A Multicenter Noninferior Randomized Controlled Study Comparing the Efficacy of Laparoscopic Versus Abdominal Radical Hysterectomy for Cervical Cancer(Stage IB3,IIA2)
Phase: NA
Conditions: Cervical Cancer
Sponsor: Obstetrics & Gynecology Hospital of Fudan University

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1
A
m ulti c e nt er n o ni nf eri or r a n d o mi z e d
c o ntr oll e d st u d y c o m p ari n g t h e effi c a c y of
l a p ar os c o pi c v ers us a b d o mi n al r a di c al
h yst er e ct o m y f or c er vi c al c a n c er
( St a g e I B 3, II A 2)
( Pr ot o c ol n u m b er: N C T 0 4 9 3 9 8 3 1)
Pri n ci pl e i n v esti g at or: H u a Ji a n g ( O bst etri cs a n d G y n e c ol o g y H os pit al of F u d a n
U ni v ersit y) (si g n e d, d at e d D ec e m b er 2 0 2 0)
Pr oj e ct t e a m
m e m b ers:
Xi n
W u,
W eili
Y a n ( C hil dr e n's
H os pit al
of
F u d a n
U ni v ersit y), Xi p e n g
W a n g ( Xi n h u a H os pit al), Li bi n g Xi a n g ( Z h o n gs h a n H os pit al),
W ei h u a
L o u ( R e nji
H os pit al),
T a o
Z h u ( T ai z h o u
H os pit al,
Affili at e d
C a n c er
H os pit al of t h e U ni v ersit y of C hi n es e A c a d e m y of S ci e n c es), Y u y a n g Z h a n g ( T h e
First
Affili at e d
H os pit al
of
W e n z h o u
M e di c al
U ni v ersit y),
Y o n gr ui
B ai ( R e nji
H os pit al), Y a nli H o u ( R e nji H os pit al), Y a n D u,
W ei g u o H u, Z hili n g Z h u, Xi a o h o n g
X u e, H aili n Y u, H a o F e n g, Li n g Qi u, S h ur o n g Z h u ( all p e o pl e di d n’t n ot e d a b o v e
b el o n g t o O bst etri cs a n d G y n e c ol o g y H os pit al of F u d a n U ni v ersit y)
V er si o n n u m b er: 1. 0, v ersi o n d at e: D e c e m b er 2 1, 2 0 2 0
O B & G Y  o f  F u d a n  U n i v e r s i t y

C o n ten ts
I. R esearc h In fo rm atio n
II. R esearch B a ck g ro u n d
2 .1 R esearch B ac k g ro u n d
2 .2 R esearch O b jectiv es
2 .3 R esearch D esig n
III. R esearc h M eth o d s
3 .1 R esearch S ettin g
3 .2 E lig ib ility C riteria
3 .3 In terv e n tio n s
IV .A llo catio n , B lin d in g an d U n b lin d in g
4 .1 M eth o d o f A llo catio n o f th e In terv en tio n
4 .2 B lin d in g
V . M eth o d s o f D ata C o llectio n , M an ag em en t an d A n aly sis
5 .1 D ata C o llectio n an d P atien t R eten tio n
5 .2 D ata M an ag e m en t (D ata en try, co d in g , en cry p tio n an d sto rag e sch em es)
5 .3 S tatistical A n aly ses
V I. Q u ality o f L ife Q u estio n n aire
6 .1 P atien t-rep o rted C lin ical O u tco m e A ssessm en t S cale P R O 1 4 7 (V 1 .0 ) fo r C erv ical
C an cer
6 .2 G en eric q u ality o f life q u estio n n aire
V II. M eth o d s o f D ata M o n ito rin g
7 .1 S tu d y M o n ito rin g
7 .2 In terim A n aly sis
7 .3 Q u ality C o n tro l
V III. D efin itio n an d T reatm en t o f A d v erse E v en ts
8 .1 D efin itio n o f A d v erse E v en ts
8 .2 O b serv a tio n , R eco rd in g an d T reatm en t o f A d v erse E v en ts
IX . C o st-b en efit A n aly sis
X . R ev iew
X I. E th ics an d D issem in atio n
1 1 .1 E th ical A p p ro v al
1 1 .2 S tu d y P ro to co l M o d ificatio n P lan
1 1 .3 In fo rm ed C o n sen t
X II. C o n fid en tiality
X III. D ecla ratio n o f C o m p etin g In terests
X IV . D ata C o llectio n
X V .A ffiliatio n an d P o st-test C are
X V I. D issem in atio n P o licy
X V II. A p p en d ice s
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2
I. Rese arc h I nf or m ati o n
1) Article title: A m ultice nter ra n d o mize d, c o ntr olle d, n o n-i nferi orit y trial c o m pari n g t he
efficac y of la par osc o pic vers us a b d o mi nal ra dical h ysterect o m y f or cer vical ca ncer ( Sta ge
I B 3a n d II A 2)
2)
Cli nic al Tri al
Re gistr ati o n: t he pr ot oc ol has bee n re gistere d b y t he
O bstetrics a n d
G y n ec ol o g y
H os pital
of
F u da n
U ni versit y
at
htt ps://cli nicaltrials. g o v/ , re gistrati o n
n u m ber: N C T 0 4 9 3 9 8 3 1; all data s heets are i ncl u de d i n t he
W H O cli nical trial re gistrati o n
data ( w w w.a n nals. or g)
3) Versi o n n u m ber: L A U N C H 3 1. 0, versi o n date: Dece m ber 2 1, 2 0 2 0.
4) F u n di n g: S ha n g hai S he n ka n g H os pital De vel o p me nt Ce nter's S he n ka n g Pr o m oti o n of
Cli nical S kills a n d Cli nical I n n o vati o n i n
M u nici pal
H os pitals T hree- Year Acti o n Pla n
( 2 0 2 0- 2 0 2 3)
Maj or Cli nical Researc h Pr oject
( Gra nt N o. S H D C 2 0 2 0 C R 1 0 4 8 B).
5) List of i n vesti gat ors a n d t heir res pecti ve rese arc h r oles a n d res p o nsi bilities
Na me
Affiliate d I nstit uti o n
R ole
H ua Jia n g
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Pri nci ple I n vesti gat or
Xi n
W u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Lea der of
Mai n
Ce nter
Xi pe n g
Wa n g
Xi n h ua H os pital Affiliate d t o S ha n g hai
Jia o T o n g U ni versit y Sc h o ol of
Me dici ne
Lea der of S u b-ce nter
Wei h ua L o u
S ha n g hai Jia o T o n g U ni versit y Sc h o ol of
Me dici ne, Re nji H os pital
Lea der of S u b-ce nter
Li b i n g Xia n g
Z h o n gs ha n H os pital Affiliate d t o F u da n
U ni versit y
Lea der of S u b-ce nter
Ta o Z h u
Taiz h o u H os pital Affiliate d Ca ncer
H os pital of t he U ni versit y of C hi nese
Aca de m y of Scie nces
Lea der of S u b-ce nter
Y u ya n g Z ha n g
T he First Affiliate d H os pital of
We nz h o u
Me dical U ni versit y
Lea der of S u b-ce nter
Wei g u o H u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Cli nical Researc hers
Z hili n g Z h u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Cli nic al Researc h ers
Xia o h o n g X ue
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Cli nical Researc hers
Y o n gr ui Bai
S ha n g hai Jia o T o n g U ni versit y Sc h o ol of
Me dici ne, Re nji H os pital
Ra di ot hera p y
researc her
Ya nli H o u
S ha n g hai Jia o T o n g U ni versit y Sc h o ol of
Me dici ne, Re nji H os pital
Ra di ot hera p y
researc her
Weili Ya n
C hil dre n’s H os pital of F u da n U ni versit y
Statisticia n
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3
Ya n D u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
E pi de mi ol o gist
S h uj u n Ga o
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
We nji n g Dia o
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Mi n g D u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
H ua Fe n g
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
H o n g wei Z ha n g
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
R o n g Jia n g
Z h o n gs ha n H os pital Affiliate d t o F u da n
U ni versit y
Researc her
Jiar ui Li
Xi n h ua H os pital Affiliate d t o S ha n g hai
Jia o T o n g U ni versit y Sc h o ol of
Me dici ne
Researc her
X u h o n g Fa n g
Xi n h ua H os pital Affiliate d t o S ha n g hai
Jia o T o n g U ni versit y Sc h o ol of
Me dici ne
Researc her
Haili n Y u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Ha o Fe n g
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Li n g Qi u
O bstetrics a n d G y n ec ol o g y H o s pital of
F u da n U ni versit y
Researc her
S h ur o n g Z h u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Mi n g Li
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Ya na n Y o u
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
Pe n g ya o Jia n g
O bstetrics a n d G y n ec ol o g y H os pital of
F u da n U ni versit y
Researc her
6)
T he c o m p ositi o n, r oles a n d res pecti ve res p o nsi bilities of t he trial s p o ns or, trial
c o or di nati n g
ce nter,
steeri n g
c o m mittee,
e n d p oi nt
deter mi nati o n
c o m mittee,
data
ma na ge me nt tea m a n d ot her tea ms.
T he trial is s p o ns ore d b y S ha n g hai S he n ka n g H os pital De vel o p me nt Ce nter (c o ntact:
0 2 1- 9 6 8 8 6),
w hic h is res p o nsi ble f or t he
ma na ge me nt
of
h os pital
de vel o p me nt i n
S ha n g hai a n d has o versi g ht res p o nsi bilit y f or t his pr oject. T he st u d y desi g n, c ollecti o n,
ma na ge me n t, a nal ysis a n d i nter pretati o n of data, re p ort
writi n g, a n d p u blicati o n of t his
trial are t he res p o nsi bilit y of t he
mai n ce nter of t he O bstetrics a n d G y n ec ol o g y H os pital
of
F u da n
U ni versit y, a n d t he
pri nci ple i n vesti gat or
has t he fi nal
decisi o n- ma ki n g
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
4
a ut h orit y. T he et hics c o m mittee a n d t he i n de pe n de nt data m o nit ori n g b o d y ha ve t he ri g ht
of s u per visi o n.
T his st u d y is c o n d ucte d b y H ua Jia n g a n d Xi n
W u of t he O bstetrics a n d G y n ec ol o g y
H os pital of F u da n U ni versit y, w h o are res p o nsi ble f or t he st u d y desi g n, i m ple me ntati o n,
a n d
ma na ge me nt.
Weili
Ya n a n d
Ya n
D u are res p o nsi ble f or statistical a nal ysis, a n d
q ualit y c o ntr ol of t he i m ple me ntati o n. T he all-r o u n d i m ple me ntati o n r ules ha ve bee n
de vel o pe d a n d vali date d pre v i ousl y, a n d ca n be a p plie d n or mall y. T he s ur gical tea m of
t his st u d y c o nsists of se veral gr o u ps i n nati o nal or re gi o nal ce nter h os pitals, i ncl u di n g:
H ua Jia n g a n d
Xi n
W u’s tea m, Z hili n g Z h u’s tea m,
Wei g u o
H u’s tea m a n d
Xia o h o n g
X ue’stea m i n t he O bstetrics a n d G y n ec ol o g y H os pital of F u d a n U ni v ersit y; R o n g y u Za n g,
Li bi n g Xia n g, a n d Jia n gr o n g Yu’s tea m i n Z h o n gs ha n H os pital of F u da n U ni versit y;
We n
Di a n d
Wei h ua L o u’s tea m i n Re nji H os pital of S ha n g hai Jia o To n g U ni versit y ; Xi pe n g
Wa n g, Jiar ui Li a n d
X u h o n g Fa n g’s tea m i n
Xi n h ua
H os pital of S ha n g hai Jia o To n g
U ni versit y; t he tea m of
Z h u
Ta o fr o m
Taiz h o u
Ca ncer
H os pital ( Taiz h o u
H os pital
Affiliate d Ca ncer H os pital of t he U ni versit y of C hi nese Aca de m y of Scie nces); a n d t he
tea m of Yu ya n g Z ha n g fr o m t he First Affiliate d H os pital of
We nz h o u
Me dical U ni versit y.
I n ter ms of statistical a nal ysis,
Weili Ya n's tea m fr o m C T U, Cli nical Trial Ce nter of t he
C hil dre n’s
H os pital
of
F u da n
U ni versit y is t he ra n d o mize d cli nical researc h tea m
(c o m p ose d
of e pi de mi ol o gists a n d statisticia ns), res p o nsi ble f or statistical a nal ysis,
dra wi n g gra p hs a n d e x plai ni n g statistical res ults.
Xi n
W u, Ta o Z h u, a n d Li bi n g
Xia n g
f or m t he s ur gical q ualit y c o ntr ol c ore tea m, are res p o nsi ble f or s ur gical q ualit y c o ntr ol.
Ya n
D u, as a n e pi de mi ol o gist, is res p o nsi ble f or t he q ualit y c o ntr ol of cli nical st u d y
i m ple me ntati o n.
T he
mai n ce nter a n d s u b-ce nters of t his st u d y eac h esta blis he d a n i n ter nal staff
or ga nizati o n str uct ure. T he hea d of t he
mai n ce nter re g ularl y c o n ve nes t he hea d of t he
s u b-ce nter f or p hase meeti n gs. Eac h ce nter has a fi x e d i nf or mati o n c o ntact pers o n, w h o is
ma na ge d
b y t he
mai n ce nter.
T he i nf or mati o n c o or di nat or
of t he
mai n ce nter is
res p o nsi ble f or c ollecti n g a n d releasi n g data, a n d recei vi n g fee d bac k fr o m t he s u b-ce nters
at a n y ti me, c o or di nati n g a n d ha n dli n g te m p orar y sit uati o ns t hat arise i n t he w or k of t he
s u b-ce nters, a n d ens u ri n g t hat t he pr o gress of eac h ce nter i n t he researc h is c o nsiste nt.
T he e n d p oi nt deter mi nati o n c o m mittee c o nsists of t he C o- PIs of eac h ce nter, t he
et hics
c o m mittee, t he
data i ns pecti o n
c o m mittee,
a n d
ke y
me m bers
of t he
data
ma na ge me nt tea m t o
ma ke a p pr o priate deter mi nati o ns base d o n trial
pr o gress a n d
a nal ysis.
II. B ac k gr o u n d
2. 1 Rese arc h B ac k gr o u n d
2. 1. 1 O ver vie w of Cer vic al C a ncer
Cer vical ca ncer is o ne of t he
maj or
mali g na ncies t hat t hreate n w o me n's healt h a n d
li ves w orl d wi de, a n d it is c urre ntl y t he 4t h
m ost pre vale nt
mali g na nc y i n w o me n [ 1]. T he
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
5
Nati o nal C o m pre he nsi ve Ca ncer
Net w or k ( N C C N) g ui deli nes f or cer vical ca ncer state
t hat 5 2 8, 0 0 0 ne w cases of cer vical ca ncer occ urre d
w orl d wi de i n 2 0 1 2, a n d 8 5 % of
cer vical ca ncers occ ur i n de vel o pi n g c o u ntries. Persiste nt H P V i nfecti o n is a n i m p orta nt
ris k fact or i n t he de vel o p me nt of cer vical ca ncer.
