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Prostat NDQVHULHUNHNWHHQVÕNUDVWODQÕODQNDQVHUGLU [1]. Neyse ki, serum Prostate Specific Antigen
(PSA), \Dú, Dijital Rektal 0XD\HQH'50 \DUGÕPÕ\ODWP|UQHUNHQG|QHPGHWHúKLVHGLOPHVL
mümkündür.
+DVWDGDSURVWDWNDQVHULQGHQúSKHOHQLOGL÷LQGHKHNLPELUEL\RSVLDOÕQPDVÕQÕ|QHULU. Kimi zaman,
JoOEXOJXODUQHGHQL\OHEL\RSVLNDUDUÕYHUPHNNROD\GÕUgWH\DQGDQH÷HUEXlgular gri alandaysa,
hekim ve hasta gereksiz yere biyopsi alÕQPDVÕ YH\D YDURODQ SURVWDW NDQVHULQLQ DWODQPDVÕ JLEL
ULVNOHUOHLoLoHELUNDUDUYHUPHN]RUXQGDNDOÕU [2].
+DVWDQÕQ VHUXPXQGD EXOXQD PSA UXWLQ ELU EL\RNLP\DVDO LúOHPOH NROD\FD |OoOHELOLU. Serum
düzeyinin 4 ng/mL ]HULQGHROPDVÕSURVWDWNDQVHULRODVÕOÕ÷ÕQÕQJ|VWHUJHVLRODUDNDOJÕODQÕUYHKDVWD
NDQVHUDoÕVÕQGDQNOLQLNGH÷HUOHQGLUPH\HDOÕQÕU. *HQLúHUNHNVHULOHULQGH\DSÕODQoDOÕúPDODUGDVHUXP
36$|OoPQQLOHELUOLNWH'50NRPELQHRODUDNGH÷HUOHQGLULOGL÷LQGHNDQVHULVDSWDPDDoÕVÕQGDQ
ID\GDOÕ ROGX÷X J|UOPúWU [3, 4]. gWH \DQGDQ GL÷HU ED]Õ oDOÕúPDODU 36$¶QÕQ GX\DUOÕOÕ÷Õ YH
VHoLFLOL÷LNRQXVXQGDFLGGLVRUXLúDUHWOHULRUWD\DNR\PXúWXU [5, 6].
*HUHNVL] EL\RSVLOHUGHQ NDoÕQPDN DPDFÕ\OD 1989’den beri PSA’nÕQ WDQÕVDO GR÷UXOX÷XQX
JoOHQGLUPHN LoLQ oDOÕúPDODU \DSÕOPDNWDGÕU [7]. Bu amaçla, ancak transrektal ultrasonografi
(TRUS) \DUGÕPÕ\OD |OoOHELOHQ PSA \R÷XQOX÷X ve transizyonel bölgenin PSA \R÷XQOX÷X JLEL
kaYUDPODURUWD\DoÕNPÕúWÕU [8, 9]. TRUS ile saptanan SURVWDWKDFPLFLGGLGH÷LúNHQOLNJ|VWHUHELOLU
'DKDVÕ, TRUS KHU\HUGHEXOXQPD\DELOLU]DPDQDOÕFÕGÕUYHJ|UHFHRODUDNSDKDOÕGÕU.
36$¶QÕQ VHoLFLOL÷LQL DUWÕUPDN LoLQ UHJUHV\RQ DQDOL]L \DSD\ VLQLU D÷ODUÕ YH QRPRJUDPODU JLEL
NDUPDúÕN \|QWHPOHU GH YDUGÕU [10-14]. Bu yöntemlerle yararOÕ VRQXoODU HOGH HGLOPHNOH ELUOLNWH
EXQODUKHQ]JQONUXWLQHJLUHFHNNDGDUoDOÕúÕOPDPÕúWÕU.
Free PSA (fPSA) RUDQÕ (serum fPSA/PSAx100) \DUGÕPÕ\OD VHoLFLOL÷LQ DUWÕUÕODELOHFH÷L GH |QH
VUOPúWU. fPSASOD]PDSURWHLQOHULQHED÷OÕROPD\DQ36$PLNWDUÕGÕU [15]. %DúNDELUoDOÕúPD\D
J|UH IUHH 36$ RUDQÕ \DOQÕ]FD 36$¶\D J|UH GDKD ID]OD GX\DUOÕOÕ÷D VDKLSWLU. Free PSA
RUDQÕQÕQ¶WHQNoNROPDVÕKDOLQGH4 - 10 ng/mL DUDOÕ÷ÕQGDGX\DUOÕOÕNELOGLULOPLúWLU[16].
