Real World Evidence Study on Metastatic Prostate Cancer Patient Characteristics, Treatment Patterns and Outcomes in the Pirkanmaa Hospital District in Finland
Conditions: Metastatic Castration Sensitive Prostate Cancer (mCSPC), Metastatic Castration Resistant Prostate Cancer (mCRPC)
Sponsor: Pfizer

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 1 of 2 8
N O N-I N T E R V E N TI O N A L ( NI) S T U D Y P R O T O C O L
St u d y i nf o r m ati o n
Title
Re al W orl d E vi d e n c e st u d y o n m etastatic pr ostate 
c a n c er p atie nt c h ara cteristics, tre at m e nt p atter ns a n d 
o utc o m es i n t h e Pir k a n m a a H os pital District i n Fi nla n d 
Pr ot o c ol n u m be r
C 3 4 4 1 0 5 7
Pr ot o c ol v e rsi o n i de ntifie r
V ersi o n 1
D ate
1 3  D e c e m b er 2 0 2 2
A cti v e s u bst a nc e
E n z al uta mi d e ( A T C-c o d e L 0 2 B B 0 4) 
Tala z o p ari b ( A T C -c o d e L 0 1 X K 0 4)
Me dici n al pr o d uct
Xta n di, Talz e n n a
R es e a r c h q uesti o n a n d o bje cti v es
C urre nt u n d ersta n di n g of t h e e pi d e mi ol o g y a n d dis e ase 
b ur d e n of m P C p atie nts i n Fi nla n d is la c ki n g. T his stu d y 
will atte m pt t o a ns w er t h e f oll o wi n g q u esti o ns:
W h at are t h e d e m o gra p hic a n d cli nic al 
c h ara cteristics of m P C p atie nts ?
H o w are m P C p atie nts c urre ntl y tre ate d a n d 
h o w eff e cti ve are t h es e tre at m e nts ?
H o w d o es t h e d e v el o p me nt of c astrati o n-
resista n c e aff ect p atie nt o utc o mes ?
W h at is t h e e c o n o mic b ur d e n of m P C?
A ut h o r
, P h D, 
, Pfiz er Fi nla n d
A d dress: Tiet o k uja 4, 0 0 3 3 0 H elsi n ki
e m ail: 
tel. 
T his d o c u me nt c o ntai ns c o nfi de ntial i nf or mati o n b el o n gi n g t o Pfiz er.  E x c e pt as ot her wise a gre e d t o i n writi n g, 
b y a c c e pti n g or re vie wi n g t his d o c u me nt, y o u a gre e t o h ol d t his i nf or mati o n i n c o nfi de nc e a n d n ot c o p y or 
discl ose it t o ot h ers (e x c e pt w h ere re q uire d b y a p plic a ble la w) or use it f or u n a ut h oriz e d p ur p oses.  I n t he e v ent 
of a n y a ct ual or s us p e cte d brea c h of t his o bli gati o n, Pfiz er m ust b e pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
P P D
P P D
P P D
P P D

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 of 2 8 
1.  T A B L E O F C O N T E N T S 
 
1. T A B L E O F C O N T E N T S ................................................................................................ 2  
2. LI S T O F A B B R E VI A TI O N S ......................................................................................... 4  
3. R E S P O N SI B L E P A R TI E S ............................................................................................. 6  
4. A M E N D M E N T S A N D U P D A T E S ................................................................................. 7  
5. MI L E S T O N E S ............................................................................................................... 8  
6. R A TI O N A L E A N D B A CK G R O U N D  ............................................................................ 8 
7. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S ............................................................... 9  
7. 1. Pri m ar y o bje cti ve.............................................................................................. 1 0  
7. 2. Se c o n d ar y o bje cti ves ........................................................................................ 1 0  
8. R E S E A R C H M E T H O D S ............................................................................................. 1 0 
8. 1. St u d y desi g n ..................................................................................................... 1 0  
8. 2. Setti n g.............................................................................................................. 1 0  
8. 3. V aria bles .......................................................................................................... 1 5  
8. 4. D ata s o urces ..................................................................................................... 1 6  
8. 5. St u d y size ......................................................................................................... 1 8  
8. 6. D ata m a n a ge me nt ............................................................................................. 1 8  
8. 7. D ata a n al ysis .................................................................................................... 1 9  
8. 8. Q ualit y c o ntrol.................................................................................................. 2 4  
8. 9. Li mitati o ns of t h e res earc h m eth o ds .................................................................. 2 5  
8. 1 0.  Oth er as pe cts .................................................................................................. 2 5  
9. P R O T E C TI O N O F H U M A N S U BJ E C T S ..................................................................... 2 5  
9. 1. Patie nt inf or m ati o n ........................................................................................... 2 5  
9. 2. Patie nt c o ns e nt.................................................................................................. 2 5  
9. 3. I nstit utio n al re vie w b o ard (I R B)/I n d e p e n d e nt ethics c o m mitte e (I E C) ................ 2 6 
9. 4. Et hic al c o n d u ct of t he st u d y .............................................................................. 2 6  
1 0. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S .............................................................................................................. 2 6  
1 1. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ...... 2 6  
1 2. R E F E R E N C E S........................................................................................................... 2 7  
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 3 of 2 8 
1 3. LI S T O F T A B L E S ..................................................................................................... 2 7  
1 4. LI S T O F FI G U R E S .................................................................................................... 2 8  
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S  ..................................................... 2 8 
A N N E X 2. A D DI TI O N A L I N F O R M A TI O N.................................................................... 2 8  
 
 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 4 of 2 8 
2.  LI S T O F A B B R E VI A TI O N S 
 
A b br e vi ati o n  
D efi niti o n  
A D T 
A n dr o ge n d e pri v ati o n t h era p y 
A E 
A d v ers e e v e nt 
AJ C C 
A m eric a n J oi nt C o m mitte e o n Ca n c er 
A T C 
A n at o mic t h era p e utic c he mic al classific ati o n s yste m 
CI 
C o nfi d e n ce I nter v al 
B MI 
B o d y m ass i n d e x 
E C O G 
Easter n C o o p erati v e O n c ol o g y Gr o u p 
E M A 
E ur o p e a n Me dici n es A ge n c y 
E O F 
E n d of f oll o w- u p 
E S M O 
E ur o p e a n S o cie y f or Me dic al O n c ol o g y 
G n R H 
G o n a d otr o pi n-rele asi n g h or m o n e 
H C R U 
H e alt h c are res o urc e utiliz ati o n 
I C D- 1 0 
I nter n ati o n al Classific ati o n of Dis e as es 1 0t h re visi o n 
L O T 
Li n e of tre at m e nt 
m C R P C 
Metastatic c astrati o n resista nt pr ostate c a n c er 
m C S P C 
Metastatic c astrati o n s e nsiti v e pr ostate c a n cer 
m P C 
Metastatic pr ostate c a n c er 
m O S 
Me dia n o v erall s ur vi v al 
n m P C 
N o n- m etastatic pr ostate c a nc er 
O S 
O v erall s ur vi v al 
P F S 
Pr o gressi o n-fre e s ur vi val 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 5 of 2 8 
P H D 
Pir k a n m a a h os pital district 
P O 
Pri m ar y O bje cti v e 
P S A 
Pr ostate-s p e cific a nti ge n 
P S M A 
Pr ostate-s p e cific m e m bra ne a nti ge n 
R W E 
Re al- w orl d e vi d e n c e 
R W D 
Re al- w orl d d ata 
S A P 
Statistic al a n al ysis pla n 
SII 
S o cial I ns ura n c e I nstit ute 
S O 
Se c o n d ar y o bje cti ve 
S S R E 
S y m pt o m atic s k eletal-relate d e v e nt 
T A Y S 
Ta m p ere U ni v ersit y H os pital 
T N M 
T u m or –  N o d e –  Metastasis (classific ati o n of m ali g n a nt 
t u m ors) 
T T N T 
Ti m e t o n e xt tre at m e nt  
 
 
 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 6 of 2 8 
3.  R E S P O N SI B L E P A R TI E S 
Pri nci p al I n v esti g at o r(s) of t he Pr ot o c ol 
N a m e, de g r e e(s)  
J o b Titl e  
Affili ati o n  
A d dr ess  
Kaisa Teitti n en, P h D 
Sr M e dic a l Affairs 
Scie ntist, O n c ol o g y 
Pfiz er NI St u d y Le a d 
Pfiz er O y 
Tiet o k uja 4, 0 0 3 3 0 
Helsi n ki, Fi nla n d 
Mi k k o K os u ne n, M Sc 
Sr, H e a lt h Ec o n o mics 
M a na ger 
Pfiz er O y 
Tiet o k uja 4, 0 0 3 3 0 
Helsi n ki, Fi nla n d 
Le e n a Le h m us, M D 
Sr M e dic a l Affairs 
Scie ntist, O n c ol o g y 
Pfiz er O y 
Tiet o k uja 4, 0 0 3 3 0 
Helsi n ki, Fi nla n d 
Te e m u M urt ola , 
Pr of ess or 
Pr of ess or  of Ur ol o g y, 
C hief P h ysicia n  
T A Y S 
Elä mä na u ki o, 
K u nt o kat u 2, 3 3 5 2 0 
Ta m per e 
Mi k k o M oisa n der, M D 
O n c ol o gist
 T A Y S
 
Elä mä na u ki o, 
K u nt o kat u 2, 3 3 5 2 0 
Ta m per e 
Ka i K yse ni us, P h D 
Scie ntific A d vis or 
M e d affco n O y  
Metsä n nei d o n k uja 8, 
0 2 1 3 0 Es p o o, Fi nla n d 
Oli via  H ölsä , B. Sc. 
( Te c h.) 
J u ni or Da t a Scie ntist 
M e d affco n O y  
Metsä n nei d o n k uja 8, 
0 2 1 3 0 Es p o o, Fi nla n d 
Sa  m uli T u o mi n e n, 
M. Sc. ( S t atistics) 
Sr. Da t a  Scie ntist 
M e d affco n O y  
Metsä n nei d o n k uja 8, 
0 2 1 3 0 Es p o o, Fi nla n d 
M aria n n La sse ni us, 
P h D 
R W E Te a m L e a d,  
st u d y s u p p ort 
M e d affco n O y  
Metsä n nei d o n k uja 8, 
0 2 1 3 0 Es p o o, Fi nla n d 
Iir o T o p pila, M Sc 
Dat a a nal ysis Le a d, 
st u d y s u p p ort 
M e d affco n O y  
Metsä n nei d o n k uja 8, 
0 2 1 3 0 Es p o o, Fi nla n d 
 
