Vol. 106, Issue 3 | dju007 | Ma ch 12, 2014
DOI:10.1093/jnci/dju007
Fi s published online Ma ch 4, 2014
1 o 9 A icle | JNCI
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A icle
P os a e cance Mo ali y in A eas Wi h High and low P os a e
cance incidence
Pä S a in, Sig idCa lsson, BennyHolms öm, And ewVicke s, JonasHugosson, HansLilja, HåkanJonsson
Manusc ip ecei ed June 14, 2013; e ised No embe 25, 2013; accep ed Decembe 19,2013.
Co espondence o: Pä S a in, MD, PhD, Depa men o Su ge y and Pe iope a i e Sciences, U ology and And ology, Umeå Uni e si y, Umeå, Sweden
(e-mail: pa .s a [email p o ec ed]).
Backg ound The e ec o p os a e-speci ic an igen (PSA) sc eening on p os a e cance mo ali y emains deba ed, despi e
e idence om andomized ials. We in es iga ed he associa ion be ween p os a e cance incidence, e lec ing
up ake o PSA es ing, and p os a e cance mo ali y.
Me hods The s udy popula ion consis ed o all men aged 50 o 74yea s esiding in eigh coun ies in Sweden wi h an ea ly
inc ease in p os a e cance incidence and six coun ies wi h a la e inc ease du ing wo ime pe iods. Incidence o
me as a ic p os a e cance was in es iga ed in he pe iod om 2000 o 2009, and p os a e cance –speci ic mo al-
i y and excess mo ali y we e in es iga ed in he pe iod om 1990 o 1999 and he pe iod om 2000 o 2009 by
calcula ing a e a ios o high- s low-incidence coun ies and a e a ios o he pe iod om 2000 o 2009 s he
pe iod om 1990 o 1999 wi hin hese wo g oups. All s a is ical es s we e wo-sided.
Resul s The e we e 4 528 134 pe son-yea s a isk, 1577 dea hs om p os a e cance , and 1210 excess dea hs in men wi h
p os a e cance in high-incidence coun ies and 2 471 373 pe son-yea s a isk, 985 p os a e cance dea hs, and
878 excess dea hs in low-incidence coun ies in he pe iod om 2000 o 2009. Ra e a ios in coun ies wi h high s
low incidence adjus ed o ime pe iod we e 0.81 (95% con idence in e al [CI]=0.73 o 0.90) o p os a e cance –
speci ic mo ali y and 0.74 (95% CI=0.64 o 0.86) o excess mo ali y, and he a e a io o me as a ic p os a e
cance was 0.85 (95% CI=0.79 o 0.92).
Conclusions The lowe p os a e cance mo ali y in high-incidence coun ies e lec ing a high PSA up ake sugges s ha mo e-
in ense as compa ed wi h less-in ense oppo unis ic PSA sc eening educes p os a e cance mo ali y.
JNCI J Na l Cance Ins (2014) 106(3): dju007 doi:10.1093/jnci/dju007
The use o p os a e-speci ic an igen (PSA) sc eening o de ec ion
o p os a e cance emains con o e sial. Two la ge, popula ion-
based, andomized clinical ials— he Eu opean Randomized
S udy o Sc eening o P os a e Cance (ERSPC) and he Gö ebo g
ial—demons a ed 21% o 44% s a is ically signi ican dec eases
in p os a e cance –speci ic mo ali y a e 11 o 14yea s o ollow-
up in sc eened s unsc eened men (1,2). In con as , he p os a e
a m o he US P os a e, Lung, Colo ec al, and O a ian cance
sc eening ial (PLCO) ound no bene i om sys ema ic sc een-
ing compa ed wi h oppo unis ic sc eening (3).
Thus, a con o e sy on PSA sc eening s ill emains, and in
2012 he US P e en i e Se ices Task Fo ce ecommended agains
sc eening, s a ing “ he e is mode a e o high ce ain y ha he
bene i s o PSA-based sc eening o p os a e cance [in e ms o
educed p os a e cance mo ali y] do no ou weigh he ha m [in
e ms o o e diagnosis]” (4). This ecommenda ion has been c i i-
cized (5–7), and mo e da a on he associa ion be ween PSA sc een-
ing and p os a e cance mo ali y a e needed.