Ot her hi g h-ris k fact ors f or cer vical
ca ncer i ncl u de earl y se x ual i nterc o urse,
m ulti ple se x ual part ners,
m ulti ple pre g na ncies,
m ulti ple birt hs, s m o ki n g, l o n g-t er m oral c o ntrace pti ve use, a n d se x uall y tra ns mitte d
diseases. T he fact ors s uc h as earl y se x ual i nterc o urse a n d
m ulti ple se x ual part ners are
i m p orta nt s y n er gistic fact ors f or H P V i nfecti o n.
Wit h t he i ncrease of H P V i nfecti o n, t he
i nci de nce of cer vical ca ncer is i ncreasi n g a n d t he a ge bec o mes y o u n ger. H P V vacci nati o n
is t he
mai n strate g y t o pre ve nt
H P V-relate d cer vical ca ncer.
Acc or di n g t o t he
W H O
Gl o bal Cer vical Ca ncer Eli mi nati o n Pr o gra m,
H P V vacci nati o n is o ne o f t he i m p orta nt
c o m p o ne nts of t he Pr o gra m.
H o we ver, d ue t o relati vel y late i m ple me ntati o n of
H P V
vacci ne i n C hi na, t he i nci de nce a n d
m ortalit y of cer vical ca ncer i n C hi na ha ve s h o w n
i ncreasi n g tre n ds, wit h ar o u n d 1 1 0, 0 0 0 ne w cases a n d 5 0, 0 0 0 deat hs of cer vical ca ncer i n
C hi na i n 2 0 1 8, acc o u nti n g f or a b o ut 2 0 % a n d 1 6 % of t he t otal gl o bal i nci de nce a n d
deat hs, res pecti vel y. A m o n g cer vical ca ncer patie nts, t he y o u n g a ge gr o u p ( ≤3 5 years ol d)
acc o u nts f or 8. 5 %- 1 2. 6 % of cer vi cal ca ncer patie nts, a n d t he s ur vi val be nefits a n d q ualit y
of life of t his gr o u p nee d partic ular atte nti o n.
S q ua m o us cell carci n o ma of t he cer vi x acc o u nts f or a p pr o xi matel y 8 0 % of cer vical
ca ncers a n d a de n ocarci n o ma f or r o u g hl y 2 0 %. I n de vel o pe d c o u ntries, t he i nci de nce a n d
m ortalit y of cer vical s q ua m o us cell carci n o ma ha ve decrease d si g nifica ntl y d ue t o
effecti ve
cer vical
c yt ol o gic
scree ni n g.
H o we ver,
t he
i nci de nce
of
cer vical
a de n ocarci n o ma
has
gra d uall y i nc rease d
over t he
past
3 0
years
pr o ba bl y
d ue t o
i nse nsiti vit y
t o
c yt ol o gic
scree ni n g,
w hile
t he
earl y
i de ntificati o n
of
cer vical
a de n ocarci n o ma
ma y be i m pr o ve d if
H P V testi n g is use d as a scree ni n g
met h o d f or
cer vical ca ncer;
H P V
vacci nati o n
ma y re d uce
n ot
o nl y t he i nci de nce
of cer vical
s q ua m o us cell carci n o ma b ut als o t he i nci de nce of cer vical a de n ocarci n o ma [ 2,
3]. I n
a d diti o n t o s q ua m o us a n d a de n ocarci n o ma, cer vical
mali g na ncies i ncl u de ot her s pecific
pat h ol o gica l t y p es: s mall cell ne ur oe n d ocri ne carci n o ma of t he cer vi x,
micr o biase d
a de n ocarci n o ma of t he cer vi x, a n d mali g na nt mela n o ma of t he cer vi x.
Cer vical ca ncer ca n i nfiltrate t hr o u g h a n d directl y s prea d t o t he para metrial tiss ues,
va gi na, uteri ne c or p us a n d a djace nt or ga ns ( bla d der a n d rect u m) or t hr o u g h l y m p hatic
vessels t o re gi o nal l y m p h n o des s uc h as cl ose d f ora me n, e xter nal a n d i nter nal iliac l y m p h
n o des a n d t he n t o t he c o m m o n iliac a n d para-a b d o mi nal a ortic l y m p h n o des. T he stat us of
l y m p h n o des c orrelates wit h t he pr o g n osis of cer vical ca ncer. Pre vi o usl y, FI G O sta gi n g of
cer vical ca ncer
was cli nical sta gi n g, a n d s ur gical pat h ol o gical sta gi n g
was n ot use d. I n
2 0 1 8,
FI G O u p date d t he sta gi n g s yste m of cer vical ca ncer t o i ncl u de pre o perati ve
i ma gi n g a n d p ost o perati ve l y m p h n o de stat us. I n a d diti o n, t he A merica n J oi nt C o m mittee
o n Ca ncer ( AJ C C) als o u p date d t he T N M sta gi n g s yste m of cer vical ca ncer i n 2 0 1 8, s o
t he FI G O 2 0 1 8 a n d AJ CC ( 2 0 2 1) T N M sta gi n g s yste m are b ot h use d i n t his st u d y [ 4].
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
6
2. 1. 2 Tre at me nt of cer vic al c a ncer
T he
mai n treat me nt
met h o ds of cer vical ca ncer i ncl u de s ur ger y a n d ra di ot hera p y.
W hile s ur ger y is t he treat me nt of c h oice f or earl y-sta ge cer vical ca ncer (i ncl u di n g sta ges
I A 1, I A 2, I B 1, I B 2, a n d II A 1), it ca n als o be use d f or t he i nitial treat me nt of sta ges I B 3
a n d II A 2. T he mai n treat me nt m o dalities f or cer vical ca ncer are as f oll o ws:
•
Ra dical cer vical ca ncer s ur ger y
+
pel vic l y m p h
n o de
dissecti o n
± a b d o mi nal
para-a ortic l y m p h n o de dissecti o n ± a dj u va nt t hera p y
•
Ra dical ra di ot hera p y
•
E xte nsi ve h ysterect o m y (ca pa ble of I A 2 t o I B 1 sta ge, preser vi n g fertilit y)
•
Cer vical c o nizati o n (sta ge I A 1, preser vi n g fertilit y)
T he
m ost a p pr o priate treat me nt f or cer vical ca ncer re q uires c o nsi derati o n of a
c o m bi nati o n of patie nt a ge, fertilit y re q uire me nts, cer vical ca ncer sta ge, c o m or bi dities,
patie nt a n d p h ysicia n prefere nces, a n d t he prese nce of ris k fact ors ass ociate d
wit h
rec urre nce i n t he
p osto perati v e
pat h ol o g y re p ort.
N C C N rec o m me n ds
c o nc urre nt
ra di ot hera p y as t he pri mar y treat me nt f or sta ge I B 3 t o I V A cer vical ca ncer.
2. 2. 1 S ur gic al tre at me nt
Ra dical cer vical ca ncer s ur ger y is t he
mai n pr oce d ure f or t he treat me nt of earl y-sta ge
cer vical ca ncer a n d is
mai nl y a p plica ble t o cer vical ca ncer a b o ve sta ge I A 1 (i ncl u di n g
I A 1 wit h L V SI, I A 2, I B 1, I B 2, II A 1; a n d I B 3 a n d II A 2). C o m pare d wit h sta n dar d t otal
h ysterect o m y, ra dical h ysterect o m y f or cer vical ca nce r has hi g her s ur gical diffic ult y a n d
c orres p o n di n g c o m plicati o ns beca use of t he lar ger s ur gical sc o pe.
A b d o mi nal ra dical
h ysterect o m y f or cer vical ca ncer has a hist or y of
m ore t ha n 1 2 0 years, a n d t he s ur gical
a p pr oac h has bec o me ver y
mat ure,
w hile
mi ni mall y i n vasi ve ra dical h ysterect o m y f or
cer vical ca ncer has als o bec o me i ncreasi n gl y mat ure after nearl y 2 0 years of de vel o p me nt.
C o m pare d wit h tra diti o nal A b d o mi nal Ra dical H ysterect o m y ( A R H), mi ni mall y i n vasi v e
ra dical h ysterect o m y has u ni q ue a d va nta ges, s uc h as less a b d o mi nal
wall tra u ma, less
pai n, clearer visi o n a n d less blee di n g, less i nterfere nce
wit h t he i ntesti ne, a n d l o wer
p ost o perati ve i nfecti o n
rate.
T heref ore, t he
2 0 1 4
N C C N
g ui deli ne
rec o m me n ds
la par osc o pic ra dical h ysterect o m y ( L R H) t o perf or m ra dical cer vical ca ncer s ur ger y.
M o der n sta n dar d s ur ger y i ncl u des la par osc o pic s ur ger y ( di vi de d i nt o c o n ve nti o nal
la par osc o pic s ur ger y a n d r o b otic-assiste d la par osc o pic s ur ger y, or m ulti p ort la par osc o pic
s ur ger y a n d si n gle- p ort la par osc o pic s ur ger y), o pe n s ur ger y, a n d tra ns va gi nal s ur ger y.
Beca use t hese t hree pr oce d ures are perf or me d o n differe nt r o utes wit h t he sa me e xte nt of
resecti o n, it is i nt uiti vel y ass u me d t hat t he res ults of t hese t hree pr oce d ures are t he sa me,
a n d t heref ore
m ost pre vi o us st u dies ha ve f oc use d o n o perati ve ti me, i ntra o perati ve
blee di n g, le n gt h of h os pital sta y, a n d c ost, rat her t ha n s ur vi v al i ndicat ors s uc h as
pr o gressi o n free s ur vi val ( P F S) a n d o verall S ur vi val ( O S).
O nl y a fe w pre vi o us s mall
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
7
st u dies ha ve e val uate d t he s ur vi val be nefit of La par osc o pic Ra dical H ysterect o m y ( L R H)
f or cer vical ca ncer: i n ter ms
of
P F S
[ 5- 1 0],
L R H
was
n ot i nferi or t o
A R H,
w hile
la par osc o p y
was s u peri or t o o pe n s ur ger y i n ter ms of o perati ve ti me, i ntra o perati ve
blee di n g, a n d le n gt h of h os pital sta y. I n N o ve m ber of 2 0 1 8, t he Ne w E n gla n d J o ur nal of
Me dici ne p u blis he d t w o researc h re p orts c o m pari n g a b d o mi nal a n d
mi ni mall y i n vasi ve
ra dical cer vical ca ncer s ur ger y i n t he sa me perio d,
w h ic h ha ve s h oc ke d t he e ntire
g y n ec ol o g y fiel d.
T he retr os pecti ve c o h ort st u d y c o ncl u de d
[ 1 1] t hat o ver a
me dia n
f oll o w- u p of 4 5
m o nt hs, t he 4- year
m ortalit y rate was 9. 1 % f or w o me n w h o u n der we nt
mi ni mall y i n vasi ve s ur ger y a n d 5. 3 % f or w o me n
w h o u n der we nt o pe n s ur ger y ( hazar d
rati o 1. 6 5; 9 5 % c o nfi de nce i nter val 1. 2 2- 2. 2 2); pri or t o t he use of
mi ni mall y i n vasi ve
ra dical h ysterect o m y (i.e., fr o m 2 0 0 0 t o 2 0 0 6), t he 4- year o verall s ur vi val rate f or w o me n
u n der g oi n g ra dical
h ysterect o m y re mai ne d sta ble;
w hile t he
o verall s ur vi val rate
decrease d b y 0. 8 % ( 9 5 %
CI, 0. 3- 1. 4) per year after 2 0 0 6
wit h t he a p plicati o n of
mi ni mall y i n vasi ve s ur ger y,.
A n ot her st u d y p u blis he d i n t he
Ne w E n gla n d J o ur nal of
Me dici ne i n late 2 0 1 8 (t he La par osc o pic A p pr oac h t o Cer vical Ca ncer, L A C C trial) was a
Ra n d o mize d Cli nical Trial ( R C T), w hic h s h o we d t hat t he 4. 5- year P F S rate was 8 6. 0 % i n
t he
mi ni mall y i n vasi ve s ur ger y gr o u p a n d 9 6. 5 % i n t he o pe n s ur ger y gr ou p,
wit h a
d iffere nce of - 1 0. 6 perce nta ge p oi nts ( 9 5 % CI - 1 6. 4 t o - 4. 7); mi ni mall y i n vasi ve s ur ger y
was ass ociate d
wit h l o wer disease-free s ur vi val ( P F S) c o m pare d
wit h o pe n s ur ger y
[( 3- year P F S was 9 1. 2 % vs. 9 7. 1 %; hazar d rati o f or rela pse or deat h of cer vical ca ncer
was 3. 7 4; 9 5 % CI ( 1. 6 3 t o 8. 5 8)]
[ 1 2]. B ot h st u dies s u g gest t hat mi ni mall y i n vasi ve ra dical
cer vical s ur ger y is ass ociate d wit h l o wer P F S a n d O S rates c o m pare d wit h o pe n s ur ger y.
F oll o wi n g t he p u blicati o n o f t hese st u dies, t he versi o n 3. 2 0 1 9 of t he N C C N g ui deli nes
rec o m me n de d
o pe n s ur ger y
as t he sta n dar d
pr oce d ure f or
cer vical
ca ncer,
w hile
la par osc o pic s ur ger y is n o l o n ger rec o m me n de d, w hic h has ca use d a h u ge i m pact o n t he
g y n ec ol o g y c o m m u nit y.
L y m p h n o de resecti o n
Cer vical ca ncer n ot o nl y i n v ol ves a djace nt or ga ns t hr o u g h direct i nfiltrati o n, b ut als o
ca n
metastasize t o t he pel vis a n d para-a ortic l y m p h n o des t hr o u g h l y m p hatic vessels.
T heref ore, l y m p h n o de dissect i on is us uall y perf or me d at t he sa me ti me as ra dical
cer vical ca ncer s ur ger y. T he e xte nt of l y m p h n o de dissecti o n de pe n ds o n t he de gree of
disease pr o gressi o n.
F or sta ge I A 1 cer vical ca ncer
wit h o ut L V SI, t he ris k of l y m p h n o de
metastasis is
ver y l o w, s o l y m p h n o de dissecti o n is n ot re q uire d. F or sta ge I A 1 cer vical ca ncer wit h
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
8
L V SI, i ntra o perati ve e val uati o n of l y m p h n o de stat us a n d l y m p h n o de dissecti o n or
se nti nel l y m p h n o de bi o ps y are re q uire d.
F or sta ge I A 2 cer vical ca ncer,
m o difie d ra dical cer vical ca ncer s ur ger y + bilateral
pel vic l y m p h n o de dissecti o n is rec o m me n de d. If pre o perati ve i ma gi n g assess me nt of
pel vic l y m p h n o de
metastasis is s usce pte d, si m ulta ne o us a b d o mi nal para-a ortic l y m p h
n o de dissecti o n is rec o m me n de d.
F or sta ge I B 1, I B 2, a n d II A 1 cer vical ca ncer, t he preferr e d s ur gical pr oce d ure is
ra dical cer vical ca ncer s ur ger y + bilateral pel vic l y m p h n o de dissecti o n ± a b d o mi nal
para-a ortic l y m p h n o de dissecti o n. It is f o u n d t hat i n I B-II B cer vical ca ncer, pel vic l y m p h
n o de
metastasis, t u m or > 2c m a n d c o m m o n iliac l y m p h n o de
metastasis are cl osel y
relate d t o a b d o mi nal para-a ortic l y m p h n o de
metastasis. T heref ore, f or patie nts
wit h
s us pecte d pel vic l y m p h n o de
metastasis, parietal a ortic l y m p h n o de dissecti o n s h o ul d be
perf or me d i n tra operati vel y [ 1 3, 1 4].
