ProstateCancer

Epidemiology
ProstateCanceristhemostfrequentlydiagnosedmalignancyandthesecond
leading cause of cancer death in man in the United States, with 232,090 new
diagnosesprojectedin2005(AmericanCancerSociety).Incidentratesareexpectedto
rise drastically, and by 2025, as the babyboom population ages, new cases are
estimatedtobe38,000peryear.Themedianageatdiagnosisis71years,withthe
incidenceratesteadilyincreasingforeachdecadeafterage50.ForAfricanAmerican
mentheincidencerateisapproximately170caseper100,00men,andthedeathrate
isslightlymorethattwicethatoftheirCaucasiancounterparts.In1995,110cases
per 100,000 Caucasian men were diagnosed, and 104 per 100,000 were affected
among Hispanic men. Rates for Asian American Men were 82 per 100,000. A
disturbing trend towardincreasing incidence andmortality has beennoted among
NativeAmericans.Overtheperiodfrom1969to1994,ProstateCancerdeveloped
intotheleadingcaseofmalecancermortalityamongNativeAmericans.
TheglobaldistributionofprostatecancerrevealspredominanceintheUnited
States and Canada. Additionally Scandinavia and parts of the Caribbean have
particularly high rates of incidence and mortality, whereas Japan and China have
extremelylowrates.Thehighestmortalityratesfor2005areestimatedtooccurinthe
Caribbean,SouthAmerica,andNorthernandWesternEurope.
ETIOLOGYANDRISKFACTORS
The exact etiology of prostate cancer remains unknown,although it
appearstoresultfrominterplaybetweenendogenoushormonesandenvironmental
influences. Age, Ethnicity, and family history are the only well established risk
factors.Morethan90%ofdeathsfromprostatecancerandmorethan75%ofnew
casesoccurinmen65yearsofageorolder,makingageaparticularlysalientrisk
factor.Autopsystudiesdemonstratedsomedegreeofprostatecancerinatleast30%
ofmenovertheageof50years.

ThedifferentialincidenceandmortalityamongAfricanAmericanmaleshas
been suggested to be related to hormonal factors, as higher rates of bioavailable
testosteronehavebeennotedamongAfricanAmericanmales,alongwithhigherrates
ofmutationsintheprostatesusceptibilitygene.
Although many links between lifestyle and prostate cancer have been
postulated, there remains no conclusive evidence. Increased fat intake, the
consumptionofredmeat,andincreaseddietaryanimalfatingeneralwerepositively
correlatedwithanincreasedcancerriskinoneprospectivecohortstudyinvolving
51,529men.Otherfactorshavebeenimplicated.Althoughlaboratorydataidentify
Cadmium as a prostate carcinogen, epidemiologic studies do not convincingly
implicateCadmiumasacausativefactor.DietsinSelenium,VitaminsE&D,and
Lycopenehaveallbeensuggestedtobeprotective,yetevidenceremainsinconclusive
at this point. Epidemiologic studies have suggested that vitamin D shows great
promise as a chemoprotectant. AfricanAmerican Men have greater melanin
depositionandhavehigherprostatecancerrates.VitaminDsynthesisisinhibitedby

melanin.MenlivinginhigherlatitudewithlesssunexposureandVitaminDhave
higherratesofprostatecancer.OldermenareoftenVitaminDdeficient,andtheyalso
have higher incidence rates of prostate cancer, suggesting a correlation between
VitaminDandprostatecancer.ClinicaltrialshavedemonstratedthatVitaminDcan
slowtherateofprostatespecificantigen(PSA)riseamongmenwhohaveexperience
biochemicalfailuresaftertreatment.Hypercalcemiaandtheformationofrenalcalculi
werelimitingfactors,however.Theeffectsofdietarylycopenesupplementationhave
been examined in atleast one prospective clinical trial. Before undergoing radical
prostatectomy,menwerefedtomatobasedpastadishesforthreeweeks.Analysesof
theprostateglandsrevealedincreasedlycopenelevels,andincreasedlycopenelevels
were also found in the blood, along with reductions in serum PSA levels and
oxidativeDNAdamage.
Occupationalexposureshavelongbeensuspectedtobepotentiallycausative
factorsinthedevelopmentofprostatecancer.Farmingandpesticideexposurehave
beencorrelatedwithincreasedprostatecancerincidence,althoughatthispointthere
arenoconclusivedatatosupportanyrecommendations.
Genetic links are now being examined more extensively. A possible
susceptibilitylocusonchromosome1isnowthoughttoberesponsibleforupto33%
of hereditary cancers; an autosomal dominant pattern of inheritance is suggested.
Amongmenwith1affected1stdegreerelative,therelativeriskis2.5;however,with
twoaffectedrelatives,theriskisfivefold.Therelativeriskincreasestoelevenfoldif
three relatives are affected. Overall, 9% of all malignancies are thought to be
hereditary.Chromosomes1,8,10,16,17and20,aswellasthexchromosomehave
been associated with prostate cancer, the strongest association being with
chromosome1.Othergeneticassociationshavebeenimplicatedinthedevelopment
ofprostatecancer,includingBRCA1andBRCA2.
The literature is replete with research findings examining the relationship
between vasectomy and prostate cancer risk. Although numerous studies have
documentaslightincreaseinrelativerisk,otherstudieshavefailedtodemonstrate
similarfindings.Ifthisrisktrulyexists,itissmallandmaybetiedinwiththefactthat
menwhoobtainedvasectomiesdemonstratehealthseekingbehaviorsandaremore
likelytobescreenedforandthusdiagnosedwithprostatecancer.
Infectionhasbeenproposedasapossibleriskfactor,butresearchhasfailedto
demonstrateaclearassociation.Thistheoryappearstologic,giventhatnumerous
cancers are associated with chronic inflammation and prior infection. Despite a
century of theorizing, sexual behavior, venereal disease, and fertility fail to
demonstrateaclearrelationshipwiththedevelopmentofprostatecancer.
Highgradeprostaticintraepithelialneoplasia(PIN)isaknownmarkerforthe
laterdevelopmentofprostatecancer.PINisonlydetectedonbiopsy,anddoesnot
significantly correlated to elevated PSA. PIN is not detectable by ultrasound. Its
presenceishighlypredictiveofthedevelopmentofprostatecancerwithin10years.
Insummary,nosinglefactorhasbeenidentifiedtoaccountforcarcinogenesis.
Histologicpresenceofthediseaseappearstobesimilarworldwide,whereasclinically
significantdiseasehas substantialgeographicvariation.Currentscientificthinking
suggeststhatprostatecancerresultsfromacombinationofenvironmentalfactorsas
wellaspersonalriskfactors.
PREVENTION,SCREENING,ANDDETECTION

