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Platinum Priority – Review – Prostate Cancer
Editorial by Chris H. Bangma, Riccardo Valdagni, Peter R. Carroll, Hein van Poppel, Laurence Klotz and Jonas Hugosson on pp. 646–648 of this issue

How Does Active Surveillance for Prostate Cancer Affect Quality of Life? A Systematic Review

By: Lara Bellarditaa , Riccardo Valdagnia b, Roderick van den Berghc, Hans Randsdorpe, Claudia Repettoa, Lionne D.F. Venderbosd, J. Athene Lanef and Ida J. Korfageg

European Urology, Volume 67 Issue 4, April 2015, Pages 637-645

Published online: 01 April 2015

Keywords: Prostate cancer, Active surveillance, Health-related quality of life, Depression, Anxiety, Well-being, Systematic review

Abstract Full Text Full Text PDF (350 KB) Patient Summary

Abstract

Context

The optimal management of screen-detected, localised prostate cancer remains controversial, related to overtreatment issues of screening and the nonrandomised evidence base. Active surveillance (AS) aims to delay or avoid curative therapy but may potentially harm patients’ well-being through living with untreated prostate cancer.

Objective

To systematically review the literature on quality of life (QoL) in patients undergoing AS.

Evidence acquisition

Embase, Medline, Psychinfo, Cochrane Central, Web of Science, and PubMed databases were searched in May 2014 using quality of life, active surveillance, prostate cancer, their synonyms, and targeted manual searches. The psychological dimensions related to health-related QoL (HRQoL) outcomes were anxiety and depression, distress, decisional conflict, and mental health.

Evidence synthesis

Ten clinical and research-based AS studies worldwide measured HRQoL and related psychological facets in six cross-sectional studies and four cohorts (follow-up: 9–36 mo; published: 2006–2014). Six studies were linked to published AS cohorts. In total, 966 men undergoing AS (mean: 102 per study) were assessed (mean age: 66 yr). AS patients had good overall HRQoL scores, which were comparable or better than those of patients undergoing postradical treatment (comparator group in four studies), men's partners (one study) and population-based data (three studies). Anxiety and depression scores were favourable. Selection bias may be present, as none were randomised comparisons. Decreased psychological well-being may be partly predicted by AS patients’ baseline and clinical characteristics.

Conclusions

Patients undergoing AS reported good QoL and did not appear to suffer major negative psychological impacts. Longer follow-up is required as well as investigation into which patients are predisposed to negative impact and leaving AS prematurely.

Patient summary

We reviewed the published evidence for quality-of-life impact on men with prostate cancer being monitored by active surveillance. The men who were on active surveillance usually reported good levels of well-being and did not appear to suffer major negative psychological impacts. The research findings suggest little presence of anxiety and depression and high overall quality of life related to their disease. However, there are few long-term studies, so more high-quality research is needed to make definitive recommendations.

Take Home Message

Active surveillance for prostate cancer appears to have no major impacts on health-related quality of life and psychological well-being in the first few years; however, there is no randomised evidence, and results are limited over the longer term.

Keywords: Prostate cancer, Active surveillance, Health-related quality of life, Depression, Anxiety, Well-being, Systematic review.

1. Introduction

The incidence of prostate cancer (PCa) worldwide is increasing as opportunistic screening becomes more widespread and average life expectancy rises [1]. A large randomised controlled trial showed disease-specific mortality benefits to population-based PCa screening in Europe [2] and [3] with less clear results in a similar trial in the United States [4], possibly due to the high rates of prostate-specific antigen (PSA) testing in their control group. However, both overdiagnosis and resulting overtreatment are problematic sequelae of PCa screening, due to the low diagnostic specificity of PSA levels and prostatic biopsies.