F or sta ge I B 3
a n d II A 2
cer vical
ca ncer, t he
N C C N
g ui deli nes rec o m me n d
si m ulta ne o us
ra di ot hera p y
( Class
I
e vi de nce)
as t he
preferre d treat me nt; it is
c o ntr o versial w het her s ur ger y is feasi ble f or sta ge I B 3 a n d II A 2 cer vical ca ncer. H o we v er,
s o me o nc ol o gists a d v ocate s ur ger y si nce sta ge I B 3 a n d II A 2 t u m ors are lar ger ( > 4 c m)
a n d ha ve a hi g her ris k of
metastasis t o t he para-a ortic l y m p h n o des. S o if s ur ger y is
perf or me d, ra dical cer vical ca ncer s ur ger y + b ilateral pel vic l y m p h n o de dissecti o n +
a b d o mi nal para-a ortic l y m p h n o de dissecti o n s h o ul d be perf or me d.
Se nti nel L y m p h N o de
M a p pi n g ( S L N)
Rece nt st u dies ha v e s h o w n certai n si g nifica nce of S L N i n earl y-sta ge cer vical ca n cer.
A meta-a nal ysis has s h o w n t hat t he detecti o n rate of se nti nel l y m p h n o de ma p pi n g bi o ps y
is 8 9- 9 2 % a n d t he se nsiti vit y is 8 9- 9 0 % [ 1 5, 1 6]. At t he sa me ti me, st u dies ha ve s h o w n t hat
se nti nel l y m p h n o de
ma p pi n g bi o ps y has s o me li mitati o ns, a nd i ntra o perati ve e val uati o n
of
se nti nel
l y m p h
n o de
met h o ds
(e. g.,
freezi n g
or
cell
bl otti n g)
ma y
miss
micr o- metastases i n se nti nel l y m p h n o des or is olate d t u m or cell
metastases
[ 1 7- 1 9]. It has
bee n s u g geste d t hat t he se nsiti vit y of se nti nel l y m p h n o de bi o ps y see ms t o be hi g her i n
cer vical ca ncer wit h t u m or size ≤2 c m [ 2 0, 2 1]; w hile t he a p pr oac h of se nti nel l y m p h n o de
h y p ersta gi n g i m pr o ves t he detecti o n of l y m p h n o de micr o metastases [ 2 2, 2 3].
S ur ger y t o preser ve fer tilit y
Cer v ic al c o niz ati o n f or st a ge I A 1 cer vic al c a ncer
F or patie nts wit h sta ge I A 1 cer vical ca ncer wit h fertilit y preser vati o n re q uire me nts,
cer vical c o nizati o n ± pel vic l y m p h n o de dissecti o n is rec o m me n de d
[ 2 4, 2 5]. T he ai m of
cer vical c o nizati o n is t o e ns ure ne gati ve
mar gi ns [a bse nce of i n vasi ve ca ncer a n d
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
9
hi g h- gra de s q ua m o us i ntrae pit helial lesi o ns ( H SI L)]. F or t h ose wit h ne gati ve mar gi ns a n d
n o L V SI, p ost o perati ve o bser vati o n a n d f oll o w- u p is s ufficie nt;
w hereas i n cases
wit h
p ositi ve
mar gi ns, a sec o n d c o nizati o n
ma y
be c o nsi dere d t o clarif y t he
de pt h
of
i nfiltrati o n (t o e x cl u de sta ge I A 2/I B) or t o perf or m ra dical cer vical h ysterect o m y. F or
sta ge I A 1
wit h
L V SI, cer vical c o nizati o n ( ne gati ve
mar gi ns) + la par osc o pic se nti nel
l y m p h
n o de
ma p pi n g
bi o ps y/ pel vic
l ym p h
n o de
dissecti o n
or
ra dical
cer vical
h ysterect o m y + S L N/ pel vic l y m p h n o de dissecti o n ma y be perf or me d.
R a dic al cer vic al h ysterect o m y f or st a ge I A 2/I B 1 cer vic al c a ncer
Patie nts wit h sta ge I A 2 cer vical ca ncer w h o ha ve fertilit y preser vati o n re q uire me nts
are rec o m me n de d t o u n der g o ra dical h ysterect o m y + pel vic l y m p h n o de dissecti o n, or
ca n c o nsi der ra dical h ysterect o m y + S L N. If cer vical c o ne
mar gi ns are ne gati ve, pel vic
l y m p h n o de dissecti o n ca n als o be perf orme d t o assess l y m p h n o de stat us. If l y m p h n o de
stat us is ne gati ve, f oll o w- u p ca n be perf or me d. Patie nts
wit h sta ge I B 1 cer vical ca ncer
w h o
ha ve fertilit y
preser vati o n re q uire me nts are rec o m me n de d t o
u n der g o ra dical
h ysterect o m y + pel vic l y m p h n o de dissecti o n ± para-a ortic l y m p h n o de dissecti o n [ 2 6- 2 8].
2. 2. 2 I n dic ati o ns f or a dj u v a nt t her a p y after cer vic al c a ncer s ur ger y
T he nee d f or a dj u va nt t hera p y after ra dical s ur ger y f or cer vical ca ncer is deter mi ne d
b y t he st a ge of t he disease a n d s ur gical pat h ol o gical fact ors. Patie nts wit h sta ge I A 2, I B 1
or II A 1
w h o ha ve n o p ost o perati ve l y m p h n o de
metastases, ne gati ve s ur gical
mar gi ns,
ne gati ve para metri u m a n d n o ot her ris k fact ors f or rela pse ( Se dlis criteria) d o n ot nee d
a dj u va nt t hera p y after s ur ger y a n d s h o ul d be f oll o we d 0 u p re g ularl y.
H o we ver, if a n y
re plase ris k fact ors are prese nt, p ost o perati ve a dj u va nt t hera p y is rec o m me n de d.
Hi g h ris k dise ase cer vic al c a ncer
After ra dica l cer vical s ur ger y, patie nts wit h t hree hi g h-ris k fact ors ( p ositi ve l y m p h
n o des, p ositi ve s ur gical
mar gi ns, a n d p ositi ve para metri u m) are rec o m me n de d t o recei ve
p ost o perati ve a dj u va nt t hera p y: e xter nal- bea m ra diati o n t hera p y ( E B R T) + s y n c hr o n o us
plati n u m- base d c he m ot hera p y + va gi nal brac h yt hera p y. Va gi nal brac h yt hera p y is a ver y
effecti ve l ocal t hr ust f or patie nts
wit h p ositi ve va gi nal
mar gi ns;
w hile s y n c hr o nize d
ra di ot hera p y si g nifica ntl y i m pr o ves OS i n p atie nts wit h all t hree hi g h-ris k fact ors
after
ra dical cer vical s ur ger y f or earl y-sta ge cer vical ca ncer [ 2 9].
I nter me di ate-ris k dise ase cer vic al c a ncer
P ost o perati ve a dj u va nt pel vic E B R T +-s y n c hr o n o us plati n u m- base d c he m ot hera p y is
re q uire d after ra dical cer vical s ur ger y f or cer vical ca ncer i n t he a bse nce of hi g h-ris k
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 0
fact ors, b ut i n t he prese nce of lar ge t u m or size, dee p i nterstitial i nfiltrati o n, a n d L V SI (see
N C C N g ui deli nes, Se dlis criteria)
[ 3 0- 3 2].
2. 2. 3 R a dic al r a di ot her a p y
Ra dical ra di ot hera p y is i n dicate d f or t he treat me nt of sta ge I B 3, sta ge II A 2, a n d
a d va nce d (sta ge II B-I V A) cer vical ca ncer.
F or sta ge I B 3 or II A 2 cer vical ca ncer, t he N C C N rec o m me n d ati o n ( Class 1 e vi d e n ce)
is t hat c o nc urre nt ra di ot hera p y is preferre d: ra dical E B R T + c o nc urre nt plati n u m- base d
c he mot h era p y + va gi nal brac h yt hera p y. F or t h ose
wit h sta ge I B 1, I B 2, or II A cer vical
ca ncer
t hat
ca n n ot
t olerate
s ur ger y,
pel vic
E B R T
+
va gi nal
brac h yt hera p y
±
plati n u m- base d c o nc urre nt c he m ot hera p y ca n be perf or me d.
F or patie nts wit h a d va nce d cer vical ca ncer recei vi n g ra dical ra di ot hera p y, t he tar get
area of ra di ot hera p y is critical, w hic h is deter mi ne d b y pel vic a n d a b d o mi nal para-a ortic
l y m p h n o de
metastases.
Ma g netic res o na nce i ma gi n g ( M RI) hel ps t o descri be the e xte n t
of l ocalize d lesi o ns a n d ai ds i n ra di ot hera p y pla n ni n g.
H o we ver, fi ne nee dle as pirati o n
bi o ps y
ma y be c o nsi dere d f or s us pici o us i ma gi n g prese ntati o ns o utsi de t he uter us t o
clarif y t he dia g n osis. S ur gical e val uati o n of l y m p h n o de stat us (i.e., e xtra perit o neal or
la par osc o pic l y m p h n o de dissecti o n) is als o a n o pti o n f or t hese patie nts (cate g or y 2 B),
a n d s ur gical e val uati o n ca n als o detect
micr osc o pic l y m p h n o de
metastases t hat are n ot
detecta ble o n i ma gi n g
[ 3 3,
3 4].
F or t h ose
wit h o ut l y m p h n o de
metastases or lesi o ns
c o nfi ne d t o t he pel vis, pel vic
E B R T + s y n c hr o n o us plati n u m- base d c he m ot hera p y +
va gi nal brac h yt hera p y is feasi ble (class 1 e vi de nce)
[ 3 5] [ 3 6]. F or patie nts
wit h p ositi ve
pel vic a n d para-a ortic l y m p h n o des, i ma gi n g is rec o m me n de d t o assess f or dista nt
metastases. If t here
are
n o
dista nt
metastases,
pel vic
e xte nsi o n fiel d
E B R T
+
si m ulta ne o us
plati n u m-c o ntai ni n g
c he m ot hera p y
+
va gi nal
brac h yt hera p y
is
rec om me n de d; i n t he prese nce of dista nt met astases a n d p ositi ve para-a ortic l y m p h n o d es,
s yste mic c he m ot hera p y ±i n di vi d ualize d E B R T is rec o m me n de d [ 3 7].
Eit her
pel vic ra di ot hera p y
or ra di ot hera p y
c o ul d lea d t o
o varia n fail ure i n
pre me n o pa usal
w o me n. To pr otect e n d ocri ne f u ncti o n of t he o varies, y o u n g
w o me n
( u n der 4 5 years of a ge, s q ua m o us carci n o ma) ca n u n der g o o varia n tra ns p ositi o n s ur ger y
bef ore pel vic ra di ot hera p y [ 3 8- 4 0].
2. 2. 4 S ur ger y vs. r a di ot her a p y
B o t h ra dical cer vical s ur ger y a n d ra dical ra di ot hera p y are
mai n treat me nts f or
earl y-sta ge
cer vical
ca ncer;
w hile
ra dical
ra di ot hera p y/ra di oc he m ot hera p y
is
rec o m me n de d f or a d va nce d-sta ge cer vical ca ncer. T heref ore, t he c h oice of treat me nt
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 1
m o dalit y nee ds t o ta ke i nt o acc o u nt disease sta ge, fertilit y re q uire me nts, c o m or bi dities,
q ualit y of life, a n d t he pers o nal prefere nce of b ot h p h ysicia ns a n d patie nts. S ur ger y is
i n dicate d f or patie nts wit h earl y sta ge cer vical ca ncer, es peciall y f or t h ose wit h fertilit y
preser vati o n re q uire me nts. F or patie nts wit h sta ge I A, I B 1, I B 2, a n d sta ge II A 1 cer vical
ca ncer, t he N C C N g ui deli nes rec o m me n d e d s ur ger y f or t he f oll o wi n g reas o ns:
．Yo u n g w o me n ca n preser ve o varia n f u ncti o n.
．T he p ossi bilit y of preser vi n g va gi nal f u ncti o n after s ur ger y is hi g her c o m pare d t o
ra di ot hera p y.
．I ntra o perati ve l y m p h n o de dissecti o n ca n be perf or me d si m ulta ne o usl y d uri n g t he
s ur gical treat me nt, if p ost o perati ve ra di ot hera p y is nee de d. I n di vi d ualize d ra di ot hera p y
f or m ulati o n ca n be ac hie ve d.
F or sta ge I B 3
a n d II A 2
cer vical
ca ncer, t he
N C C N
g ui deli nes rec o m me n d
c o nc urre nt c he m ora di ot hera p y ( C C R T): ra dical
E B R T
+ c o nc urre nt
plati n u m- base d
c he m ot hera p y + va gi nal brac h yt hera p y. After s y n c hr o n o us ra di oc he m ot hera p y, patie nts
ma y e x perie nce va gi nal f u ncti o n l oss, o varia n f u ncti o n decli ne, a n d p o or q ualit y of life. A
pr o p orti o n of t hese patie nts are y o u n g
w o me n. C urre ntl y i n C hi na, t here are iss ues of
u ne ve n
distri b uti o n
of
ra di ot hera p y
res o urces
a n d i m bala nce i n t he
q ualit y
of
ra di ot hera p y. T heref ore, patie nts wit h I B 3 a n d II A 2 sta ge are als o i ncl u de d as t he tar get
p o p ulati o n of recei vi n g ra dic al treat me nt i n t his st u d y.
2. 3 Pr o g n osis
T he mai n pr o g n ostic fact ors affecti n g s q ua m o us cer vical ca ncer i ncl u de t u m or sta ge,
l y m p h
n o de
stat us, t u m or
size,
de pt h
of
cer vical i nterstitial i nfiltrati o n,
L V SI
(l y m p h o vasc ular i nterstitial i nfiltrati o n), a n d hist ol o gical t y p e a n d gra di n g of t he t u m or.
T u m or sta ge is t he
m ost i m p orta nt pr o g n ostic fact or, f oll o we d b y l y m p h n o de stat us.
After ra dical cer vical ca ncer s ur ger y + l y m p h n o de dissecti o n f or cli nical sta ge I B o r II A
patie nts, t he 5- year
O S
was 8 8- 9 6 % f or t h ose
wit h o ut l y m p h n o de
metastasis,
w hile it
was 6 4- 7 4 % f or t h ose wit h l y m p h n o de metastasis
[ 4 1, 4 2]. T he 2 0 1 8 L A C C trial f o u n d t hat
i n sta ge I A 1 wit h L V SI, I A 2 a n d I B 1 cer vical ca ncer patie nts, t he P F S a n d O S rates of
patie nts recei vi n g
mi ni mall y i n vasi ve ra dical cer vical ca ncer s ur ger y
were l o wer t ha n
t h ose of recei vi n g o pe n s ur ger y, wit h a P F S rate of 9 1. 2 % vs. 9 7. 1 % at 3 years, a n d a n
O S rate of 9 3. 8 % vs. 9 9. 0 % at 3 years f or
mi ni mall y i n vasi ve s ur ger y vers us o pe n
s ur ger y, res pecti vel y [ 1 2]. I n c o ntrast, a n ot her retr os pecti ve st u d y i n 2 0 1 8 f o u n d [ 11] t hat
t he relati ve s ur vi val of patie nts wit h cer vical ca ncer decrease d b y 0. 8 % per year i n t he 4
years si nce t he use of
mi ni mall y i n vasi ve s ur ger y be ga n i n 2 0 0 6. T heref ore, t he N C C N
g ui deli nes n o l o n ger rec o m me n d
mi ni mall y i n vasi ve ra dical cer vical ca ncer s ur ger y. To
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 2
s u m u p, t he 5- year o verall s ur vi val rate f or sta ge I cer vical ca ncer is a b o ut 9 0 % a n d f or
sta ge II cer vical ca ncer is a b o ut 6 0 %.