%HOOL ELU FR÷UDIL DODQGDNL KDVWDODUÕQ LQFHOHQGL÷L EDúND ELU oDOÕúPDGD NDQVHUOHULQ ¶LQLQ
36$¶QÕQ1–3 ng/mL DUDOÕ÷ÕQGDROPDVÕKDOLQGHIUHH36$RUDQÕQÕQ¶QLQDOWÕQGDROGX÷XROJXODUGD
UDVWODQGÕ÷Õ ELOGLULOPLúWLU [17]. %LU EDúND oDOÕúPD\D J|UH [18], tarama popülasyonunda free PSA
RUDQÕQÕQ¶LQDOWÕQGD ROGX÷XROJXODUGD¶LQVWQGHROGX÷XROJXODUDJ|UHGDKDVÕNNDQVHU
görülmektedir. Türki\H¶GH \DSÕODQ ELU oDOÕúPDGD J|UH, IUHH 36$ RUDQÕQÕQ UHFeiver operator
characteristic (ROC) area under curve (AUC) GH÷HUL0.553 olarak bildirilmLúWLU. 3URVWDWÕFF¶QLQ
DOWÕQGDRODQROJXODUGDLVHDrea under the ROC curve 0.615’ti [19].
)UHH 36$¶\Õ GD LoHUHQ oRN GH÷LúNHQOL PRGHOOHU JHQHOOLNOH EX GH÷LúNHQLQ HN ELU GH÷HUL ROGX÷X
sonucunu verir [20]. <LQHGHIUHH36$GH÷HULGLNNDWOHHOHDOÕQPDOÕGÕU oQNED]ÕDQDOL]|QFHVLYH
NOLQLNIDNW|UOHUIUHH36$RUDQÕQÕHWNLOH\HELOLU)ree PSA 4 °C YH\DRGDVÕFDNOÕ÷ÕQGDLQVWDELOGLU|WH
yandan büyük prostatlarda bir dilüsyon etkisinden söz edilebilir [8].
.DUDU D÷DoODUÕQÕQ ROXúWXUXOPDVÕ LoLQ ELUNDo DOJRULWPD YDUGÕU. Bunlardan birisi Loh and Shih
69
WDUDIÕQGDQ JHOLúWLULOHQ QUEST’ tir (Quick, Unbiased and Efficient Statistical Tree) [21]. Karar
D÷DFÕQÕ ROXúWXUDQ algoritma, ROJXODUÕ ELUNDo ULVN G]H\LQH D\ÕUÕU. Bu algoritma, sadece verilerin
DUDúWÕUÕOPDVÕ\NVHNULVNOLDOWJUXSODUÕQEHOLUOHQPHVLHWNLOHúLPOHULQEHOLUOHQPHVLYH\DSURJQRVWLN
faktörlerin LQFHOHQPHVLDPDFÕ\ODNXOODQÕODELOLU.
.DUDU D÷DFÕ DQDOL]L úLPGL\H NDGDU WÕSWD oHúLWOL SUREOHPOHULQ DQDOL]LQGH NXOODQÕOPÕúWÕU EXQODUÕQ
içinde prostat kanserinin öngörülPHVL SUREOHPL GH YDUGÕU. Garzotto YH DUNDGDúODUÕ [22] prostat
NDQVHULúSKHVLRODQKDVWDODUGDclassification and regression tree (CART) analL]LLOHELUNDUDUD÷DFÕ
ROXúWXUPXúWXU. Serum PSA düzeyi ”QJP/RODQKDVWDLQFHOHQPLúWLU. Analiz, demografik,
laboratuvar ve ultrason verilerini içermektedir. &$57 DQDOL]L LOH DWODQDQ ROJXODUÕQ ¶
Gleason skoru 6 YH\D GDKD D] RODQ ROJXODUGÕU. ROC curve analizine göre CART ile lojistik
regresyon modelleri EHQ]HUGR÷UXOX÷DVDKLSWLU (VÕUDVÕ\ODAUC= 0.74 ve 0.72). %XoDOÕúPDGDYHUL
setinde free PSA yoktur.