 
 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 7 of 2 8 
4.  A M E N D M E N T S A N D U P D A T E S 
N o n e. 
 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 8 of 2 8 
5.  MI L E S T O N E S 
 
Mil est o ne  
Pl a n ne d d ate  
Pr oj e ct kic k- off (It e m 1) 
 
J u n e 2 0 2 2  
St u d y pr ot o col a n d st atistic al a nal ysis pla n ( S A P) (It e ms 2, 3) 
 
N o v e m b er 2 0 2 2 
St u d y p er missi o n (It e m 4) 
 
D e c e m b er 2 0 2 2  
St a rt of d ata c olle cti o n  
 
Q 1 2 0 2 3 
Dat a a nal ysis a n d q ualit y c o ntr ol ( Q C) c h e c ks (Ite m 6) 
 
Q 1 2 0 2 3 –  Q 2 2 0 2 3 
E n d of d ata c olle cti o n   
 
Q 1 2 0 2 3  
St u d y re p ort draft (It e m 7) 
 
Q 1- Q 2 2 0 2 3 
Fi n al st u d y re p ort (It e m 8) 
 
Q 2 2 0 2 3  
6.  R A TI O N A L E A N D B A C K G R O U N D 
Pr ostate c a n c er ( P C) is t h e m ost c o m m o n c a nc er t y pe i n Fi n nis h m e n, c o m prisi n g of 3 3 % of all a n n ual 
c a n c er dia g n os es. I n 2 0 2 1, o v er 5 1 0 0 n e w c as es w ere dia g n os e d wit h t h e m e a n a ge  of 7 0 y e ars at 
dia g n osis. O v er 5 5 0 0 0 m e n are c urre ntl y li vi n g wit h t h e dis e as e. I n 2 0 2 0, 9 2 8 P C-relate d d e at hs were 
re p orte d, of w hic h 7 9 9 w ere i n m e n > 7 0 y e ars of a ge ( Ca n c er re gistr y ( 1)). T h e c urre nt 5- y e ar s ur vi val 
rate is 9 3 %. H o w e v er, dis e as e sta ge, diff ere ntiati o n ( Gle as o n s c ore) a n d pr ostate s p e cific a nti ge n 
( P S A) s c ores at dia g n osis h a v e a si g nific a nt i m p a ct o n pr o g n osis. Hi g h er sta ge, l o w diff ere ntiatio n 
( hi g h Gle as o n s c ore > 8) a n d hi g h P S A  le v els are i n dic ati v e of a m ore a g gressi v e dis e as e a n d p o orer 
pr o g n osis. I nteresti n gl y, 5 5 % of P C c as es h a v e l o c aliz e d dis e as e a n d 2 3 % are m etastatic at dia g n osis. 
First  s y m pt o ms m a y b e  si milar t o  s y m pt o ms of b e ni g n pr ostatic h y p er plasia, b ut t h e y m a y als o b e 
b o n e p ai n or p at h ol o gic al b o ne fract ures, i n dicati v e of a d va nc e d dis e as e ( 2 – 4). 
Tre at m e nt of P C  is  hi g hl y d e p e n d e nt o n t h e  s e v erit y of s y m pt o ms, t h e dis e as e sta ge  a n d p atie nt 
c h ara cteristics. N o n- m etastatic P C  ( n m P C)  c a n b e tre ate d wit h  a cti v e s ur v eilla n c e, ra dic al  s ur ger y, 
ra di ot h era p y a n d/ or a dj u v a nt h or m o ne tre at m e nt. Pr o g n osis f or l o w-ris k p atie nts is e x c elle nt e v e n 
wit h o ut tre at m e nt a n d if t h e lif eti m e pr o b a b ilit y of c a n c er pr o gressi o n is c o nsi d ere d l o w d u e t o hi g h 
a ge or c o m or bi dities, s y m pt o ms are m a n a ge d wit h h or m o nal tre at m e nt ( 3).  
Metastatic P C  ( m P C)  tre at m e nt o pti o ns i n cl u d e s ur gic al or c h e mic al c astrati o n wit h  g o n a d otr o pin 
rele asi n g h or m o n e ( G n R H)-a nta g o nists or G n R H-a g o nists (s u c h as g os ereli n) p aire d wit h a nti-
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 9 of 2 8 
a n dr o ge ns (s u c h as e n z al uta mi d e), d e p e n di n g o n t h e e xte nt of s y m pt o ms. Castrati o n a n d G n R H 
a nta g o nist is t h e pri m ar y tre at m e nt c h oic e f or p atie nts wit h hi g h ris k of s pi n al c or d c o m pressi o n, brain 
m etastasis a n d/ or s e v ere p ai n. Ma n y p atie nts i nitiall y res p o n d w ell t o t h e c urre nt tre at me nts, b ut ma n y 
c a n c ers d e v el o p fr o m c astrati o n s e nsiti v e P C  ( C S P C)  i nt o c astrati o n resista nt  P C  ( C R P C)  wit h  a 
si g nific a nt n e gati v e c o ns e q u e n c e f or pr o g n osis. Metastatic P C ( m P C) m e dia n o v erall s ur vi v al ( m O S) 
is 2- 3 y e ars, b ut o nl y 6- 1 8 m o nt hs f or c astrati o n resista nt m P C ( m C R P C) ( 3, 4). 
Si n c e t h e a p pr o v al of d o c eta x el f or m C R P C  i n 2 0 0 4 si g nific a ntl y i m pr o v e d p atie nt o utc o m es f or 
m C R P C, t h e i m pr o v e m e nts i n pr o g n osis f or m P C h a v e b e e n ste a d y. I n cli nic al trial  s e tti n g, m a n y 
n o v el dr u gs  h a v e d e m o nstrate d si g nific a nt i n cre as es i n  pr o gressi o n-fre e s ur vi v al ( P F S) a n d  o v erall 
s ur vi v al ( O S), b ut t h e e vi d e n c e fr o m re al- w orl d e vi d e n c e ( R W E) st u dies is  n ot as c o m pre h e nsive. 
Re c e nt m ulti- n ati o n al a n d R W E st u dies i n U S A a n d S w e d e n h a v e d es cri b e d tre at m e nt pra ctic es a n d 
o utc o m es b ut are n ot e ntirel y refle cti v e of  t h e Fi n nis h s etti n g a n d are la c ki n g i n ter ms of  dr u g 
utiliz ati o n a n d l o n g-ter m o utc o m es ( 5 – 8).  
D es pite t h e i ntr o d u cti o n of n o v el t h era p e utic o pti o ns wit hi n t h e p ast  d e c a d es a n d i m pr o v e m e nts in 
pr o g n osis, t h e o v erall b ur de n of dis e ase i n Fi nla n d re m ai ns si g nific a nt wit h p ote ntial f or i m pr o v e me nt 
es p e ciall y i n  t h e m a n a ge m e nt of hi g h-ris k m P C p atie nts.  T h us,  it is cr u cial t o  u n d ersta n d  t he  
e pi d e mi ol o g y a n d dis eas e b ur de n of m P C p atie nts as w ell as t h e d e v el o p m e nt of c astrati o n resista nce. 
T h ere is a p a u cit y of i nf or m ati o n o n t h es e f e at ures i n Fi nla n d, le a di n g t o t h e n e e d of t h e pr o p ose d 
R W E st u d y. 
T his R W E st u d y w ill pr o vi d e u p t o d ate re al- w orl d d ata ( R W D) o n Fi n nis h m etastatic C S P C ( m C S P C) 
a n d m C R P C  p atie nt c h ara cteristics, tre at m e nt p atter ns, i n ci d e n c e a n d h e alt h c are res o urce utiliz atio n 
( H C R U) i n Pir k a n m a a H os pital District ( P H D), c o v eri n g c. 2 0 % of t h e Fi n nis h p o p ulati o n. T h ese 
d ata will pr o vi d e u p d ate d i nf or m ati o n o n re al- w orl d m P C p atie nt p o p ulati o ns, t h eir c urre nt tre at me nt 
pra ctic es a n d o utc o m es. T his c o ntri b uti o n will s u p p ort t h e ass ess m e nt of c urre nt tre at m e nt pra ctices 
i n Fi nla n d a n d t h e N or dics a n d h el p i d e ntif y are as i n n e e d of i m pr o ve me nt i n t h e tre at m e nt pra ctice of 
t h e hi g h est ris k P C  p atie nts. 
 
7.  R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S 
C urre nt u n d ersta n di n g of t h e e pi de mi ol o g y a n d dis e as e b ur d e n of m P C p atie nts i n Fi nla n d is la c ki n g. 
T his st u d y w ill a d dress t h e f oll o wi n g q u esti o ns: 
 W h at are t h e d e m o gra p hic a n d cli nic al c h aracteristics of m P C p atie nts ? 
 H o w are m P C p atie nts c urre ntl y tre ate d a n d h o w effe cti ve are t h es e tre at m e nts ? 
 H o w d o es t h e d e v el o p me nt of c astrati o n-resista n ce affect p atie nt o utc o mes ? 
 W h at is t h e e c o n o mic b ur d e n of m P C? 
T h es e q u esti o ns are a d dress e d i n t h e f oll o wi n g st u d y o bje cti v es: 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 1 0 of 2 8 
7. 1.  Pri m a r y o bje cti v e 
1.  Cli nic all y c h ara cteriz e p atie nts wit h m etastatic c astrati o n s e nsiti v e a n d/ or c astrati o n resista nt 
pr ostate c a n c er 
7. 2.  Se c o n d a r y o bje cti v es 
1.  Ass ess ti m e t o dis e as e pr o gressi o n fr o m c astrati o n s e ns iti v e t o c astrati o n resista n t 
2.  Ass ess t h e f a ct ors ass o ciate d wit h dis e as e pr o gressi o n t o c astrati o n resista nc e 
3.  D es cri b e tre at m e nt li n es 
4.  Ass ess o utc o m es b y tre at m e nt li n e, tre at m e nt s e q u e n c e a n d b y m e dic ati o n re c ei ve d, as 
f e asi ble: 
a. ti m e t o n e xt tre at m e nt 
b.  o v erall s ur vi v al + c h a n ges i n s ur vi v al o v er ti m e 
5.  Ass ess a n n u al i n ci d e nc e of m C R P C 
6.  Ass ess t h e h e alt h c are res o urce utiliz ati o n 
 