Active surveillance (AS) is an option for patients with favourable risk, localised PCa; AS aims to avoid or delay radical treatments without compromising long-term, disease-specific survival. AS involves regular monitoring by multimode imaging, PSA levels, and prostatic biopsies [5], [6], and [7]. AS has existed for around 15 yr worldwide, although uptake has generally been modest outside established research cohorts such as the Prostate Cancer International Active Surveillance (PRIAS) study [8]. However, recent prominence of AS in American and European PCa management guidelines will potentially further increase use of this approach [9].

Radical treatment can have lifelong impact on patients’ quality of life (QoL), including erectile, rectal, and urinary dysfunction [10]. Patients undergoing AS can potentially avoid these consequences of radical treatment but may suffer negative psychological effects due to living with an untreated cancer and the fear of disease progression [11], [12], and [13]. If AS patients experience heightened distress and anxiety, they are potentially more likely to opt for radical treatment in advance of protocol-based recommendations [14].

The need to understand the potential psychological burden of AS was identified during an international AS conference in February 2014 in Amsterdam. This systematic review aimed to evaluate the published evidence on the health-related quality of life (HRQoL) and its related psychological dimensions in men undergoing AS, to help inform clinical practice and treatment decision making. Previous literature reviews in this area were nonsystematic [13], [14], and [15], combined HRQoL studies of AS patients and of those undergoing passive observation without radical intervention (watchful waiting [WW]) for patients unsuitable for radical treatment [12], or were focused on the clinical outcomes of AS [5].

2. Evidence acquisition

This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines [16] with predefined search terms, inclusion and exclusion criteria, data collection, and analysis processes.

2.1. Study eligibility criteria

All study designs with quantitative HRQoL data from men with localised PCa receiving AS were eligible (without age restriction). This review focused on overall HRQoL and on the psychological dimensions related to HRQoL, namely, anxiety, depression, decisional conflict, coping, distress, satisfaction, and mental health, as well as other psychological factors potentially related to AS as shown in previous qualitative studies (eg, uncertainty) and measured with standardised or validated questionnaires. Studies purely reporting on the physical aspects of HRQoL (eg, urinary or bowel symptoms or erectile function) were ineligible. Studies either with men receiving WW or where it was unclear if they were AS patients were excluded as QoL data, for data on men on WW are not comparable to that of men on AS, given the palliative aim of WW versus the curative intent of AS [9] and [17]. Full-text original articles in English were eligible without restriction on publication date. If multiple papers originated from one dataset, we included the one with the longest follow-up period.

2.2. Search strategy and study selection

Studies were identified by searching electronic databases and scanning reference lists of selected articles. In May 2014, Embase, Medline, Psychinfo, Cochrane Central, Web of Science, and PubMed (Supplement 1) were searched using quality of life, active surveillance and prostate cancer and their relevant synonyms. Reference lists were also searched for potentially eligible publications and previous literature reviews of QoL and AS [13], [14], and [15]. Two authors (I.J.K., L.B.) independently screened all the titles and abstracts and the resulting reference list was compiled by a third author (J.A.L.) for full-text screening and data extraction. Disagreements were resolved by consensus.

2.3. Data collection

Three authors (J.A.L., I.J.K., L.B.) extracted data onto a form that was designed and piloted on six AS studies for one-third of the selected references. Two other authors (L.D.F.V., R.vdB.) each checked one-half of the data extraction forms (randomly assigned) against the full-text papers. Data extracted included study design, setting, timing of HRQoL assessments, country, AS protocol, outcomes, follow-up duration, study population (clinical, research, or population registry), HRQoL data collection methods, inclusion and exclusion criteria, risk of bias, standardised and validated questionnaires, number of participants, response rates, responder and nonresponder characteristics, effect estimates for outcomes, and rates of leaving AS due to anxiety.

3. Evidence synthesis

The literature search identified 1157 unique citations (Fig. 1); 1087 citations were excluded as they were reviews, commentaries, abstracts, validation of questionnaires, or participants were on WW. Three citations were identified by searches of bibliographies, thus leaving 73 citations for a full-text screening. Of these, 63 citations were excluded. Major reasons for exclusion were that patients did not meet eligibility criteria for AS (n = 27), no mental QoL data were reported (n = 9), papers reported on reviews (n = 8), or that combined data were reported for men treated by various therapies (n = 4). Data extraction from these papers was concordant between the first and second reviewers. Table 1 presents the design, sample, and key methodological features of the 10 included studies.

gr1

Fig. 1 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) flow diagram [16].