In addi ion o ex ended da a om ERSPC and he Gö ebo g
ial and he awai ed esul s om he ongoing UK P o ecT ial,
ca e ully designed and conduc ed obse a ional popula ion-based
s udies may p o ide aluable in o ma ion on he associa ion
be ween PSA es ing, ea ly diagnosis, and ea men and p os a e
cance mo ali y (8,9). Resul s om p e ious obse a ional s ud-
ies ha e been inconsis en ; some s udies ha e shown dec eased
p os a e cance mo ali y in a eas wi h high PSA es ing (10,11),
whe eas o he s ha e ound no such di e ence (12,13).
In Sweden, as in many o he Wes e n coun ies, he in oduc-
ion o PSA es ing in he 1990s esul ed in an inc ease in p os-
a e cance incidence. Excep o a andomized ial on sys ema ic
sc eening conduc ed in he ci y o Gö ebo g, he in oduc ion
o PSA es ing was in he o m o oppo unis ic sc eening (14).
Among he 24 Swedish coun ies, he e we e la ge di e ences in
p os a e cance incidence, wi h an es ima ed ou old a ia ion in
he p opo ion o men unde going PSA es ing despi e a uni o m,
equal-access heal h-ca e sys em (15).
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To capi alize on his na u al expe imen , we e ie ed ou come
da a om h ee na ion-wide, popula ion-based egis ies in Sweden
and assessed he incidence o me as a ic p os a e cance , p os a e can-
ce –speci ic mo ali y, and excess mo ali y in coun ies wi h an ea ly
inc ease in he incidence o p os a e cance and in coun ies wi h a la e
inc ease, e lec ing di e ences in up ake o PSA es ing, o in es iga e
he associa ion be ween PSA es ing and p os a e cance mo ali y.
Me hods
The Swedish Cance Regis e , Cause o Dea h Regis e ,
and Na ional P os a e Cance Regis e
Swedish law manda es and egula es he egis a ion o inciden can-
ce cases in he Swedish Cance Regis e and dea hs in he Cause o
Dea h Regis e . The Cance Regis e con ains each pa ien ’s 10-digi
pe sonal iden i y numbe , da e o diagnosis, coun y o esidence, and
cance si e. The Cause o Dea h Regis e con ains he pe sonal iden-
i y numbe , da e o dea h, and unde lying and con ibu o y causes
o dea h. Since 1998, app oxima ely 98% o all inciden p os a e
cance cases in he Swedish Cance Regis e we e also egis e ed in
he Na ional P os a e Cance Regis e , including he eason o he
wo k-up ha led o diagnosis, umo s age, Gleason sco e, se um
PSA a ime o diagnosis, and p ima y ea men (16,17).
Iden i ica ion o P os a e Cance Case Pa ien s and
Endpoin s
We used he Swedish Cance Regis e o iden i y p os a e cance case
pa ien s diagnosed om Janua y 1, 1980, o Decembe 31, 2009, and
linked by pe sonal iden i y numbe s (18) o he Na ional P os a e
Cance Regis e o ob ain in o ma ion on me as ases a he ime o
diagnosis, e idenced by adiog aphic e alua ion (bone scans) o he
la ge majo i y o men o se um PSA le els g ea e han 100 ng/mL
(16). We ob ained da e and cause o dea h by linkage o he Swedish
Cause o Dea h Regis e o dea h a ibu ed o p os a e cance when
i was coded as “unde lying cause o dea h.” The s udy was app o ed
by he Resea ch E hics Boa d a Umeå Uni e si y Hospi al.
S a is ical Analysis
We calcula ed he p edic ed p os a e cance incidence— ha is, he
incidence ha would be expec ed i no PSA es ing had occu ed.
