Issues Faced by Unaffected Men With a FamilyHistory of Prostate Cancer: A Multidisciplinary OverviewC. E. Wakefield,* B. Meiser, C. L. Gaff, A. Barratt, M. I. Patel, G. Suthers, E. A. Lobb, J. Ramsayand G. J. MannFrom the Psychosocial Research Group, Department of Medical Oncology, Prince of Wales Hospital, Randwick (CEW, BM), School ofPsychiatry, Faculty of Medicine, University of New South Wales (CEW, BM), School of Public Health (AB) and Department of Surgery(MIP), University of Sydney, Sydney, Medical Psychology Research Unit, University of Sydney, Camperdown (EAL), Urology OncologyProgram, Collaboration for Cancer Outcomes Research & Evaluation, Liverpool Hospital, Liverpool (JR), Westmead Institute for CancerResearch, University of Sydney at Westmead, Millennium Institute, Westmead (GJM), Familial Cancer Unit, Department of GeneticMedicine, Women’s & Children’s Hospital, North Adelaide and Department of Paediatrics, University of Adelaide, Adelaide, SouthAustralia (GS), Western Australia Center for Cancer & Palliative Care, Curtin University of Technology, Perth, Western Australia (EAL),and Genetic Health Services, Victoria and Department of Medicine, The University of Melbourne, Victoria (CLG), Australia

Purpose: Despite the established importance of the role of family history in prostate cancer, relatively little researchencompasses the psychosocial issues relevant to unaffected men with a family history of prostate cancer. To determine thecompleteness and quality of available literature on the issues faced by men with a high risk of prostate cancer, we conducteda multidisciplinary review of the literature to provide some guidance on the information that clinicians might provide to menwho are concerned about family history.Materials and Methods: A structured literature search was conducted by a multidisciplinary team of clinicians andresearchers who reviewed the medical and psychosocial literature, and identified 21 relevant studies.Results: Research suggests that many high risk patients are concerned about the risk of prostate cancer, and some maysignificantly overestimate that risk. Several studies have shown high screening rates among high risk patients and highlevels of interest in genetic testing for prostate cancer risk should it become available, yet many men also report a desire formore information about their personal risk and risk management options.Conclusions: Given the lack of clear data on the efficacy of prostate cancer screening among high risk patients, clinicianscould consider providing men who are concerned about family history with information on their personal risk, help them toclarify the potential benefits, limitations and harms of prostate cancer screening in their situation, and then support theirchoice regarding the management of prostate cancer risk.

Key Words: prostatic neoplasms, risk factors, psychology

After age the strongest risk factor for prostate cancer isfamily history, with approximately 10% to 20% ofmen with prostate cancer having a significant family

history of the disease.1 Currently prostate cancers arisingfrom genetic predisposition cannot be distinguished fromsporadic disease on the basis of clinical characteristics, withlong-term survival rates being similar in patients with andwithout a strong family history.1 Possibly the most promi-nent clinical feature of prostate cancer in men with a familyhistory is its comparatively early onset, with these mentypically being diagnosed 6 to 7 years earlier than men withno family history of the disease.1

A distinction can be made between FPC, which involvesclustering of prostate cancer in families, and HPC, which is

Submitted for publication August 6, 2007.Supported by a Strategic Research Partnership (STREP) Grant

(ID SRP, 06-X5) from The Cancer Council of New South Wales anda Career Development Award from the National Health and Medi-cal Research Council, of Australia (ID 350989) (BM).

* Correspondence: Psychosocial Research Group (PRG), Dickinson3, Department of Medical Oncology, Prince of Wales Hospital, Rand-

wick, NSW 2031, Sydney, Australia (telephone: 0061-2-9382-4229;FAX: 0061-2-9382-3372; e-mail: c.wakefield@unsw.edu.au).

0022-5347/08/1801-0038/0THE JOURNAL OF UROLOGY®

Copyright © 2008 by AMERICAN UROLOGICAL ASSOCIATION

38

a subset of familial prostate cancer. HPC is defined by stron-ger familial clustering in association with earlier onset dis-ease. As in other hereditary cancer syndromes, these areessentially pragmatic criteria to identify high personal andfamilial risk, with a higher probability of detection of high-risk gene mutations. Beyond this fact there is no clear bio-logical distinction between stronger and weaker forms offamilial cancer clustering. Families with HPC can be char-acterized by having 1) 3 or more affected relatives within thenuclear family, 2) 3 or more affected relatives over 3 gener-ations on the same side of the family or 3) 2 relatives withprostate cancer before age 55 years.2 Some genetic segrega-tion studies suggest that HPC is best explained as an auto-somal dominant disorder, but there is also evidence of lowpenetrant, recessive or X-linked effects.3 However, subse-quent studies have failed to confirm these findings, makinggenetic testing for prostate cancer risk not possible at thistime.3 Given the varied definitions and use of the 2 terms(FPC and HPC) in the literature, this review encompassesarticles that describe familial or hereditary prostate cancersyndromes.