2. 4 L a p ar osc o pic s ur ger y
La par osc o pic ra dical cer vical ca ncer s ur ger y
was ori gi nall y re p orte d b y Ca nis
[ 4 3]
a n d
Nez hat [ 4 4] et
al. I n t he last t w o
deca des, la par osc o pic s ur ger y
has
bec o me
i ncreasi n gl y s o p histicate d. I n a d diti o n t o tra diti o nal la par osc o pic s ur ger y, r o b otic-assiste d
s ur ger y has bee n deri ve d.
M ost st u dies ha ve s h o w n t hat lapar o sc o pic s ur ger y has less
i ntra o perati ve blee di n g a n d s h orter h os pital sta y, a n d s o me st u dies ha ve re p orte d t hat t he
P F S rate of L R H was n ot i nferi or t o t hat of A R H
[ 5- 1 0]. T heref ore, la par osc o pic s ur ger y
has bec o me t he mai n treat me nt f or earl y-sta ge cer vical ca ncer i n ma n y c o u ntries, a n d t he
2 0 1 4 N C C N g ui d eli nes rec o m me n d e d a la p ar osc o pic a p pr oac h f or ra dical cer vical ca ncer.
I n
m ost of t he presti ge h os pitals i n C hi na, la par osc o pic ra dical cer vical ca ncer treat me nt
acc o u nts f or m ore t ha n 9 0 % of t he cases.
As pre vi o usl y
me nti o ne d, t he L A C C trial a n d t he retr os pecti ve st u d y p u blis he d i n
t he Ne w E n gla n d J o ur nal of
Me dici ne i n late 2 0 1 8 ca use d a h u ge i m pact i n t he
me dical
c o m m u nit y
w he n t he y c o ncl u de d t hat b ot h P F S a n d
O S rates f or patie nts u n der g oi n g
mi ni mall y i n vasi ve ra dical cer vical ca ncer treat me nt
were l o wer t ha n t h ose u n der g oi n g
a b d o mi nal ra dical cer vical ca ncer treat me nt. F oll o wi n g t he p u blicati o n of t hese articles,
t he versi on 3. 2 0 1 9
N C C N g ui deli nes ha ve rec o m me n de d o pe n s ur ger y as t he sta n dar d
pr oce d ure f or cer vical ca ncer, a n d la par osc o pic s ur ger y is n o l o n ger rec o m me n de d.
H o we ver, at o ur h os pital ( O bstetrics a n d G y n ec ol o g y H os pital of F u da n U ni versit y),
a b o ut 1, 5 0 0- 2, 0 0 0 cer vical ca ncer s ur geries
were perf or me d eac h year o ver t he past 8
years. Acc or di n g t o o ur data, f or la par osc o pic ra dical cer vical ca ncer s ur ger y, t he 5- year
O S rates are 1 0 0 % i n sta ge I A 2 a n d 9 6. 9 3 % i n sta ge I B 1 p atie nts, w hic h are si milar t o
o pe n s ur ger y i n t he L A C C trial. I n a d diti o n, data fr o m e n d o metrial ca ncer ha ve s h o w n
t hat la par osc o p y is s u peri or t o o pe n s ur ger y i n ter ms of b ot h rece nt s ur ger y-relate d
c o m plicati o ns a n d s ur vi val
be nefits, s o
N C C N
g ui deli nes rec o m me n d la par osc o pic
s ur ger y as t he sta n dar d pr oce d ure f or e n d o metrial ca ncer. U ntil n o w, t here is o nl y o ne
R C T (t he L A C C trial) t hat c o m pare d mi ni mall y i n vasi ve a n d o pe n ra dical cer vical ca ncer
treat me nts. I n vie w o f t he res ults of t he L A C C trial, s h o ul d
we c o m pletel y a ba n d o n
mi ni mall y i n vasi ve s ur ger y f or cer vical ca ncer, or are we l o o ki n g f or t he r o ot ca use a n d
i m pr o ve me nt met h o ds t o pr o m ote me dical de vel o p me nt? T heref ore, we pr o p ose t o desi g n
t his st u d y i n acc or da nce
wit h t he hi g h re q uire me nts of o ur a bilit y a n d i ntra o perati ve
t u m or-free pri nci ple,
wit h t he ai m of f urt her c o m pari n g L R H ( or r o b otic-assiste d) a n d
A R H i n patie nts
wit h earl y-sta ge cer vical ca ncer: I A 1
wit h
i ntra vasc ular i nfiltrati o n
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 3
( L V SI), sta ge I A 2; I B 1, I B 2, II A 1; sta ge I B 3, II A 2 i n ter ms of efficac y as well as q ualit y
of life.
2. 5 Q u alit y of life
Q ualit y of life st u dies all o w e val uate a n d c o m paris o n of s ur gical o utc o mes fr o m t he
patie nt's pers pecti ve a n d are t heref ore a n e xtre mel y i m p orta nt assess me nt e n d p oi nt. T he
q ualit y of life s ur ve y use d i n t his p hase III cli nical trial will i ncl u de t he use of t he E O R T C
Q ualit y of Life
Meas ure me nt Scale Q L Q C 3 0 ( V 3. 0), t he E O R T C Q L Q- C X 2 4 scale, a n d
t he P R O 1 4 7 ( V 1. 0), a patie nt-re p orte d cli nical o utc o me e val uati o n scale f or cer vical
ca ncer de vel o pe d i n- h o use b y t he researc h tea m.
R ef er e n c es:
[ 1]. Br a y, F.,
et
al.,
Gl o b al c a n c er st atistics
2 0 1 8:
G L O B O C A N
esti m at es
of i n ci d e n c e a n d
m ort alit y w orl d wi d e f or 3 6 c a n c ers i n 1 8 5 c o u ntri es. C A C a n c er J Cli n, 2 0 1 8. 6 8( 6): p. 3 9 4 - 4 2 4.
[ 2]. C ast ells a g u e,
X.,
et
al.,
W orl d wi d e
h u m a n
p a pill o m a vir us
eti ol o g y
of
c er vic al
a d e n o c ar ci n o m a a n d its c of a ct ors: i m pli c ati o ns f or scr e e ni n g a n d pr e v e nti o n. J N atl C a n c er I nst,
2 0 0 6. 9 8( 5): p. 3 0 3 - 1 5.
[ 3]. D a hlstr o m, L. A., et al., Pr os p e cti v e st u d y
of
h u m a n
p a pill o m a vir us a n d ris k
of c er vi c al
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[ 4]. Ol a w ai y e, A. B., et al., T h e n e w ( V ersi o n 9) A m eri c a n J oi nt C o m mitt e e o n C a n c er t u m or, n o d e,
m et ast asis st a gi n g f or c er vic al c a n c er. C A C a n c er J Cli n, 2 0 2 1.
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[ 6]. M a gri n a, J. F.,
et
al.,
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c o m p aris o n
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W. Z.
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M e d, 2 0 1 8. 3 7 9( 2 0): p. 1 8 9 5 - 1 9 0 4.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 4
[ 1 3]. S a k ur a gi, N., et al., I n ci d e n c e a n d distri b uti o n p att er n of p el vic a n d p ar a a ortic l y m p h n o d e
m et ast asis i n
p ati e nts
wit h
St a g es I B, II A,
a n d II B c er vic al c ar ci n o m a tr e at e d
wit h r a dic al
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[ 1 4]. H u a n g, H., et al.,
M et ast asis t o d e e p o bt ur at or a n d p ar a - a orti c l y m p h n o d es i n 6 4 9 p ati e nts
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[ 2 5]. Wri g ht, J. D., et al., F ertilit y - c o ns er vi n g s ur g er y f or y o u n g
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[ 2 6]. B er n ar di ni,
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A m J
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[ 2 7]. Di a z, J. P., et al., O n c ol o gic o ut c o m e of f ertilit y -s p ari n g r a di c al tr a c h el e ct o m y v ers us r a di c al
h yst er e ct o m y f or st a g e I B 1 c er vi c al c arci n o m a. G y n e c ol O n c ol, 2 0 0 8. 1 1 1( 2): p. 2 5 5 - 6 0.
[ 2 8]. R aj u, S. K., et al., F ertilit y -s p ari n g s ur g er y f or e arl y c er vic al c a n c er - a p pr o a c h t o l ess r a di c al
s ur g er y. I nt J G y n e c ol C a n c er, 2 0 1 2. 2 2( 2): p. 3 1 1 - 7.
[ 2 9]. P et ers,
W. R., et al., C o n c urr ent c h e m ot h er a p y a n d p el vic r a d i ati o n t h er a p y c o m p ar e d wit h
p el vi c r a di ati o n t h er a p y al o n e as a dj u v a nt t h er a p y aft er r a di c al s ur g er y i n hi g h -ris k e arl y -st a g e
c a n c er of t h e c er vix. J Cli n O n c ol, 2 0 0 0. 1 8( 8): p. 1 6 0 6 - 1 3.
[ 3 0]. S e dlis, A., et al., A r a n d o mi z e d tri al of p el vi c r a di ati o n t h er a p y v ers us n o f urt h er t h er a p y i n
s el e ct e d p ati e nts
wit h st a g e I B c arci n o m a of t h e c er vix aft er r a dic al h yst er e ct o m y a n d p el vic
l y m p h a d e n e ct o m y:
A
G y n e c ol o gi c
O n c ol o g y
Gr o u p
St u d y.
G yn e c ol
O n c ol,
1 9 9 9.
7 3( 2):
p.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 5
1 7 7 - 8 3.
[ 3 1]. R ot m a n,
M., et al., A p h as e III r a n d o mi z e d tri al of p ost o p er ati v e p el vic irr a di ati o n i n St a g e I B
c er vic al c arci n o m a
wit h p o or pr o g n ostic f e at ur es: f oll o w - u p of a g y n e c ol o gi c o n c ol o g y gr o u p
st u d y. I nt J R a di at O n c ol Bi ol P h ys, 2 0 0 6. 6 5( 1): p. 1 6 9 - 7 6.
[ 3 2]. C h er n ofs k y,
M. R., et al., I nfl u e n c e of q u a ntit y of l y m p h v asc ul ar s p a c e i n v asi o n o n ti m e t o
r e c urr e n c e i n
w o m e n
wit h e arl y -st a g e s q u a m o us c a n c er of t h e c er vix.
G y n e c ol
O n c ol, 2 0 0 6.
1 0 0( 2): p. 2 8 8 - 9 3.
[3 3]. K o hl er, C ., et al., P eri o p er ati v e
m or bi dit y a n d r at e of u pst a gi n g aft er l a p ar osc o pi c st a gi n g
f or p ati e nts wit h l o c all y a d v a n c e d c er vi c al c a n c er: r es ults of a pr os p e cti v e r a n d o mi z e d tri al. A m J
O bst et G y n e c ol, 2 0 1 5. 2 1 3( 4): p. 5 0 3. e 1 - 7.
[ 3 4]. G off, B. A., et al., I m p a ct of s ur gi c al st a gi n g i n w o m e n wit h l o c all y a d v a n c e d c er vi c al c a n c er.
G y n e c ol O n c ol, 1 9 9 9. 7 4( 3): p. 4 3 6 - 4 2.
[ 3 5]. R os e, P. G.,
C o m bi n ati o n t h er a p y:
N e w tr e at m e nt p ar a di g m f or l o c all y a d v a n c e d c er vic al
c a n c er? N at R e v C li n O n c ol, 2 0 1 1. 8( 7): p. 3 8 8 - 9 0.
[ 3 6]. W hit n e y,
C. W.,
et
al.,
R a n d o mi z e d
c o m p aris o n
of fl u or o ur a cil
pl us
cis pl ati n
v ers us
h y dr ox y ur e a as a n a dj u n ct t o r a di ati o n t h er a p y i n st a g e II B -I V A c ar ci n o m a of t h e c er vix
wit h
n e g ati v e p ar a - a orti c l y m p h n o d es: a
G y n e c ol o gic
O n c ol o g y
Gr o u p a n d S o ut h w est
O n c ol o g y
Gr o u p st u d y. J Cli n O n c ol, 1 9 9 9. 1 7( 5): p. 1 3 3 9 - 4 8.
[ 3 7]. L ut z, S. T., et al., A r e vi e w of h y p ofr a cti o n at e d p alli ati v e r a di ot h er a p y. C a n c er, 2 0 0 7. 1 0 9( 8): p.
1 4 6 2 - 7 0.
[ 3 8]. W o, J. Y. a n d A. N. Vis w a n at h a n, I m p a ct of r a di ot h er a p y o n f ertilit y, pr e g n a n c y, a n d n e o n at al
o ut c o m es i n f e m al e c a n c er p ati e nts. I nt J R a di at O n c ol Bi ol P h ys, 2 0 0 9. 7 3( 5): p. 1 3 0 4 - 1 2.
[ 3 9]. P a his a, J., et al., L a p ar osc o pi c o v ari a n tr a ns p ositi o n i n p ati e nts wit h e arl y c er vic al c a n c er. I nt
J G y n e c ol C a n c er, 2 0 0 8. 1 8( 3): p. 5 8 4 - 9.
[ 4 0]. M ori c e, P., et al.,
O v ari a n tr a ns p ositi o n f or p ati e nts
wit h c er vic al c arci n o m a tr e at e d b y
r a di os ur gic al c o m bi n ati o n. F ertil St eril, 2 0 0 0. 7 4( 4): p. 7 4 3 - 8.
[ 4 1]. D el ga d o,
G.,
et
al.,
Pr os p e cti v e s ur gi c al - p at h ol o gic al st u d y
of
dis e as e -fr e e i nt er v al i n
p ati e nts
wit h st a g e I B s q u a m o us c ell c ar ci n o m a of t h e c er vix: a G y n e c ol o gic
O n c ol o g y Gr o u p
st u d y. G y n e c ol O n c ol, 1 9 9 0. 3 8( 3): p. 3 5 2 - 7.
[ 4 2]. A v er ett e,
H. E.,
et
al.,
R a di c al
h yst er e ct o m y f or i n v asi v e
c er vi c al
c a n c er.
A
2 5 - y e ar
pr os p e cti v e ex p eri e n c e wit h t h e
Mi a mi t e c h ni q u e. C a n c er, 1 9 9 3. 7 1( 4 S u p pl): p. 1 4 2 2 - 3 7.
[ 4 3]. C a nis,
M., et al., [ D o es e n dos c o pic s ur g er y h a v e a r ol e i n r a di c al s ur g er y of c a n c er of t h e
c er vix ut eri?]. J G y n e c ol O bst et Bi ol R e pr o d ( P aris), 1 9 9 0. 1 9( 7): p. 9 2 1.
[ 4 4]. N e z h at,
C. R., et al., L a p ar osc o pi c r a di c al h yst er e ct o m y
wit h p ar a a ortic a n d p el vi c n o d e
diss e cti o n. A m J O bst et G y n e c ol, 1 9 9 2. 1 6 6( 3): p. 8 6 4 - 5.