Because PSA es ing was in oduced in clinical p ac ice in Sweden
in he 1990s, he p edic ion o each yea up o 2009 was based on
he obse ed incidence o he pe iod om 1980 o 1990. We used
a linea eg ession model wi h a common slope o calenda yea
bu sepa a e in e cep s o each coun y. Age-adjus ed p os a e can-
ce incidence o men aged 50 o 74yea s was calcula ed by di ec
s anda diza ion wi h weigh s om he Swedish popula ion census
o 2000 (19). We hen calcula ed he cumula i e di e ence be ween
he obse ed and p edic ed age-adjus ed p os a e cance incidence
in men aged 50 o 74yea s s a ing om 1995 and ound a ange
o −126 pe 100 000 o 1634 pe 100 000. We used his di e ence
o ca ego ize coun ies as ha ing high, in e media e, o low p os a e
cance incidence and chose he cu o s o 100 pe 100 000 be ween
low- and in e media e-incidence coun ies and 800 pe 100 000
be ween in e media e- and high-incidence coun ies.
We used wo measu es o p os a e cance mo ali y—p os a e can-
ce –speci ic mo ali y, which was based on he unde lying cause o dea h
gi en in he Cause o Dea h Regis e (20,21), and excess mo ali y (22),
based on he excess numbe o dea hs (obse ed minus expec ed) ega d-
less o cause o dea h among men wi h p os a e cance . We calcula ed
he expec ed numbe o dea hs as he p oduc o pe son-yea s among
he inciden p os a e cance case pa ien s and he o al mo ali y a e
in he popula ion, calcula ed pe yea and pe a ained age in g oups o
5yea s. We de e mined p os a e cance mo ali y du ing wo calenda
pe iods, 1990 o 1999 and 2000 o 2009. We calcula ed incidence-based
mo ali y o each o he mo ali y measu es based on dea hs among
men diagnosed wi h p os a e cance du ing he s udy pe iod (20,21). In
addi ion, we calcula ed he 2000 o 2009 incidence o me as a ic p os a e
cance (23). To de e mine incidence and mo ali y a es, we used pe son-
yea s based on popula ion s a is ics by yea and by 5-yea age g oup. All
a es we e measu ed a he popula ion le el (wi h he male popula ion,
no he numbe o men wi h p os a e cance as denomina o ).
We calcula ed a e a ios (RRs) o high- s low-incidence coun-
ies and he a e a ios o he pe iod om 2000 o 2009 s he pe iod
om 1990 o 1999 wi hin hese wo g oups. Finally we also de e -
mined a e a ios o high- s low-incidence coun ies adjus ed o
ime pe iod by di iding by he co esponding a e a io in he pe iod
om 1990 o 1999. We calcula ed a e a ios o men aged 50 o
74yea s and he subg oup aged 55 o 69yea s, which was he co e
age g oup in he ERSPC s udy (24). We based con idence in e als
(CIs) on he assump ion o a Poisson dis ibu ion o he numbe o
e en s and calcula ed a iances using he del a me hod on he loga-
i hm o he es ima es ollowed by no mal app oxima ion (25).
esul s
Be ween 1980 and 2009, 197 014 Swedish men aged 50 o 74yea s
we e diagnosed wi h p os a e cance , and o hose, 6900 men wi h
nonin asi e o seconda y p os a e cance s we e excluded om he
s udy. Figu e1 p esen s a low cha o he s udy coho .
The e we e 4 528 134 pe son-yea s a isk, 1577 dea hs om
p os a e cance , and 1210 excess dea hs in men wi h p os a e cance
in high-incidence coun ies and 2 471 373 pe son-yea s, 985 p os-
a e cance dea hs, and 878 excess dea hs in low-incidence coun-
ies in he pe iod om 2000 o 2009. A apid inc ease in p os a e
cance incidence began in some coun ies in 1990 bu no un il
10yea s la e in o he coun ies (Figu e2A). Figu e2B shows he
cumula i e di e ence be ween obse ed and p edic ed p os a e
cance incidence in each coun y om 1995 o 2009. The di e -
ence in incidence be ween he high- and low-incidence coun ies
was la ges in 2005 and dec eased he ea e , disappea ing in 2009
(Supplemen a y Figu e1, a ailable online).
In he pe iod om 2000 o 2009, he cumula i e incidence o
me as a ic disease, p os a e cance –speci ic mo ali y, and excess
mo ali y was s a is ically signi ican ly lowe in high-incidence
coun ies han in low incidence coun ies (Figu e3, A–C), wi h a e
a ios o 0.85 (95%=0.79 o 0.92) o me as a ic disease, 0.87 (95%
CI=0.81 o 0.95) o p os a e cance –speci ic mo ali y, and 0.75
(95% CI=0.66 o 0.86) o excess mo ali y (Figu e4A).
