Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations Elizabeth K. Bancroft*† , Sibel Saya*†, Elizabeth C. Page*†, Kathryn Myhill*†, Sarah Thomas*†, Jennifer Pope*†, Anthony Chamberlain*†, Rachel Hart‡, Wayne Glover‡, Jackie Cook§, Derek J. Rosario¶, Brian T. Helfand**, Christina Hutten Selkirk**, Rosemarie Davidson††, Mark Longmuir††, Diana M. Eccles‡‡§§, Neus Gadea¶¶, Carole Brewer***, Julian Barwell†††‡‡‡, Monica Salinas§§§, Lynn Greenhalgh¶¶¶, Marc Tischkowitz****, Alex Henderson††††, David Gareth Evans‡‡‡‡, Saundra S. Buys§§§§, IMPACT Study Steering Committee1, IMPACT Collaborators1, Rosalind A. Eeles*† and Neil K. Aaronson¶¶¶¶ *Oncogenetics Team, Royal Marsden NHS Foundation Trust, †Oncogenetics Team, Institute of Cancer Research, London, ‡Clinical Genetics Unit, Birmingham Women’s Hospital, Birmingham, §Sheffield Clinical Genetics Service, Sheffield Children’s Hospital, ¶Department of Urology, Royal Hallamshire Hospital, Sheffield, UK, **John and Carol Walter Center for Urological Health, NorthShore University HealthSystem, Evanston, IL, USA, ††Clinical Genetics Department, Queen Elizabeth University Hospital, Glasgow, ‡‡Wessex Clinical Genetics Service, Princess Anne Hospital, §§ Faculty of Medicine, University of Southampton, University Hospital Southampton NHS Foundation Trust, Southampton, UK, ¶¶High Risk and Cancer Prevention Clinic, Vall d’Hebron University Hospital, Barcelona, Spain, ***Clinical Genetics Department, Royal Devon and Exeter Hospital, Exeter, †††Department of Genetics, University of Leicester, ‡‡‡Clinical Genetics, University Hospitals Leicester, Leicester, UK, §§§Hereditary Cancer Programme, Catalan Institute of Oncology (ICO-IDIBELL, CIBERONC), L’Hospitalet de Llobregat, Barcelona, Spain, ¶¶¶Cheshire and Mersey Clinical Genetics Service, Liverpool Women’s Hospital, Liverpool, ****Academic Department of Medical Genetics, University of Cambridge, Cambridge, ††††Northern Genetics Service, Newcastle upon Tyne Hospitals, Newcastle, ‡‡‡‡Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK, §§§§ Huntsman Cancer Institute, University of Utah Health, Salt Lake City, UT, USA, and ¶¶¶¶Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands E.K.B. and S.S. are joint first authors. 1 Full listing supplied in Appendix S1. Objectives Results To report the baseline results of a longitudinal psychosocial A total of 432 men completed questionnaires: 98 and 160 had study that forms part of the IMPACT study, a multi-national mutations in BRCA1 and BRCA2 genes, respectively, and 174 investigation of targeted prostate cancer (PCa) screening were controls (familial mutation negative). Participants’ among men with a known pathogenic germline mutation in perception of PCa risk was influenced by genetic status. the BRCA1 or BRCA2 genes. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within Particpants and Methods normal range. IES mean intrusion and avoidance scores were Men enrolled in the IMPACT study were invited to significantly higher in BRCA1/BRCA2 carriers than in controls complete a questionnaire at collaborating sites prior to and were higher in men with increased PCa risk perception. each annual screening visit. The questionnaire included At the multivariate level, risk perception contributed more sociodemographic characteristics and the following significantly to variance in IES scores than genetic status. measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form Conclusion health survey (SF-36), Memorial Anxiety Scale for Prostate This is the first study to report the psychosocial profile of men Cancer, Cancer Worry Scale-Revised, risk perception and with BRCA1/BRCA2 mutations undergoing PCa screening. No knowledge. The results of the baseline questionnaire are clinically concerning levels of general or cancer-specific distress presented. or poor quality of life were detected in the cohort as a whole. A © 2018 The Authors BJU Int 2019; 123: 284–292 BJU International | doi:10.1111/bju.14412 wileyonlinelibrary.com published by John Wiley & Sons Ltd on behalf of BJU International. www.bjui.org This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Psychosocial impact of prostate screening small subset of participants reported higher levels of distress, Keywords suggesting the need for healthcare professionals offering PCa #pcsm, #ProstateCancer, BRCA1, BRCA2, psychosocial, screening to identify these risk factors and offer additional quality of life information and support to men seeking PCa screening. [15–17]. As