Atthispoint,noprescriptiverecommendationscanbemadebasedonclear
scientificdata.Advisingpatientsregardingaprudentlowfatandhighfiberdietalong
with consumption of lycopenerich products may be the best advice that can be
offeredatthistime.Identificationofpatientsathighriskbecauseoffamilyhistoryis
another important nursing function. These men should participate in PSA testing
regularlyandbeginatanearlierage.
PSATESTING
PSA remains the single best for early diagnosis. PSA is a serine protease
produced by malignant cells in the prostate as well as normal and hyperplastic
prostatecells.AnelevatedPSAisanotdiagnosticofprostatecancer.Anydisruption
ofnormalprostateepithelialcellarchitectureallowsPSAtodiffuseintothetissueand
ultimately into the circulation. Elevated levels are seen following digital rectal
examination(DRE)(thoughthisisthoughttobeclinicallyinsignificant),inmenwith
benign prostatic hyperplasia (BPH) and prostatitis following transrectal
ultrasonographyandinthosewithurinaryretention.AmajordrawbackofPSAtesting
isitshighfalsepositiverate.
Efforts to enhance the specificity of PSA have included examining PSA
densityandvelocityandthedevelopmentofagespecificPSAreferenceranges.PSA
density represents the quality of serum PSA divided by one half of the prostatic
volume.PSAdensitywasthoughttobeimportantonthebasisofobservationsthat
serumPSAvaluescouldbenormalizedbybasingthemonthevolumeofprostate,
known to be larger in cases of BPH. Theoretically, data resulting from these
calculationscouldleadtofewerunnecessaryprostatebiopsies.PSAdensitytesting
has lost favor in recent years because of concerns regarding the significant costs
associated with subjecting men to transrectal ultrasound (TRUS) with each PSA
testing.
PSAvelocityreferstotheevaluationofserialPSAreadingsovertime.Some
researchers have noted that the velocity is useful in differentiationg men with
carcinomafromthosewithout,ifthreeconsecutivereadingsaretakenovera2year
timeperiod.VelocityappearedtobemostrelevantinmenwithPSAvaluesgreater
that4.0ng/ml.OthershavequestionedthevalueofPSAvelocitybecauseithasbeen
foundthatPSAvaluesvaryfromdaytoday;theconcernisthatnormalbiologic
variationscanmasksignificantPSAchangesthatmaybeindicativeofcarcinoma.
AlthoughanumberofresearchershaveproposedagespecificPSAreference
ranges, the predictive value of the 4.0ng/ml has been suggested as the cutoff for
AfricanAmericanmen.Researchhasfailedtosupporttheapplicationofagespecific
referenceranges.
Substantialcontroversysurroundstheissuesofprostatecancerscreeningand
earlydetection,andpublishedguidelinesbytheleadinghealthcareauthoritiesreflect
a lackofconsensus.Thecentral issueis anunderstanding that screening reveals,
clinicallyinsignificanttumorsthataresubsequentlytreated,perhapsunnecessarily.
Suchtreatmentresultsinsignificantlossofqualityoflife(QOL)andincreasedcosts.
The most recently updated guidelines published by the American Cancer Society
(ACS) recommend that both PSA testing and DRE should be offered annually,
beginning at age 50, to men who have at least a 10year life expectancy and to
youngermenwhoareathighrisk.HighriskmenareidentifiedasthoiseofAfrican
Americandescentandmenwithafamilyhistoryofprostatecancer.Forthesemen,