In high-incidence coun ies, p os a e cance –speci ic mo aliy
and excess mo ali y we e s a is ically signi ican ly lowe du -
ing he pe iod om 2000 o 2009 han du ing he pe iod om
1990 o 1999, and we obse ed simila , albei somewha weake
di e ences in low-incidence coun ies (Figu e4B). When aking
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bo h coun y g oup and ime pe iod in o conside a ion, he di e -
ences in cance -speci ic mo ali y and excess mo ali y be ween
high- s low-incidence coun ies emained s a is ically signi ican
(Figu e4C). The a e a ios adjus ed o ime pe iod o high- s
low-incidence coun ies we e 0.81 (95% CI=0.73 o 0.90) o
p os a e cance –speci ic mo ali y and 0.74 (95% CI = 0.64 o
0.86) o excess mo ali y, and he a e a ios o he subg oup o
men aged 55 o 69yea s we e simila . The es ima ed a e a io o
p os a e cance speci ic mo ali y o 0.81 would co espond o an
annual absolu e educ ion a 0.23 pe 1000 men when applied o
he Swedish p os a e cance mo ali y yea 2000 in he age g oup
55 o 79yea s.
Da a in he Na ional P os a e Cance Regis e om 2000
o 2009 indica ed ha diagnos ic and he apeu ic ac i i y was
highe in high-incidence coun ies han in low-incidence coun ies
(Table1). In he high-incidence coun ies, median age a diagno-
sis was lowe , a highe p opo ion o men had low- isk cance
(clinical s age T1–T2, Gleason sco e 2–6, and PSA < 10 ng/mL a
diagnosis), a highe p opo ion unde wen adical p os a ec omy,
and median se um PSA a diagnosis was lowe . The di e ence
be ween high- s low-incidence coun ies in diagnos ic PSA le els
was la ges in 2000 (10.0 s 17.6 ng/mL) and dec eased s eadily
a e ha (Supplemen a y Table1, a ailable online). The use o
adio he apy and adical p os a ec omy showed simila empo al
ends wi h he highes use in high-incidence coun ies and wi h a
dec easing di e ence o e ime (Supplemen a y Figu e2, a ail-
able online).
Discussion
In his egis e -based, popula ion-based s udy in Sweden, incidence
o me as a ic p os a e cance was 15% lowe , and p os a e cance –
speci ic mo ali y and excess mo ali y adjus ed o ime pe iod
we e 19% and 26% lowe , espec i ely, in coun ies wi h high s
low incidence o p os a e cance , e lec i e o ea ly s la e up ake o
PSA es ing. These esul s sugges ha oppo unis ic PSA sc een-
ing dec eases p os a e cance mo ali y.
The s eng h o ou s udy lies in i s popula ion-based design, i s
magni ude, he comple eness o he egis e s, and he equal access
heal h ca e in he wo s udy g oups. I co e ed nea ly 7 million
pe son-yea s a isk and 2562 p os a e cance dea hs egis e ed
be ween 2000 and 2009 and had he powe o de ec mode a ely
s ong associa ions be ween PSA es ing and p os a e cance dea h.