Three systematic reviews4–6 have examined the risk of

prostate cancer in men who have a family history of the

Vol. 180, 38-46, July 2008Printed in U.S.A.

DOI:10.1016/j.juro.2008.03.020

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER 39

condition, the results of which are presented in table 1.Briefly prostate cancer risk increases with 1) earlier onset ofthe disease in other family members, 2) increased total num-ber of affected relatives in the family and 3) increased num-ber of FDRs affected by prostate cancer. It has been reportedthat having a brother with prostate cancer carries a higherrisk than having a father diagnosed with prostate cancer.5

This phenomenon might be explained by temporal and en-vironmental influences being more strongly shared by broth-ers than by fathers and sons, by recessive genetic effects, orby ascertainment or measurement biases such as discount-ing the genetic contribution of females in the family.5 Fam-ilies with multiple cases of prostate cancer do not appear tohave an increased risk of other cancers, except a weak as-sociation with brain, gastric and breast cancers in somefamilies.7 This observation is in keeping with reports thatmale carriers of breast/ovarian cancer mutations (ie in theBRCA1 and BRCA2 genes) are at increased risk for prostatecancer and gastric cancer. However, the increased risk ofprostate cancer in these families is small (2 to 4-fold) and thebreast/ovarian cancer related mutations cannot account forthe majority of familial prostate cancer cases.7

Screening for prostate cancer may be offered using aquantitative assay for PSA in the blood, and this can becombined with a DRE. While studies have shown that thePSA test can detect cancers at an earlier and possiblymore curable stage in the general population, there isdisagreement about the value of the test because of lowpositive predictive value, false-positive results, and lackof evidence that early detection and treatment lead tobetter health outcomes.8,9 In addition, the PSA test has lowsensitivity but a high false-positive rate, contributing to alow positive predictive value.8,9 Moreover, many prostatecancers are slow growing, potentially leading to the overdiagnosis of up to 50% of prostate cancers that would neverhave been diagnosed in the absence of screening.10 Severalpopulation studies11,12 as well as large scale randomizedcontrolled trials13,14 are currently under way to gather moredata on PSA screening effectiveness.

As genetic testing for prostate cancer risk is not currentlyavailable, men at increased risk must make decisions aboutrisk management and screening on the basis of family his-tory alone. Despite the controversy regarding PSA screeningin the general population, the positive predictive value and,

TABLE 1. Summary of results of the 3 systemat

References Sample Size � Study Type

Zeegers et al4,* Meta-analysis of 33 studies published upto December 2002

Bruner et al5,† Meta-analysis of 24 studies published upto November 2000

Johns and Houlston6,† Meta-analysis of 13 studies published upto August 2002

* Summary recurrence risk ratio statistics.

† Pooled relative risks.

hence, the benefit-to-harm ratio of PSA screening is greaterin men with a strong family history of prostate cancer be-cause of the higher risk. Moreover, the earlier onset of pros-tate cancer in these families has the potential to increase thegain in terms of years of life saved and reduce the potentialover diagnosis of nonsignificant tumors, thereby theoreti-cally increasing the value of PSA testing in this population.Thus, several studies and professional groups recommendmore frequent or earlier screening in this population.Table 2 presents the current positions of key professionalgroups with regard to PSA screening in the general popula-tion vs in men at higher risk for prostate cancer.

AIMS

Despite the high incidence of prostate cancer in most popu-lations worldwide and the established importance of the roleof family history in the development of the disease, surpris-ingly little literature is available that describes the psycho-logical and social issues relevant to unaffected men with astrong family history of prostate cancer. Thus, we havebrought together previous research in many specialty areasto provide a comprehensive, multidisciplinary review of theavailable data on psychological morbidity in this group ofmen, the perceived risk of prostate cancer, attitudes towardand participation in screening, and interest in genetic test-ing for prostate cancer risk (if it becomes available). Thisreview will help clinicians and researchers be aware of thebroad range of psychosocial issues to consider when coun-seling unaffected men presenting to the clinic who are con-cerned about their family history of prostate cancer.