8.  R E S E A R C H M E T H O D S  
8. 1.  St u d y desi g n  
T his  st u d y is  a  n o n-i nter v e nti o n al retr os p e cti v e re gistr y- b as e d c o h ort st u d y w h ere all  a d ult p atie nts 
(a ge ≥1 8 y e ars) wit h P C dia g n osis ( C 6 1 *; ‘ *’ i n dic ates a n y n u m b er)  b et w e e n 1. 1. 2 0 1 0 a n d 3 1. 1 2.2 0 2 2 
will b e i d e ntifie d fr o m Pir k a n m a a H os pital District ( P H D) d ata la k e. All a v aila ble p atie nt d ata will be 
c olle cte d as p er t h e v aria bles liste d i n S u bs e cti o n 9. 3. 
T h e m ai n f o c us of t his st u d y is  t o c h ara cteriz e p atie nts wit h eit h er m C S P C  or m C R P C,  a n d t h eir 
tre at m e nt p atter ns a n d o utc o m es. A d diti o nall y, i n ci de nc es a n d H C R U are c o m p ute d, res p e cti v el y. 
8. 2.  Setti n g 
T h e c o h ort i n t his st u d y c o v ers all p atie nts wit h i n ci d e nt m P C dia g n osis. All P C p atie nts ( p atie nts wit h 
I C D- 1 0 dia g n osis c o d e C 6 1 *) are re q ueste d fr o m t h e P H D d ata la k e. Metastatic p atie nts are i d e ntifie d 
fr o m t h es e p atie nts a c c or di n g t o t h e i n cl usi o n criteria f or m P C c o h ort d es cri b e d i n  t h e S u bs e ctio n 
9. 2. 1. T h e e x cl usi o n criteria are d es cri b e d i n t h e S u bs e cti o n 9. 2. 2. D e p e n di n g o n t h e c o v era ge of the 
re c ei v e d d ata, mi n or m o dific ati o ns t o t h e i n cl usi o n a n d e x cl usi o n criteria m a y b e c o nsi d ere d w he n 
fi n alizi n g t h e st u d y c o h ort a n d b ef ore t h e d ata a n al ysis p h ase. 
T h e st u d y i n cl u d es t w o p atie nt gr o u ps, m etastatic c astrati o n s e ns iti v e pr ostate c a n c er ( m C S P C) 
p atie nts a n d m etastatic c astrati o n resista nt pr ostate c a n c er ( m C R P C)  p atie nts. T h e i d e ntific ati o n of 
t h es e p atie nts a n d t h e s ele cti o n of t h e i n d e x d ate f or t h es e p atie nts is d escri b e d i n t h e S u bs ecti o n 9. 2.3. 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 1 1 of 2 8 
T h e f oll o w- u p p eri o d f or t his st u d y is esti m ate d t o b e 1. 1. 2 0 1 4- 3 1. 1 2. 2 0 2 2, b ut it c a n b e e xte n d e d or 
s h orte n e d b as e d o n d ata c o v era ge or d ata c olle cti o n s c h e d ule (e. g. if d ata is c olle cte d b ef ore t h e e n d 
of 2 0 2 2, t h e st u d y ti m e fra m e w ill b e s h orte n e d).  
A p atie nt c a n b e i n cl u d e d i n b ot h m C S P C  a n d m C R P C c o h orts (t h e s c e n ari o vis u aliz e d i n Fi g ure 1) 
or o nl y o n e of t h os e c o h orts ( Fi g ure 2 a n d Fi g ure 3). T h e d efi n iti o ns f or i n d e x a n d e n d of f oll o w-u p 
( E O F) d ates are d es cri b e d b el o w. 
I n de x 
1.  Patie nts dia g n os e d wit h m etastatic c astrati o n s e nsiti v e pr ostate c a nc er ( m C S P C) 
 D ate f or t h e first re c or d of m etastatic pr ostate c a nc er ( m P C) 
2.  Patie nts dia g n os e d wit h m etastatic c astrati o n resist a nt pr ostate c a n cer ( m C R P C) 
 D ate  f or pr o gressi o n t o  c astrati o n resista nt  (if ≤3  m o nt hs  fr o m  c astrati o n-s e nsitive  
tre at m e nt i nitiati o n [ 1st c o ntr ol us u all y at 3 m o], c o nsi dere d d e n o v o C R P C) 
 
E n d of f oll o w- u p: 
1.  Patie nts dia g n os e d wit h m C S P C 
 E n d of st u d y ( 3 1. 1 2. 2 0 2 2) 
 D e at h 
 M o vi n g o utsi d e of Pir k a n m a a 
 Pr o gressi o n t o m C R P C 
2.  Patie nts dia g n os e d wit h m C R P C 
 E n d of st u d y ( 3 1. 1 2. 2 0 2 2) 
 D e at h 
 M o vi n g o utsi d e of Pir k a n m a a 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2  
Pa ge 1 2 of 2 8
Fi g ur e 1. I n de x defi niti o n f o r a p atie nt w h o is i ncl u de d b ot h i n t he  m C S P C a n d t he m C R P C 
c o h o rts.
Fi g ur e 2. I n de x defi niti o n f o r a p atie nt w h o is i ncl u de d  i n t he  m C S P C c o h o rt.
Fi g ur e 3. I n de x defi niti o n f o r a p atie nt w h o is i ncl u d e d i n t he m C R P C c o h o rt.
8. 2.1. I ncl usi o n c rite ri a
Patie nts  m ust m e et all of t h e f oll o wi n g i n cl usi o n cr iteria t o b e eli gi ble f or i n cl usi o n i n t h e st u d y:
1.  Dia g n osis of P C (I C D- 1 0: C 6 1) b et w e e n 1. 1. 2 0 0 7 ( or as e arl y as p ossi ble) - 3 1. 1 2. 2 0 2 2
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 1 3 of 2 8
2. Resi d e nt of Pir k a n m a a at i n d e x d ate ( dia g n osis of m C S P C a n d/ or m C R P C)
3.  D ete cti o n of m P C
A n y of t h e f oll o wi n g criteria:
I C D- 1 0: C 7 7 *, C 7 8 * or C 7 9 * re p orte d wit h C 6 1 *
T N M M 1 (re g ular e x pressi o n s “ T 1 ”,“ T 2 ” , “ T 3 ” ,“ T 4 ” )
I nitiati o n of tre at m e nt f or m P C ( Ta ble 1)
Pr o c e d ures: R a diati o n of m etastasis ( W F 0 4 9; 
)
Dia g n os es: M 4 9. 5 * C 7 9.5 or M 8 4. 4
Metastatic c a n c er re c or d e d i n t h e cli nic al n otes
(re g ular e x pressi o ns 
)
4.  Dia g n osis d ate of m C S P C or m C R P C b et w e e n 1. 1. 2 0 1 4- 3 1. 1 2. 2 0 2 2 (start d ate c a n b e m o difie d 
b as e d o n d ata c o v era ge at P H D d ata la k e)
T a ble 1. List of me dic ati o ns f o r i ncl usi o n of m P C p atie nts. 
A cti v e i n g r e die nt
A T C c o de
E M A a p pr o v al d ate / SII r ei m b urs e me nt/
E S M O 2 0 2 0 r e c o m me n d ati o ns ( 4)
a birater o n e
L 0 2 B X 0 3
E M A a p pr o v e d 0 9/ 0 5/ 2 0 1 1 f or m P C; SII: 
0 1/ 0 9/ 2 0 1 2 ( 4 2 %) f or m C R P C ( p ost-d oceta xel); 
0 1/ 1 0/ 2 0 1 4 f or m C R P C ( p ost- d oceta xel); 
0 1/ 0 2/ 2 0 1 8 m C R P C ( p ost- A D T;
After 0 1/ 1 1/ 2 0 2 1, als o f or n m C R P C.
Re c o m m e n d e d f or 1.- 3. L O Ts
e n z al uta mi d e
L 0 2 B B 0 4
E M A a p pr o v e d 0 2/ 0 7/ 2 0 1 3 f or m C R P C; 2 0 1 9
f or m C S P C
SII: 0 1/ 0 4/ 2 0 1 4 ( 4 2 %) f or m C R P C ( p ost-
d oceta xel ); 0 1/ 1 0/ 2 0 1 4 f or m C R P C ( p ost-
d oceta xel );
After 0 1/ 1 1/ 2 0 2 1, als o f or n m C R P C.
Re c o m m e n d e d f or 1.- 3. L O Ts
d o c eta x el
L 0 1 C D 0 2
E M A a p pr o v e d 2 0 0 5 f or m P C
N o SII rei m b urs e m e nt ( h os pital m e dici ne)
Re c o m m e n d e d f or 1.- 2. L O Ts
c a b a zita x el
L 0 1 C D 0 4
E M A A p pr o v e d 1 7/ 0 3/ 2 0 1 1 f or m C R P C
N o SII rei m b urs e m e nt ( h os pital m e dici ne)
Re c o m m e n d e d f or p ost- d o c eta x el/ 2. L O T
a p al uta mi d e
L 0 2 B B 0 5
E M A a p pr o v e d 1 4/ 0 1/ 2 0 1 9 f or n m C R P C; 
2 7/ 0 1/ 2 0 2 0 f or m C S P C
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 1 4 of 2 8
Re c o m m e n d e d f or 1. L O T
Ra di u m- 2 2 3
V 1 0 X X 0 3
E M A a p pr o v e d 1 3/ 1 1/ 2 0 1 3 f or m C R P C
Re c o m m e n d e d f or C R P C, p ost- d o ceta xel/ 3.
L O T
A b bre viati o ns: A D T = a n dr o ge n d e pri v ati o n t h era p y; A T C = a n at o mic al t h era p e utic c h e mical; E M A
= E ur o p e a n Me dici n es A ge n c y; E S M O = E ur o p e a n S o ciet y f or Me dic al O n c ol o g y; L O T = li n e of 
tre at m e nt,  m C R P C = m etastatic c astrati o n-resista nt pr ostate c a n cer;  m C S P C = m etastatic c astrati o n-
s e nsiti v e P C;  m P C = m etastatic P C; n m C R P C = n o n- m etastatic C R P C; SII = S o cial I ns ura n c e 
I nstit uti o n
8. 2.2. E x cl usi o n c rite ri a
Patie nts  m e eti n g a n y of t h e f oll o wi n g criteria will n ot b e i n cl u d e d i n t h e st u d y:
1. Pre v ale nt m C S P C a n d m C R P C p atie nts ( m C S P C or m C R P C dia g n osis d ate b ef ore 1. 1. 2 0 1 4)
2. Patie nt h as a n ot h er c a n c er dia g n osis (all I C D- 1 0 dia g n osis c o d es starti n g wit h C * e x c e pt C 6 1 *, or
C 4 4 or C 7 7 *, C 7 9 *), or t h e p atie nt h as re c ei ve d c he m ot h era p y ot h er t h a n d o c eta x el or c a b a zita xel
(all L 0 1 *  A T C c o d es e x c e pt L 0 1 C D 0 2 a n d L 0 1 C D 0 4)  wit hi n 2 y e ars of m P C dia g n osis.
8. 2.3. P atie nt g r o u ps
I n t his st u d y, all  m P C p atie nts  m e eti n g t h e i n cl usi o n criteria are s plit i nt o t w o p atie nt gro u ps:
1. Patie nts dia g n os e d wit h m etastatic c astrati o n s e nsiti v e pr ostate c a nc er ( m C S P C)
1.  D ete cti o n of m P C
2.  N ot pr o gress e d t o c astrati o n resista nt
2. Patie nts dia g n os e d wit h m etastatic c astrati o n resista nt pr ostate c a n cer ( m C R P C)
1.  D ete cti o n of m P C
2.  U n d er w e nt orc hie ct o m y or re c ei vi n g/re c ei v e d c h e mic al c astrati o n m e dicati o n 
o
S ur gic al c astrati o n: pr o c e d ure K F C 1 0 ( bilateral orc hie ct o m y) or,
o
C h e mic al c astrati o n:  A T C c o d es i n Ta ble 2
3. Castrati o n resista nt
o
Re c ei v e d C R P C-s p e cific m e dic ati o n ( Ta ble 3) or,
o
Castrati o n resista n c e re c or d e d i n t h e cli nic al n otes
or,
o
> 1 ( or 1 b as e d o n d ata c o v era ge) p ost-c astrati o n test oster o n e res ult b el o w
c astrati o n t hres h ol d ( < 1. 7 3 n m ol/l)  A N D (if f e asi ble) > 1 P S A i n cre as es of 5 0 % 
fr o m tr o u g h le v els ( pri m ar y c are d ata n ot a v aila ble)
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 1 5 of 2 8 
T a ble 2. List of me dic ati o ns f o r c he mic al c astr ati o n. 
A cti v e i n g r e die nt 
A T C c o de 
d e gareli x 
L 0 2 B X 0 2 
g os ereli n 
L 0 2 A E 0 3 
le u pr oreli n 
L 0 2 A E 0 2 
tri pt oreli n 
L 0 2 A E 0 4 
 