Fu he mo e, PSA es ing is likely o be pa icula ly e ec i e in
Sweden because p os a e cance mo ali y is highe in Sweden han
in o he coun ies, wi h a li e ime isk o p os a e cance dea h o
5% o 6%, so Swedish men wi h p os a e cance a e a high isk o
disease p og ession (26). O he s eng hs o ou s udy we e he use
o incidence-based mo ali y, which enabled us o a oid dilu ing
isk es ima es by including dea hs among men diagnosed be o e
P os a e cance case pa ien s
1980−2009
(n = 197 014)
Exclusion o men wi h
nonin asi e p os a e
cance s ( = PIN) and
second p os a e cance
(n=6900)
S udy popula ion
(n = 190 114)
In o ma ion on da e and
cause o dea h 1980−2009
(n = 118 150)
In o ma ion on dis an
me as asis 1996−2009
(n = 18 117)
Low-incidence
coun ies
In e media e-incidence
coun ies High-incidence
coun ies
The Swedish Cance
Regis e
The Swedish Cause o
Dea h Regis e
The Na ional P os a e Cance
Regis e o Sweden
1990−1999
P os a e cance -speci ic
mo ali y and excess
mo ali y among p os a e
cance case pa ien s
(2 195 294 pe son-yea s)
2000−2009
Incidence o dis an me as ases
p os a e cance -speci ic mo ali y
and excess mo ali y among
p os a e cance case pa ien s
(2 471 373 pe son-yea s)
1990−1999
P os a e cance -speci ic
mo ali y and excess
mo ali y among p os a e
cance case pa ien s
(3 925 621 pe son-yea s)
2000−2009
Incidence o dis an me as ases
p os a e cance -speci ic mo ali y
and excess mo ali y among
p os a e cance case pa ien s
(4 528 134 pe son-yea s)
Figu e1. Flow cha o linkages be ween he Swedish Cance Regis e , he Swedish Cause o Dea h Regis e , and he Na ional P os a e Cance Regis e
o Sweden and inal s udy popula ion. * Dis an me as asis de ined as M1 and/o p os a e-speci ic an igen ≥ 100 ng/mL.
======= indica es egis y linkage.
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Figu e 2. Coun ies anked by he cumula i e di e ence be ween
obse ed and p edic ed p os a e cance incidence pe 100 000 om
1995 h ough 2002. A) Obse ed and p edic ed age-s anda dized
p os a e cance incidence in men aged 50–74 yea s in 24 Swedish
coun ies du ing he pe iod om 1980 o 2009. S eady line is p e-
dic ed incidence, and undula ing line is obse ed incidence. B)
Cumula i e di e ence be ween obse ed and p edic ed incidence o
p os a e cance du ing he pe iod om 1995 o 2009. Nega i e di e -
ences esul ing om he p edic ed incidence being highe han he
obse ed incidence in low-incidence coun ies we e se o ze o. G &
B=Gö ebo g and Bohus coun y; H=high-incidence coun y; L=low
incidence coun y.
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Figu e3. P os a e cance incidence and mo ali y in men in Sweden aged 50 o 74yea s, 2000 o 2009. A) Cumula i e incidence o me as a ic dis-
ease. B) P os a e cance -speci ic mo ali y. C) Excess mo ali y.

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Figu e4. Risk o p os a e cance mo ali y acco ding o coun y o esi-
dency (in g oups o coun ies wi h high and low incidence) and ime
pe iod in g oups o coun ies wi h high, in e media e and low incidence o
p os a e cance A) Ra e a io (RR) o incidence o me as a ic p os a e can-
ce , p os a e cance –speci ic mo ali y, and excess mo ali y in high- s
low-incidence coun ies. B) Ra e a io o p os a e cance –speci ic mo ali y
and excess mo ali y in he pe iod om 2000 o 2009 s he pe iod om
1990 o 1999. C) Ra e a io o high- s low-incidence g oup adjus ed o
ime pe iod. * Me as a ic p os a e cance de ined as M1 and/o p os a e-
speci ic an igen ≥ 100 ng/mL a diagnosis. ** Excess mo ali y de ined as
he excess numbe o dea hs (obse ed minus expec ed), ega dless o
cause o dea h among men wi h p os a e cance . CI=con idence in e al.
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he in oduc ion o PSA es ing, and he use o h ee sepa a e end-
poin s—incidence o me as a ic p os a e cance , p os a e cance -
speci ic mo ali y, and excess mo ali y.
The Swedish Cance Regis e cap u es 96% o all cance
diagnoses, and he cap u e a e is pa icula ly high o solid
umo s and in subjec s aged less 70yea s (27). The alidi y o he
Cause o Dea h Regis e is high o p os a e cance . Fo exam-
ple, in he Gö ebo g sc eening ial, he e was a 96% ag eemen
be ween a cha e iew o dea h ce i ica es and he Cause o
Dea h Regis e (28), and in ano he s udy wi h a wide ange
in s age and g ade, he ag eemen was 86% (29). Besides p os-
a e cance –speci ic mo ali y, we also in es iga ed he incidence
o me as a ic p os a e cance , which was he i s indica ion o
he e icacy o PSA sc eening in he Eu opean ials (1,2). We
assessed he occu ence o me as a ic disease a da e o diagnosis
by use o da a on he p esence o bone me as ases o a se um
le el g ea e han 100 ng/mL a ailable om 2000 in he Na ional
P os a e Cance Regis e .