BRCA1/BRCA2 mutations confer an increased Introduction disease risk and psychological distress [18], it is possible that Prostate cancer (PCa) is the most common non-melanoma higher levels of anxiety may exist in people with this tumour in men worldwide, with an estimated 1.1 million men mutation; however, risk perception has been shown not to diagnosed with PCa in 2012 [1]. Men with germline BRCA1 reflect true risk in both men with and without a family or BRCA2 gene mutations are known to be at an increased history of PCa. It has also been reported that cancer worry is risk of PCa. This risk is estimated to be 1.8–3.75-fold and high in men with a family history of PCa, with the number 2.5–8.6-fold increased by the age of 65 years for BRCA1 and of relatives dying from the disease predicting level of worry BRCA2 mutation carriers, respectively [2,3]. Whilst there is [18]; however, a low level of PCa worry has also been some debate about whether there is a true increased risk of reported in men with a close relative with PCa [19]. PCa for BRCA1 mutation carriers, there is solid evidence that Many issues arise when counselling men with BRCA1/BRCA2 BRCA2 mutation carriers present at a younger age and with mutations, and many factors affect the way in which men aggressive disease [4,5]; therefore, prostate screening and early react to and use information about their genetic status and detection could have an important role in reducing the risk of developing cancer [20–22]. So far, there have been few disease burden, particularly among BRCA2 mutation carriers investigations either into the HRQoL impact for a man with a [6]. BRCA1/BRCA2 mutation living with an increased risk of PCa, There is controversy about PCa screening using PSA testing or in those men who have gone on to develop PCa [23]. in the general population and the benefits and harms of Several studies have confirmed the feasibility of collecting screening have been widely debated [7]. The US Prevention HRQoL and psychosocial data as part of large PCa screening Services Task Force currently recommends shared decision- trials [16,24–28]. making for screening healthy men aged 55–69 years [7,8]. In the present study, we report the baseline results of a Additionally, PCa treatments have significant long-term side longitudinal HRQoL investigation carried out as part of the effects that can have an impact on masculine identity, IMPACT study. The specific aims of the study were to physical and psychosocial symptoms and health-related evaluate the baseline psychosocial profile of men in the quality of life (HRQoL). Research is therefore needed to IMPACT study and to identify possible predictors of high identify targeted screening tools that can improve the benefit levels of psychological distress or poor HRQoL. to harm ratio for PCa screening. The limited number of studies evaluating men with a family history of PCa have generally supported the use of screening Participants and Methods in this population [9–12]. To our knowledge, no studies, to Study Sample and Procedures date, have prospectively evaluated a PCa screening programme for BRCA1/2 mutation carriers. The IMPACT The IMPACT study recruited men from families with BRCA1 study (Identification of Men with a genetic predisposition to or BRCA2 mutations, with or without the familial mutation, ProstAte Cancer: Targeted Screening in men at higher genetic to a programme of annual PCa screening via PSA testing, for risk and controls) is an international, multicentre study a minimum of 5 years. The IMPACT study opened in 2005 evaluating the role of targeted PSA screening in men with and screening will end in 2019. The full design and methods BRCA1/2 mutations [6]. of the IMPACT study have previously been reported [6]. The IMPACT study protocol was approved by the West Midlands Evidence supports the theory that genetic testing for BRCA1 Research and Ethics Committee in the UK (reference 05/ and BRCA2 mutations does not have a significant long-term MRE07/25) and subsequently by each participating psychological impact on most people tested [13,14]. Studies in institution’s local ethics committee. men undergoing PCa screening suggest that a minority experience some anxiety, usually while waiting for results All men eligible for IMPACT were also eligible for the [15–17]. Risk factors for anxiety include having a family HRQoL study. Men were eligible for participation if they history of PCa, symptoms or abnormal genetic test results tested either positive, negative