METHODS

Three strategies were used to conduct the literature search.1) The electronic databases from MEDLINE®, MEDLINEIn-Process or other nonindexed citations, PsycINFO® andEMBASE® were searched from 1980 onward using the key-words “prostate cancer” and “family history,” “hereditary” or“familial” in combination. 2) The reference lists of all iden-tified publications were examined. Studies were consideredeligible for inclusion in the review if they were published ina peer reviewed journal, involved human subjects, werepublished in the English language, and covered the popula-

views of prostate cancer risk by family history

Family History Risk Figure (95% CI)

Rer only

er onlyore FDRs

R diagnosed younger than 65 yrsR diagnosed older than 65 yrs

2.57 (2.32–2.84)3.37 (2.97–3.83)2.17 (1.90–2.49)5.08 (3.31–7.79)2.47 (1.71–3.55)1.72 (1.41–2.10)

ffected family memberr more affected FDRsr more affected second degree relatives

er onlyer only

1.93 (1.65–2.26)2.22 (2.06–2.40)1.88 (1.54–2.30)2.12 (1.82–2.51)2.87 (2.21–3.73)

ffected FDRore FDRs

er onlyer only

ected family member diagnosed under 60 years

2.5 (2.2–2.8)3.5 (2.6–4.8)2.5 (2.1–3.1)3.4 (2.9–4.1)4.3 (2.9–6.3)

ic re

1 FDBrothFath2 or M1 FD1 FDAny aOne oOne oFathBrothAny a2 or MFathBroth1 Aff

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER40

tion and topics of interest (ie psychological morbidity, per-ceived risk, attitudes toward and participation in screening,and interest in genetic testing in men with a family historyof prostate cancer). Articles were excluded from the litera-ture review if they were reviews, single case reports, letters,commentaries or conference abstracts. 3) We grouped to-gether multiple articles that appeared to describe the samestudy samples and, when necessary, we incorporated onlythe data from the largest data set or the most recent articlein these groups.

RESULTS

A total of 943 articles were identified using the aforemen-tioned search terms and 21 articles met all inclusion crite-ria. Table 3 describes the search criteria and provides a listof the main reasons each excluded article was not includedin the analysis. The majority of articles originated from theUnited States (16), with the remainder from Sweden (3),France (1) and Australia (1). Most studies ascertained studyparticipants through FDRs who had previously been diag-nosed with prostate cancer. However, 1 population basedstudy was also available.15

Psychological Morbidity and Perceived RiskSeveral articles reported that psychological morbidity inFDRs of patients with prostate cancer is within the normalpopulation range.16,17 However, most unaffected men witha family history of prostate cancer are concerned aboutthe risk of cancer, and men who are younger, have a son orhave more than 1 affected relative have been shown toexperience increased psychological morbidity and cancerspecific worry.17–21

A small number of studies have shown that men with afamily history of prostate cancer overestimate the risk of

TABLE 2. Summary of current positions of key

Professional Group Recommended Community Screen

American Urological Association39 Annual PSA and DRE from age 50for men with a life expectancy ofmore than 10 yrs

American Cancer Society40 Annual PSA and DRE from age 50for men with a life expectancy ofmore than 10 yrs

U.S. Preventive Services Task Force41 Insufficient evidence to recommendfor or against routine screeningusing PSA or DRE

National Health Service NationalScreening Committee, UnitedKingdom42

No screening, but concerned men cbe offered annual PSA and DREafter education about benefits andharms

Urological Society of Australia andNew Zealand43

No screening, but concerned men 570 years old with at least a 10-yrexpectancy should be offered annPSA and DRE

The Cancer Council Australia44 No screening

Cancer Society of New Zealand45 No screening

* No major medical or professional groups, including the American CancerAmerican College of Physicians, National Cancer Institute, American Acadpopulation based screening for prostate cancer at this time. All groups recbenefits of screening to make an informed decision.

prostate cancer,22,23 and that high perceived risk is associ-

ated with depression and cancer worry that affect dailyliving.18 Moreover, a recent study reported that 75% of menwith a family history of prostate cancer indicated a need forhelp to deal with the fears of cancer, suggesting that these

essional groups on prostate cancer screening

Definition of Higher RiskGroups

Recommended Screening in HigherRisk Groups

1 Affected FDR or AfricanAmerican

Annual PSA and DRE from age 40 yrs

1 Affected FDR diagnosed beforeage 65 yrs or African American

Annual PSA and DRE at or before age45 yrs

Several affected FDRs diagnosedat an early age

PSA and DRE at age 40 yrs, annualscreening, or next screen at age 45yrs depending on test results

Not applicable No screening

Not applicable No definitive guidelines for screeningin high risk families in the UnitedKingdom