Ou s udy also had some limi a ions because we we e unable o
di ec ly measu e he ex en o PSA es ing in he popula ion. Ins ead,
we used he di e ence be ween he obse ed and p edic ed cumula-
i e incidence o p os a e cance unde he assump ion ha a high
incidence indica ed an ea ly in oduc ion and a high p e alence o
PSA es ing wi h ensuing ea ly p os a e cance diagnosis and ea -
men . This assump ion was co obo a ed by da a in he Na ional
P os a e Cance Regis e on dis ibu ion o isk ca ego ies wi h lowe
median se um PSA le els a diagnosis, highe p opo ion o clinically
localized low- isk cance s, highe p opo ion o cu a i e ea men s,
and a lowe age a diagnosis in high- s low-incidence coun ies.
Geog aphical compa isons can be hampe ed by di e ences in
baseline isk, and p io obse a ional s udies compa ing high and
low p os a e cance incidence a eas in he Uni ed S a es epo ed
no di e ence in p os a e cance mo ali y (12,13). In he i s ime
pe iod o ou s udy, p os a e cance –speci ic mo ali y was highe
in high-incidence coun ies han in low-incidence coun ies, showing
ha he subsequen ly lowe p os a e cance mo ali y in high-inci-
dence coun ies was no simply he esul o di e ences in baseline
isk. Tempo al compa isons can be hampe ed by changes in diagnos-
ic c i e ia o e ime and hus can also be a ec ed by bias. To add ess
hese issues, we made sepa a e geog aphical and empo al compa i-
sons and used a combined app oach as well, including adjus men
o ime pe iods in he analysis o geog aphical di e ences.
Ou isk es ima es we e a ec ed by o he sou ces o bias. The
dec ease in excess mo ali y was consis en ly la ge han he dec ease
in p os a e cance –speci ic mo ali y. Excess mo ali y likely o e es-
ima es he bene i o sc eening because i e lec s a lowe mo ali y
om causes o he han p os a e cance . The e may be selec ion bias
o heal hy Swedish men wi h a long li e expec ancy who unde go
PSA es ing and ea ly de ec ion, as sugges ed in a p e ious s udy
in he Na ional P os a e Cance Regis e , which showed lowe
10-yea all-cause mo ali y among men wi h low- and in e medi-
a e- isk p os a e cance compa ed wi h he backg ound popula ion,
indica ing a heal hy sc eenee e ec (30). In con as , p os a e can-
ce –speci ic mo ali y unde es ima es he isk educ ion because i
Table1. Cha ac e is ics o men aged 50 o 74yea s wi h p os a e cance in he Na ional P os a e Cance Regis e o Sweden, 2000 o 2009*
Cha ac e is ic
Coun y Incidence
High (n=33 780) In e media e (n=37 624) Low (n=16 377)
Age a diagnosis, y
Median (IQR) 70 (63–77) 70 (63–77) 72 (65–79)
Mean (SD) 70.0 (9.3) 70.2 (9.2) 71.7 (9.1)
Se um PSA le el, ng/mL
Median (IQR) 10.8 (6.0–27.0) 12.0 (6.6–32.0) 15.0 (7.6–43.0)
No. missing (%) 506 (1.5) 1114 (3.0) 385 (2.4)
Mode o de ec ion, No. (%)
PSA es ing as a pa o heal h check-up 10 684 (31.6) 10 101 (26.8) 3646 (22.3)
Lowe u ina y ac symp oms 10 533 (31.2) 10 668 (28.4) 5793 (35.4)
O he symp oms/unknown 12 563 (37.2) 16 855 (44.8) 6938 (42.4)
Planned ea men , No. (%)†
Su eillance 8937 (26.5) 8613 (22.9) 4079 (24.9)
Radical p os a ec omy 8444 (25.0) 8425 (22.4) 2419 (14.8)
Radia ion he apy 4198 (12.4) 4891 (13.0) 2501 (15.3)
Ho monal he apy 10 931 (32.4) 12 600 (33.5) 6620 (40.4)
O he /missing 1270 (3.8) 3095 (8.2) 758 (4.6)
Risk ca ego y, No. (%)‡
Low isk 9874 (29.2) 9593 (25.5) 3366 (20.6)
In e media e isk 8651 (25.6) 8997 (23.9) 3867 (23.6)
High isk 7908 (23.4) 9917 (26.4) 4570 (27.9)
Regionally me as a ic 2097 (6.2) 2735 (7.3) 1407 (8.6)
Dis an me as ases 4524 (13.4) 5158 (13.7) 2891 (17.7)
Missing 726 (2.1) 1224 (3.3) 276 (1.7)
* IQR=in e qua ile ange; PSA=p os a e-speci ic an igen; SD=s anda d de ia ion.