or were at 50% risk of © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International 285 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Bancroft et al. inheriting the familial BRCA1/BRCA2 mutation and were used the PCa anxiety (11 items) and PSA anxiety (3 items) aged 40–69 years. Men who tested negative for their familial scales [33]. The PCa anxiety scale is scored from 0 to 33 and mutation constituted the control group. Men were excluded if the PSA anxiety scale from 0 to 9, with a higher score they were known to have PCa at enrolment or if they had indicating higher anxiety levels. another cancer with a prognosis of <5 years survival. The HRQoL study was added to the IMPACT study protocol Health-Related Quality of Life in 2009. All sites were invited to participate in this sub-study. We assessed HRQoL using the 36-item short-form health Men enrolled in the IMPACT study at participating sites survey (SF-36) version 2.0 [34,35]. This questionnaire consists were approached by letter prior to their next scheduled study of eight subscales: physical functioning; social functioning; appointment inviting them to take part in the HRQoL study. role limitations attributable to physical problems; role The HRQoL study involves completing a set of questionnaires limitations attributable to emotional problems; mental health; annually for 5 years, with each assessment taking place prior vitality; pain; and general health. Summary scores are to the annual PSA test. Men were sent the questionnaires calculated for two broad areas of subjective well-being: ~4 weeks before their appointment and asked to post it back physical health and mental health. All scales are linearly or bring the completed questionnaire to their appointment. converted to a 0–100 scale, with a higher score representing Men were split into two cohorts: (i) a prospective arm, which better functioning. included men who joined the HRQoL study before their first PSA screening within the IMPACT study; and (ii) a truncated prospective arm, which included men already enrolled in the Risk Perception IMPACT study before joining the HRQoL study. The total Men were asked to rate their perceived risk of PCa compared target sample was a minimum of 300 men in each arm. In with the average man’s risk: lower; the same; slightly the present analysis, we report the results of the baseline increased; moderately increased; or strongly increased [36]. questionnaires in the prospective (not truncated) cohort. Study Measures Knowledge We developed a ‘knowledge’ questionnaire based on a measure Psychological Distress developed by Lerman et al. [37] and Wonderlick and Fine Distress was assessed using the Hospital Anxiety and Depression [38]. The nine true/false items (Fig. 1) assessed knowledge of Scale (HADS), the Impact of Event Scale (IES), the Cancer inheritance of BRCA1/BRCA2, the effect of having an altered Worry Scale-Revised (CWS-R), and the Memorial Anxiety Scale gene, and risk of PCa. Knowledge scores were created by for Prostate Cancer (MAX-PC). The HADS contains two sub- taking the sum of the correct responses to the nine items. scales of seven items that measure the presence and severity of The internal consistency reliability, as assessed by Cronbach’s general anxiety and depression [29]. Each subscale generates a coefficient a, was high for all measures used, ranging from score ranging from 0 to 21, and a score of >10 indicates clinically 0.79 for the SF-36 General Health scale to 0.96 for the SF-36 relevant levels of anxiety or depression. Role Physical scale. Fourteen of the 15 scales had an a The IES is a 15-item scale measuring PCa-specific distress coefficient >0.80. through the frequency of intrusive or avoidant thoughts about PCa [30]. Total scores on the intrusion and avoidance scales Statistical Analysis range from 0–35 to 0–40, respectively. A higher score The dataset contained a small amount of missing data. For all indicates more frequent intrusive/avoidant thoughts about scales, except the SF-36, if ≥75% of a subscale was complete risk of cancer; a score of >8.5 indicates clinically relevant then a total score (corrected for the total number of levels of distress. questions) was calculated. If <75% was completed, data were The CWS-R is a six-item scale that measures worry about the excluded. For the SF-36 score, scales were excluded when risk of developing cancer and the frequency and impact of there was <50% of a sub-scale completed, as per the that worry on mood and