T a ble 3. List of me dic ati o ns f o r c astr ati o n r esist a nt pr ost ate c a nc er. 
A cti v e i n g r e die nt 
A T C c o de 
a birater o n e 
L 0 2 B X 0 3 
e n z al uta mi d e 
L 0 2 B B 0 4 
D o c eta x el ( U ntil 3 1. 1 2. 2 0 1 5) 
L 0 1 C D 0 2 
c a b a zita x el 
L 0 1 C D 0 4 
d ar ol uta mi d e  
L 0 2 B B 0 6 
Ra di u m- 2 2 3  
V 1 0 X X 0 3 
L uteti u m- 1 7 7 ( 1 7 7 L u)- Pr ostate-s pe cific 
m e m bra n e a nti ge n ( P S M A)  - 6 1 7 
V 1 0 X X 0 4  
 
8. 3.  V a ri a bles 
T h e re q u este d v aria bles are liste d i n Ta ble 4, wit h ass o ciate d o bje cti v es a n d o p erati o nal d efi niti o ns. 
D etaile d d efi niti o ns a n d c o m p utati o ns are d es cri b e d i n t h e i nte grate d statistic al  a n al ysis pla n ( S A P) 
o utli n e d i n t h e f oll o wi n g s e cti o ns. 
T a ble 4. List of v a ri a bles  
V a ri a bl e  
R ol e/ Rel ev a nt o bje cti ve  
O pe r ati o n al defi niti o n  
I C D- 1 0 dia g n oses 
Patie nt i n cl usi o n/e xcl usi o n 
C o m or bi dities  
P O 1, S O 2, S O 6  
 
y es/ n o 
Dat e of birt h 
Patie nt i n cl usi o n 
P O 1 , S O 2 
 
Da t e; a ge d efi ne d a t i n d e x b ased o n 
birt h d at e  
Dat e of d e at h 
E n d of f oll o w- u p 
S O 2, S O 3, S O 4 
 