† Ini ia ed o planned wi hin he 6mon hs a e diagnosis.
‡ Risk g oups acco ding o modi ica ion o he Na ional Comp ehensi e Cance Ne wo k. Low isk: T1 o 2, Gleason sco e 2 o 6, and PSA < 10 ng/mL. In e media e
isk: T1 o 2, Gleason sco e 7, and/o PSA 10 o <20 ng/mL. High isk: T3, and/o Gleason sco e 8 o 10, and/o PSA 20 o <50 ng/mL. Regionally me as a ic disease:
T4 and/o N1 and/o PSA 50 o <100 ng/mL in he absence o dis an me as ases (M0 o Mx). Dis an me as ases: M1 and/o PSA ≥100 ng/mL.
JNCI | A icle 8 o 9
jnci.ox o djou nals.o g
is a ec ed by a ibu ion bias; dea h om an unce ain cause is mo e
likely a ibu ed o p os a e cance in men wi h a p os a e cance
diagnosis han in o he men (31). Fu he mo e, ou ollow-up ime
was 10yea s a maximum, which is likely oo sho a ime o eap
he ull e ec o ea ly de ec ion. Finally, con ounding by unknown
ac o s canno be uled ou . Despi e hese sho comings, a highe
incidence o p os a e cance was consis en ly associa ed wi h lowe
isk es ima es in all 18 isk analyses.
The ERSPC s udy, he la ges andomized sc eening ial o
da e wi h 761 p os a e cance dea hs, showed i ually he same
educ ion (21%) in mo ali y obse ed a e 11yea s o ollow-up
as ou s udy (1). In he Gö ebo g sc eening ial in Sweden, based
on 122 p os a e cance dea hs, a la ge educ ion in mo ali y was
obse ed (44%), likely because o he longe median ollow-up o
14yea s. Specula i ely, he la ge e ec in he Gö ebo g ial com-
pa ed wi h ou obse a ions may, in addi ion o a longe ollow-up,
also be because o a mo e s ingen wo k-up o men wi h ele a ed
se um PSA in a ial se ing and o a supe io diagnos ic and he -
apeu ic le el o ca e in a high- olume se ing as compa ed wi h
ou esul s ha we e based on ou ine clinical p ac ice among all
heal h-ca e p o ide s in 14 Swedish coun ies.
Ou esul s om a popula ion-based, eal-li e s udy indica e
ha mo e-in ense as compa ed wi h less-in ense oppo unis ic
PSA sc eening dec eases p os a e cance mo ali y, which econ-
ciles he indings o he wo la ges ials on PSA sc eening o da e,
namely ERSPC (o ganized s no sc eening) and PLCO (o ganized
s oppo unis ic sc eening) and is cong uen wi h he educ ion o
p os a e cance mo ali y ha has occu ed in he Uni ed S a es
du ing he las decades, du ing which ime pe iod ea ly diagnosis
and ea ly ea men has inc eased d as ically (32).
Howe e , oppo unis ic sc eening as i is cu en ly imple-
men ed in eal li e is ine icien and is implemen ed oo equen ly
in he w ong age g oups. In a ecen Swedish s udy, 6% o men
aged 40 o 49yea s, 16% o men age 50 o 59yea s, 27% o men
aged 60 o 69yea s, 30% o men aged 70 o 79yea s, and 23%
o men age 80 o 89yea s had an annual PSA es (33), whe eas
in he Uni ed S a es, 45% o men aged 75 yea s and olde ha e a
yea ly PSA es (34). The equen PSA es ing o olde men leads
o o e de ec ion and o e ea men , and o maximize he bene i s
while a he same ime minimizing he ad e se e ec s o sc eening
and ensuing ea men , isk-s a i ied sc eening wi h egula bu
in equen PSA es ing o middle-aged men holds p omise (35).