Table 1 Overview of quality-of-life studies of active surveillance for prostate cancer

Study, publication dateQoL study designAssessment periodAS protocol: setting, country; total sample/response rateAS men, no. (mean age, yr)Men in control group, no. (mean age, yr); population data
Bellardita et al, 2013 [18]Cohort2007–2012PRIAS, research, Italy; 154/67%154 (67)None
Burnet et al, 2007 [19]Cross-sectionalNRRoyal Marsden Hospital, research, United Kingdom; 493/72% (24 excluded)100 (67)Radical treatment (HT or RT: 81) or postradical treatment (148)
Daubenmier et al, 2006 [20]Cross-sectionalNRUCSF, research, United States; 93/NR44 men on AS assigned to a lifestyle intervention (65)49 men on AS assigned to usual-care control group (66)
Punnen et al, 2013 [21]Cohort2007–2010UCSF, clinical, United States; 864/77%122 newly diagnosed, no active treatment >6 mo postdiagnosis (61)557 post-RP (60)
Seiler et al, 2012 [22]Cross-sectional2010NR, clinical, Switzerland; 282/47%133 with Epstein eligibility criteria (69)133 partners of AS men
PD
Thong et al, 2010 [23]Cross-sectional2004Not protocol-based, clinical, The Netherlands; 128 from registry data eligible for AS/55%71 (76)71 men post-RT (76) patients of similar age and comparable disease characteristics
PD
van den Bergh et al, 2010 [24]Cohort2007–2008PRIAS, research, The Netherlands; 150/86%129 (65)None
Vanagas et al, 2013 [25]Cross-sectional2010–2011NR, clinical, Lithuania; 650/79%61 (NR)92 post-RP, 73 post-RT, and 187 on HT, plus 88 including CH and combined therapy (NR)
Vasarainen et al, 2012 [26]Cohort2006PRIAS, research, Finland; 124/85%105 (64)None
PD
Wilcox et al, 2014 [27]Cross-sectional2013NR, clinical, Australia; 61/77%47 (NR)None

AS = active surveillance; CH = chemotherapy; HT = hormone therapy; NR = not reported; PD = population data; PRIAS = Prostate Cancer International Active Surveillance; QoL = quality of life; RP = radical prostatectomy; RT = radiotherapy; UCSF = University of California, San Francisco.

3.1. Study and characteristics of patients on active surveillance

Seven of the 10 included AS studies were conducted in Europe, two in Northern America, and one in Australia (Table 1). Three AS studies reported using the PRIAS protocol for monitoring patients; two used the University of California, San Francisco (UCSF) protocol; and one used the Royal Marsden Hospital protocol. The HRQoL assessments were reported between 2006 and 2014, and all the study designs were observational: six cross-sectional and four cohorts with follow-up up to 3 yr in one cohort and up to 1 yr in the others. Eight studies reported on QoL assessment at different time points after opting for AS; one of the selected studies reported specifically on predictors of QoL, and one assessed the impact of a lifestyle change intervention in men on AS. The total number of AS patients was 996, ranging from 61 to 150 men per study (mean: 102), with 557 patients who had undergone radical prostatectomy as the largest comparator group [21]. Mean age across the different studies was 66 yr. Four studies used combinations of comparison groups of PCa patients. These were men undergoing or having undergone active treatment after radical prostatectomy (n = 2), radiotherapy (n = 4), and hormonal therapy (n = 2). One study assessed men's partners, and three used population-based data.