daily functioning [31,32]. The CWS- recommendation of the scale’s authors [39]. Ten percent of R uses a score of 1 (no worry) to 4 (maximum worry), giving the data entered were double-checked for coding accuracy a summative score between 4 and 24. A high score indicates and completeness, and no errors were identified. greater worry, but no clinical thresholds for the scores are The SPSS 22.0 statistical computer package (SPSS Inc., available. Chicago, IL, USA) was used to manage and analyse the data. The MAX-PC includes three scales assessing PCa anxiety, Scores for each questionnaire were calculated in accordance PSA anxiety, and fear of recurrence. In the present study, we with each scale’s scoring system. Descriptive statistics, © 2018 The Authors 286 BJU International published by John Wiley & Sons Ltd on behalf of BJU International 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Psychosocial impact of prostate screening Fig. 1 Knowledge questionnaire. True False 1. One-half of all cases of prostate cancer are caused by BRCA1/2 mutations. 2. A father can pass BRCA1/2 mutations to his daughters. 3. About one in 10 men have an altered BRCA1/2 gene. 4. There are many different genes that cause prostate cancer. 5. A man with an altered BRCA1/2 gene has a 50% chance of passing it to each of his children. 6. Even if a man does not have an altered BRCA1/2 gene, his children can get it from their grandmother / grandfather (his parents) i.e. the gene alteration can skip generations. 7. If a man carries a gene mutation associated with prostate cancer, he will always develop prostate cancer at some point during his lifetime. 8. If a man does not carry a gene mutation associated with prostate cancer, he will not develop prostate cancer. 9. Every man who has been diagnosed with prostate cancer carries a gene mutation associated with prostate cancer. including means and standard deviations, were used to Comorbidity Index score [40]. Knowledge of genetics and summarize the sample characteristics and questionnaire data. PCa and risk perception were also included as independent variables, to examine their impact on psychosocial outcomes. All psychometric scales (HADS, IES, SF-36, MAX-PC and CWS-R) were skewed towards better scores. Neither log nor The associations were investigated initially with ANOVA, square-root transformations of these scales produced normal Student’s t-tests, chi-squared tests and Pearson’s distributions, but given the large sample size within each correlations, as appropriate. For categorical independent genetic cohort, parametric tests were used. To minimize the variables, strength of association was calculated with potential effect of multiple testing on the Type I error rate, a Cohen’s d for any significant relationship. Subsequently, P value of <0.01 was regarded as statistically significant. multivariate linear regression analyses were performed employing all independent variables found to be associated Univariate analysis was used to examine if there were any significantly at the univariate level with a psychosocial measurable differences at baseline between BRCA1 mutation outcome. carriers, BRCA2 mutation carriers and controls on the dependent variables risk perception, HRQoL (SF-36), the psychological measures (HADS, IES, MAX-PC) or knowledge. As UK participants made up the largest proportion of Results participants, a UK dataset was used as a normative Sample Characteristics and Response Rate comparator for HRQoL, by randomly selecting individuals Of the 65 centres participating in the IMPACT study, 23 matched to our sample on age. Means were then compared agreed to take part in the HRQoL sub-study, including all 19 using a paired Student’s t-test [34]. Only those aged up to UK centres, two in Spain and two in the USA. The main 64 years were recruited to this large population-based study reasons for electing not to participate as a centre were therefore we limited the analysis to men aged 40–64 years financial; there was no specific funding to support this sub- from the IMPACT cohort for the comparison. study at collaborating sites outside of the UK. A total of 780 The impact of other variables on psychosocial outcomes was men enrolled in the HRQoL study, of whom 476 enrolled also explored. Independent variables included demographics prior to their first screening visit (prospective cohort, (age, employment status and education), prior PSA screening, reported in the present paper). This corresponds to 26% of family history