Da t e 
H o m e m u nici palit y 
Patie nt i n cl usi o n 
E n d of f oll o w- u p 
H o m e m u nici palit y a t e a c h 
h e alt care c o nta ct 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 1 6 of 2 8
Wei g ht
P O 1
k g
H ei g ht
P O 1
m
B o d y mass i n d e x ( B MI)
P O 1
d eri v e d fr o m wei g ht a n d h ei g ht
O ut p atie nt visits (i n cl u di n g 
e m er ge n c y r o o m visits)
S O 6
All a ss o ciat ed data i n cl u di n g d ate, 
p h ysicia n’s s p e cialt y, t y p e of 
a rri v a l 
H os pit aliz ati o ns
S O 6
St art a n d e n d d ates
Pr o c e d ures, o perati o ns, s ur geries,
i n cl u di n g ra di ot h era p y
Patie nt i n cl usi o n/e xcl usi o n
S O 3, S O 4, S O 5, S O 6
Pr o c e d ure c o de, d at e
M e dic al i m a gi n g
S O 1, S O 2, S O 3, S O 4, S O 6
I m a gi n g c o d e, d at e
M e dic ati o ns; i n cl u di n g
-
h os pit al m e dic ati o ns
-
prescri pti o ns
Patie nt i n cl usi o n/e xcl usi o n 
a n d i n d e x d efi niti o n
P O 1, S O 1- S O 6
Da t es, A T C-c o des, a cti v e 
s u bst a n ce
La b orat or y a n d p at h ol o g y t ests
P O 1, S O 1, S O 2, S O 6
Dat es, t est i d ’s,r es ults f o r s pe cific 
tests ( P S A, Kre a , t est ost er o ne, A-
f os res ults es p e ciall y i m p orta nt)
T u m or- n o de- metastasis ( T N M) 
cla ssific ati o n
Patie nt i n cl usi o n a n d i n d ex 
d efi niti o n
P O 1
T x N x M x T 1- T4 * c/r/ p - prefi x es 
cli nic a l/ ra di ol o g y/ pat h ol o g y; n o 
s p a c es i n t e xt d efi niti o ns
Te xt mi ni n g: m etastatic dise ase, 
c a strati o n -resist a nt
Patie nt i n cl usi o n a n d i n d ex 
d efi niti o n
P O 1, S O 1
Te xt mi ni n g wit h rele v a nt p hrases: 
Gle a s o n sc ore
P O 1, S O 2
Te xt mi ni n g wit h rele v a nt p hrases: 
“ Gle a s * ”; ra n ge fr o m 1- 1 0
E C O G
Te xt mi ni n g “ E C O G ” ,“ W H O ” ,
“ Z 1 -4 ”
8. 4.  D at a s o ur c es
T his st u d y is c o n d u cte d usi n g e xisti n g a n d a v aila ble ele ctr o nic h e alt h re c or ds a c cessi ble fr o m Ta m pere 
U ni v ersit y H os pital ( T A Y S). T h e st u d y pr ot o c ol a n d ass ociate d d ata re q u est f or all d ata w ill t h eref ore 
b e s u b mitte d t o T A Y S Res e arc h Ser vic es f or a p pr o val.
T h e d ata will b e c olle cte d fr o m ele ctr o nic h e alt h re c or ds of Pir k a n m aa H os pital District of t h e p atie nts 
dia g n os e d wit h P C (I C D- 1 0 c o d e C 6 1 *). Ea c h of t h e c olle cte d d ata s et  will i n cl u d e p ers o n al i d e ntity 
c o d e t h at is u ni q u e f or e v er y i n di vi d ual i n Fi nla n d. T h e i d e ntific ati o n of t h e P C c o h ort a n d c olle ctio n 
of t h e d ata wit h p ers o n al i d e ntific ati o n n u m b ers will b e h a n dle d s olel y b y t h e p ers o n n el of T A Y S
Res e arc h Ser vic es. T h e i d e ntific ati o n c o des will b e re m o v e d after li n k a ge s o t h at o nl y ps e u d o n y mize d 
d ata is pr o vi d e d f or t h e a n al ys es.
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 1 7 of 2 8
F or t h e P C p atie nts, all of t h e f oll o wi n g d atas ets are re q ueste d
-
Me dic ati o n d ata ( h os pital m e dic ati o n, pres cri pti o ns,
, all ot h er c a n c er m e dic atio n
s o urc es if a p plic a ble)
-  
Dia g n os es, h e alt h c are c o nta cts
- 
Patie nt d e m o gra p hics
o
D ate of birt h, s e x, h o m e m u nici p alit y, d ate of d e at h, w ei g ht, h ei g ht, B MI
- 
La b orat or y a n d p at h ol o g y tests
- 
Pr o c e d ures, o p erati o ns, s ur geries, ra diati o n, i m a gi n g
- 
Patie nt te xts wit h re g ular e x pressi o ns of  AJ C C sta ge, m etastasis, c astrati o n resista nt or Gle aso n 
s c ore
T h e  m C S P C a n d m C R P C c o h orts are f or m e d fr o m t h e re c ei v e d d ata ( Fi g ure 4). All  of t h e re q u este d 
d ata is str u ct ure d e x c e pt t h e p atie nt te xts. Te xt mi ni n g of i nf or m ati o n is p erf or m e d al g orit h mic ally 
wit h o ut m a n u al c olle cti o n, re vie w or v ali d ati o n.
T h e d ata q u alit y a n d v ali dit y will b e e ns ure d b y p erf or mi n g Me d affc o n’s q u alit y c o ntr ol ste ps (s e e 
9. 8. Q u alit y C o ntr ol f or f urt h er i nf or m ati o n). D u e t o t h e retr os p e cti v e n at ure of t h e st u d y, missi n g 
a n d/ or i n c o m plete d ata are e x pe cte d i n s o m e of t h e m e dic al re c or ds. T h es ere c or ds  will n ot b e e x cl u de d 
b e c a us e of missi n g v al u es, a n d missi n g d ata will n ot b e i m p ute d, i. e. t h e d ata will b e a n al y z e d as the y 
are re c or d e d i n t h e ele ctr o nic m e dic al re c or ds. T h e pr o p orti o n of missi n g v al u es p er v aria ble will be 
re p orte d.
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2  
Pa ge 1 8 of 2 8
Fi g ur e 4. O v e r vie w of d at a s o ur c es a n d c o h o rt f o r m ati o n.
8. 5. St u d y siz e
Alt h o u g h s a m ple siz e c alc ulati o ns are n ot a p plic a ble f or d es cri pti v e st u dies, b as e d o n re p orte d P C
n ati o n wi d e a n n u al i n ci d e n c e of 1 9 1 p er 1 0 0 0 0 0 i n h a bita nts f or 2 0 1 6- 2 0 2 0 i n Fi nla n d (fr o m Fi n nish 
Ca n c er Re gistr y), w e esti m ate c. 1 0 2 1 n e wl y dia g n os e d P C  p atie nts p er y e ar i n t h e P H D re gi o n
( p o p ulati o n b as e of c. 5 3 5 0 0 0 i n h a bita nts). Wit h a 9 y e ar f oll o w- u p p eri o d ( 1. 1. 2 0 1 4 – 3 1. 1 2. 2 0 2 2),
w e e x p e ct c. 9 1 8 9 c as es, of w hic h 5- 8 % are e x p e cte d t o b e  m etastatic ( 8). H e n c e, t h e d e n o v o 
m etastatic c o h ort is e x p e cte d t o b e 4 5 9 – 7 3 5 p atie nts.
8. 6.  D at a m a n a g e me nt 
All  d ata  c olle cti o n,  st ora ge  a n d  h a n dli n g will  b e  c o or di n ate d b y  Ta ys  Res e arc h  Ser vic es.  Ta ys  
Res e arc h Ser vic es c olle cts t h e re q uire d d ata, ps e u d o n y miz es t h e I Ds a n d rele as es t h e r o w le v el 
ps e u d o n y miz e d d ata t o a s e c ure a n al ysis e n vir o n m e nt m ai ntai n e d b y Fi n d ata. All d ata-a n al ys es will 
b e p erf or m e d b y t h e  Me d aff c o n O y a n al ytics te a m  i n  t h e s e c ure a n al ysis e n vir o n m e nt usi n g t h e 
statistic al s oft w are R ( v ersi o n 3. 6.1. or hi g h er). N o patie nt le v el d ata will b e tra nsferre d o utsi d e of t his 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 1 9 of 2 8 
s yste m. O nl y  a g gre gate  le v el a n d/ or f ull y  a n o n y m o us d ata  a n d/ or s u m m ar y  statistics m a y  b e  
tra nsf erre d o utsi d e t his s yste m f or re p orti n g a n d p u blic ati o n p ur p os es. T h us, i n di vi d ual p atie nts c a n n ot 
b e i d e ntifie d fr o m t his d ata s et. 
8. 7.  D at a a n al ysis  
D ata will b e a n al y z e d usi n g pri m aril y d es cri pti v e m e as ures, w hic h i n cl u d e m e a n a n d m e dia n v alues 
f or c o nti n u o us v aria bles a n d fre q u e ncies a n d pr o p orti o ns f or c ate g oric al v aria bles. C osts  will b e 
esti m ate d usi n g d ata of o ut p atie nt visits, h os pitaliz ati o ns, etc. a n d utilizi n g p u blicl y a v aila ble price 
listi n gs.   F or  tre at m e nt  o utc o m es,  K a pla n- Meier  esti m ates  a n d/ or  c orres p o n di n g  ti m e  t o  e v e nt  
c o m p eti n g ris k m o d els will b e utiliz e d.  
All of t h e o utc o me res ults will b e re p orte d f or t h e b ot h m C S P C a n d m C R P C c o h orts w h e n a p plic a ble.  
A n al ys es are m ostl y b as e d o n str u ct ure d d ata. H o w e v er, t h e v aria bles AJ C C sta ge a n d Gle as o n s c ore 
are e xtra cte d usi n g te xt mi ni n g. Als o, m P C a n d c astrati o n resista nt p o p ulati o n is s u p ple m e nte d b y te xt 
mi ni n g. 
A n al ys es will b e p erf or m e d usi n g R, a la n g u a ge a n d e n vir o n m e nt f or statistic al c o m p uti n g, i n Rst u di o-
s er v er e n vir o n m e nt. 
8. 7.1.  Pri m a r y o bje cti v e 1 –  P atie nt c h a r a cte ristics 
D e m o gra p hic al a n d cli nic al v aria bles of m C S P C a n d/ or m C R P C p atie nts will b e s u m m ariz e d at i n d e x. 
Tre ate d a n d n o n-tre ate d p atie nts will b e b ot h i n cl u de d.  
T a ble 5. P atie nt c h a r a cte ristics v a ri a bles  
V a ri a ble 
D es c ri pti o n  
A ge  
(i n d e x –  birt h d ate + 1 d a y) / 3 6 5. 2 5 
B o d y m ass i n d e x ( B MI)  
T h e cl os est v al u e fr o m 3 m o nt hs b ef ore i n d e x  
C h arls o n C o m or bi dit y I n de x ( C CI)  
Cate g ories: 1, 2, 3, 4 +  
P S A at i n d e x  
T h e cl os est v al u e fr o m 3 m o nt hs b ef ore i n d e x  
Gle as o n s c ore  
Cate g ories: 6- 1 0 
T h e cl os est v al u e fr o m i n d e x 
T N M classific ati o n 
T c ate g ories: T 1, T 2, T 3, T 4 
N c ate g ories: N 0, N 1, N 2, N X 
M c ate g ories: M 0, M 1  
T h e cl os est v al u e +/- 3 m o nt hs fr o m i n de x 
D e n o v o m etastatic  
Y es / N o ( ≤2 m o fr o m dia g n osis)  
Re c ei v e d tre at m e nt f or m C S P C/ m C R P C 
Y es / N o 
Pr o gress e d i nt o m C R P C ( o nl y f or m C S P C) 
Y es / N o 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 0 of 2 8 
P- A F O S (al k ali n e p h os p h atas e) 
La b v al u e (at i n d e x) 
Orc hie ct o m y p erf or me d ( K F C 1 0) 
Y es / N o 
Palliati v e ra di ol o g y ( W F 0 4 9 ) 
Y es / N o 
E C O G ( Easter n C o o p erati v e O n c ol o g y Gr o u p) 
p erf or m a nc e stat us   
0- 4; Str u ct ure d or n ot , c ost of mi ni n g (if 
f e asi ble) E C O G X ( 0- 4 Z.. etc) 
S y m pt o m atic s k eletal-relate d e v e nt ( S S R E, 
I C D- 1 0 M 4 9. 5 * C 7 9.5, M 8 4. 4 a n d S * 2 *) 
Y es / N o 
Oste o p or osis (I C D- 1 0 M 8 0 *, M 8 1 *)  
Y es / N o 
B o n e m e dic ati o n ( d e n os u m a b, z ole dr o nic a ci d) 
Y es / N o 
 