3.2. Outcomes

Fifteen different measures were used to assess the various facets of HRQoL and psychological dimensions (Table 2). Global HRQoL indexes were obtained by using the Short Form (SF)-36 [28] or SF-12 [29], the European Organisation for Research and Treatment of Cancer QLQ-C30 [30] and the Quality of Life–Cancer Survivors scale [31]. The Functional Assessment for Cancer Therapy (FACT) scale was also used in one study to assess both general and prostate-related HRQoL [32]. Mental health was measured with the SF-36 or SF-12 (four studies) mental health subscale. Two studies measured anxiety and depression with the Hospital Anxiety and Depression Scale [33] and one with the Patient Health Questionnaire [34]; depression was also measured by the Center for Epidemiologic Studies Depression Scale in one study [35]. The tools to assess anxiety were also the General Anxiety Disorder Scale [36] and the State Trait Anxiety Inventory [37]. Specific PCa-related anxiety was measured with the Memorial Anxiety for Prostate Cancer scale [38] in three studies. One study assessed stress levels by using the Perceived Stress Scale [39], another assessed decisional conflict [40], and another assessed coping, using the Mini-Mental Adjustment to Cancer Scale [41]. One study used the Distress Thermometer [42], which specifically measures psychological burden in oncology patients.

Table 2 Measurement, outcomes, and key findings from quality-of-life studies of active surveillance for prostate cancer

Study, publication yearQoL outcomesQoL standardised measuresBaseline assessment; follow-upKey findingsQoL on AS
Bellardita et al, 2013 [18]HRQoL, copingFACT-P, FACT-G, Mini-MACt1 = AS enrolment;
t2 = 10 mo
QoL predicted by lack of a partner; recent diagnosis, influence of physicians on decision, number of biopsy cores; impaired MH at enrolmentOnly a minority of patients reported low levels of QoL, which could be predicted by patients’ characteristics at baseline
Burnet et al, 2007 [19]Anxiety, depressionHADSt1 = AS enrolment; during or after treatment for control subjects33% of participants had high anxiety (mean: 6.14; SD: 3.76) and 11% met criteria for depression (mean: 3.68; SD: 3.07); threshold ≥8 based on normative sampleNo major treatment effects on anxiety or depression
Daubenmier et al, 2006 [20]HRQoL (MH index), stressSF-36, Perceived Stress Scalet1 = after randomisation before intervention;
t2 = 12 mo
MH scores did not change between t1 and t2 in both lifestyle change and control group (mean: 51 and 56, respectively); perceived stress scores remained about 1 in both groups at t1 and t2Men in the intervention group improved their lifestyle, but no significant differences between groups were found from baseline to 12-mo follow-up as far as QoL; lifestyle index scores were significantly related to scores on SF-36 subscales
Punnen et al, 2013 [21]Anxiety, depression, distressPatient Health Questionnaire; General Anxiety Disorder Scale; Distress Thermometert1 = before RP or <6 mo from diagnosis for AS; t2 = <1 yr after t1; t3 = between 1 and 3 yr after t1Rates of moderate-to-severe depression were <5% in both groups; mild depression was reported by 3% to 12% of participants; anxiety was moderate to severe in <5% of men, mild in 4% to 16% in both groups; ≥4% of men reported high distress scoresNo significant differences between AS and RP in severity of anxiety and/or depression nor in the proportion of men with high distress scores
Seiler et al, 2012 [22]HRQoL, general and PCa-specific anxiety, depressionHADS, MAX-PC, EORTC QLQ-C30t1 = median 45 mo from diagnosis; 17, 32, 59, or 136 moPatients’ HRQoL scores were similar or higher to normative population scores; MAX-PC scores were lower than the reference value for 91.7%; 85.7% scored below the reference value of the HADS domainsNo major overall or disease-specific anxiety or distress at four times postdiagnosis for men; possibly more impact for partners
Thong et al, 2010 [23]HRQoL (MH index)SF-36, QoL–Cancer Survivorst1 = mean 8 yr on ASNo significant differences between AS, RT groups, and PD; AS men with disease progression had worse mental and emotional healthNo major impacts on QoL for men up to 10 yr on AS compared with RT; negative impacts for those with disease progression on AS
van den Bergh et al, 2010 [24]HRQoL (MH index), anxiety, depression, decisional conflictDCS, CES-D, STAI-6, MAX-PC, SF-12t1 = <6 mo from diagnosis; t2 = 9 moAnxiety scores decreased as STAI (p = 0.016) and MAX-PC fear of progression (p = 0.005) with decreases >0.5 SD (not clinically relevant); the incidence of men scoring above clinical thresholds at t1 and t2 was 20% and 25%, respectively, for DCS; 6% and 8% for CES-D, respectively; 17% and 12%, respectively, for STAI-6; and 7% and 9%, respectively, for MAX-PCAnxiety and distress were clinically stable over 9 mo; baseline characteristics partly predicted distress and anxiety during follow-up
Vanagas et al, 2013 [25]HRQoLEORTC QLQ-C30NRMean score range for EORTC QLQ-C30 functional scales range was 73–90 for men on AS; AS men had highest emotional, role, and social functioning scores of PCa treatmentsFavourable QoL profile for AS patients compared with radical treatment or HT
Vasarainen et al, 2012 [26]HRQoL (MH index)SF-36t1 = start of AS; t2 = 12 moSF-36 scores ranged from 65 (general health index) to 91 (social functioning) at t1 and remained stable at t2; MH index mean score was 81 at both timesNo differences were found between baseline and follow-up assessment; men on AS had better QoL than the reference group (normative population)
Wilcox et al, 2014 [27]PCa-related anxietyMAX-PCNRThe mean overall MAX-PC was 15.5 (95% CI, 13.4–17.6) with subscale results of 7.4/33 for general anxiety (95% CI, 5.5–9.3), 0.8/9 for PSA-specific anxiety (95% CI, 0.3–1.3), and 7.3/12 for fear of recurrence (95% CI, 6.5–8.2)No disease-specific anxiety reported in Australian men