2. 2 Rese arc h O bjecti ves
2. 2. 1
M ai n st u d y o bjecti ves
To c o m pare t he 5- year o verall s ur vi val ( O S) of patie nts u n der g oi n g La par osc o pic
Ra dical
H ysterect o m y ( L R H)
v ers us
A b d o mi nal
Ra dical
H ysterect o m y ( A R H) f or
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 6
cer vical ca ncer.
2. 2. 2 Sec o n d ar y rese arc h o bjecti ves
To c o m pare t he 5- year pr o gressi o n free s ur vi val ( P F S) of t he t w o gr o u ps of patie nts
wit h differe nt s ur gical pr oce d ures.
To c o m pare t he rela pse rate a n d rela pse patter n bet wee n t he t w o gr o u ps of patie nts
wit h differe nt s ur gical pr oce d ures.
To c o m pare t he f u ncti o nal stat us of eac h or ga n i n t he t w o gr o u ps.
To c o m pare t he effects of t he t w o differe nt s ur gical pr oce d ures o n q ualit y of life of
t he patie nts i n t he t w o gr o ups.
To c o m pare t he differe nce i n c ost effecti ve ness bet wee n t he t w o gr o u ps of patie nts.
To c o m pare t he a m o u nt of s ur gical blee di n g, t he i nci de nce of s ur ger y-relate d diseases,
a n d i ntra o perati ve a n d p ost o perati ve c o m plicati o ns bet wee n t he t w o gr o u ps.
2. 3 Rese arc h Desi g n
S T A G E 1
T he p u blicati o n of t he L A C C trial has ca use d a h u ge i m pact i n t he g y n ec ol o g y fiel d, a n d
t he versi o n 3. 2 0 1 9
N C C N g ui deli nes n o l o n ger rec o m me n de d la par osc o pic s ur ger y f or
patie nts wit h cer vica l ca ncer. H o we ver, t he i n vesti gat ors re vie we d data fr o m o ur h os pital
f or t he last 8 years of la par osc o pic ra dical cer vical ca ncer s ur ger y,
w hic h s h o we d
differe nt res ults fr o m t he
L A C C trial.
D uri n g t he
Gl o bal
Cli nical Sc h olar
Researc h
Trai ni n g ( G C S R T) pr o gra m h oste d b y
Har var d
Me dical Sc h o ol, t he lea der of t he
mai n
ce nter disc usse d
wit h l ocal cli nical researc h e x perts a b o ut t he et hical feasi bilit y of
re desi g ni n g t he
R C T st u d y t o vali date t he t o pic, a n d i n t he first draft of t his pr oject
desi g n was c o m plete d as part of t he Ca pst o ne Pr oject c o urse pla n, a n d t he st u d y desi g n
was rec o m me n de d i n t he e n d- of-se mester prese ntati o n.
S T A G E 2
Acc or di n g t o t he trial desi g n, after t he st u d y passe d b y et hics, t he researc h tea m starte d t o
tr y t he pr ot oc ol acc or di n g t o t he desi g n pr ocess a n d s uccessf ull y recr uite d 8 4 s u bjects. At
t he be gi n ni n g of t he st u d y desi g n, t he st u d y mi xe d cer vical ca ncer sta ges I A 1 wit h L V SI,
I A 2, I B 1, I B 2, II A 1, I B 3, a n d II A 2 in o ne trial.
H o we ver, as t he trial pr o gresse d,
we
f o u n d t hat t he s pa n of t he trial sta ges was t o o lar ge f or a s pecific assess me nt of eac h sta ge
a n d f or g ui di n g t he s pecific pr oce d ure f or eac h sta ge.
Als o,
w he n
we s u b mitte d t he
pr ot oc ol, we recei ve d t he sa me s u g gesti o n fr o m t he re vie w res p o nses.
S T A G E 3
T his pr oject is di vi de d i nt o t hree parallel st u dies base d o n t he sta gi n g, L A U N C H 1 ( L A 1
wit h L V SI, I A 2), L A U N C H 2 (I B 1, I B 2, II A 1), a n d L A U N C H 3 (I B 3, II A 2). Pre vi o usl y
we
c o n d uct e d
a
si ngle-ce nter
st u d y
(st u d y
pr ot oc ol
re gistrati o n
n u m ber:
C hi C T R 1 9 0 0 0 2 5 9 4 6) w hic h i ncl u de d all a b o ve
me nti o ne d sta ges. T here are 8 4 patie nts
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 7
e nr olle d i n t hat st u d y
w hic h
will n ot be i ncl u de d i n t he c urre nt pr oject, si nce t h ose
patie nts d o n ot meet t he ra n d o mizati o n strate g y of t he c urre nt pr oject.
S T A G E 4
T his st u d y i nte n ds t o sa m ple a n d c ollect i ntra o perati ve t u m or tiss ues fr o m t u m or patie nts,
a n d t o c o n d uct basic scie nce researc h o n t he e val uati o n of ge netic testi n g f or s pecific
t u m or sta ges,
w hic h ca n be use d t o g ui de later treat me nts s uc h as tar gete d or i m m u ne
t hera pies.
At t he sa me ti me,
we
will c o n d uct rele va nt
hist ol o gical st u dies
o n t he
m olec ular tiss ues relate d t o t u m ors i n or der t o fi n d t he pat h o ge nesis patter n t hat
ma y
g ui de treat me nt.
III. Rese arc h met h o ds
1.
St u d y set u p
T his pr oject is a
m ultice nter st u d y le d b y t he
O bstetrics a n d
G y n ec ol o g y
H os pital of
F u da n
U ni versit y,
w hic h is o ne of t he first nati o nal cli nical class I ke y s pecialties i n
C hi na a n d a ke y disci pli ne of t he
Mi nistr y of E d ucati o n. T he O bstetrics a n d G y n ec ol o g y
H os pital of F u da n U ni versit y u n derta kes t h e tas k of dia g n osis a n d treat me nt of mali g na nt
t u m ors of t he fe male re pr o d ucti ve s yste m nati o n wi de, wit h a lea di n g a n n ual v ol u me of
cer vical ca ncer s ur ger y a n d treat me nt i n C hi na. T he cli nical ce nters of t his st u d y i ncl u des
O bstetrics a n d
G y n ec ol o g y
H os pital of
F u da n
U ni versit y ( mai n ce nter),
Z h o n gs ha n
H os pitalaffiliate d t o F u da n U ni versit y, Re nji H os pital of S ha n g hai Jia o To n g U ni versit y,
Xi n h ua
H os pital of S ha n g hai Jia o To n g
U ni versit y, Taiz h o u
H os pital Affiliate d Ca n cer
H os pital of t he
U ni versit y of C hi nese Aca de m y of Scie nces a n d t he First
H os pital of
We nz h o u
Me dical U ni versit y (s u b-ce nters). T he C T U of t he Cli nical Trial Ce nter of t he
C hil dre n's H os pital of F u da n
U ni versit y is res p o nsi ble f or statistical a nal ys es. All t hese
ha ve pr o vi de d a de q uate tec h nical s u p p ort a n d g uara ntee f or t he st u d y.
2.
Q u alific ati o n criteri a
2. 1 St u d y s u bjects a n d st u d y ti me
A t otal of 1 1 0 4 patie nts dia g n ose d wit h cer vical ca ncer (sta ge I B 3 a n d II A 2) a n d meeti n g
t he e nr oll me nt criteria
will be recr uite d fr o m t he af ore me nti o ne d
mai n ce nter a n d
s u b-ce nters. T his pr oject is e x pecte d t o be c o m plete d i n 3 years ( A pril 2 0 2 1 t o A pril 2 0 2 4)
fr o m t he date of f or mal et hical a p pr o val a n d c o m pleti o n of e nr oll me nt, a n d t he patie nts
will be f oll o we d- u p f or 5 years ( A pril 2 0 2 1 t o A pril 2 0 2 6).
2. 2 P atie nt i ncl usi o n a n d e xcl usi o n criteri a
P atie nt i ncl usi o n criteri a:
a) Cli nical dia g n osis of s q ua m o us carci n o ma of t he c er vi x, a de n ocarci n o ma, s q ua m o us
a de n ocarci n o ma (sta ge I B 3 a n d II A 2).
b) A ge ≥2 1 years a n d ≤7 0 years.
c) S ur ger y t y p e C (refer t o Q- M s ur gical sta gi n g)
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 8
d) N or mal ra n ge of li ver a n d ki d ne y f u ncti o n, a n d bl o o d c o u nt:
He m o gl o bi n > 6 0 g/ L;
Platelets > 7 0 * 1 0 9/ L;
Le u k oc yt es > 3 * 1 0 9/ L;
Creati ni ne < 5 0 m g/ d L;
Tra nsa mi nase a b n or mal i n dicat ors ≤3;
Ma xi m u m val ue of tra nsa mi nases n ot e x cee di n g 3 ti mes t he c orres p o n di n g n or mal
val ue.
e) N o hist or y of ot her mali g na ncies.
f) N o n- pre g na nc y.
g) P h ysical stre n gt h classificati o n: Kar n ofs k y sc ore ≥6 0.
h)
Vol u ntaril y j oi n t he st u d y, si g n t he i nf or me d c o nse nt f or m, are c o m plia nt a n d
c oo perati ve wit h t he f oll o w- u p.
i)
N o ps yc hiatric dis or ders a n d ot her seri o us i m m u ne s yste m dis or ders (e. g. l u p us
er yt he mat os us, m yast he nia gra vis, HI V i nfecti o n, etc.)
( N ote:
Ma xi m u m dia meter
meas ure me nt of cer vical lesi o n is base d o n P E T- C T, C T, or
M RI)
P atie nt e xcl usi o n criteri a:
a) C o ntrai n dicate d f or vari o us s ur geries a n d ca n n ot u n der g o s ur ger y.
b) Ha ve recei ve d pel vic/a b d o mi nal ra di ot hera p y irra diati o n or ne oa dj u va nt c he m ot hera p y
f or cer vical ca ncer.
c)
Wit h rec urre nt cer vical ca ncer
d)
Wit h C T,
M RI or P E T- C T s u g gesti n g s us pici o us metastasis of pel vic l y m p h n o des wit h
ma xi m u m dia meter > 2c m after f urt her i m pr o ve me nt of pre o perati ve e x a mi nati o n.
2. 3 Re q uire me nts of i n vesti g at ors a n d s ur ge o ns
S ur ge o ns i n v ol ve d i n t his pr oject were selecte d fr o m eac h partici pati n g h os pital a n d are
s kille d i n cer vical ca ncer s ur ger y. T he lea d s ur ge o n
m ust ha ve e x perie nce i n at least 5 0
s ur geries eac h f or b ot h L R H a n d A R H a n d be a ble to p r o vi de t he me dical hist or y of t hese
cases. T he pri nci pal i n vesti gat or a n d me m bers of t he s ur gical q ualit y c o ntr ol tea m will be
o n site t o o bser ve eac h s ur ge o n's pr oce d ure a n d re vie w t he u ne dite d vi de o of t he
pr oce d ure ( 1
A R H
a n d
1
L R H)
pr o vi de d
b y
eac h s ur ge o n f or s ur gical
q ualit y
meas ure me nt a n d d oc u me ntati o n t o e ns ure t he e xte nt of s ur gical resecti o n a n d t u m or-free
ma na ge me nt of eac h s ur ge o n.
3.
I nter ve nti o ns
3. 1 O verall i nter ve nti o n pla ns
Mi ni mall y i n vasi ve ra di cal cer vical ca ncer treat me nt i ncl u des la par osc o pic ra dical
cer vical ca ncer treat me nt ( L R H) a n d r o b otic-assiste d la par osc o pic ra dical cer vical ca ncer
treat me nt, eit her of
w hic h ca n be c h ose n b y t he o perat or. T his pr oject f oc uses o n t he
s ur vi val be nefit of patie nts after
mi ni mall y i n vasi ve a n d o pe n ra dical cer vical ca ncer
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
1 9
treat me nt, s o ra dical cer vical ca ncer treat me nt wit h preser vati o n of re pr o d ucti ve f u ncti o n
will n ot be i ncl u de d. F or b ot h o pe n a n d
mi ni mall y i n vasi ve ra dical cer vical ca ncer
s ur ger y, t he o perati o n be gi ns
wit h a t h or o u g h a b d o mi nal e x pl orati o n, i ncl u di n g caref ul
e x pl orati o n of t he dia p hra g m, a n d a n y
metastatic lesi o ns a n d
metastatic sites s h o ul d be
descri be d i n detail i n t he o perati ve rec or d,
wit h bi o ps y f or c o nfir mati ve dia g n osis. If
i ntra-a b d o mi nal lesi o ns are f ou n d, ra dical cer vical ca ncer s ur ger y s h o ul d n ot be use d a n d
s h o ul d c ha n ge t o palliati ve treat me nt.
Pel vic l y m p h n o de dissecti o n s h o ul d be perf or me d d uri n g ra dical cer vical ca ncer
s ur ger y. Se nti nel L y m p h N o de
Ma p pi n g ( S L N) is n ot i ncl u de d i n t his pr oject, si nce t here
is n o s ufficie nt e vi de nce f or its se nsiti vit y a n d s pecificit y, a n d als o t he diffic ult y i n
ac hie vi n g l y m p h n o de h y p ersta gi n g c o nsi deri n g t he lar ge sa m ple size of t his pr oject. If
t he t u m or is ≥2 c m, or if t he c o m m o n iliac l y m p h n o de is p ositi ve f or i ntra o perati ve
freezi n g ( o pti o nal), or if t he pre o perati ve e val uati o n of t he paraa ortic l y m p h n o des is
p ositi ve, paraa ortic l y m p h n o de dissecti o n is preferre d a n d f oll o we d b y paraa ortic l y m p h
n o de bi o ps y.
W he n clear t he para-a ortic l y m p h n o des, t he u p per b or der reac hes t he le vel
of t he i nferi or mese nteric arter y is e n o u g h. T he c o m m o n iliac l y m p h n o des s h o ul d be se nt
se paratel y f or e x a mi nati o n, a n d t he resecti o n s h o ul d i ncl ude b ot h si des of t he c o m m o n
iliac vessels,
wit h t he u p per b or der reac hi n g t he
mi d p oi nt of t he bif urcati o n of t he
a b d o mi nal a orta a n d t he c o m m o n iliac vessels a n d t he l o wer b or der reac hi n g t he le vel of
t he bif urcati o n of t he c o m m o n iliac vessels.
If defi nite pel vic l y m p h n o de
metastasis is f o u n d i ntra o perati vel y, c o nti n uati o n of
pel vic l y m p h n o de dissecti o n, a n d e ve n ra dical cer vical ca ncer s ur ger y is n ot re q uire d,
b ut a b d o mi nal para-a ortic l y m p h n o de sa m pli n g is rec o m me n de d t o assess t he de gree of
disease pr o gressi o n a n d t o de vel o p s u bse q ue nt ra di ot hera p y re gi me ns. If s ur ger y is
c o nti n ue d, ra dical cer vical ca ncer s ur ger y + pel vic l y m p h n o de dissecti o n + a b d o mi nal
para-a ortic l y m p h n o de dissecti o n/ bi o ps y is rec o m me n de d.