Men with a strong familyhistory

PSA and DRE after age 40 yrs forconcerned men

Not applicable Screening decisions should considerindividual risk factors such as familyhistory, but no recommendedsurveillance

Not applicable No screening

ty, American Urological Association, U.S. Preventive Services Task Force,f Family Physicians and American College of Preventive Medicine supportnd that interested or concerned patients be told the potential harms and

TABLE 3. Systematic review of prostate cancer and family historystudies from January 1980 to July 2007

No. StudiesMeeting Criteria

Inclusion search criteria:“Family history” � “prostate cancer” � limited to1980–2007

943

Duplicate articles 343Subtotal 600

Non-English language 41Nonhuman studies 4

Subtotal 555Exclusion criteria:

Epidemiological/risk factor/prevention studies,eg studies of occupational exposure, smoking,physical activity, obesity

93

Molecular genetics studies 84Diagnosis/treatment/outcome studies 83Prostate cancer risk studies 29Screening studies (not psychosocial) 28Other primary cancer site, eg breast cancer,melanoma, lymphoma

56

Other primary conditions, eg cardiovasculardisease, diabetes, asthma, osteoporosis

7

Reviews 68Editorial comments/letters 30Case studies 7Clinical guidelines/recommendations 6Psychosocial study including only unaffected menwith no family history, only affected men with afamily history or no specified family history

28

Other, eg studies of cancer survivors, clinicianattitude surveys, studies of accuracy of familyhistory reporting, general population surveys

30

Total 21

Databases searched included MEDLINE, MEDLINE In-Process or other

prof

ing*

yrs

yrs

an

0–life

ual

Socieemy oomme

nonindexed citations, EMBASE and PsycINFO.

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER 41

men may benefit from appropriate counseling to managecancer specific worry and anxiety.24

Attitudes Toward and Participation in ScreeningMost studies have demonstrated a positive relationship be-tween the presence of family history and screening behav-iors (table 4).21,22,25–28 However, self-reported screening up-take rates vary significantly among studies, with dataranging from a United States based study which reportedthat 50% of the sample had a PSA test before study entry21

to recent Australian data which showed that more than 75%of the 280 men with a family history of prostate cancer hadundergone PSA testing and a DRE.29 The highest screeningrates in unaffected men with a family history were reportedby Bock et al, who found that of 64 unaffected sons ofpatients with prostate cancer approximately 95% reportedhaving had a PSA test and 97% reported having undergonea previous DRE.25

While high screening rates have been reported in manypopulations of men with a family history of prostate cancer,it seems that not all groups have similar screening rates,with a recent study showing significantly lower screeningrates in African-American men with a strong family historyof prostate cancer compared to Caucasian men with a simi-lar family history profile.30 In this study only 45% of African-American men with a strong family history of prostate can-cer (more than 4 affected relatives) reported ever having aPSA test and only 35% reported ever having a DRE.30 Inanother United States based study 56 men with an affectedFDR were no more likely to have undergone PSA testing orDRE compared to 100 men with no FDRs previously affectedby prostate cancer.23

Several studies have assessed the sociodemographic,medical and psychological characteristics associated withprostate cancer screening in men with a family history ofprostate cancer. It has been reported that men with a familyhistory of prostate cancer who are older,17,21,23,29 married15

and have higher incomes15,19,21,29 are more likely to undergoPSA screening. In addition, having a greater number ofaffected relatives18,19,29 and having discussed screeningwith a clinician17 have been reported as predictors of in-creased screening frequency. By contrast, men appear lesslikely to screen regularly if they have high cancer specificdistress. Specifically a Swedish study showed that men witha strong family history of prostate cancer (3 or more affectedrelatives) were less likely to engage in screening if they hadhigh levels of avoidant thoughts related to their risk ofprostate cancer.18

Two studies have investigated the psychological impact ofscreening on men in this population,17,31 and have showedlittle effect on anxiety,17,31 depression,31 cancer worry31 andhealth related quality of life17 when undergoing screening.However, both these studies were small (220 and 57 patients,respectively) for assessing the impact of screening and in-cluded no or few men with an abnormal screening test result.

Interestingly a recent Australian study found that femalepartners of men with a family history of prostate cancer didnot significantly influence men’s interest in attending mul-tidisciplinary familial prostate cancer services.24 However,partner involvement in male screening was associated withincreased PSA screening. Little information is currently

available about the role, needs and concerns of women

whose unaffected partners have a strong family history ofprostate cancer. However, these women may have a criticalrole in the ability to cope with the family history of cancer aswell as in the medical decision making. More research inthis area could help further distinguish predictors of screen-ing in this population.