AS = active surveillance; CES-D = Center for Epidemiologic Studies Depression Scale; CI = confidence interval; DCS = Decisional Conflict Scale; EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30; FACT-G = Functional Assessment of Cancer Therapy–General; FACT-P = Functional Assessment of Cancer Therapy–Prostate version; HADS = Hospital Anxiety and Depression Scale; HRQoL = health-related quality of life; HT = hormone therapy; MAX-PC = Memorial Anxiety scale for Prostate Cancer; MH = mental health; Mini-MAC = Mini-Mental Adjustment to Cancer; NR = not reported; PCa = prostate cancer; PD = population data; PSA = prostate-specific antigen; QoL = quality of life; RP = radical prostatectomy; RT = radiotherapy; SD = standard deviation; STAI-6 = State-Trait Anxiety Inventory; t1 = time 1, baseline assessment; t2 = time 2, follow-up; t3 = time 3, follow-up.

High overall HRQoL scores were reported in seven AS studies, thus indicating good QoL. No major differences were observed between the HRQoL scores of AS patients and their comparison groups [19], [21], [23], [25], and [26]. There were also no major changes in HRQoL after 9 or 12 mo on AS in two PRIAS cohorts [24] and [26]. Finnish men in the PRIAS also reported higher scores than a population sample at baseline and follow-up assessments, which the authors suggested may result from men with favourable psychological characteristics choosing AS. Vanagas et al [25] highlighted that men on AS reported significantly better HRQoL than men who underwent radical treatment in both functional and symptom scales, although these results by treatment group were not subdivided by tumour stage.

Bellardita et al [18] found that high levels of HRQoL were predicted by a patient having consulted several physicians about the choice of AS, by the presence of a partner, and a diagnostic biopsy with >18 core specimens. Daubenmier et al [20], comparing two groups of patients undergoing or not a lifestyle intervention, pointed out that participants of both groups reported high HRQoL at baseline; interestingly, those who improved their lifestyle also enhanced their HRQoL further.