of PCa, time since genetic testing, and the participants in the IMPACT study taking part in this sub- comorbidities coded from clinical interview into a Charlson study. Those who returned their questionnaire >1 month © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International 287 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Bancroft et al. after their initial screening visit or had not returned the study Table 2). BRCA2 mutation carriers were more likely to rate consent form were excluded (n = 35), as were nine men who their risk of PCa as moderately or strongly increased were untested for their familial mutation, remaining at 50% compared with the general population than the control risk. The data presented are therefore from 432 men, 351 of group. whom were recruited in the UK, 50 from the USA and 31 Knowledge scores were not affected by the genetic status of from Spain. No significant differences in responses were the participant, time since genetic testing or education level. observed between nationalities. Family history of PCa, education level, time since genetic Uptake into the HRQoL sub-study was 85–100% at testing and age were not significantly associated with any of participating sites. There was no significant difference in the the outcome variables. participants’ sociodemographics (employment status or education) between the men in this sub-study and those in SF-36 Questionnaire the parent IMPACT study. Overall physical functioning SF-36 scores did not differ In all, 98 men (22.7%) carried a mutation in the BRCA1 gene, significantly from the normative sample (IMPACT sample 160 (37.0%) carried a mutation in the BRCA2 gene and 174 aged 40–64 years mean score: 48.1; matched normative (40.3%) were controls. The median time from undergoing sample mean score: 47.5; P = 0.52). The overall mental genetic testing to joining the IMPACT study was 7.2 months functioning SF-36 score was significantly better in the study (range 0 months–15.4 years); 47.4% of men joined within cohort compared with the normative sample, but the effect 6 months of testing, and 39.6% of men had had at least one size was small and both mean values were close to the PSA measurement before they joined the IMPACT study. standardized mean of 50 (IMPACT sample aged 40–64 years The sociodemographic characteristics and family cancer mean score: 52.0; matched normative sample mean score: history of the cohort are shown in Table 1. The mean age of 49.8; P = 0.008, Cohen’s d = 0.21). Means also did not differ the men when they completed the baseline questionnaire was significantly across genetic groups. 53.1 years. The majority were white (98.9%) and in higher managerial or professional occupations (55.3%), and HADS Questionnaire employment and educations levels were similar to the UK The overall mean anxiety and depression scores for the general population, with 4.4% unemployed and 37.7% having HADS were 4.9 and 2.8, respectively, which were not higher college degrees or postgraduate qualifications [41,42]. than previously reported general population norms [43]. The means across different genetic risk groups also did not differ Risk Perception and Knowledge significantly (Table 2; anxiety: P = 0.99; depression: P = 0.75). Participants’ perception of their lifetime risk of PCa was None of the independent variables showed a significant influenced significantly by their carrier status (P < 0.001; association with either the anxiety or depression scores. Those with higher risk perception had slightly higher scores on the anxiety and depression scales (P = 0.02 and P = 0.03, respectively; Table 3), although the difference was not Table 1 Sociodemographic characteristics of the cohort. clinically significant. n % Education 415 96.1 IES, CWS, MAX-PC Questionnaires Pre-high school 108 25.0 High school or technical 144 33.3 At the univariate level, the mean intrusion and avoidance Degree or postgraduate 163 37.7 scores on the IES scale were significantly higher in both Employment 429 99.3 In active paid work 328 75.9 BRCA1 and BRCA2 mutation carriers compared with controls Retired 82 19.0 (intrusion: P = 0.001; avoidance: P < 0.001; Table 2) and Unemployed 19 4.4 higher in those who perceived their PCa risk as moderately Family history of prostate cancer 432 100 None 293 67.8 or strongly increased (intrusion: P < 0.001, avoidance: P = In ≥1 first degree relative 139 32.2 0.001; Table 3); however, at the multivariate level, risk Time since genetic testing 424 98.1 perception contributed more significantly to the variation in 0–3 months prior to enrolment 125 28.9 3–6 months 76 17.6 IES scores than genetic status (Table 4). 