Attitudes Toward GeneticTesting for Prostate Cancer RiskIf it becomes available in clinics, the introduction of genetictesting for prostate cancer risk would likely impact the de-mand for genetic counseling and testing in men with astrong family history of prostate cancer. Indeed, researchsuggests that these men show a strong interest in learningabout the inheritance of cancer predisposition and genetictesting, as well as in actually undergoing genetic testing.Specifically the studies listed in table 5 indicate that up to90% of men at risk for familial prostate cancer were inter-ested in undergoing genetic testing if it becomes avail-able.16,18,32,33 These figures are relatively consistent acrosscountries and cultural backgrounds, with data from France,for example, reporting that 98% of men with at least 1 FDRwith prostate cancer were interested in genetic testing,while a similar proportion (94%) of unaffected men with astrong family history in Sweden reported that they wouldundergo genetic testing if it becomes available.18

Figures in the United States are comparable, ranging from74% to 89% in 2 studies.33,34 In both studies levels of interestin genetic testing were similar in all participants, irrespectiveof family history. However, in a study by Diefenbach et al menwith a family history of the disease reported being more willingto pay for genetic testing than men with no family history.34

Interestingly despite a reported lack of uptake of prostatecancer screening in African-American men with a strong fam-ily history of prostate cancer,30 Weinrich et al reported that87% of African-American men with a strong family history ofprostate cancer were interested in genetic testing for pros-tate cancer risk if it becomes available.32

However, it must be noted that previous surveys of atti-tudes toward genetic testing for other hereditary cancer syn-dromes have shown that the anticipated uptake of genetictesting to predict the development of a condition is likely to behigher than the observed rate of uptake once such testingbecomes available.35 Also, the actual uptake rate appears to bedependent on the perceived treatability of the condition, withthe actual uptake of genetic testing being higher for hereditarycolorectal cancer than for hereditary breast or ovarian cancer.35

Previous studies demonstrate that intent to undergo ge-netic testing is determined by a complex set of family his-tory, sociodemographic and psychological variables. Thepredictors of interest in genetic testing for prostate cancerrisk that have been identified in men at increased riskinclude having a greater number of relatives with prostatecancer;17,34 having children;16,18 educational level, withmen with lower education levels showing greater interest inundergoing genetic testing in the future;16 marital status,with married men being more likely to report interest ingenetic testing;32 emotional distress and worry;34 and con-cerns about treatment side effects and efficacy.34 Men mayalso feel concerned about the prostate cancer risks impartedto their sons by the family history, with 1 study reportingthat 93% of men who had sons wanted their sons to know the

risk and 89% wanted their sons to have a genetic test.18

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER42

DISCUSSION

In this review of original studies on psychosocial issues

TABLE 4. Studies of psychosocial aspects of prostate cancer scr

ReferencesCountry of

Origin Outcomes (test) Sam

Meiser et al29 Australia Screening rate (PSA � DRE) 280 Uhisto

Shah et al26 United States Screening rate (PSA) 3,995FDR

Spencer et al15 United States Screening rate (PSA) 8,713whopros

Bloom et al27 United States Screening rate (PSA � DRE) 208 Awhorepo(FPC

Sweetman et al19 United States Predictors of PSA screening 128 Fyoun(FPC

Weinrich30 United States Screening rate (PSA � DRE) 134 A4 or(HP

Ross et al28 United States Screening rate (PSA) 736 Asom(FPC

Jacobsen et al22 United States Screening rate 83 Mfamiwith

Vadaparampil et al21 United States Predictors of screening 82 Unold w(FPC

Bock et al25 United States Screening rate (PSA � DRE) 60 Afsons(FPC

Bratt et al31,§ Sweden Impact of screening 74 Unmor

Cormier et al46 United States Screening rate 138 Fwith

Cormier et al47,� United States Attitudes toward screening 139 Fwith

Cormier et al17 France Impact of screening 334 Fmen

Miller et al23 United States Screening rate � perceivedrisk

56 M(FPCaffec

Bratt et al18 Sweden Screening rate 110 Uold)rela

Bratt et al16 Sweden Attitudes toward screening 100 SCa (

Taylor et al48 United States Reasons for screening 50 Mprosno fa

* FPC studies included men with any family history of prostate cancer (iefamilies, most with at least 3 affected relatives.† Data from the 2000 National Health Interview Survey, an annual, nationa

32,374 adults.‡ Data from African American Hereditary Prostate Cancer Study compare§ Same sample as Bratt et al.18

� Same sample as Cormier et al.46

affecting men with a family history of prostate cancer pub-

lished between 1980 and July 2007 we found 21 relevantarticles from 4 countries. The review demonstrated thatwhile unaffected men with a strong family history of pros-

g in unaffected men with a family history of prostate cancer

haracteristics (test)* Findings

cted men with familyprostate Ca (FPC)

More than 75% reported ever undergoing PSA andDRE. PSA test more common in men with moreaffected relatives and married men. DRE morecommon in older men, men with high perceivedrisk and men with sons.