3.2.2. Mental health

Four studies reported on mental health by using the SF-36 mental health index and found that patients were doing well [20], [23], [24], and [26]. Thong et al [23] found the mean mental health score of men on AS was about 80 and was similar to the mean score for a normative population, matched for age and sex, and up to 10 yr after diagnosis. In the same study, it was highlighted that 17 AS patients with subjective perception of disease progression showed worse mental health scores than AS patients without such a perception of disease progression. In the Dutch PRIAS cohort, the baseline mental health score was associated with 9-mo follow-up scores [24] and there were no changes over 9- or 12-mo follow-up in either of the two PRIAS cohorts [24] and [26].

In summary, these findings do not seem to justify the concern that living with untreated cancer negatively affects the mental health of patients on AS. Longer-term follow-up will be essential, however, to elucidate whether there may be later, subtle erosion of patients’ mental health and well-being over time on AS.

3.2.3. Anxiety

There was a low frequency of general and disease-specific anxiety in all five AS studies that assessed anxiety (usually in the range of 4–15%) [19], [21], [22], [24], and [27]. Two studies also highlighted that anxiety scores of AS patients were comparable to those of radical prostatectomy patients [19] and [21]. Punnen et al [21] compared a group of patients managed with AS with another group of men who underwent RP, finding that in both samples, moderate to severe levels of anxiety were reported by <5%, and levels of mild anxiety ranged from 4% to 16%. Burnet et al [19] highlighted that anxiety scores in patients who chose AS did not differ from those of patients who were being treated for PCa or were followed-up after radical treatment. In particular, authors noticed that younger men were more anxious than older men, and the longer the time since diagnosis, the more anxious the men became. The general and PCa-specific anxiety declined slightly (<0.5 of a standard deviation) over 9 mo in Dutch PRIAS patients, but this was not clinically significant [24]. The fear of disease progression declined significantly over 9 mo (mean score: 4.2–3.5; p = 0.005) in the Dutch PRIAS cohort, which warrants further exploration in other AS cohorts. Furthermore, baseline scores were predictive of scores at 9 mo in this PRIAS cohort.

Seiler et al [22] investigated the level of anxiety not only in patients with PCa but in their wives as well, arguing that the partners could suffer more from the diagnosis than the men themselves. As predicted, the partners’ anxiety scores indicated higher levels of concern than their husbands: Overall, among men, the domain for PSA anxiety was rated very low (it should be noticed that in this cohort, men do not dread PSA testing, despite having to undergo it regularly). More generally, since the values scored by both men and their partners were within the normal range of the general population, the authors concluded that anxiety for these individuals was not clinically relevant. Similarly, Wilcox et al [27] underlined that the level of anxiety relating specifically to PCa in a cohort of Australian patients on AS was below the defined threshold of clinical relevance.

3.2.4. Depression

Depression is an established response to a diagnosis of cancer, which is unrelated to disease stage or severity [43]. Four studies showed that few AS patients reported depressive symptoms [19], [21], [22], and [24]. No major changes in depressive symptoms were observed over the first 9 mo of AS in the Dutch cohort [24]. There were no major differences in depressive symptoms between AS and radical prostatectomy patients in the American study [21] nor in the Swiss cohort [22] with men's partners or population data. For instance, <5% of men in the UCSF cohort reported moderate-to-severe depression [21]. Burnet et al [19], comparing three groups of patients (one on AS, one currently undergoing radical treatment, and one on follow-up after radical treatment), found that the extent of reported depression was associated with a longer interval since diagnosis, but not with being on AS.

3.2.5. Decisional conflict

The decisional conflict scale aims to elicit patients’ uncertainty in making a health-related decision, the factors contributing to the uncertainty, and patients’ perceived effective decision making. Van den Bergh et al [24] found that the extent of reported decisional conflict was associated with shared decision making (largely perceived as a physician role) and emotional insecurity. Considering the score of decisional conflict over time, authors highlighted that it appeared quite stable between the time of diagnosis (t1) and 9 mo (t2) after diagnosis (only few men who scored within the normal range at t1 then exceeded the clinical threshold at t2). In a previous study on the same cohort, the same authors reported that men who elected AS in their cohort reported less decisional conflict than a cohort of American patients with localised PCa who had decided on their treatment (mostly radical prostatectomy) [44].