6–12 months 48 11.1 12–24 months 49 11.3 A similar pattern was seen for the cancer worry score. Scores 2–5 years 76 17.6 were generally low and univariately associated with genetic >5 years 50 11.6 status (CWS-R: P = 0.004; Table 2) and risk perception Age Mean: 53.1; Median: 53.0 SD: 8.5 (CWS: P < 0.001; Table 3). Again, risk perception was more © 2018 The Authors 288 BJU International published by John Wiley & Sons Ltd on behalf of BJU International 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Psychosocial impact of prostate screening Table 2 Descriptive statistics and summary of group comparisons for the psychosocial variables. Scale Scale range / Overall BRCA1 mutation BRCA2 mutation Controls Cohen’s d* threshold carriers carriers N Mean (SD) N Mean (SD) % N Mean (SD) N Mean (SD) % above above % above % above threshold threshold threshold threshold SF-36 physical Range 0–100 404 47.4 (10.0) 90 46.4 (10.7) 148 47.1 (10.1) 166 48.3 (8.6) component summary SF-36 mental Range 0–100 404 52.4 (10.2) 90 52.1 (11.1) 148 51.2 (10.5) 166 53.7 (9.3) component summary Total Range 0–21 431 4.9 (3.6) 97 4.9 (3.5) 160 4.8 (3.8) 174 4.9 (3.4) anxiety Abnormal ≥11 28 6.5% 6 6.2% 12 7.5% 10 5.7% (HADS) threshold Total Range 0–21 431 2.8 (3.0) 97 2.9 (3.2) 160 2.9 (3.1) 174 2.7 (2.7) depression Abnormal ≥11 9 2.1% 3 3.1% 4 2.5% 2 1.1% (HADS) threshold Total Range 0–35 423 2.3 (4.9) 94 3.0† (5.7) 158 3.1† (5.5) 171 1.3† (3.5) 0.02; 0.35; 0.38 intrusion Abnormal ≥19 12 2.8% 4 4.3% 6 3.8% 2 1.2% (IES) threshold Total Range 0–40 418 4.3 (7.0) 93 6.0† (8.4) 156 5.1† (7.4) 169 2.6† (5.2) 0.11; 0.48; 0.39 avoidance Abnormal ≥19 32 7.7% 12 12.9% 15 9.6% 5 3.0% (IES) threshold Total Range 0-33 420 3.5 (5.4) 94 4.1 (5.5) 156 3.9 (6.2) 170 2.8 (4.6) MAX-PC Total cancer Range 4–24 430 9.5 (2.5) 97 9.7† (2.7) 160 9.9† (2.7) 173 9.1† (2.0) 0.09; 0.25; 0.36 worry Risk 423 N/A 91 N/A 156 N/A 171 N/A perception Moderately 133 31.4% 31 32.3%‡ 86 55.1%‡ 16 9.4%‡ 0.43§ or strongly increased Total Range 0–9 404 7.1 (1.7) 92 6.9 (1.8) 151 7.2 (1.6) 161 7.1 (1.7) knowledge score HADS, Hospital Anxiety and Depression Scale; IES, Impact of Event Scale; MAX-PC, Memorial Anxiety Scale for Prostate Cancer; SF-36, 36-item short-form health survey. *Cohen’s d values are listed comparing BRCA1 mutation carriers with BRCA2 mutation carriers; BRCA1 mutation carriers with controls; BRCA2 mutation carriers with controls. † P < 0.01 using ANOVA. ‡P < 0.01 using a chi-squared test for independence. §Cramer’s V test for nominal association. Bold font indicates statistically significant values. Table 3 Means of psychosocial scales according to risk perception categories. Discussion Scale (mean Risk perception P Cohen’s d This study investigated the baseline HRQoL and psychosocial scores) profiles of men taking part in the IMPACT study, prior to Not or Moderately/ slightly strongly their first screening appointment. The results indicate that increased increased participants, in general, do not have clinically concerning HADS anxiety 4.54 5.43 0.02 levels of general or cancer-specific distress (i.e. indicative of HADS depression 2.55 3.23 0.03 the presence of clinical depression or anxiety) or poor IES intrusion 1.33 4.42 <0.001 0.57 HRQoL. A small subset of participants had higher levels of IES avoidance 3.32 6.11 0.001 0.39 MAX-PC (PCa) 2.62 5.32 <0.001 0.47 distress, but perception of risk contributed more to explaining CWS-R 8.89 10.84 <0.001 0.76 the variance in distress level than did genetic status. General CWS-R, Cancer Worry Scale-Revised; HADS, Hospital Anxiety and Depression Scale; population screening studies in the UK and European series IES, Impact of Event Scale; MAX-PC, Memorial Anxiety Scale for Prostate Cancer; have reported similar findings: that PCa screening does not PCa, prostate cancer; SF-36, 36-item short-form health survey. have a detrimental effect on measures of HRQoL and psychological health [28,44,45]. highly associated with higher cancer worry than genetic status It was reassuring that participants’ perceptions of PCa risk in the multivariate model (Table 4). were influenced by carrier status, largely reflecting what Scores for PCa anxiety (MAX-PC) were only associated with would have been communicated during genetic counselling risk perception (P < 0.001), therefore, a multivariate analysis [2,3]. As expected, BRCA2 