, of whom 226 hadprostate Ca (FPC)*

Men with a family history of prostate Ca morelikely to undergo PSA test.

45–79 yrs old, ofhad FDR witha (FPC)†

Men with family history more likely to undergoPSA test 12 months before study. Age wasstrongest predictor of screening uptake.

-American men, ofhad at least 1 self-DR with prostate Ca

Men with a family history more likely to undergoPSA test, but not DRE.

of young (65 years orpts with prostate Ca

Only predictor of screening was past screening,which was associated with greater No. affectedrelatives, perceived risk, perceived benefits ofPSA, social class � education.

-American men withaffected relatives

African-American men with a strong familyhistory reported low screening rates ofapproximately 35% for DRE � 45% for PSA test.

-American men,family history

Men with family history of prostate Ca more likelyto undergo PSA test.

–80 yrs old withtory (FPC) vs 83mily history

Men with family history reported more PSAtests � higher levels of intention to undergo PSAtests in future � were more likely to requestinformation about prostate Ca.

ted men 40–75 yrsDR with prostate Ca

50% Underwent PSA test before study � 50%during study. No relationship between perceivedrisk � PSA test. PSA test more likely in oldermen and men with higher incomes and self-efficacy.

� 64 unaffecteds with prostate Ca

Approximately 95% of unaffected men reportedundergoing PSA test and 97% DRE.

ted men with 3 orcted relatives (HPC)

Anxiety and depression no greater than generalpopulation. No significant change in anxiety,depression or Ca worry on day of screening vs4–6 wks later.

(40–70 yrs old) of ptstate Ca (FPC)

62% Underwent PSA and DRE in the last 2 yrs.Screening more likely in older men, those whohad discussed screening with doctor � those withgood screening knowledge.

(40–70 yrs old) of ptstate Ca (FPC)

Most held favorable attitudes toward screening.Only 62% believed they were at higher risk thanthe average American man.

(40–70 yrs old) ofprostate Ca (FPC)

Approximately 20% had increased anxiety andreduced health related quality of life after PSAtest (largest impact in men 50–60 yrs old withmore than 2 affected relatives, an anxiouspersonality, higher education � no children).

th affected FDR100 men with noDR

FDRs not more likely to have PSA or DRE, butreported greater vulnerability to prostate Ca andoverestimated their risk. PSA screening mostlikely in older men.

cted men (40–72 yrs3 or more affectedHPC)

Of men older than 50 yrs 68% regularly screened.Screening more likely in men with more affectedrelatives and those with less avoidant thoughts.

f men with prostate 90% Reported that they probably or definitelywanted screening.

th family history ofa (FPC) and 76 withhistory

Self-referral most common reason for attendingscreening � men with not more distressed thanthose without a family history.

st 1 affected relative) and HPC studies included only men from high risk

s-sectional household interview. In 2000, the study included interviews with

h the data collected for the 2000 National Health Interview Survey.

eenin

ple C

naffery of

MenwithMen

m 492tate Cfrican

m 88rted F)DRsger))

fricanmore

C)‡frican

e with)†

en 40ly hisno fa

affecith F)

fectedof pt)affec

e affe

DRspros

DRspros

DRswith

en wi) vsted F

naffewithtives (ons oFPC)en witate Cmily

at lea

l, cros

d wit

tate cancer are concerned about their prostate cancer risk,

r Stud

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER 43

the majority do not experience clinically relevant psycholog-ical morbidity as a result of their family history. In mostgroups men with a family history of prostate cancer have apositive attitude toward screening, are more likely to par-ticipate in screening programs and are interested in genetictesting for prostate cancer if it becomes available in thefuture. However, the review revealed a lack of relevantstudies, particularly those that focus primarily on men atsignificantly high risk for prostate cancer (ie 3 or moreaffected relatives) and more detailed studies of thesemen’s perceptions of prostate cancer (eg perceived sever-ity, treatability and causes of prostate cancer, which couldbe additional predictors of psychological distress and/orscreening). The majority of studies originated in theUnited States, and this may limit the broader significanceof these findings when considering different health sys-tems and cultural contexts.