F or c ate g oric al v aria bles, t h e n u m b er ( N) a n d t h e pr o p orti o n ( %) of p atie nts i n e a c h class will b e 
re p orte d. F or c o nti n u o us v aria bles m e a n, sta n dar d d e viati o n ( S D), m e dia n, t h e 1 st a n d t h e 3r d q u artile 
will b e re p orte d.  
8. 7.2.  Se c o n d a r y o bje cti v e 1 –  Ass ess ti me t o dis e as e pr o g r essi o n 
Ass ess t h e ti m e  t o dis e as e pr o gressi o n f or t h e m C S P C  c o h ort usi n g A ale n-J o h a ns e n c o m p eti n g risk 
ti m e-t o-e v e nt m o d el. D efi n e t h e ti m e t o e v e nt as ti m e fr o m m C S P C i n d e x u ntil m C R P C  i n d e x (e v e nt), 
d e at h (c o m p eti n g e v e nt) or e n d of st u d y ( D e c e m b er 3 1 st 2 0 2 2; c e ns ori n g e v e nt). Vis u aliz e t h e fit b y 
pl otti n g t h e c ur v es a n d re p ort t h e esti m ates at e. g., 1, 3, 6, 1 2, 2 4, 3 6, 6 0 m o nt h ti m e p oi nts wit h 9 5 % 
c o nfi d e nc e i nter v als ( CI), a n d re p ort t h e m e dia n ti m e wit h 9 5 % CIs. 
8. 7.3.  Se c o n d a r y o bje cti v e 2 –  Ass ess t he f a ct o rs ass o ci ate d wit h dis e as e pr o g r essi o n t o c astr atio n 
r esist a nc e  
F or   ti m e-t o-e v e nt  m o d el  ass essi n g  ti m e   t o  dis e as e  pr o gressi o n  ( Se c o n d ar y  o bje cti v e  1),  fit  
c orres p o n di n g m u ltistate ( or si n gle-e v e nt if n u m b er of p atie nts is s m all) e xte nsi o n of C o x- pr o p orti o nal 
h a z ar d m o d el, wit h v aria bles d es cri b e d i n pri m ar y o bje cti v es as c o v ariates (e. g. Gle as o n s c ore, a ge, 
C CI, B MI). Us e o nl y c o v ariates wit h c o m plete c o vera ge. 
8. 7.4.  Se c o n d a r y o bje cti v e 3 –  D es c ri be tr e at me nt li nes 
T h e  tre at m e nt li n es  will  b e d efi n e d usi n g dr u g  a d mi nistrati o n a n d pres cri pti o n d ata . T h e  tre at m e nt 
o pti o ns a n d li n es will b e vis u aliz e d usi n g Sa n k e y pl ots a n d t h e  n u m b er a n d pr o p orti o n of p atie nts per 
tre at m e nt t y p e will  b e re p orte d. F or  c h e m ot h era p y tre at m e nt o pti o ns ( d o c eta x el a n d c a b a zita x el), 
a v era ge n u m b er of c y cles will b e re p orte d. 
Tre at m e nt  li n e  c h a n ges  w h e n  t h e  a cti v e  s u bsta n c e  c h a n ges,  as  t h e  tre at m e nts  are  m ai nly  
m o n ot h era pies (si m ulta n e o us a n dr o ge n d e pri v ati o n t h era p y ( A D T) n ot c o nsi d ere d as c o m bi n atio n 
tre at m e nt) f or b ot h m C S P C a n d m C R P C tre at m e nt o pti o ns, a n d o nl y a f e w o pti o ns c o nsist of t wo 
s u bsta n c es. All of t h e tre at m e nt o pti o ns f or P C a n d c o n c o mita nt m e dicati o ns are liste d i n Ta ble 6. 
T h e tre at m e nt li n es will b e d efi n e d p ost h o c usi n g t h e f oll o wi n g pr o cess: 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 1 of 2 8 
- 
F or e a c h  a cti v e  s u bsta n c e,  si n gle   a d mi nistrati o ns/ pres cri pti o ns  are  m er ge d  t o  tre at m e nt 
c o nti n u u ms.  
- 
T o i d e ntif y w h et h er t h e tre at m e nt is m o n ot h era p y or c o m bi n ati o n of t w o a cti v e s u bsta n c es, the 
first re c or ds of t h e a cti v e s u bsta n ces will b e c o nsi d ere d  
 if  t h e first re c or ds of  t h e t w o a cti v e s u bsta n c es are wit hi n 2 8 d a ys, t h e tre at m e nt is 
c o nsi d ere d as c o m bi n ati o n t h era p y of t h es e t w o m e dic ati o ns 
 ot h er wis e t h e t w o a cti v e s u bsta n c es are c o nsi d ere d as t w o s e p arate tre at m e nt li n es  
T h e i nitiati o n of t h e tre at m e nt li n e is d efi n e d as t h e d ate of first re c or d ( d osi n g or pres cri pti o n) of the 
a cti v e s u bsta n c e, a n d t h e e n d of t h e tre at m e nt li n e as i nitati o n of n e xt tre at m e nt li n e, e n d of f oll o w-u p 
or dia g n osis of p alliati v e c are (I C D- 1 0 Z 5 1. 5). A d diti o n all y, f or e a c h a cti v e i n gre die nt/tre at m e nt 
o pti o n t h e n u m b er a n d pr o p orti o n of p atie nts re c ei vi n g o pi oi ds d uri n g t h e tre at m e nt is re p orte d. T he 
p atie nt is c o nsi d ere d t o h a v e re c ei v e d o pi oi ds d uri n g t h e tre at m e nt, if t h e p atie nt is pres cri b e d a n y 
m e dic ati o n liste d i n Ta ble 7 fr o m i nitiati o n of t h e tre at m e nt u ntil i nitiati o n of t h e n e xt tre at m e nt. 
N u m b er a n d pr o p orti o n of p atie nts o n A D T p er tr e at m e nt c a n b e a d diti o nall y re p orte d. 
T a ble 6. Tr e at me nt o pti o ns f o r P C a n d c o nc o mit a nt me dic ati o ns 
Acti ve i n gre die nt 
A T C c o d e 
Rele v a nt SII rei m b u rse me nt c o d e/ d at e f or 
rei m b u rse me nt ( or esti m at e)  
Tre at me nt I n dic ati o n 
( rele v a nt t o P C) 
de gar eli x 
L 0 2 B X 0 2 
1 1 6 / 2 0 1 2 
c h e mic al c astrati o n, A D T 
g oser eli n 
L 0 2 A E 0 3 
1 1 6 / 2 0 1 1 
c h e mic al c astrati o n, A D T 
l e u pr or eli n 
L 0 2 A E 0 2 
1 1 6 / 2 0 1 1 
c h e mic al c astrati o n, A D T 
tri pt or eli n 
L 0 2 A E 0 4 
1 1 6 / 1 9 9 3 
c h e mic al c astrati o n, A D T 
nil ut a mi de 
L 0 2 B B 0 2 
- 
m C S P C 
d ocet a xel 
L 0 1 C D 0 2 
- 
m P C 
ca bazit a xel 
L 0 1 C D 0 4 
- 
m P C 
pr e d nis o ne, 
pr e d nis ol o ne  
A 0 7 E A 0 3, 
A 0 7 E A 0 2 
1 6 3 / 2 0 1 4 
P C 
a pal ut a mi de 
L 0 2 B B 0 5 
1 5 2 8, 3 0 3 1 /  
0 1/ 0 8/ 2 0 2 0 ( 4 0 %) f or m C S P C a n d n m C R P C 
w/ hi g h ris k f or m C R P C  
0 1/ 1 1/ 2 0 2 1 ( 4 0 %) f or m C S P C w/ A D T  
0 1/ 0 5/ 2 0 2 2 ( 1 0 0 %) f or m C S P C a n d n m C R P C 
w/ hi g h ris k f or m C R P C  
m C S P C , n m C R P C  fr o m 
0 1/ 0 8/ 2 0 2 0  
bi cal ut a mi de   
L 0 2 B B 0 3 
1 1 6 / 2 0 1 1 
m P C 
dar ol ut a mi de  
L 0 2 B B 0 6 
1 1 6, 1 5 2 5, 3 0 3 6 /  
n m C R P C 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 2 of 2 8 
SII: 0 1/ 1 2/ 2 0 2 0 ( 4 0 %) f or n m C R P C 
0 1/ 0 2/ 2 0 2 2 ( 1 0 0 %) f or n m C R P C  
fl ut a mi de 
L 0 2 B B 0 1 
1 1 6 / 1 9 9 7 
P C 
Ra di u m- 2 2 3  
V 1 0 X X 0 3 
- 
m C R P C 
L ut eti u m- 1 7 7 
( 1 7 7 L u)-Pr ostate-
s pecifi c 
m e m br a ne 
a nti ge n ( P S M A)  
- 6 1 7 
V 1 0 X X 0 4 
- 
m C R P C 
mit o xa ntr o ne 
L 0 1 D B 0 7 
- 
m C R P C 
z ol e dr o ni c aci d 
M 0 5 B A 0 8 
Basic ( 4 0 %) / 2 0 1 1 
B o ne fr ailt y, pat h ol o gical 
b o ne fr act ur es  
de n os u m a b 
M 0 5 B X 0 4 
1 1 6 / SII: 0 1/ 0 3/ 2 0 1 1 ( 4 2 %) f or h or m o ne-
tr eat me nt r elate d b o ne fr ailt y; 0 1/ 0 1/ 2 0 1 2 ( 4 2 %) 
as per S P C i n dicati o ns 
B o ne fr ailt y, pat h ol o gical 
b o ne fr act ur es  
r a di ot her a p y 
Ra diati o n of 
m et astasis 
( W F 0 4 9) 
- 
m P C 
ol a pari b 
L 0 1 X X 4 6, 
L 0 1 X K 0 1 
(si nce 2 0 2 1) 
-  
m C R P C ( B R C A 
m ut ati o n)  
a birater o n e  
L 0 2 B X 0 3  
1 6 3, 3 5 2 / SII: 0 1/ 0 9/ 2 0 1 2 ( 4 2 %) f or m C R P C 
( wit h pr e d nis o ne/ pr e d nis ol o ne, p ost-d oceta xel);  
0 1/ 1 0/ 2 0 1 4 ( 1 0 0 %) f or m C R P C ( wit h 
pr e d nis o ne/ pr e d nis ol o ne, p ost - d oceta xel);  
0 1/ 0 2/ 2 0 1 8 f or m C R P C ( wit h 
pr e d nis o ne/ pr e d nis ol o ne, p ost - A D T);  
After 0 1/ 1 1/ 2 0 2 1, als o f or n m C R P C  
m C R P C, n m C R P C f r o m 
0 1/ 1 1/ 2 0 2 1  
e n z al uta mi d e  
L 0 2 B B 0 4  
1 6 3, 3 5 2 ( 1 5 2 3, 3 0 5 4 after 0 1/ 1 1/ 2 0 2 1) / 
SII: 0 1/ 0 4/ 2 0 1 4 ( 3 5 %) f or m C R P C ( p ost-
d oceta xel );  
0 1/ 1 2/ 2 0 1 5 ( 1 0 0 %) f or m C R P C ( p ost -
d oceta xel);  
0 1/ 0 1/ 2 0 1 8 ( 1 0 0 %) f or m C R P C ( p ost - A D T) 
0 1/ 1 1/ 2 0 2 1, als o f or n m C R P C.  
m C R P C, n m C R P C f r o m 
0 1/ 1 1/ 2 0 2 1  
A b br e vi ati o ns: A D T = a n dr o ge n de pri vati o n t her a p y; A T C = a nat o mi cal t her a pe uti c c he mi cal; m P C = 
m et ast ati c pr ostate ca ncer; m C R P C = metastatic castr ati o n-r esista nt pr ostate ca ncer; m C S P C = metastatic 
castr ati o n-se nsiti ve pr ostate ca ncer; n m C R P C = n o n- metastatic castr ati o n-r esista nt pr ostate ca ncer; P C = 
pr ost at e ca ncer; SII = S ocial i ns ur a nce i nstit uti o n; S P C = S u m mar y of pr o d uct c har acteristics  
 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 3 of 2 8 
T a ble 7. List of str o n g o pi oi ds us e d i n m P C tr e at me nt. 
A cti v e i n g r e die nt 
A T C c o de 
m or p hi n e 
N 0 2 A A 0 1 
o x y c o d o ne 
N 0 2 A A 0 5 
f e nta n yl 
N 0 2 A B 0 3 
m et h a d o n e 
N 0 7 B C 0 2 
h y dr o m or p h o ne 
N 0 2 A A 0 3 
 