F or
patie nts
ra n d o ml y
assi g ne d
t o
L R H,
t he
s ur ge o n
s h o ul d
perf or m
la par osc o pic/r o b otic-assiste d ra dical la par osc o pic cer vical ca ncer s ur ger y or perf or m
la par osc o pic-assiste d ra dical tra ns va gi nal cer vical ca ncer s ur ger y.
I n perf or mi n g ra dical cer vical ca ncer s ur ger y, t he s ur ge o n s h o ul d pr o vi de detaile d
descri pti o ns of t he s pecial s ur gical i nstr u me nts use d i n t he la par osc o pic/r o b otic-assiste d
la par osc o pic gr o u p. I n a d diti o n, t he s ur ge o n s h o ul d d oc u me nt t he f oll o wi n g i nf or mati o n
i n t he o perati ve rec or d:
．Ti me of s ur ger y: ti me fr o m t he start of ra dical cer vical ca ncer s ur ger y t o t he
cl os ure of all a b d o mi nal p u nct ure sites or a b d o mi nal i ncisi o ns.
．A m o u nt of i ntra o perati ve bl o o d l oss.
．I ntra o perati ve c o m plicati o ns.
．If patie nts are ra n d o mize d t o t he la par osc o pic s ur ger y gr o u p a n d are c o n verte d
t o o pe n s ur ger y i ntra o perati vel y, t he reas o ns s h o ul d be rec or de d.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 0
．I n case of r o b otic-assiste d la par osc o pic ra dical cer vical ca ncer s ur ger y, t he ti me
re q uire d t o asse m ble a n d d oc k t he r o b ot s h o ul d be rec or de d i n t he o perati ve rec or d,
w hic h s h o ul d be de d ucte d fr o m t he t otal o perati ve ti me.
．
If i ntra o perati ve
parietal
a ortic l y m p h
n o de
dissecti o n is
perf or me d
si m ulta ne o usl y, t he ti me re q uire d f or t his
o perati o n s h o ul d be rec or de d i n t he
o perati ve rec or d.
T he s ur gical a p pr oac h f or sta ge I A 1
wit h L V SI a n d sta ge I A 2 is t y p e B ( m o difie d
ra dical h ysterect o m y wit h bilateral pel vic l y m p h n o de dissecti o n, i.e., resecti o n of 1- 2 c m
of t he para metri u m a n d 1- 2 c m of t he va gi na) wit h para-a ortic l y m p h n o de dissecti o n if
necessar y (s ur gical sta gi n g acc or di n g t o
FI G O 2 0 1 8, s ur gical sta gi n g acc or di n g t o
Q uerle u- M orr o w sta gi n g).
F or sta ge I B 1, I B 2, a n d II A 1, t he s ur gical a p pr oac h is t y p e C 1 (ra dical cer vical
s ur ger y
wit h
preser vati o n
of
a ut o n o mic
ner ves
+
pel vic l y m p h
n o de
dissecti o n,
rec o m me n de d f or t u m or dia meter < 2 c m) or t y p e
C 2 (ra dical cer vical s ur ger y
wit h
bilateral pel vic l y m p h n o de dissecti o n, resecti o n of 3- 4 c m of t he para metri u m a n d t he
u p per 1/ 4 t o 1/ 3 of t he va gi na)
wit h a b d o mi nal para-a ortic l y m p h n o de dissecti o n if
necessar y
(s ur gical
sta gi n g
acc or di n g
t o
FI G O
2 0 1 8,
sta gi n g
acc or di n g
t o
Q uerle u- M orr o w sta gi n g). T he de pt h of para metrial tiss ue re m o ve d s h o ul d be bel o w t he
dee p uteri ne vei n, a n d if pre o perati ve i n v ol ve me nt of t he va gi nal wall is c o nsi dere d, 1- 2
c m of para metrial tiss ue s h o ul d be re m o ve d.
Sta ge I B 3, II A 2 T he s ur gical a p pr oac h is t y p e C 2 (ra dical cer vical ca ncer + bilateral
pel vic l y m p h
n o de
dissecti o n
+
para-a ortic l y m p h
n o de
dissecti o n,
3- 4
c m
of
para metri u m a n d u p per 1/ 4 t o 1/ 3 of t he va gi na) (s ur gical sta gi n g acc or di n g t o FI G O
2 0 1 8, s ur gical sta gi n g acc or di n g t o Q uerle u- M orr o w sta gi n g). Para metrial tiss ue s h o ul d
be re m o ve d t o a de pt h bel o w t he dee p uteri ne vei n, a n d 1- 2 c m of para metrial tiss ue
s h o ul d be rem o ve d if pre o perati ve i n v ol ve me nt of t he va gi nal wall is c o nsi dere d.
Fi g ure 1 A
Fi g ure 1 B
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 1
Fi g ure 1 A. Ty p e B: S ur gical resecti o n ra n ge of m o difie d ra dical h ysterect o m y
Fi g ure 1 B. Ty p e C 2: S ur gical resecti o n ra n ge ra dical cer vical ca ncer
T he t u m or-free pri nci ple d uri n g s ur ger y i ncl u des:
1) Se veri n g t he va gi na bef ore va gi nal cl os ure b y: cl os ure of t he va gi na wit h a n o bt urat or;
li gat ure ri n g li gati o n of t he va gi na; tra ns va gi nal s ut ure of t he va gi na.
2) After la par osc o pic li gati o n of t he va gi na, t he va gi na is irri gate d wit h sterile water, a n d
t he n t he va gi na is se vere d a n d s ut ure d; after o pe n s ur ger y, t he va gi na is cl ose d wit h re nal
cla m ps a n d t he a nteri or va gi nal wall is i ncise d, ga uze is i nserte d, t he n t he p osteri or wall
is se vere d a n d t he va gi nal st u m p is sterilize d.
3) E nc o ura ge s har p a n d ge ntle e x cisi o n, a n d tr y t o a v oi d vi g or o us teari n g a n d pl uc ki n g
m o ve me nts.
4)
W h ole l y m p h n o des are re m o ve d
wit h o ut t o uc hi n g ot her parts a n d place d i n a
s peci me n ba g f or fi nal re m o val; e xte nsi ve h ysterect o m y is perf or me d i n
w h ole a n d
e x cessi ve strai ni n g is a v oi de d i ntra o perati vel y.
5) Ri nse t he i nstr u me nts t hat ha ve c o ntacte d t he t u m or i n t he va gi na a n d se parate t he m
fr o m ot her i nstr u me nts; if s us pici o us
metastatic tiss ue is e nc o u ntere d i n t he pel vic a n d
a b d o mi nal ca vit y, re m o ve it directl y i nt o t he s peci me n ba g wit h o ut c o ntacti n g ot her parts
after e x cisi o n.
6) As pirate t he pel vic a n d a b d o mi nal ca vit y after f ull p ost o perati ve ri nsi n g
wit h sterile
water, a n d a v oi d bac kfl o w of pel vic ri nsi n g fl ui d i nt o t h e u p per a b d o me n w he n t he hea d
is l o w a n d t he feet are hi g h.
7) D o n ot lift t he uter us. Use ot her met h o ds s uc h as sil k t hrea d t o p ull t he uteri ne b o d y.
3. 2
St a n d ar d tre at me nt pl a n:
O pe n ra dical h ysterect o m y f or cer vical ca ncer + pel vic l y m p h n o de dissecti o n/ para-a ortic
l y m p h n o de dissecti o n
a)
T he pre o perati ve pr o p h yl actic a nti bi otics are gi ve n at least 1 5 mi n utes bef ore i ncisi o n
of t he s ki n.
b)
T he se q ue ntial c o m pressi o n de vice (a ntit hr o m b otic press ure p u m p) is i ns talle d.
c)
T he patie nt is place d i n t he s u pi ne p ositi o n or bla d der lit h ot o m y p ositi o n.
d)
C o nsi deri n g t he wi de ra n ge of s ur gical i nstr u me nts use d i n t his t y p e of s ur ger y, t he
use of la par osc o pic i nstr u me nts de pe n ds o n t he o perat or's pers o nal c h oice.
e)
T he i ncisi o n is c h ose n as a me dia n a b d o mi nal i ncisi o n or a l o w tra ns verse i ncisi o n.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 2
f)
After
e nteri n g t he
a b d o me n,
a t h or o u g h
a b d o mi nal
e x pl orati o n is
perf or me d,
i ncl u di n g caref ul e x pl orati o n of t he dia p hra g m. A n y metastatic lesi o ns a n d metastatic
sites s h o ul d be descri be d i n detail i n t he s ur gical rec or d, a n d bi o ps y is perf or me d t o
c o nfir m t he dia g n osis.
g)
T he lateral pel vic perit o ne u m is o pe ne d a n d a n y e nlar ge d, s us pici o us l y m p h n o des
s h o ul d be re m o ve d (if feasi ble) f oll o we d b y i ntra o perati ve freezi n g. If t hese l y m p h
n o des are p ositi ve, a b d o mi n al para-a ortic l y m p h n o de bi o ps y s h o ul d be perf or me d,
b ut ra dical cer vical ca ncer s ur ger y ma y be f or g o ne a n d t he treat me nt re gi me n f or t his
patie nt will be s witc he d t o ra dical ra di ot hera p y; or ra dical cer vical ca ncer s ur ger y +
pel vic l y m p h n o de dissecti o n + a b d o mi nal para-a ortic l y m p h n o de dissecti o n/ bi o ps y
ma y c o nti n ue.
h)
T he ra dical cer vical ca ncer s ur ger y wit h or wit h o ut bilateral sal pi n g o- o o p h orect o m y
will be perf or me d if t here are n o s usce pte d pel vic l y m p h n o des.
i)
T he
Re m o val of o varies: t he o varies
ma y be preser ve d or re m o ve d, or o varia n
tra ns p ositi o n ma y be perf or me d, de pe n di n g o n t he s u bject's c o n diti o n.
j)
T he sc o pe of pel vic l y m p h n o de dissecti o n: l y m p h n o des a djace nt t o t he c o m m o n
iliac arter y, e xter nal iliac arter y, i nter nal iliac arter y a n d l y m p h n o des i n t he cl ose d
f ossa s h o ul d be re m o ve d.
k)
T he a b d o mi nal para-a ortic l y m p h n o de dissecti o n s h o ul d reac h t he le vel of t he
i nferi or mese nteric arter y.
l)
T u m or-free pri nci ple: use o pe n s ur gical ki d ne y pe dicle f orce ps t o cla m p t he va gi na
cl ose, t he n i ncisi o n of t he a nteri or va gi nal
wall, i nserti o n of ga uze, f oll o we d b y
se vera nce of t he p osteri or wall a n d disi nfecti o n of t he va gi nal st u m p.
m) T he a b d o mi nal drai na ge t u be is n o n-c o m p uls or y a n d ca n be c h ose n b y eac h ce nter.
n)
T he cl os ure of t he a b d o me n la yers: cl os ure of t he fascia a n d cl os ure of t he s ki n.
o) I n d welli n g uri ne cat heter.
3. 3
I nter ve nti o n tre at me nt:
La par osc o pic or r o b o t-assiste d la par osc o pic ra dical h ysterect o m y f or cer vical ca ncer +
pel vic l y m p h n o de dissecti o n/ para-a ortic l y m p h n o de dissecti o n.
1)
T he pre o perati ve pr o p h yl actic a nti bi otics are gi ve n at least 1 5 mi n utes bef ore i ncisi o n
of t he s ki n.
2)
T he se q ue ntial c o m pressi o n de vice (a ntit hr o m b otic press ure p u m p) is i nstalle d.
3)
T he patie nt is place d i n bla d der lit h ot o m y p ositi o n
wit h t he u p per ar ms flat o n t he
si des of t he b o d y or o n t he c hest.
4)
T he c h oice of la par osc o pic i nstr u me nts de pe n ds o n t he s ur ge o n's pers o nal prefere nce,
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 3
c o nsi deri n g t he wi de ra n ge of s ur gical i nstr u me nts use d f or t his t y p e of pr oce d ure.
5)
T he a p pr oac h t o t he a b d o me n a n d t he n u m ber of p u nct ure p oi nts f or la par osc o pic
s ur ger y de pe n d o n t he o perat or's pers o nal c h oice.
6)
After e nteri n g t he a b d o me n, a t h or o u g h a b d o mi nal e x pl orati o n, i ncl u di n g caref ul
e x pl orati o n of t he dia p hra g m, s h o ul d be perf or me d first. A n y
metastatic lesi o ns a n d
metastatic sites s h o ul d be descri be d i n detail i n t he o perati ve rec or d, a n d a bi o ps y
sh o ul d b e perf or me d t o clarif y t he dia g n osis.
7)
T he r o u n d li ga me nt is se parate d i n or der t o o pe n t he retr o perit o ne u m. T he lateral
pel vic perit o ne u m is o pe ne d a n d a n y e nlar ge d, s usce pte d l y m p h n o des s h o ul d be
resecte d (if feasi ble) f oll o we d b y i ntra o perati ve cr y o pe x y. If t hese l y m p h n o des are
p ositi ve, a b d o mi nal para-a ortic l y m p h n o de bi o ps y s h o ul d be perf or me d, b ut ra dical
cer vical ca ncer s ur ger y
ma y be f or g o ne a n d t he treat me nt pla n
will be c ha n ge d t o
ra dical ra di othera p y i n t his s u bject; or ra dical cer vical ca ncer s ur ger y + pel vic l y m p h
n o de resecti o n
+ a b d o mi nal
para-a ortic l y m p h
n o de
dissecti o n/ bi o ps y
ma y
be
c o nti n ue d.
8)
T he ra dical cer vical ca ncer s ur ger y wit h or wit h o ut bilateral sal pi n g o- o o p h orect o m y
will be perf or me d if t here are n o s usce pte d pel vic l y m p h n o des.
9)
T he re m o val of o varies: t he o varies
ma y be preser ve d or re m o ve d or o varia n
tra ns p ositi o n ma y be perf or me d de pe n di n g o n t he patie nt's s pecific sit uati o n.
1 0 ) The sc o pe of pel vic l y m p h n o de resecti o n: t he l y m p h n o des a djace nt t o t he c o m m o n
iliac arter y, e xter nal iliac arter y, i nter nal iliac arter y a n d t he l y m p h n o des i n t he cl ose d
f ossa s h o ul d be re m o ve d.
1 1) T he uter us is n ot lifte d, a n d met h o ds s uc h as sil k tracti o n of t he uteri ne b o d y are use d.
1 2) T he uteri ne arter y is i de ntifie d a n d diss ociate dat t he p oi nt
w here t he i nter nal iliac
arter y di vi des fr o m t he uteri ne arter y.
1 3) T he para metrial tiss ue a n d t he uter osacral li ga me n t are e x cise d t o e ns ure a de q uate
s ur gical
mar gi ns. Pa yi n g atte nti o n t o t he t u m or- free pri nci ple, t he va gi na is cl ose d
bef ore se veri n g it,
w hic h ca n be d o ne b y: cl os ure of t he va gi na
wit h a n o bt urat or;
cl os ure of t he va gi na wit h a li gat ure ri n g; a n d cl os ure of t he va gi na wit h tra ns va gi nal
s ut ures. After la par osc o pic cl os ure of t he va gi na, t he va gi na is irri gate d
wit h sterile
water, after w hic h t he va gi na is se vere d a n d t he va gi nal st u m p is s ut ure d.