Men at increased risk for prostate cancer on the basisof family history are confronted with difficult decisionsregarding the management of prostate cancer risk and theabsence of evidence exacerbates the difficulty of thesedecisions. Due to the lack of clear data on the performanceof prostate cancer screening in high risk patients, manyprofessional groups promote an informed choice model ofprostate cancer screening for this group whereby individ-ual clinicians may recommend screening to interestedmen, and provide information on the benefits, limitationsand harms of screening.9,36 It can also be argued that inthe absence of clear guidelines and evidence of benefitclinicians should not be raising issues of prostate cancer

TABLE 5. Studies of interest in genetic testing for prostate can

References Country of Origin Outcomes

Weinrich et al32 USA Interest in genetic testing

Cormier et al49 France Worry and interest ingenetic testing

Diefenbach et al34 USA Interest in genetic testing

Miesfeldt et al33 USA Interest in learning aboutor undergoing testing

Bratt et al18 Sweden Interest in genetic testing

Bratt et al16 Sweden Attitudes toward genetictesting

* FPC studies included men with any family history of prostate cancer (ie afamilies, most with at least 3 affected relatives.† NHIS, Data collected from African American Hereditary Prostate Cance

screening or recommending a particular course of action

to this population. In such circumstances the decisionregarding screening should certainly lie with the personat risk but, given the concern expressed by this populationand their high uptake of PSA testing, it seems preferablethat this decision is informed with accurate informationprovided by a clinician or other reputable source.

Research suggests that some men who are or perceivethemselves to be at increased risk for prostate cancer onthe basis of family history have significant unmet infor-mation needs, and desire more information about per-sonal risk and management options.16,24 The risk assess-ment of men at high risk for prostate cancer wouldnecessarily involve the recording of age and family his-tory, the 2 strongest determinants of prostate cancer risk.In addition, PSA in relation to age, especially in youngmen, and the trend in PSA with time may also be usefulparameters in risk assessment. The figure presents aflowchart of information exchange that concerned unaf-fected men at high risk for prostate cancer may find help-ful in ascertaining the risk and making decisions aboutscreening options.

There are several routes by which information aboutprostate cancer risk could be delivered. Health profession-als, particularly urologists and general practitioners, werenamed as the preferred source of information in a recentAustralian study of unaffected men with a family history ofprostate cancer,24 and these clinicians are well placed torespond to men’s concerns. Men concerned about their riskmay well present to general practitioners requesting infor-mation, but there may also be value in identifying men at

sk in unaffected men with a family history of prostate cancer

Sample Characteristics* Findings

320 Black men (HPC) comparedwith 249 men with no familyhistory†

87% Interested in genetic testingirrespective of family history,married men more likely toreport interest.

277 Men with FDR withprostate Ca (FPC)

98% Interested in genetictesting, men with more affectedrelatives more likely to reportinterest.

43 Men with FDR with prostateCa (FPC) vs 83 men without afamily history

74% Would undergo testing,irrespective of family history.Higher interest in testing inmen with high cancer relateddistress and concerns abouttreatment side effects.

342 Men attending prostatescreening, 38 of whom had atleast 1 affected FDR (FPC)

92% Interested in learning aboutthe availability of genetictesting � 89% willing toundergo testing, irrespective offamily history.

110 unaffected men with 3 ormore affected relatives (HPC)

98% Interested in finding out ifprostate Ca in their family wasinherited and 94% wouldundergo testing.

100 Sons (older than 18 yrs) ofmen with prostate Ca (FPC)

Approximately 90% wouldundergo genetic testing if therewere multiple affected men inthe family. Men who were mostconcerned about Ca and hadless education were mostinterested in genetic testing.

t one affected relative) and HPC studies included only men from high risk

y and South Carolina Prostate Cancer Education and Screening Study.

cer ri

t leas

risk through routine collection of cancer family history and,

ncern

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER44

if the family history is suggestive of a high risk of prostatecancer, referring the patient to a familial cancer clinic forgenetic counseling. A recent systematic review suggests thatdiscussing risk information in a genetics context can resultin improvement of risk perception without causing adverseoutcomes such as anxiety, cancer related worry and depres-sion.37 Genetic counseling for cancer risk encompassesissues such as perceived risk, experiences of cancer, lossand anxiety, and it is the supportive or emotional ele-ments of the consultation rather than the communicationof risk alone that have been found to provide the greatestbenefit.37

Written information, another preference of at-riskmen,24 can be provided by clinicians to complement aconsultation or may be accessed via cancer or men’shealth information services. Written information has theadvantage of allowing men to consider the available op-tions in their own time, to discuss issues with their part-ner and to pass information on to other at-risk relatives.Online delivery of patient information is becoming in-creasingly popular because of increased accessibility forpatients, and decreased production and distribution costs,although the design and usability of Internet based edu-cation are crucial factors which need to be carefully con-

Clarification of the individual’s preferences

Identification of individual’s pre-existing belief about their risk and

cause of prostate cancer in their family

Support the individual’s choice and implement an appropriate surveillance plan if requested

Provision of education regarding the principles of familial prostate cancer and discussion of personal

implications, including a discussion of the individual's responses to this information

Suggested flowchart of information exchange for co

sidered when developing online resources for patients.