PSA WP|U WDUDPDVÕQGD NXOODQÕODQ HQ |QHPOL EHOLUWHoWLU, IDNDW GX\DUOÕOÕ÷Õ YH VHoLFLOL÷L ]D\ÕIWÕU.
36$¶QÕQGX\DUOÕOÕ÷ÕYHVHoLFLOL÷LQLDUWÕUPDNLoLQJQP]HNDGDUoHúLWOLoDOÕúPDODU\DSÕOPÕúWÕU. Bu
oDOÕúPDQÕQ DPDFÕQUEST analL]LLOHHOGHHGLOHQNDUDUD÷DFÕQÕQGH÷HULQLLQFHOHPHNWLU.
*HUHoYH<|QWHP
2OJXODU
Akdeniz Üniversitesi Hastanesi’ ne Ocak 2001 ile Nisan 2007 DUDVÕQGDEDúYXUDQWPQH7586
HúOL÷LQGH EL\RSVL \DSÕOPÕú ROJXODU LQFHOHQPLúWLU. øQFHOHQHn dönemde, 1830 hastaya ilk prostat
EL\RSVLVL\DSÕOPÕúWÕU. %XoDOÕúPDGDserum fPSA GH÷HULEDNÕOPÕúYHVHUXPPSA GH÷HUL 0-10 ng/mL
DUDVÕQGDRODQROJXGDKLOHGLOPLúWLU 2OJXODUÕQSURVWDWÕQGDQHQD]DOWÕSDUoDEL\RSVLDOÕQPÕúWÕUYH
tümünün histopatolojik WDQÕODUÕPHYFXWWXU.
$QDOL]
Veriler, forward stepwise lojistik regresyon analizi (LR) YH .DUDU $÷DFÕ DQDOL]L .$ LOH
LQFHOHQPLúWLU. +HUELU \DNODúÕPLoLQROC AUC KHVDSODQPÕúWÕU .$GÕúÕQGDNL WHVWOHU SPSS 11.0
(SPSS Inc., Chicago) LOH \DSÕOPÕúWÕU. Tüm LVWDWLVWLNVHODQDOL]OHULNL\|QOGUYHDOIDGH÷HUL0.05
RODUDN NDEXO HGLOPLúWLU. .DUDU D÷DFÕ DQDOL]L QUEST Classification Tree LOH \DSÕOPÕúWÕU (version
1.9.2, http://www.stat.wisc.edu/~loh/quest.html).
$QDOL]GH ED÷ÕPOÕ GH÷LúNHQ WDQÕGÕU YH PDOLJQ LOH EHQLJQ ROPDN ]HUH LNL VÕQÕIWDQ ROXúPDNWDGÕU.
%D÷ÕPVÕ] GH÷LúNHQOHU úXQODUGÕU \Dú (nümerik), PSA (nümerik), free PSA (nümerik), free PSA
RUDQÕ(nümerik), Dijital Rektal Muayene I (DRM I, oVÕQÕInegatif, úSKHOL, pozitif), DRM II (iki
VÕQÕInegatif- úSKHli veya pozitif).
Veri rastJHOH úHNLOGH oDOÕúPD (%75) ve test (validasyon) (%25) JUXSODUÕQD E|OQPúWU. <DQOÕú
VÕQÕIODPD EHGHOL HúLW ROPD\DFDN úHNLOGH D\DUODQPÕúWÕU NDQVHU ROJXVXQXQ EHQLJQ RODUDN
VÕQÕIODQPDVÕQÕQEHGHOLDOWÕNDWGDKD\NVHNWLU.