3.3. Predictors of quality of life

HRQoL was predicted by baseline sociodemographic, clinical, or other characteristics in two AS studies [18] and [24]. In one study [24], greater decisional conflict (linked to a higher perceived physician role in treatment decision making) or a higher score in emotional instability predicted increased anxiety and distress at 9 mo, whilst better physical health was associated with lower scores. In patients within their first 10 mo of AS, having a partner, multiple physicians during AS selection, and an extended diagnostic biopsy (>18 cores) decreased the risk of experiencing poor QoL [18]. Additionally, AS patients with good coping or adjustment to cancer scores (ie, fighting spirit, anxious preoccupation, and helplessness/hopelessness) had higher QoL scores, whereas low coping scores were associated with the time taken between diagnosis and commencing AS.

3.4. Intervention studies

One intervention trial aimed to improve eating habits and physical exercise levels of AS patients [20]. There were no differences in HRQoL between the randomised groups from baseline to 12-mo follow-up. It was also noted that some control group AS patients pursued lifestyle changes. Men participating in the Prostate Testing for Cancer and Treatment (ProtecT) randomised trial of active monitoring (a surveillance strategy), radical prostatectomy, and radiotherapy, generally made healthy dietary changes following diagnosis (eg, less red meat) with greater changes made by those on active monitoring [45].

3.5. Limitations of quality-of-life active surveillance studies

Summarising the 10 studies gave novel insights into the QoL of AS patients. However, none of the AS studies had a randomised comparison group; some were rather small or had limited follow-up. Most studies lacked an appropriate control group, making it difficult to disaggregate the psychological impact for AS patients of living with untreated disease and the general burden for cancer survivors [46] and [47]. Measurement of the HRQoL across a wider demographic range of AS patients could enhance the generalizability of these results, given that most studies did not report the ethnicity or sociodemographics of their patients. All 10 studies lacked assessment of men's HRQoL before commencing on AS, which may have introduced a self-selection bias, and few studies made analytic adjustments for age or other demographic variables or missing data. Only two studies included men who left AS. Questionnaire performance metrics were poorly reported (eg, the reliability, responsiveness, and sensitivity of measures), thus making it difficult to assess the quality of findings. Moreover, the statistical significance of some HRQoL scores needs to be translated into QoL differences that are meaningful to both patients and clinicians.

3.6. Limitations of the systematic review

Some relevant studies may have been omitted from this review, as there are at least seven published AS cohorts worldwide, and yet we only identified HRQoL results from three institutions participating in PRIAS, the Royal Marsden Hospital, and UCSF cohorts. This may reflect the absence of HRQoL results from the other AS cohorts, as HRQoL research into AS is relatively recent, but it is unlikely to be a language bias, as clinical data from theses cohorts have been published in English. We excluded interview-based studies [48], which can give useful insights into men's perspectives, as they could not be combined with quantitative data, and also studies where it was not possible to determine if patients were receiving WW or AS. Finally, the QoL outcomes could not be combined in a meta-analysis because there were no universal measures across the 10 studies, so we were also unable to assess the overall impact of different AS protocols on HRQoL, including triggers for radical treatment.