In conclusion, in ou popula ion-based s udy we obse ed lowe
incidence o me as a ic p os a e cance , lowe p os a e cance –spe-
ci ic mo ali y, and lowe excess mo ali y in coun ies wi h high
s low incidence o p os a e cance , e lec ing PSA up ake. This
indica es ha mo e-in ense as compa ed wi h less-in ense oppo -
unis ic PSA sc eening educes p os a e cance mo ali y.
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Funding
This wo k was unded by The Swedish Resea ch Council 825-2008-5910 and
he Swedish Cance Socie y 11 0471, Väs e bo en Coun y Council, and Lions
Cance Resea ch Founda ion a Umeå Uni e si y, Sweden. HL is suppo ed by
g an s om he Na ional Cance Ins i u e (R33 CA 127768-03, P50-CA92629);
he Swedish Cance Socie y (11–0624); he Sidney Kimmel Cen e o P os a e
and U ologic Cance s; Da id H.Koch h ough he P os a e Cance Founda ion;
he Na ional Ins i u e o Heal h Resea ch, Ox o d Biomedical Resea ch
Cen e, Ox o d Uni e si y Hospi als NHS T us and Uni e si y o Ox o d; and
Fundación Fede ico SA. SC is suppo ed by g an s om he Swedish Cance
Socie y, he Sweden Ame ica Founda ion, he Swedish Council o Wo king Li e
and Social Resea ch, and he Swedish Socie y o Medical Resea ch.
No es
None o he s udy sponso s had any ole in he design o he s udy, he da a col-
lec ion, analysis, in e p e a ion o he da a, manusc ip w i ing, o decision o
submi he manusc ip o publica ion.
The p ojec was made possible by he con inuous wo k o he Na ional
P os a e Cance Regis e o Sweden s ee ing g oup: Pä S a in (chai man),
Ande s Widma k, Camilla Thellenbe g, O e And én, Anna Bill-Axelsson, Ann-
So i F ansson, Magnus Tö nblom, S e an Ca lsson, Ma ie Hjälm-E iksson,
Bodil Wes man, Bill Pe e sson, Da id Robinson, Ma s Andén, Jan-E ik Dambe ,
Jonas Hugosson, Ingela F anck-Lissb an , Ma ia Nybe g, Gö an Ahlg én, Ola
B a , René Blom, La s Ege ad, Calle Walle , Jan-E ik Johansson, Olo Ak e,
Pe F ansson, E a Johansson, F ed ik Sandin, Hans Ga mo, Ma s Lambe,
Ka in Hells öm, Anne e Wige z, and E ik Holmbe g. Mi iam Bloom, PhD
(SciW i e Biomedical W i ing & Edi ing Se ices), p o ided linguis ic edi ing.
A ilia ions o au ho s: Depa men o Su ge y and Pe iope a i e Sciences,
U ology and And ology (PS, BH) and Depa men o Radia ion Sciences,
Oncology (HJ), Umeå Uni e si y, Umeå, Sweden; Depa men o Su ge y,
U ology Se ice (PS, SC), Depa men o Epidemiology and Bios a is ics
(AV), Depa men o Labo a o y Medicine (HL), Depa men o Su ge y
(HL), and Depa men o Medicine (HL), Memo ial Sloan-Ke e ing Cance
Cen e , New Yo k, NY; Depa men o U ology, Sahlg enska Academy a
Gö ebo g Uni e si y, Gö ebo g, Sweden (SC, JH); Nu ield Depa men
o Su gical Sciences, Uni e si y o Ox o d, Ox o d, UK (HL); Ins i u e o
Biomedical Technology, Uni e si y o Tampe e, Tampe e, Finland (HL);
Depa men o Labo a o y Medicine in Malmö, Lund Uni e si y, Malmö,
Sweden (HL).