mutation carriers had the highest was not undertaken. perceived risk of PCa, most frequently classifying risk as © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International 289 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Bancroft et al. Table 4 Results of multivariable linear regression analysis for the Hospital Anxiety and Depression Scale, Impact of Events Intrusion and Avoidance, and Cancer Worry Scale-Revised. Variables B SE T P R2 R2 change IES intrusion Risk perception 2.92 0.55 5.32 <0.001 0.087 0.087 BRCA2 status 0.42 0.58 0.72 0.47 0.087 0.000 BRCA1 status 0.98 0.62 1.59 0.11 0.092 0.006 IES avoidance Risk perception 2.18 0.81 2.70 0.007 0.058 0.017 BRCA2 status 1.50 0.85 1.76 0.08 0.042 0.025 BRCA1 status 2.88 0.91 3.18 0.002 0.017 0.017 CWS-R Risk perception 1.98 0.27 7.46 <0.001 0.137 0.137 BRCA2 status –0.07 0.28 –0.24 0.81 0.138 0.001 BRCA1 status 0.14 0.30 0.47 0.64 0.138 0.000 CWS-R, Cancer Worry Scale-Revised; HADS, Hospital Anxiety and Depression Scale; IES, Impact of Event Scale. Variables included represent those significant on the univariate level. ‘slightly’ or ‘moderately’ increased, and controls most In terms of general distress, scores were within previously frequently classifying risk as the ‘same’ as the general reported population norms [43] and no differences were population. observed between mutation carriers and controls. For cancer- specific distress, a significant difference was found between Knowledge levels were high across the cohorts, irrespective of BRCA mutation carriers and controls for both the IES and genetic status, education level and time since testing, showing CWS; however the differences were small and mean scores that men retained accurate information about inheritance of remained below clinically relevant levels for the IES. BRCA1/BRCA2 mutations and cancer risk. The knowledge Importantly, at the multivariate level, risk perception was questionnaire was designed specifically for this study, but was found to have a stronger association with distress levels than adapted from that used in other studies [37,38]. These studies genetic status itself. reported knowledge levels to be ~50% in women at risk of breast cancer prior to BRCA1/BRCA2 testing. The high levels No significant association was observed between anxiety and of knowledge reported in our cohort could reflect that they having a family history of PCa, supporting previous reports have recently revisited their risk status in making a decision [15,24,28,44,46]. Men reporting higher PCa risk perception to undergo screening in the IMPACT study; however, men were found to have consistently higher scores across all were asked to complete these questionnaires prior to their psychological distress scales (general and cancer-specific). first screening appointment and so may not have had a Similar results were reported by Taylor et al. [24]; however, the detailed discussion about risk of PCa since being informed effect size was small across all scales and no group had a mean about their genetic status. distress score that reached clinically significant levels, where such thresholds were available [30,43]. It is therefore fair to The sociodemographic characteristics of the cohort indicate conclude that, whilst having a modest impact on men’s distress that employment and education levels are similar to those levels, a high perceived PCa risk is not associated strongly with observed in the UK general population [41,42]; however, clinically significant levels of distress in this cohort. participants were predominantly white, which is not representative of the general UK population, and therefore A number of studies have reported that anxiety about cancer caution should be exercised in generalizing these results to screening affects a small number of people who are other ethnic groups. predisposed to anxiety, and that this anxiety continues throughout participation in cancer screening [16,27,28,44,47]. The HRQoL assessments did not detect any clinically relevant Our data support this finding, with a small proportion of differences in either physical or mental health when men reporting clinically significant levels of distress. It will be compared with general population samples, both matched important to compare these baseline levels with subsequent and unmatched by age [34]. Our results support those of the screening rounds in the IMPACT study and to include Finnish European Randomized Screening for Prostate Cancer previous high PSA results