8. 7.5.  Se c o n d a r y o bje cti v e 4 –  Ass ess o utc o mes 
T h e tre at m e nt o utc o m es will  b e ass ess e d usi n g ti m e-t o-e v e nt a n al ysis, n a m el y K a pla n- Meier fits or 
ot h er rele v a nt c o m p eti n g ris k m o d els. F or e a c h o utc o m e, t h e ti m e w ill b e d efi n e d as f oll o ws : 
1.  Ti m e t o n e xt tre at m e nt ( T T N T) 
 ti m e fr o m i nitiati o n of t h e c urre nt tre at m e nt li n e u ntil t h e i nitiati o n of t h e n e xt tre at m e nt 
li n e (e v e nt), d e at h (e v e nt), or e n d of st u d y (c e ns ori n g e v e nt) 
 m a xi m u m n u m b er of tre at m e nt li n es f or re p orti n g T T N T is 5  
2.  O v erall s ur vi v al ( O S) 
 ti m e fr o m i n d e x u ntil d e at h (e v e nt) or e n d of stu d y (c e ns ori n g e v e nt) 
 T h e O S will b e stratifie d b y 
1.  F or m C S P C p atie nts wit h i n d e x b et w e e n 2 0 1 4- 2 0 1 6 a n d 2 0 1 7- 2 0 2 2 
2.  F or m C R P C Patie nts wit h i n d e x b et w e e n 2 0 1 4- 2 0 1 7 a n d 2 0 1 8- 2 0 2 2 
3.  D e n o v o m etastatic p atie nts a n d later m etastasi z e d p atie nts 
T h e K a pla n- Meier fits will b e vis u aliz e d, a n d t h e m e dia n s ur vi v al/ T T N T a n d 9 5 % c o nfi de nce 
i nter v als f or t h e m e dia ns will b e re p orte d. 
O utc o m es a n al ys es will b e d o n e i n s u b gr o u ps d eter mi ne d b y i n di vi d ual tre at m e nt li n e, m aj or tre at me nt 
s e q u e n c e a n d/ or b y m e dic ati o n re c ei ve d/ prescri b e d ( wit h m ai n f o c us o n e n zal uta mi d e a n d a biratero ne) 
w h e n f e asi ble b as e d o n d ata c o v era ge.  
A d diti o n all y, c orres p o n di n g C o x  pr o p orti o n al- h az ar ds m o d el w ill  b e  fitte d,  i n cl u di n g  v aria bles  
d es cri b e d i n pri m ar y o bje cti v es as c o v ariates (e. g. Gle as o n s c ore, a ge). Us e o nl y c o v ariates wit h 
c o m plete c o v er a ge. T h e h a z ar d rati os, 9 5 % c o nfi d e nc e i nter v als a n d p- v al u es c orres p o n di n g t o e a c h 
c o v ariate will b e re p orte d. 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 4 of 2 8 
8. 7.6.  Se c o n d a r y o bje cti v e 5 –  Ass ess an n u al i nci de nc e of m C R P C 
1.  I n ci d e n c e of m etastatic pr ostate c a n c er ( m P C) 
2.  I n ci d e n c e of m etastatic c astrati o n s e nsiti v e pr ostate c a nc er ( m C S P C) 
3.  I n ci d e n c e of m etastatic c astrati o n resista nt pr ostate c a n cer ( m C R P C) 
Re p ort t h e n u m b er of i n ci d e nt p atie nts ( n e w p atie nts e a c h y e ar  b et w e e n 2 0 1 4- 2 0 2 2) a n d c alc ulate 
i n ci d e n c e b y di vi di n g t h e n u m b er of i n ci d e nt p atie nts e a c h y e ar ( 2 0 1 4- 2 0 2 2) b y t h e siz e of b a c k gro u n d 
p o p ulati o n i n Pir k a n ma a H os pital District. A d d iti o n all y, re p ort  t h e o verall i n ci de n ce a n d c o m p ute the 
y e arl y a ge-sta n d ar diz e d i n ci d e n ces. 
8. 7.7.  Se c o n d a r y o bje cti v e 6 –  Ass ess t he he alt hc a r e r es o ur c e utiliz ati o n 
H e alt h c are res o urc e utiliz ati o n ( H C R U)  will  b e d efi n e d as t h e n u m b er of o ut p atie nt cli nic visits, 
h os pitaliz ati o n a n d h os pital i n p atie nt d a ys. T h e pric es will b e e v al u ate d f or e a c h e ntr y usi n g p u blicly 
a v aila ble pric e listi n gs n a m el y Mä kli n et al 2 0 1 7 ( 9). Pric es w ill  b e d eri v e d b as e d o n s p e cialt y a n d 
t y p e of visit ( 9). 
T h e a bs ol ute n u m b er of e a c h H C R U t y p e a n d t h e a bs ol ute c osts ass o ciate d w ill  b e  re p orte d.  
A d diti o n all y, t h e esti m ates will b e s c ale d t o “ p er -p atie nt” esti m ates ( b y di vi di n g t h e a bs ol ute esti m ates 
wit h t h e n u m b er of c o ntri b uti n g p atie nts) a n d t o “ p er p atie nt y e ar” esti m ates ( b y di vi di n g t h e a bs olute 
esti m ates b y t h e n u m b er of c o ntri b uti n g p atie nt y e ars). 
N o statistic al testi n g f or diff ere nc e b et w ee n gr o u ps w ill b e p erf or m e d a n d esti m ates will b e d es cri ptive 
i n n at ure. H o w e v er,  9 5 % CIs f or t h e esti m ates will b e d eri v e d usi n g b o otstra p pi n g o v er t h e p atie nts.  
A d diti o n all y, stratif y t h e H C R U a n al ysis b y s p e cialt y gr o u ps 
 ur ol o g y (s p e cialt y c o d e 2 0 U) 
 o n c ol o g y (s p e cialt y c o de 6 5) 
 ot h er s p e cialties. 
Tra nsiti o ns b et w e e n ur ol o g y a n d o n c ol o g y c o nta cts will b e vis u aliz e d i n Sa n k e y pl ots if f e asi ble. 
Alter n ati v el y, t h e n u m b er of c o ntacts at ur ol o g y a n d o n c ol o g y c a n b e vis u aliz e d i n m e a n c u m ulative 
f u n cti o ns as a f u ncti o n of le n gt h of f oll o w- u p. 
8. 8.  Q u alit y c o ntr ol 
I nter n al q u alit y will b e ass ure d b y c o ns ulti n g cli nic al e x p erts o n t h e d ata i nte grit y, t h e cli nic al 
rele v a n c e, a n d t h e pla usi bilit y of t h e res ults. 
A q u alit y c o ntr ol will  b e p erf or m e d, w h ere b y all d ata will b e s a nit y c h e c k e d b y t h e all o c a te d d ata 
s cie ntist(s). T his  q u alit y c o ntr ol i n cl u d es e. g., d ata c o v era ges, n u m b er of i n di vi d u als a n d d ata r o ws, 
c h a n ges as a f u n cti o n of ti m e a n d c h e c ks f or s yste m atic ga ps o n d ata c o v era ge a n d o utliers i n t h e d ata. 
A d diti o n all y, all t h e res ults will  b e s a nit y c h e c k e d wit h a cli nic al e x p ert a n d st u d y te a m f or pla usi bility 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 5 of 2 8 
a n d cli nic al rele v a n c e, a n d es p e ciall y i n c as e of u n e x p ecte d res ults, b ot h a n al ytic al m et h o ds a n d data 
will b e dis c uss e d a n d v ali d ate d wit h t h e w h ole Me d affc o n a n al ytics t e a m. 
All  R s cri pts t o pr o c ess a n d a n al y z e t h e d ata will b e s a v e d, a n d t h ere is v ersi o n c o ntr ol a n d e xter nal 
b a c k- u ps f or t h e s cri pts. At t h e e n d of t h e st u d y, all s cri pts w ill b e arc hi v e d t o ass ure a n al ysis 
re pr o d u ci bilit y, a n d pla usi ble later a u dits ( b y clie nt a n d/ or fr o m s cie ntific p u blic ati o n si d e). 
8. 9.  Li mit ati o ns of t he r es e a r c h met h o ds 
All t h e d ata is  re c or d e d b y t h e h os pital d uri n g e v er y d a y pra ctic e a n d m ost of t h e d ata is st ore d i n 
str u ct ure d f or m at. T h eref ore, rat h er hi g h q u alit y of t h e d ata is e x p e cte d. H o w e ver, as wit h all R W D, 
it  is pla usi ble t o h a v e err o n e o us e ntries. Als o d u e t o t h e retr os p e cti v e n at ure of t h e st u d y, missi n g 
a n d/ or i n c o m plete d ata is e x p e cte d i n s o m e of t h e m e dic al re c or ds. Patie nts’ re c or ds will n ot b e 
e x cl u d e d b e c a us e of missi n g v al u es, a n d missi n g d ata w ill n ot b e i m p ute d, i. e. t h e d ata will b e a n al y ze d 
as t h e y are re c or d e d i n t h e ele ctr o nic m e dic al re c or ds. T h e pr o p orti o n of missi n g v al u es p er v aria ble 
will b e re p orte d.  
T h e tre at m e nt li n es will b e d efi n e d b ase d o n t h e m e dic ati o n d ata fr o m t h e Pir k a n ma a h ospital district 
a n d t h eref ore, mis classific ati o n of tre at m e nt li n es is  p ossi ble. H o w e v er, t h e start  d ate of e a c h m ain 
dr u g are  e x p e cte d  t o  b e  re c or d e d  rat h er  pre cis el y,  a n d  t h e  cli nicia n s  will  b e  c o ns ulte d  w h e n  
c o nstr u cti n g t h e tre at m e nt li n es. T h us, t h e m aj orit y of t h e tre at m e nt li n es are e x p e cte d t o b e d efine d 
c orre ctl y. 
Te xt mi ni n g is  a p plie d t o e xtra ct a f e w v aria bles a n d s u p ple m e nt t h e d ata s et. T h e te xt mi ni n g m et h o ds 
are s ele cte d a n d a p plie d i n or d er t o mi ni miz e e xtra cti o n of i n c orrect i nf or m ati o n. H o w e v er, i n c orrect 
v aria ble v al u es are p ossi ble t o e xist t o a s m all e xte nt. 
8. 1 0.  Ot he r as pe cts 
N ot a p plic a ble. 
 