<|QWHP
dDOÕúPDJUXEXQXQ(n=562) RUWDODPD\DúÕVWDQGDUWVDSPDVÕ¶W2UWDQFD PSA düzeyi 5.65
ng/mL, ortanca fPSA düzeyi 0.95 ng/mL RODUDN VDSWDQGÕ. '50 ROJXODUÕQ %47.5’ unda
normal, %15.3¶QGH úSKHOL 37.2’ sinde pozitifti. Doksan sekiz (%17.4) olguda kanser
VDSWDQPÕúWÕYHEXQODUGDQ21 (%3.2) tanesi yüksek grade maligndi (Gleason grade •
70
QUEST algoritmDVÕ GH÷LúLN G]H\GH NDQVHU ROPD RODVÕOÕ÷Õ RODQ EHú JUXS VDSWDGÕ (ùHNLO 1): (1)
PSA¶VÕ 5.98 ng/mL’ den yüksek; (2) PSA ”QJP/ve DRM úSKHOi veya pozitif; (3) PSA ”
5.98 ng/mL ve DRE negatif ve fPSA 0.81’ den yüksek; (4) PSA ”QJP/ve DRM negatif ve
fPSA ”ve \Dú ”36$”QJP/ve DRM negatif ve fPSA ”ve \Dú 57’ den
yüksek. %XJUXSODUGDNDQVHURUDQÕVÕUDVÕ\OD %25, %15, %0, %4 ve %16 idi. Üçüncü ve dördüncü
G÷POHULQQHJDWLIRODUDNNDEXOHGLOPHVLKDOLQGH, sistem GX\DUOÕOÕNLOHNDQVHUKDVWDVÕQGDQ
97 tanesini saptamakta, 74 olguyu (%13) biyopsiden kurtarabilmektedir.
ùHNLO48(67DQDOL]LLOHHOGHHGLOHQNDUDUD÷DFÕ
Test grubu (n=188) LOH DQDOL] WHNUDUODQPÕú VLVWHP GX\DUOÕOÕN LOH NDQVHU KDVWDVÕQGDQ WDQHVLQL VDSWDPÕúWÕU. dDOÕúPD JUXEX LOH WHVW JUXEXQXQ NDUúÕODúWÕUÕOPDVÕ 7DEOR ,¶GH J|VWHULOPLúWLU
hoQFG÷PGHoDOÕúPDJUXEXQGDGDWHVWJUXEXQGDGDNDQVHU KDVWDVÕ\RNWXU'|UGQFG÷PGH
LNLNDQVHUKDVWDVÕYDUGÕUEXQODUGDQELULoDOÕúPDJUXEXQGDELULGHWHVWJUXEXQGDGÕU%XLNLKDVWD
Gleason grade 5 ve 6¶GÕU (GúN grade).
7DEOR.DUDUD÷DFÕVRQXoODUÕQÕQoDOÕúPDYHWHVWJUXSODUÕQGDNDUúÕODúWÕUPDVÕ
'÷P
dDOÕúPDJUXEXNDQVHUWRSODP
NDQVHU\]GHVL
7HVWJUXEXNDQVHUWRSODP
NDQVHU\]GHVL
1
62/251, 25%
22/98, 22%
2
30/205, 15%
11/58, 19%
3
0/47, 0%
0/14, 0%
4
1/27, 4%
1/7, 14%
5
5/32, 16%
2/11, 18%
Toplam
98/562, 17%
36/188, 19%
71
QUEST ile eldHHGLOHQVRQXoODUD\QÕIDNW|UOHUNXOODQÕODUDNUHWLOPLú lojistik regresyon modeli ile
NDUúÕODúWÕUÕOGÕ. .DUDU D÷DFÕQÕQ ROC curve AUC GH÷HUL 0.62 KHVDSODQGÕ (95% JYHQ DUDOÕ÷ÕQGD
0.58-0.68). /RMLVWLN UHJUHV\RQ PRGHOLQGH \Dú (p=0.036), DRM (p=0.001) ve PSA (p=0.001)
LVWDWLVWLNVHO RODUDN DQODPOÕ GH÷LúNHQOHUGL YH AUC 0.68’ di (95% JYHQ DUDOÕ÷ÕQGD 0.63-0.73).
<DOQÕ]FDI36$RUDQÕLoLQAUC GH÷HUL0.56 idi (95% JYHQDUDOÕ÷ÕQGD 0.50-0.62). <XNDUÕGDNL$8&
KHVDSODUÕWPYHULVHWL]HULQGHQ\DSÕOGÕ.
Benign olgularda yaúDJ|UHIPSA G]H\OHULYHI36$RUDQÕùHNLO¶GHJ|VWHULOPLúWLU. Serum fPSA
G]H\L\DúLOHUOHGLNoH\NVHOPHNWHYHserum fPSA RUDQÕ55-59 \DúJUXEXQDNDGDUD]DOÕUNHQGDKD
VRQUDNL\DúJUXSODUÕQGDDúDPDOÕRODUak yükselmektedir.