3.7. Future directions

Understanding the complexity of the HRQoL of AS patients requires multidimensional assessment, including interpretation of QoL scores for clinical practice and patients. Longitudinal assessment of HRQoL with a core set of QoL measures in all AS cohorts to inform future meta-analyses would be advantageous, with the PRIAS studies currently increasing the evidence base most strongly. Further investigation of the characteristics of men commencing AS that may predict subsequent psychological harms and their potential for leaving AS prematurely would be highly beneficial, including how patients interpret AS tools (eg, PSA level, imaging, and biopsy results), which may also negatively affect their QoL and their decision to remain on AS. The partners of AS patients [22] were shown to experience slightly higher depressive symptoms (but not anxiety) and lower general health status, role, and emotional functioning than the men. Partners and other family members may be influential regarding initiation and maintenance on AS, so further empirical data on the potentially mutual emotional influences and supportive role of partners/family could be instructive. Finally, the ProtecT randomised trial of PCa treatments, with HRQoL, anxiety, and depression measured prediagnosis and annually for at least 10 yr in actively monitored patients, will report in 2016 [49], which should provide detailed insights both clinically and for AS patients on the immediate and long-term psychological impacts of AS.

4. Conclusions

Controversy exists around the nature and extent of the burden of living with untreated PCa for AS patients. This systematic review, based on around 1000 AS patients in 10 studies, indicated no major perturbations to their HRQoL and psychological well-being in the first few years. These findings are, to our knowledge, from the first systematic review to focus entirely on the HRQoL of AS patients. Limitations of the review included a potential self-selection bias, as no studies were randomised, comparator groups were used infrequently, and follow-up was limited. Nevertheless, men on AS generally reported high levels of overall HRQoL in the short term, which was comparable to men who underwent radical treatments. Anxiety, depression, and distress also seemed not to represent a major burden for most AS patients in their first few years. However, assessment of anxiety, depression, and distress should nevertheless be considered for AS patients and support offered where psychological distress is severe and unremitting over time [50] or arises during AS. Further research should aim to provide robust, high-quality, long-term data that can inform clinical practice, patients, and the patient–physician decision-making process.


Author contributions: Lara Bellardita had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Bellardita, Lane, Korfage, Valdagni.

Acquisition of data: Bellardita, Lane, Korfage.

Analysis and interpretation of data: Bellardita, Lane, Korfage, van den Bergh, Venderbos.

Drafting of the manuscript: Bellardita, Lane, Korfage.

Critical revision of the manuscript for important intellectual content: Bellardita, Lane, Korfage, van den Bergh, Valdagni, Venderbos, Randsdorp, Repetto.

Statistical analysis: None.

Obtaining funding: None.

Administrative, technical, or material support: None.

Supervision: Korfage, Valdagni, Lane.

Other (specify): None.

Financial disclosures: Lara Bellardita certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: None.

Funding/Support and role of the sponsor: L. Bellardita acknowledges Fondazione I. Monzino for funding the psychological support activities for prostate cancer patients and their families at Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano and the European School of Oncology. A. Lane is funded by the ProtecT trial (UK National Institute for Health Research Health Technology Assessment Programme, project 96/20/99). I.J. Korfage's research is funded by the Dutch Cancer Society. The funding sources had no role in the study design or conduct; data collection, management, analysis and interpretation, or preparation; or review or approval of the article for all authors.

Acknowledgement statement: This paper reflects the consensus on the state of the art and future direction of AS, based on the “Active Surveillance for Low Risk Prostate Cancer Conference” (Chairs: C.H. Bangma, NL and J. Hugosson, SE – Co-Chair: L. Klotz, CAN – Honorary Chair: L.J. Denis, BE – ESO Prostate Programme Coordination: R. Valdagni, IT – Scientific Coordinators: M.J. Roobol, NL – S. Carlsson, SE/US). The Conference has been organized in collaboration with EAU and endorsed by Europa Uomo.

Appendix A. Supplementary data

References

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Footnotes

a Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

b Department of Radiation Oncology 1, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

c Department of Urology, Utrecht University Medical Centre, Utrecht, The Netherlands

d Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands

e Europa Uomo

f School of Social and Community Medicine, University of Bristol, Bristol, UK

g Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands

Corresponding author. Prostate Cancer Program, Fondazione IRCCS Istituto Nazionale dei Tumori, via Giacomo Venezian 1, 20133 Milano, Italy. Tel. +39 0223903023; Fax: +39 0223903015.

Contributed equally.

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