as a covariate, as both the study cohort in which HRQoL was also assessed with the SF- European and US screening studies report high levels of 36 [45]. As in our cohort, HRQoL scores were observed to be anxiety in men with previously elevated PSA levels [26,27]. higher than in the general Finnish population [45], but not at Identifying men with a predisposition to high levels of clinically significant levels; this was hypothesized to be psychological distress could facilitate providing timely support because the men were generally healthy and well educated; to manage this distress and potentially increase adherence to however the Finnish cohort was not age-matched, which may screening recommendations. have conferred some bias. © 2018 The Authors 290 BJU International published by John Wiley & Sons Ltd on behalf of BJU International 1464410x, 2019, 2, Downloaded from https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.14412 by Readcube (Labtiva Inc.), Wiley Online Library on [24/11/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License Psychosocial impact of prostate screening We did not observe a significant association between distress to be aware of these predictors of distress so that men with and age. While this supports several earlier studies [16,44], potential for heightened distress can be identified and one study reported an inverse relationship between age and adequate counselling and support can be offered. Follow-up distress levels [27]. data will determine whether these factors have an impact on adherence to screening and whether men experiencing It is important to consider whether we would have observed abnormal PSA results experience more distress. different results if all men in the IMPACT study had been included in this psychosocial sub-study; however we found no difference in sociodemographic characteristics between Acknowledgements the men in the sub-study and those in the IMPACT study This research was coordinated by the Institute of Cancer as a whole. It could be that those more predisposed to Research, London, UK and is supported by grants from anxiety may be inclined not to join the psychosocial sub- Cancer Research UK (Grant references (C5047/A21332, study; however, no evidence of this has been found by C5047/A13232 and C5047/A17528) and the Ronald and Rita others [28]. McAulay Foundation. We acknowledge support from the National Institute for Health Research (NIHR) to the We obtained a very high uptake level for the psychosocial Biomedical Research Centres at The Institute of Cancer sub-study, with at least 85% opting in at participating sites. Research and Royal Marsden Foundation NHS Trust, at Uptake was also found to be high in the European Central Manchester Foundation Trust and the Oxford Randomized study of Screening for Prostate Cancer Swedish Biomedical Research Centre Programme. The Institute of cohort, with 84–94% of men with abnormal PSA levels Cancer Research is the Sponsor of the IMPACT study. We completing a questionnaire measuring anxiety levels [27]. The thank Mr and Mrs Jack Baker for support for the study in high participation rate is probably attributable to the NorthShore University HealthSystem, Evanston, IL, USA. embedding of this psychosocial study into an existing screening study, and therefore inviting participants who are already highly motivated to contribute to research. Conflict of Interest Prof. Rosalind Eeles: Janssen Pharmaceutica, provided A strength of the present study is the use of a number of medical education support to GU ASCO February 2013, and different, standardized psychological measures that offer received an honorarium and expenses for attending and extensive insight into the psychosocial profile of the speaking at the UK Cancer Convention, October 2013 from participants and that allow comparison of the results with a Succinct Communications. The remaining authors have no number of other PCa screening studies that have used the other conflict of interest to declare. same or similar measures. 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Additional supporting information may be found online in 31 Lerman C, Trock B, Rimer BK, Boyce A, Jepson C, Engstrom PF. the Supporting Information section at the end of the article. Psychological and behavioural implications of abnormal mammograms. Ann Intern Med 1991; 114: 657–61 Appendix S1. The IMPACT Collaborators. © 2018 The Authors 292 BJU International published by John Wiley & Sons Ltd on behalf of BJU International