9.  P R O T E C TI O N O F H U M A N S U B J E C T S 
9. 1.  P atie nt i nf o r m ati o n  
T his st u d y i n v ol v es d ata t h at e xist i n  a n o n y miz e d str u ct ure d f or mat a n d c o ntai n n o p atie nt p ers o nal 
i nf or m ati o n. If a ut o m ate d/al g orit h mic m et h o ds, s u c h as n at ural la n g u a ge pr o c essi n g, will b e us e d t o 
c o n v ert u nstr u c t ure d d ata t o str u ct ure d d ata d uri n g t he i m ple m e ntatio n of t h e pr ot o c ol,  n o p atie nt 
p ers o n al d ata will b e a c c ess e d.   
9. 2.  P atie nt c o ns e nt 
As t his st u d y i n v ol v es a n o n y miz e d str u ct ure d d ata, w hic h a c c or di n g t o a p plic a ble le gal re q uire m e nts 
d o n ot c o ntai n d ata s u bje ct t o pri v a c y la ws, o btai ni n g i nf or me d c o ns e nt fr o m p atie nts b y Pfiz er is n ot 
re q uire d. 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 2 6 of 2 8
9. 3. I nstit uti o n al r e vie w b o a r d (I R B)/I n de pe n de nt et hics c o m mitte e (I E C)
Per t h e A ct o n Se c o n d ar y Us e of H e alt h a n d S o cial  D ata 5 5 2/ 2 0 1 9 (i n Fi n nis h: 
), n o i nstit uti o nal re vie w b o ar d or i n d e pe n de nt et hics c o m mittee 
f or t his retr os p e cti v e re gistr y st u d y is re q uire d.
9. 4. Et hic al c o n d uct of t he st u d y
T h e st u d y w ill b e co n d u cte d i n a c c or d a n ce wit h le gal a n d re g ulat or y re q uire m e nts, as w ell as wit h 
s cie ntific p ur p os e, v al u e a n d ri g or a n d f oll o w ge n erall y a c c e pte d res earc h pra ctic es d es cri be d i n:
G o o d  pra ctic es  f or  re al- w orl d  d ata  st u dies  of  tre at m e nt  a n d/ or  c o m p arati v e  eff e cti v e ness:  
Re c o m m e n d ati o ns fr o m t h e j oi nt I S P O R-I S P E  S p e cial Tas k F orc e o n re al- w orl d e vi d e n c e i n h e alth 
c are d e cisi o n m a ki n g htt ps:// w w w. n c bi. nl m. ni h. g o v/ p m c/articl es/ P M C 5 6 3 9 3 7 2 ( 1 0).
1 0.  M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E R E A C TI O N S 
T his st u d y i n v ol v es d ata t h at e xist as str u ct ure d d at a b y t h e ti m e of st u d y start or a c o m bi n ati o n of 
e xisti n g str u ct ure d d ata a n d u nstr u ct ure d d ata, w hic h will b e c o n v erte d t o str u ct ure d f or m d uri n g the 
i m ple m e ntatio n of t h e pr ot o c ol s olel y b y a c o m p uter usi n g a ut o m ate d/al g orit h mic m et h o ds, s u c h as 
n at ural la n g u a ge pr o c essi n g.
I n t h es e d ata s o urc es, i n di vi d ual p atie nt d ata are n ot retrie v e d or v ali d ate d, a n d it is n ot p ossi ble t o lin k 
(i. e., i d e ntif y a  p ote ntial ass o ciati o n b et w e e n) a p artic ular pr o d u ct a n d m e dic al e v e nt f or a n y 
i n di vi d u al. T h us, t h e mi ni m u m criteria f or re p orti n g a n a d v ers e e v e nt ( A E) (i. e., i d e ntifia ble p atie nt, 
i d e ntifia ble re p orter, a s us p e ct pr o d uct, a n d e v e nt) c a n n ot b e m et.
1 1. P L A N S F O R DI S S E MI N A TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S
T h e d etaile d res ults o btai n e d fr o m t his st u d y will b e m a d e a v aila ble u p o n p u blic ati o n. Res e arc h res ults 
fr o m t his  st u d y will b e p u blis h e d i n p e er-re vie w e d s cie ntific j o ur n als a n d/ or i nter n ati o n al s cie ntific 
c o n gress es. T h e A ut h ors hi p of a n y p u blic ati o ns res ulti n g fr o m t his st u d y will b e d eter mi n e d b ase d o n 
t h e I nter n ati o n al C o m mitte e of Me dic al J o ur nal E dit ors (I C MJ E) Re c o m m e n d ati o ns f or t h e C o n d uct, 
Re p orti n g, E diti n g a n d P u blic ati o n of Sc h olarl y W or k i n Me dic al J o ur n als.
I n t h e e v e nt of a n y pr o hi biti o n or restricti o n i m p os e d (e. g., cli nic al h ol d) b y a n a p plic a ble c o m pete nt 
a ut h orit y i n a n y are a of t h e w orl d, or if t h e i n v esti gat or is a w are of a n y n e w i nf or mati o n w hic h mi ght 
i nfl u e n c e t h e e v al u ati o n of t h e b e n efits a n d ris ks  of a  Pfiz er pr o d u ct, Pfiz er s h o ul d b e  i nf or me d 
i m m e diatel y.  
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 1 3  De c e m ber 2 0 2 2
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2
Pa ge 2 7 of 2 8
1 2.  R E F E R E N C E S
1.
. 
2. Fi n nis h Ca n c er Re gistr y 2 0 2 0. Ca n c er statistics, Fi n nis h Ca n c er Re gistr y 2 0 2 0 [I nter n et]. 
. [cite d 2 0 2 0 Ma y 2 8]. A v aila ble fr o m: htt ps://c a nc erre gistr y.fi/statistics/c a nc er-
statistics/
3.  A alt o m a a S, J o usila hti P, K or p ela M, K ujala P, La at o M, Li n d h ol m P, et al. C urre nt Care 
G ui d eli n es [I nter n et]. 2 0 1 4 [cite d 2 0 2 1 Mar 2 4]. A v aila ble fr o m: 
htt ps:// w w w. k a y p a h oit o.fi/ h oi 1 1 0 6 0 # R 1 1 4
4. Par k er C, Castr o E, Fiz a zi K, H ei d e nreic h A, Ost P, Pr o c o pi o G, et al. Pr ostate c a n c er: E S M O 
Cli nic al Pra ctic e G ui d eli n es f or dia g n osis, tre at m e nt a n d f oll o w- u p. A n n als of O n c ol o g y. 2 0 2 0
Se p; 3 1( 9): 1 1 1 9 – 3 4. 
5. C h o w d h ur y S, Bjartell A, L u m e n N, Mar ot o P, Paiss T, G o m e z- V ei ga F, et al. Re al- W orl d 
O utc o m es i n First- Li n e Tre at m e nt of Metastatic Castrati o n- Resista nt Pr ostate Ca n c er: T h e 
Pr ostate Ca n c er Re gistr y. Tar get O n c ol. 2 0 2 0; 1 5( 3): 3 0 1 – 1 5.
6.  Al g h a z ali M, L öf gre n A, J ør ge ns e n L, S v e nss o n M, Fa gerl u n d K, Bjartell A. A re gistr y- b as e d 
st u d y e v al u ati n g o v erall s ur vi val a n d tre at m e nt d urati o n i n S w e dis h p atie nts wit h m etastatic 
c astrati o n-resista nt pr ostate c a nc er tre ate d wit h e n z al uta mi de. Sc a n di n a via n J o ur nal of Ur ol o g y. 
2 0 1 9 Se p 3; 5 3( 5): 3 1 2 – 8. 
7. Is a kss o n J, Gre e n H, Pa p a nt o ni o u D, Petterss o n L, A n d e n M, R os ell J, et al. Re al- w orl d 
e v al u ati o n of u pfr o nt d o c eta xel i n m etastatic c astrati o n-s e nsiti v e pr ostate c a nc er. W orl d J Cli n 
O n c ol. 2 0 2 1 N o v 2 4; 1 2( 1 1): 1 0 0 9 – 2 2. 
8.  D es ai M M, Ca c cia m a ni G E, G ill K, Z h a n g J, Li u L, A bre u A, et al. Tre n ds i n I n ci d e n c e of 
Metastatic Pr ostate Ca n c er i n t h e U S. J A M A N et w O p e n. 2 0 2 2 Mar 1 4; 5( 3):e 2 2 2 2 4 6. 
9. Mä kli n S. Ter v e y d e n -
2 0 1 7. 2 0 1 7; 5 5. 
1 0. Ber ger M L, S o x H, Will k e RJ, Bri x n er D L, Eic hler H, G o etts c h W, et al. G o o d pra ctic es f or re al‐
w orl d d ata st u dies of tre at m e nt a n d/ or c o m p arati v e effe cti v e ness: Re c o m m e n dati o ns fr o m t h e 
j oi nt I S P O R‐I S P E  S p e cial Tas k F orc e o n re al‐w orl d e vi d e n c e i n h e alt h c are d e cisi o n m a ki n g. 
P h ar m a c o e pi d e mi ol Dr u g Saf. 2 0 1 7 Se p; 2 6( 9): 1 0 3 3 – 9. 
1 3. LI S T O F T A B L E S 
Ta ble 1. List of m e dic ati o ns f or i n cl usi o n of m P C p atie nts.  
Ta ble 2. List of m e dic ati o ns f or c h e mic al c astrati o n.  
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )
N o n- E n gli s h t e xt
N o n- E n gli s h t e xt
N o n- E n gli s h t e xt

E n z a l uta mi d e, t ala z o pari b 
C 3 4 4 1 0 5 7 N O N-I N T E R V E N TI O N A L S T U D Y P R O T O C O L 
Versi o n 1, 1 3 De c e m ber 2 0 2 2  
 
P FI Z E R C O N FI D E N TI A L  
C T 2 4- WI- G L 0 2- R F 0 2 4. 0 N o n-I nt erv enti o n al St u dy Pr ot oc ol Te m pl at e F or S e c o n d ary D at a C oll ecti o n St u d y 0 1-J u n- 2 0 2 2   
Pa ge 2 8 of 2 8 
Ta ble 3. List of m e dic ati o ns f or c astrati o n resista nt pr ostate c a n cer.  
Ta ble 4. List of v aria bles  
Ta ble 5. Patie nt c h ara cteristics v aria bles  
Ta ble 6. Tre at m e nt o pti o ns f or P C a n d c o n c o mita nt m e dicati o ns  
Ta ble 7. List of str o n g o pi oi ds us e d i n m P C tre at m e nt.  
 
 
1 4.  LI S T O F FI G U R E S 
Fi g ure 1. I n d e x d efi niti o n f or a p atie nt w h o is i n cl u d e d b ot h  i n t h e m C S P C a n d t h e m C R P C 
c o h orts.  
Fi g ure 2. I n d e x d efi niti o n f or a p atie nt w h o is i n cl u d e d i n t h e m C S P C c o h ort.  
Fi g ure 3. I n d e x d efi niti o n f or a p atie nt w h o is i n cl u d e d i n t h e m C R P C c o h ort.  
Fi g ure 4. O v er vie w of d ata s o urces a n d c o h ort f or m ati o n.  
 
A N N E X 1. LI S T O F S T A N D A L O N E D O C U M E N T S 
N o n e. 
 
A N N E X 2. A D DI TI O N A L I N F O R M A TI O N 
N ot a p plic a ble. 
0 9 0 1 7 7 e 1 9 c 1 9 d 5 3 5\ Fi n al\ Fi n al O n: 1 4- D e c- 2 0 2 2 1 3: 4 8 (G M T )