the evidence. While we extensively searched for the literature on psychosocial interventions for CP/CPPS, only seven studies were found. Due to the small number, conducting a meta-analysis was impossible. Consequently, clear estimates of effect size for different types of psychosocial interventions are not available. Also, most included studies did not use validated measure for (or did not measure) psychosocial outcomes. It is difficult to conclude how psychological intervention improves the psychosocial symptoms in patients with CP/CPPS.

Recommendations for psychological interventions for CP/CPPS

CP/CPPS is a complex condition that requires a management plan beyond the biomedical approach. Updated treatment guidelines [12, 13, 38] recommend psychological interventions as part of the treatment component for CP/CPPS. The findings of this review provide some evidence of the additive effects of psychological interventions on reducing psychological symptoms when compared with monotherapy. This supports taking a biopsychosocial or multimodal approach for managing CP/CPPS.

As biopsychosocial conceptualisation of CP/CPPS is important, it is recommended that practitioners conduct a comprehensive assessment to identify therapeutic goals. Research has shown the mediating role of pain catastrophising on the relationship between pain and physical and mental QoL [39], and a reduction in pain catastrophising is associated with improved pain outcome and QoL [40, 41]. Other potential mediators of treatment include depression and anxiety [42], [43], [44]. We recommend practitioners routinely assess for catastrophising thoughts, depression and anxiety using psychometrically sound measures with established clinical cut-offs. These measures include, but are not limited to, Pain Catastrophising Scale (PCS) [45], Depression Anxiety Stress Scales – 21 items version (DASS-21) [46], Patient Health Questionnaire Depression Scale (PHQ-9) [47], or Generalized Anxiety Disorder – 7 items (GAD-7) [48]. A referral to psychological or psychiatric services is recommended if patients with CP/CPPS indicate a clinical or moderate level in these measures.

Recommendations for further research

Further research into psychosocial interventions for CP/CPPS should use a more rigorous methodology and carefully select outcome measures congruent with research questions and the intervention type. NIH-CPSI is widely used to assess pain, urinary symptoms and impact of QoL. However, this measurement is limited in its ability to characterise the complexity of CP/CPPS, especially the psychosocial components. Researchers are recommended to incorporate recommendations from The Initiative on Methods, Measurements and Pain Assessment in Clinical Trials (IMMPACT) [49, 50] when selecting outcome measures suitable for pain clinical trials. New research on psychosocial interventions for CP/CPPS should include psychometrically sound measures of psychosocial symptoms and experiences of CP/CPPS and pain cognitions.

Since CT and CBT appear to be promising, it is crucial to test these approaches in a rigorous study design, including a large sample size to minimise the potential biases. This will undoubtedly build upon the work that has been conducted in this area to date. Future research should also examine the effects of other psychological intervention programs such as Acceptance and Commitment Therapy. Moreover, it is recommended that future research involves the development of a treatment protocol including CBT and other evidence-based interventions and examine its treatment effects on important psychosocial mechanics in CP/CPPS.