30
1,4
25
1,2
)UHH36$36$
6HUXPIUHH36$QJP/
1,6
20
1
0,8
15
0,6
10
0,4
5
0,2
0
DOWÕ
0
50-54
55-59
60-64
65-69
<Dú
Free PSA
70-74
75-79 79 üstü
Free PSA/PSA
ùHNLO.DQVHUROPD\DQROJXODUGDRUWDQFDI36$YHI36$RUDQÕGH÷HUOHUL
7DUWÕúPD
%X oDOÕúPD LOH SURVWDW NDQVHULQLQ |QJ|UOPHVL SUREOHPLQGH LON NH] QUEST NDUDU D÷DFÕ DQDOL]L
NXOODQÕOPÕúWÕU. 'DKD|QFHNLOLWHUDWUGHD\QÕSUREOHP48(67¶HEHQ]HUELUDOJRULWma olan CART ile
DQDOL] HGLOPLúWLU. %X oDOÕúPDGD 433 KDVWDQÕQ demografik verileri, DRM ve TRUS VRQXoODUÕ
serum PSA G]H\OHUL NXOODQÕOPÕúWÕU [22]. %X oDOÕúPDQÕQ VRQXoODUÕ EL]LPNL LOH ELUH ELU
NDUúÕODúWÕUÕODELOLUQLWHOLNWHGH÷LOGLUoQNEXoDOÕúPDGDEL]LPoDOÕúPDPÕ]GDNXOODQÕODQI36$YHULVL
EXOXQPD]NHQ EL]LP oDOÕúPDPÕ]GD GD sözü edilen oDOÕúPDGD NXOODQÕODQ 7586 YHULOHUL
NXOODQÕOPDPDNWDGÕU.
%XoDOÕúPDGDHOGHHGLOHQNDUDUD÷DFÕEL]HoRNGúNNDQVHURODVÕOÕ÷ÕRODQLNLG÷PYHUPLúWLU(a)
serum PSA¶VÕ6 ng/mL DOWÕQGD, DRM’ si negatif ve serum fPSA düzeyi 0.81 ng/mL üzerinde olan
olgular, (b) serum PSA¶VÕ 6 ng/mL DOWÕQGD, DRM’ si negatif, serum fPSA düzeyi ”QJP/ve
\Dú ”olan olgular. %XPRGHOoDOÕúPDJUXEXQGDWHVWJUXEXQGDGX\DUOÕOÕNJ|VWHUPLúWLU.
0RGHOHJ|UHPLQLPDOELUGX\DUOÕOÕNND\EÕLOHROJXODUÕQ¶EL\RSVLGHQNXUWXODELOLU. KA AUC
GH÷HUL fPSA RUDQÕQÕQ$8&GH÷HULQGHQKDILI \NVHN /5$8&GH÷HULQGHQKDILI GúNWU IDNDW
72
modeli anlamak da, klinik uygulamada kullanmak da görece olaraNGDKDNROD\GÕU. LRNDUPDúÕN
KHVDSODUDJHUHNVLQLPGX\PDNYHXoGH÷HUOHUGHVDSPDODU J|VWHUPHNJLELLNL|QHPOLGH]DYDQWDMD
sahiptir.
%XPRGHOLQLOJLQoELUVRQXFXGDKDYDUGÕUserum PSA düzeyi 6 ng/mL DOWÕQGD, DRM’ si negatif ve
serum fPSA düzeyi 0.81¶LQ DOWÕQGD RODQ ROJXODU LNL G÷PH E|OQPHNWHGLU. %XQODUÕQ LoLQGH \DúÕQGDQNoNHUNHNOHUNDQVHURODVÕOÕ÷ÕQDVDKLSNHQGDKD\DúOÕHUNHNOHUGHEXRUDQ¶GÕU
%X QRNWDGD ELU KDWÕUODWPD GD \DSÕOPDOÕGÕU \DSÕODQ DQDOL] I36$ RUDQÕQÕ GH÷LO GH I36$ G]H\LQL
seçmiúWLU fPSA RUDQÕ fPSA¶QÕQELUWUHYLGLUYHGúNI36$¶OÕROJXODUGDI36$RUDQÕQÕQGDGúN
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Kemal Hakan Gülkesen. Akdeniz Üni 7ÕS )DN %L\RLVWDWLVWLN YH 7ÕS %LOLúLPL $' 9, Antalya.
[email protected]
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