1 4) S yste matic l y m p ha de nect o m y: re m o val of l y m p h n o des a djace nt t o t he c o m m o n iliac
arter y, e xter nal iliac arter y, i nter nal iliac arter y a n d l y m p h n o des i n t he cl ose d f ossa ±
parietal a ortic l y m p h n o des ( u p t o t he le vel of t he i nferi or mese nteric arter y).
1 5) T he i ntra o perati ve l y m p h n o des are re m o ve d b y e n bl oc resecti o n, wit h o ut t o uc hi n g
ot her parts, a n d will be place d i n a s peci me n ba g f or fi nal re m o val.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 4
1 6) T he p ost o perati ve pel vic a n d a b d o mi nal ca vit y
will be s ucti o ne d after f ull fl us hi n g
wit h sterile water, a n d t he pel vic fl us hi n g fl ui d s h o ul d be a v oi de d t o bac k u p i nt o t he
u p per a b d o me n d uri n g tre n dele n b ur g p ositi o n.
1 7) Use of a va gi nal a pe x cl os ure de vice ca n be c h ose n b y eac h s ur ge o n.
1 8) T he la par osc o pic o perati o n ca n als o be perf or me d t hr o u g h va gi na.
3. 4
I ntr a o per ati ve se nti nel l y m p h n o de l oc aliz ati o n bi o ps y:
Se nti nel l y m p h n o de l ocalizati o n bi o ps y will n o t be use d i n t his pr oject.
3. 5 Pel vic/ P ar a- a ortic l y m p h a de nect o m y:
T he
s ur ge o n
is
re q uire d
t o
perf or m
pel vic
l y m p ha de nect o m y ±
para-a ortic
l y m p ha de nect o m y i n b ot h gr o u ps of patie nts; h o we ver, t he s ur ge o n ma y als o c h o ose n ot
t o perf or m l y m p ha de nect o m y if t he patie nt meets t he f oll o wi n g criteria:
1)
M or bi d o besit y: ( E ur o pea n a n d
A merica n criteria:
wei g ht o ver 1 0 0 p o u n ds or
B MI ≥4 0) B MI ≥3 7. 5 f or t he Asia n p o p ulati o n; or B MI ≥
3 2. 5 wit h t w o or m ore
meta b olic c o m plicati o ns.
2 )
Re q uires bl o o d t hi n ni n g me dicati o n.
3)
T he patie nt's p h ysical c o n diti o n is n ot s uita ble f or l y m p ha de nect o m y fr o m a
me dical safet y pers pecti ve.
3. 6 P ost- o per ati ve a dj u v a nt r a di ot her a p y or r a di oc he m ot her a p y
If t he p ost o perati ve pat h ol o g y re p ort s u g gests t he prese nce of ris k fact ors ass ociate d
wit h rec urre nce ( hi g h-ris k fact ors or i nter me diate ris k fact ors), p ost o perati ve a dj u va nt
t hera p y is re q uire d if necessar y.
( 1) Hi g h-ris k f act ors: p ositi ve p ar ametri u m, p o siti ve i ncisi o n al m ar gi ns,
a n d p ositi ve pel vic l y m p h n o des.
P ositi ve p ar a metri u m: e xter nal pel vic bea m ra diati o n t hera p y ( E B R T) + cis plati n
c o nc urre nt c he m ot hera p y. Cis plati n ( D D P) 4 0 m g/ m 2/ w ( wee k, w), or car b o plati n if
cis plati n is n ot t olerate d ( A U C = 2). (If p ositi ve f or para metrial tiss ue, l ocal p us h of 5- 1 0
G y ma y be a p pr o priate).
P ositi ve v a gi n al i ncisi o n al m ar gi ns: e xter nal pel vic ra diati o n t hera p y ( E B R T) +
cis plati n c o nc urre nt c he m ot hera p y + v a gi nal bac kl oa di n g ra di ot hera p y, wit h cis plati n
( D D P) 4 0 m g/ m2/ w, or car b o plati n ( A U C = 2) if cis plati n is i nt olera nt.
P ositi ve pel vic l y m p h n o des: o ne c o urse of s yste mic c he m ot hera p y + e xter nal
pel vic ra diati o n ra di ot hera p y ( E B R T) ± e xte n de d fiel d ra di ot hera p y t o t he a b d o mi nal
a orta + c o nc urre nt c he m ot hera p y wit h cis plati n ( 4 0 m g/ m 2/ w) + 3- 6 c o urses of a dj u va nt
s yste mic c he m ot hera p y after ra di ot hera p y ( paclita x el + cis plati n or car b o plati n preferre d
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 5
f or lar ge i ntra ve n o us c he m ot hera p y re gi me ns, ca n use b ot h d o mestic or i m p orte d). If t he
pat h ol o g y c o nfir ms p ositi ve a b d o mi nal a orta or p ositi ve c o m m o n iliac l y m p h n o des,
irra diati o n of para-a ortic e xte n de d fiel d will be perf or me d; w he n t he pel vic l y m p h n o des
are p ositi ve a n d t he pat h ol o g y res ult of a b d o mi nal a ortal y m p h n o des cleara nce is
ne gati ve (if o nl y a b d o mi nal mai n bi o ps y wit h o ut cleara nce, p ositi ve irra diati o n will be
perf or me d, ne gati ve is e q ui vale nt t o n o cleara nce), n o e xte n de d fiel d irra diati o n will be
perf or me d; if t he l y m p h n o des i n t he pel vic l y m p h n o des are p ositi ve a n d t he l y m p h
n o des i n t he para-a ortic l y m p h n o des are n ot cleare d, b ut t he i ma ge is s usce pte d of
metastasis i n t he para-a ortic l y m p h n o des (f ull l y m p h n o des, le n gt h t o dia meter rati o
cl ose t o 1), it is rec o m me n de d t o e xte n d fiel d irra diati o n.
( 2) I nter me di ate ris k f act ors (t u m or size, i nterstiti al i nfiltr ati o n, p ositi ve
l y m p h o v asc ul ar s p ace), s q ua m o us c arci n o m a acc or di n g t o " Se dlis criteri a ": e xter nal
pel vic ra diati o n t hera p y ( E B R T) + cis plati n c o nc urre nt c he m ot hera p y, cis plati n ( D D P)
4 0 m g/ m 2/ w.
( 3) A de n oc arci n o m a a n d a de n os q u a m o us c arci n o m a are tre ate d acc or di n g t o
i nter me di ate ris k f act ors, f oll o wi n g t he f o ur-fact or a p pr oac h (i.e. a de n ocarci n o ma or
a de n os q ua m o us carci n o ma wit h p ositi ve l y m p h o vasc ular s pace, t u m or ≥3 c m, a n d
i nfiltrati o n of t he o uter 1/ 3 of t he cer vical ca nal s h o ul d be treate d wit h c onc urre nt
ra di ot hera p y). E xter nal pel vic ra diati o n t hera p y ( E B R T) + cis plati n c o nc urre nt
c he m ot hera p y wit h cis plati n ( D D P) 4 0 m g/ m 2/ w, or car b o plati n ( A U C = 2) if cis plati n is
n ot t olerate d.
( 4) P ositi ve pr o xi m al m ar gi n ( ne g ati ve m ar gi n ≤0. 5c m), treat me nt as p ositi ve
va gi nal mar gi n, e xter nal pel vic irra diati o n t hera p y + cis plati n c o nc urre nt c he m ot hera p y +
brac h yt hera p y.
T he E B R T i m ple me nt ati o n ：
( 1) Rec o m me n d t o start at 4 wee ks p ost o perati vel y a n d n o later t ha n 8 wee ks.
Prescri be d d osa ge: s q ua m o us carci n o ma, 4 5 G y; a de n ocarci n o ma, 5 0. 4 G y; c o n ve nti o nal
se g me ntati o n 1. 8 G y per sessi o n, o nce dail y,
M o n da y t hr o u g h Fri da y eac h wee k. Lar ge
u nresecta ble metastatic l y m p h n o des are gi ve n a si m ulta ne o us a d diti o nal p us h ( SI B
2. 1- 2. 2 G y) or se q ue ntial a d diti o nal d ose of 1 0- 1 5 G y.
( 2) Sc o pe of irra diati o n: pel vic ra diati o n fiel d ± e xte n de d a b d o mi nal a ortic fiel d ±
brac h yt hera p y.
( 3) Pel vic ra diati o n fiel d: at least 3- 4 ce nti meters bel o w t he va gi nal dissecti o n,
para metrial tiss ue a n d a djace nt l y m p h n o de drai na ge areas (c o m m o n iliac, i nter nal a n d
e xter nal iliac l y m p h n o des, cl ose d f ora me n, presacral) m ust be i ncl u de d.
( 4) Para-a ortic e xte nsi o n fiel d: t he u p per b or der reac hes t he le vel of t he left re nal
vei n, t he left si de reac hes t he i n ner e d ge of t he ps oas maj or m uscle a n d t he ri g ht si de 3- 5
milli meters ar o u n d t he i nferi or ve na ca va.
( 5) I nte nsit y- m o d ulate d ra diati o n t hera p y (I M R T) or vol u metric- m o d ulate d
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 6
arca di ot hera p y ( V A M T) is rec o m me n de d f or E B R T wit h wee kl y c o ne bea m C T ( C B C T)
o nce a wee k.
T he I m ple me nt ati o n of retr o v a gi n alr a di ot her a p y
( 1) Retr o va gi nal ra di ot hera p y is starte d after t he c o m pleti o n of e xter nal pel vic
irra diati o n, t wice per wee k. (It is rec o m me n de d t hat t he t otal d urati o n of e xter nal
irra diati o n ra di ot hera p y + retr o va gi nal ra di ot hera p y treat me nt d oes n ot e x cee d 5 6 da ys).
( 2) Rec o m me n d 3- D rear-l oa di n g tec h ni q ue: C T or
M RI l ocalizati o n, usin g
c ol u m nar a n d o v oi d a p plicat ors wit h 1 9 2Ir-s o urce or 6 0C o, f or hi g h- d ose-rate rear-l oa di n g
ra di ot hera p y.
( 3) Hi g h-ris k cli nical tar get v ol u me ( H R- C T V): i ncl u di n g t he area 5 milli meters
o utsi de t he va gi nal m uc osa a n d 1 ce nti meter a b o ve t he va gi nal st u m p.
( 4)
M ore t ha n 9 0 % of t he v ol u me of H R- C T V per sessi o n is i ncl u de d i n t he
prescri be d d ose ra n ge ( 6 G y × 3 sessi o ns); f or t w o- di me nsi o nal rear-l oa di n g ra di ot hera p y
pla ns, t he prescri be d d ose p oi nt is 5 milli meters bel o w t he va gi nal m uc osa.
( 5) T he s u m of e xter nal rectal irra diati o n a n d 2 G y e q ui vale nt t otal d ose ( E Q D 2) of
p ost o perati ve ra di ot hera p y ( 2cc) is less t ha n 6 5 ~ 7 5 G y; si g m oi d c ol o n is less t ha n 7 0- 7 5
G y, a n d bla d der 2cc is less t ha n 8 0 ~ 9 0 G y.
T he i m ple me nt ati o n of C C R T.
C C R T is gi ve n wee kl y cis plati n ( D D P) i ntra ve n o us c he m ot hera p y d uri n g E B R T.
Cis plati n ( D D P) 4 0 m g/ m 2/ w is rec o m me n de d f or t he first 3 da ys of t he first wee k of
ra di ot hera p y i nitiati o n, wit h a n e x pecte d 5 c ycles.
N o te: S E D LI S criteri a
L V SI
De pt h of i nterstitial i n vasi o n
T u m or size(c m)
( deter mi ne d b y cli nical
g y n ec ol o gical e x a mi nati o n)
+
Dee p 1/ 3
Ar bitrar y
+
Me di u m 1/ 3
≥2c m
+
S hall o w 1/ 3
≥5c m
-
Me di u m or dee p 1/ 3
≥4c m
L V SI: L y m p h o vasc ular s pace i n vasi o n
3. 7 Rec or di n g of f oll o w- u p d at a:
3. 7. 1 Pre o per ati ve assess me nt:
a) Sta n dar d pre o perati ve la b orat or y tests deter mi ne d b y eac h ce nter: (e. g., r o uti ne bl o o d
a n d uri ne test, c oa g ulati o n f u ncti o n, bl o o d li ver, ki d ne y f u ncti o n, electr ol yt es, HI V, R P R,
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 7
he patitis mar kers)
b) 1 2-lea d E C G
c) T u m or i n dicat ors: S C C a nti ge n test ( S C C A) a n d C A- 1 2 5
d) H P V t y pi n g test a n d T C T test i n t he last 3 m o nt hs ( o nl y o ne pre o perati ve test is
re q uire d)
e) Pat h ol o g y or pat h ol o g y c o ns ultati o n at eac h ce nter ( L E E P or c o nizati o n is re q uire d f or
I A 1 wit h L V SI a n d I A 2).
f) I m a gi n g ( C T sca n of t he c hest, e n ha nce d C T of t he u p per a b d o me n a n d pel vis,
e n ha nce d
M RI t o assess lesi o n size or P E T- C T t o assess retr o perit o neal l y m p h n o de
metastases)
g) C olle cti on of rele va nt me dical hist or y, hei g ht a n d wei g ht, de m o gra p hic data, a n d
healt h i ns ura nce-relate d i nf or mati o n of t he patie nts
h) Rec or d all me dicati o ns (i ncl u di n g prescri pti o n dr u gs, o ver-t he-c o u nter dr u gs,
vacci nati o n, a nti bi otics, her bal me dici ne) use d b y t he patie nt i n t he past 3 m o nt hs
i) Si g n t he i nf or me d c o nse nt f or m
j) Rec or d a n i ncl usi o n criteria scree ni n g f or m
k) C o m plete t he ra n d o mizati o n pr oce d ure, e nteri n g ra n d o mizati o n c o des f or patie nts a n d
rec or di n g t he res ults
l) Si g n t he i nf or me d c o nse nt f or m f or t he rele va nt s ur ger y
m) Patie nts ma y sca n t he Q R c o de t o re gister f or t he we b- base d f oll o w- u p platf or m
[ N ote]:
- P at h ol o gic e v al u ati o n: Eac h patie nt m ust ha ve a clear hist ol o gic dia g n osis of cer vical
s q ua m o us cell carci n o ma, cer vical a de n ocarci n o ma, or cer vical a de n os q ua m o us
carci n o ma pri or t o ra dical cer vical ca ncer s ur ger y. If t he cer vical lesi o n is relati vel y
e vi de nt, alt h o u g h t he bi o ps y pat h ol o g y s h o w s patc hes of s q ua m o us cells wit h o ut clear
i nterstitial i nfiltrati o n, t he cli nical prese ntati o n of t he lesi o n is c o nsiste nt wit h i n vasi ve
cer vical ca ncer, a n d t he n t he patie nt ma y still be i ncl u de d i n t he st u d y.
- Cli nic al assess me nt: cer vical lesi o n size was meas ure d b y pel vic-e n ha nce d
M RI; t he
prese nce of metastases i n t he para metri u m was deter mi ne d b y p h ysical e x a mi nati o n of
t he o perat or; a n d l y m p h n o de stat us was assesse d b y pel vic-e n ha nce d
M RI i n
c o m bi nati o n wi t h ot her i ma gi n g s uc h as P E T- C T.