FUTURE DIRECTIONS

We reviewed and summarized the available literature onthe psychosocial issues relevant to unaffected men with afamily history of prostate cancer. The review demon-strated a dearth of psychosocial studies in unaffected menwith a strong (as opposed to only 1 affected relative)family history of prostate cancer. Future studies focusingon this population and from different international per-spectives are critical to developing a more comprehensiveview of the issues to consider when counseling this group.Another interesting topic for review would be the prostatecancer treatment choices of men with a family history ofprostate cancer to investigate whether treatment choice isdifferent in men with no family history of the disease.

Given the complexity of the issues described educationalmaterials or specific decision support materials would bevaluable to assist unaffected men with a family history ofprostate cancer in deciding whether to undergo prostatecancer screening. For men who do decide to undergo screen-ing it would also be essential to help them decide what ageto start, how often to undergo and what age to stop screen-ing. Several screening decision aids for men at averagerisk for prostate cancer have been developed, and havebeen shown to reduce uncertainty and increase knowledge

Individual risk assessment using both absolute and relative

terms

Provision of a comparative figure for risk in the general

population

Provision of education on the pros and cons of prostate cancer screening using PSA and DRE

Provision of risk estimates for unaffected men with elevated PSA levels

Surveillance plan would specify: 1) when to start and stop surveillance, 2) the tests to be employed (PSA or

PSA and DRE), and 3) the surveillance interval

ed unaffected men at high risk for prostate cancer

about prostate cancer screening.38 However, we are not

UNAFFECTED MEN WITH FAMILY HISTORY OF PROSTATE CANCER 45

aware of any screening decision aids designed specificallyfor unaffected men with a strong family history of prostatecancer.

ACKNOWLEDGMENTS

Dr. Melina Gattelari, who previously developed a prostate can-cer decision aid for men at average risk for prostate cancer, Dr.Carole Pinnock from the Australian Prostate Cancer Collabo-ration, and Drs. Nadine Kasparian and Kaaren Watts from thePsychosocial Research Group, Department of Medical Oncol-ogy, Prince of Wales Hospital, Australia provided valuableinput.

Abbreviations and Acronyms

DRE � digital rectal examinationFDR � first degree relativeFPC � familial prostate cancerHPC � hereditary prostate cancerPSA � prostate specific antigen

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EDITORIAL COMMENT

How do men who suddenly discover that a close relative hasprostate cancer deal with their own risk of prostate cancer?Although many prostate cancers are slow growing, the dis-ease accounted for 27,050 annual deaths in 2007 and is thesecond leading cause of cancer related deaths in men, de-spite the recent improvement in prostate cancer mortality.

This article summarizes the relatively sparse literatureregarding issues faced by unaffected men with a familyhistory of prostate cancer. The authors report that thesemen are proactive in getting screened for prostate cancer, attimes overestimate the personal risk of prostate cancer, donot have anxiety about the screening process and stronglydesire a genetic test to determine the true risk of prostatecancer.

Although most men desire a genetic test for prostatecancer, it is unclear from the experience with other tumortypes how many would choose this option. A recent publica-tion suggests that a genetic test evaluating 5 genetic vari-ants can predict an individual’s risk of prostate cancer.1 Thistest is particularly powerful in men with a family history ofprostate cancer. A commercially available test is in progressand should be available by the end of the year.2 If this test’svalidity is corroborated by other researchers, a powerful toolwill be available for unaffected men to determine their riskof prostate cancer. Until then, prostate cancer screening forunaffected men with a family history of prostate cancerstarting at a younger age should be encouraged.

David P. WoodDepartment of UrologyUniversity of Michigan

Ann Arbor, Michigan

1. Zheng SL, Sun J, Wiklund F, Smith S, Stattin P, Li G et al:Cumulative association of five genetic variants with prostatecancer. N Engl J Med 2008; 358: 910.

2. Kolata G: Only $300 to Learn Risk of Prostate Cancer. New

York Times January 17, 2008.