theACSrecommendsbeginningtestingatage45.Formenwithnumerousaffected
firstdegreerelatives,theACSrecommendsthattestingshouldbeinitiatedattheage
of40.TheACSfurtherrecommendsthatmenshouldbegivenspecificinformation
regarding the potential risks and benefits of screening. The ACS bases its
recommendationondatasupportingscreeningasameansofdetectingtumorsata
more favorable stage; however it notes that reductions in mortality from prostate
cancercannotdirectlybeattributedtoscreening.AnabnormalPSAisdefinedasa
valueof4.0ng/mlorhigher.TheNationalComprehensiveCancerNetwork(NCCN)
recentlyincludedinitsguidelinesforprostatecancerscreeningthatpatientswitha
PSAlevelof2.6ng/mlorhigher,eveninthepresenceofanormalDRE,shouldbe
considered forprostate biopsy. The guidelines donot strictly direct physicians to
obtainaprostatebiopsyforallpatientswith2.6ng/mlorhigherbutdostatethatthis
newlevelmaybeconsideredacutofffirwhichtoproceedtoabiopsy.
The Quebee Screening study randomly assigned men to screening or no
screeningandthencomparedmortalityovertime.MenwerescreenedwithPSAand
DRE, but only had TRUS if their PSA levels were over 3.0ng/ml. The trial
demonstratedareductioninmortalityupto70%amongmenscreenedascomparedto
thirunscreenedcounterparts.Howeverthetrialhasbeenthesubjectofwidespread
criticism because of its severe methodologic flaws. Of 46,193 men eligible to
participate,only31,00wereactuallyinvitedtoparticipate,andoftheseonly7100
were actually screened. Both randomization and statistical power were severely
compromised.Anadditionalflawwasthelagtimeof3yearsbetweenrandomization
andscreening.
A secondCanadianstudybyPerronandcolleagues examinedwhether the
declineinprostatecancerinQuebeccouldbeattributedtoPSAscreening.Changesin
incidenceratesbetween1989and1993werecomparedwithchangesinmortalityin
between 1995 and 1999. Increased screening rates among 15 birth cohorts in 15
regionsofQuebecwerenotsignificantlycorrelatedwithdecliningprostatecancer
mortalityrates.
AtpresentasidefromACSguidelines,majorhealthcareorganizationshave
notformedaclearconsensusregardingprostatecancerscreeningrecommendations.
The U.S.Preventive Services Task Force found good evidence to support PSA
screeningindetectingearlystageprostatecancer,butonlymixedandinconclusive
evidencethatearlydetectionimprovesoverallhealthoutcomes.Thisgroupdoesnot
endorse routine PSA screening. The main factor cited in favor of routine PSA
screeningisthatmenwhoarescreenedhaveahigherchanceofbeingdiagnosedatan
earlierstagethatismoreconducivetocure.Thelackofanyclearscientificevidence
demonstratingsurvivalbenefitfromscreeningdetectedprostatecanceristhemain
factorcitedagainstscreening.
Classification
Ofallprostatecancers,95%areadenocarcinomas.Theremaining5%consist
of sarcomas and transitional cell tumors. Most neoplasms of the prostate gland
developwithintheperipheralzone,withmalignantgrowthspreadinglocallyintothe
seminalvesicles,theperitoneumandthebladder.Metastasestothelungs,theliver,
the kidney and the bones occur via hematogenous spread. Lymphatic node
involvementiscommon.

Clinicalfeatures
Mostmenwithearlystagediseasemaybesymptomfree,becausethemajority
ofprostaticneoplasmsariseintheperipheralzone.Themajorityofprostatecancers
aredetectedthroughroutinescreeningwithPSAtesting.AlthoughaPSAlevelof
morethan4.0ng/mlisconsideredsuspiciousformalignancies,somemenwithPSA
levelslowerthan4.0ng/mlwillstillhaveprostatecancer.Among2,950meninthe
control group of the Prostate Cancer Prevention Study, 15% were found to have
prostatecancerbybiopsyattheconclusionofthestudy,despitehavingPSAlevels
lowerthan4ng/mlandnosuspiciousDREfindings overthe7yearcourseofthe
study.
Symptomsmaybepresentinearlystagedisease,butgenerallysymptomssuch
asurinaryhesitancy,frequency,andafeelingofincompleteemptyingofthebladder
occurlaterinthecourseandareassociatedwithdiseaseprogression.Progressionmay
also cause blood in the semen, decreased ejaculatory volume and less commonly
impotence.Impotenceoccursasthetumorencroachesuponneurovascularbundlesin
theperiprostatictissue.Bonepainandpathologicfractures,aswellasspinalcord
compression,hematuria,andanemiaarelatesignsandareassociatedwithadvanced
disease.