3. 7. 2 D oc u me nt ati o n of t he s ur gic al pr oce d ure
a) S ur ger y base d o n ra n d o mize d o utc o me: o pe n or la par osc o pic o perati o n.
b) Rec or d i ntra o perati ve a n d p ost o perati ve i nf or mati o n (i ncl u di n g details of t he
pr oce d ure, d urati o n of s ur ger y, d urati o n of a nest hesia, i ntra o perati ve blee di n g,
i ntra o perati ve c o m plicati o ns, details of bl o o d tra nsf usi o n a n d a n y ot her s pecial
circ u msta nces s urr o u n di n g t he pr oce d ure).
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 8
3. 7. 3 P ost-tre at me nt f oll o w- u p rec or ds
O ne wee k after t he e n d of treat me nt.
a) Rec or d p ost o perati ve pat h ol o g y res ults a n d c orres p o n di n g f oll o w- u p treat me nt pla n
b) Re vie w la b orat or y tests (e. g. bl o o d a n d uri ne r o uti ne test, c oa g ulati o n f u ncti o n, bl o o d
li ver, ki d ne y f u ncti o n, electr ol yt es, drai na ge fl ui d creati ni ne)
c) P ost o perati ve i n d welli n g cat heter f or 3- 6 wee ks a n d re vie w of resi d ual uri ne w he n t he
cat heter is re m o ve d
d) P ost o perati ve c o m plicati o ns (l y m p hatic c ysts, d ys uria, va gi nal blee di n g)
Re vie w e ver y 3 m o nt hs f or 2 years after c o m pleti o n of treat me nt wit h:
a) I m a gi n g e x a mi nati o ns (c hest C T + pel vic e n ha nce me nt
M RI + u p per a b d o me n
e n ha nce me nt
M RI or P E T- C T)
b) T u m or i n dicat ors: S C C a nti ge n test ( S C C A) a n d C A- 1 2 5
c) H P V a n d T C T test ( o nce a year after c o m pleti o n of treat me nt)
d) A d verse e ve nts rec or di n g
e) Assess me nt of q ualit y of s ur vi val a n d q ualit y of se x ual life usi n g t he Q ualit y of
S ur vi val Scale f or Ca ncer Pat ie nts ( E O R T C Q L Q- C 3 0 v 3. 0), t he Cer vical Ca ncer Se x ual
Life Scale ( E O R T C Q L Q- C X 2 4), a n d t he Patie nt Re p orte d Cli nical O utc o me Assess me nt
Scale f or Cer vical Ca ncer P R O 1 4 7 ( V 1. 0).
After 2 years, t he st u d y will be re vie we d e ver y 6 m o nt hs u ntil t he e n d of t he trial. T he
re vie w will i ncl u d g y n ec ol o gical e x a mi nati o n, t u m or i n dicat ors ( S C C a nti ge n detecti o n
( S C C A) a n d C A- 1 2 5), T C T e x a mi nati o n a n d H P V e xa mi nati o n, i ma gi n g (c hest C T +
pel vic e n ha nce me nt
M RI + u p per a b d o me n e n ha n ce me nt
M RI or P E T- C T), a n d a d verse
e ve nt rec or ds.
3. 8 Criteri a f or P atie nt
Wit h dr a w al
Patie nts ha ve t he ri g ht t o wit h dra w fr o m t he trial treat me nt or st u d y at a n y ti me
wit h o ut a n y reas o n. T he i n vesti gat or als o has t he ri g ht t o wit h dra w a patie nt fr o m t he trial
treat me nt or st u d y i n t he e ve nt of sec o n dar y disease, a d verse e ve nts, pr ot oc ol vi olati o ns,
a d mi nistrati ve reas o ns, or ot her reas o ns. Partici pati o n i n t he st u d y, w het her or n ot t he
affecte d patie nt partici pate s, will not affect t he relati o ns hi p bet wee n t he patie nt a n d t he
p h ysicia n a n d will n ot res ult i n a l oss of me dical or ot her be nefits t o t he patie nt. H o we ver,
i n s uc h cases, t he i n vesti gat or will ma ke a p pr o priate eff orts t o deter mi ne a n d d oc u me nt
t he reas o ns f or t he patie nt's v ol u ntar y wit h dra wal fr o m t he st u d y. If a patie nt wit h dra ws
fr o m t he st u d y, a c o m plete fi nal e val uati o n s h o ul d be c o n d ucte d at t he ti me of patie nt
wit h dra wal. T his will be re p orte d al o n g wit h t he st u d y r es ults a n d all atte m pts t o l ocate
patie nts l ost t o f oll o w- u p will als o be d oc u me nte d.
Patie nts will be see n b y t heir p h ysicia n if t he y wit h dra w fr o m t he st u d y. Acc or di n g
t o r o uti ne g y n ec ol o gic o nc ol o g y pr ot oc ols, t he y s h o ul d c o nti n ue t o recei ve care a n d
treat me nt fr o m a n e x perie nce d p h ysicia n u ntil f urt her f oll o w- u p is dee me d u n necessar y
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
2 9
b y t he treati n g p h ysicia n.
Patie nts will be wit h dra w n fr o m t he st u d y u n der t he f oll o wi n g circ u msta nces:
1) St u d y c o m pleti o n/ter mi nati o n, or deat h
2) Patie nt de ma n ds wit h dra wal
3) Patie nt is u na ble or u n willi n g t o c o o perate wit h f oll o w- u p
4) Patie nt has ot her seri o us, n o n-s ur gical c o m plicati o ns
5) Patie nt's f oll o w- u p i nf or mati o n ca n n ot be o btai ne d
6) T he st u d y is ter mi nate d or ca ncelle d at t he re q uest of t he s p o ns or
7) Ot her rele va nt reas o ns
If a patie nt m o ves t o an ot h er treat me nt ce nter a n d re q uires c ha n gi n g of p h ysicia n,
t he i n vesti gat or will ma ke a reas o na ble atte m pt t o l ocate t hat ce nter's p h ysicia n a n d
re q uest c o o perati o n i n or der t o c o m plete t he f oll o w- u p.
I n ma n y cases, patie nt wit h dra wal fr o m t he st u d y c o nstit utes disc o nti n uati o n of
treat me nt a n d/ or disc o nti n uati o n of c o m pleti o n of relate d f or ms, s uc h as q ualit y of life. I n
t hese cases, t he i n vesti gat or s h o ul d o btai n t he patie nt's per missi o n t o c o nti n ue m o nit ori ng
t heir disease stat us (rela pse, s ur vi val, t o xicit y, etc.) t hr o u g h t he patie nt's rec or d.
E x cessi ve e xit rates ca n ma ke a st u d y u ni nter preta ble, a n d t heref ore, u n necessar y
s u bject dr o p o uts s h o ul d be a v oi de d.
3. 9 C o m bi n ati o n a n d si m ult a ne o us tre at me nt ：
S u p ple me ntar y t hera p y will be a d mi nistere d acc or di n g t o t he p ost o perati ve
pat h ol o gical fi n di n gs of t he patie nts. T h ose wit h hi g h-ris k fact ors w h o ha ve p ositi ve
para metri u m will be s u p ple me nte d wit h e xter nal pel v ic irra diati o n t hera p y +
cis plati n/car b o plati n c o nc urre nt c he m ot hera p y, t h ose wit h p ositi ve va gi nal mar gi ns will
be selecte d f or e xter nal pel vic irra diati o n t hera p y + retr o va gi nal ra di ot hera p y +
cis plati n/car b o plati n c o nc urre nt c he m ot hera p y, a n d t h ose wit h p ositi ve pel vic l y m p h
n o des will be treate d wit h 1 c o urse of s yste mic c he m ot hera p y + e xter nal pel vic
irra diati o n ra di ot hera p y ± e xte n de d fiel d ra di ot hera p y a djace nt t o t he a b d o mi nal a orta +
cis plati n c onc urre nt c he m ot hera p y + 3- 6 c o urses of a dj u va nt s yste mic c he m ot hera p y after
ra di ot hera p y. T h ose wit h i nter me diate ris k fact ors will be treate d wit h e xter nal pel vic
irra diati o n ra di ot hera p y + cis plati n c o nc urre nt c he m ot hera p y, a n d t h ose wit h p ositi ve
pr o xi mal mar gi ns will be treate d wit h e xter nal pel vic irra diati o n ra di ot hera p y E B R T +
cis plati n c o nc urre nt c he m ot hera p y + retr o va gi nal ra di ot hera p y. Tar gete d
i m m u n ot hera pe utic a ge nts s uc h as be vaciz u ma b an d P D- 1 , w hic h ha ve j ust o btai ne d
s o me res ults i n cli nical st u dies, are n ot c o nsi dere d i n t his trial f or t he ti me bei n g. It c o ul d
be use d acc or di n g d oct or’s or ders.
3. 1 0 O utc o me me as ure me nts ：
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 0
1)
Mai n o utc o me i n dicat ors: 5- year O S.
2) Sec o n dar y o utc o me meas ure me nts: 5- year P F S, refer t o R E CI S T criteria.
3) Ot her o utc o me meas ure me nts: o perati o n ti me, a nest hesia ti me, i ntra o perati ve blee di n g
v ol u me, i ntra o perati ve c o m plicati o ns, p ost o perati ve c o m plicati o ns, p ost o perati ve pai n
sc ore, p ost o perati ve h os pital sta y, o ne- m o nt h p ost o perati ve s ur vi val q ualit y, o ne- year
p ost o perati ve s ur vi val q ualit y, se x ual q ualit y of life.
4)
Ot her
e val uati o n
p ara meters:
p atie nt's
de m o gra p hic
c haracteristics,
si g ns
a n d
s y m pt o ms, sta ge, pat h ol o gical t y p e, t u m or site, c o m or bi dities,
me dical hist or y, le n gt h of
h os pital sta y a n d c ost.
5) T his st u d y i nte n ds t o sa m ple a n d c ollect i ntra o perati ve t u m or tiss ues fr o m t u m or
patie nts a n d e val uate s pecific t u m or sta ges wit h ge netic testi n g t o g ui de later treat me nts
s uc h as tar gete d or i m m u ne t hera pies. Hist ol o gical st u dies a n d m olec ular st u dies will als o
be c o n d ucte d.
3. 1 1 S u bj ecti ve sc he d ule
Pre- p hase
0- 1 2
m o nt hs
1 2- 2 4
m o nt hs
2 4- 3 6
m o nt hs
3 6- 6 0
m o nt hs
Meet t he researc hers
Ⅹ
O btai n I R B a p pr o val
Ⅹ
F u n di n g a p plicati o n
Ⅹ
E nr oll me nt of st u d y patie nts
Ⅹ
Ⅹ
Ⅹ
Data m o nit ori n g
Ⅹ
Ⅹ
Ⅹ
X
Data c ollecti o n
Ⅹ
Ⅹ
Ⅹ
X
Data a nal ysis
X
S u m mar y a n d disc ussi o n
Ⅹ
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 1
N ote: F or patie nts wit h sta ge I B 1, I B 2, II A 1, I B 3, a n d II A 2, t he s ur gical
met h o d will be
selecte d acc or di n g t o t he
ma xi m u m dia meter of t he
mass. C 1 t y p e h ysterect o m y will be
use d f or dia meters < 2 c m, C 2 t y p e h ysterect o m y will be use d f or dia meters > 4 c m, a n d
C 1 t y p e or
C 2 t y p e h ysterect o m y
will be selecte d b y t he s ur gical tea m
me m bers
acc or di n g t o t he act ual i ntra o perati ve c o n diti o n f or dia meters bet wee n 2 c m a n d 4 c m.
3. 1 2 S a m ple size
T his st u d y uses a n o n-i nferi orit y trial des i gn, a n d t he pri mar y o utc o me is t he rate of O S at
5 years. T he sa m ple size is calc ulate d base d o n t he differe nce bet wee n t he t w o gr o u ps of
5- year O S rate. T he 5- year O S rate of t he patie nts i n t he o pe n s ur ger y gr o u p is esti mate d
t o be 7 2 % base d o n t he pre vi o us cli nical data fr o m o ur h os pital.
Base d o n t he ass u m pti o ns of (i) t he 5- year O S rate of 7 2 % i n t he o pe n s ur ger y gr o u p,
(ii) a n o n-i nferi orit y mar gi n of 8 %, (iii) 8 0 % p o wer, a n d (i v) a o ne-si de d al p ha of 0. 0 2 5,
t he sa m ple size esti mati on res ulte d i n 4 9 5 s u bjects per gr o u p (calc ulate d
wit h S A S
s oft ware, versi o n 9. 4). C o nsi deri n g a 1 0 % dr o p- o ut rate a n d t he ra n d o mizati o n sc he me
wit h bl oc k size of 6, a t otal of 1 1 0 4 s u bjects s h o ul d be ra n d o mize d ( 5 5 2 per gr o u p).
3. 1 3 Recr uit me nt met h o ds:
T he st u d y tea m ce nters
will a d vertise t his st u d y at t heir cer vical ca ncer cli nic. If t he
patie nts are i ntereste d, t he y
will
be f urt her i ntr o d uce d i n
detail a b o ut t he st u d y
bac k gr o u n d, ra n d o mizati o n a n d s ur gical pr oce d ures, a n d t he patie nts ca n v ol u ntaril y
c h o ose w het her t o partici pate i n t he trial. After patie nts si g n t he i nf or me d c o nse nt f or ms,
me m bers of t he st u d y tea m
will re vie w t heir eli gi bilit y acc or di n g t o t he i ncl usi o n a n d
e x cl usi o n criteria. Patie nts
will t he n be ra n d o mize d t o recei ve eit her of t he s ur gical
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 2
pr oce d ures. Fi nall y, t he patie nts will be f oll o we d u p acc or di n g t o t he f oll o w- u p sc he d ule.
I V. All oc ati o n, Bli n di n g a n d U n bli n di n g
4. 1 All oc ati o n of t he i nter ve nti o ns
4. 1. 1 All oc ati o n se q ue nce ge ner ati o n: I n t his st u d y, a ce ntralize d bl oc k ra n d o mizati o n
wit h a bl oc k size of 6 will be use d t o ra n d o ml y assi g n patie nts t o t he la par osc o pic s ur ger y
gr o u p or t he o pe n s ur ger y gr o u p at a 1: 1 rati o. T he ra n d o mizati o n sc he me
will be
c o m plete d b y a n i n de pe n de nt statistical te a m at t he Cli nical Trial Ce nter of t he C hil dre n's
H os pital of F u da n U ni versit y b y creati n g a n d se q ue nci n g ra n d o m see d n u m bers ( S A S 9. 4
s oft ware). T he i nter ve nti o n pr ot oc ols deter mi ne d b y t he ra n d o m assi g n me nt se q ue nce
will be i n se q ue ntiall y n u m bere d, n o n-tra ns pare nt, seale d e n vel o pes b y z o ne: eac h of t he
6 s u b gr o u ps f or eac h z o ne
will be place d se q ue ntiall y i n si x s mall, n o n-tra ns pare nt,
seale d e n vel o pes n u m bere d fr o m 1 t o 6, a n d t he n u nif or ml y place d i n t he sa me large
e nvel o pe
mar ke d
wit h t he c orres p o n di n g z o ne n u m ber. T he ra n d o mizati o n assi g n me nt
will be a d mi nistere d b y t he ce ntral c o or di nat or at t he O bstetrics a n d G y n ec ol o g y H os pital
of F u da n U ni versit y w h o is n ot i n v ol ve d i n t he i m ple me ntati o n of t he i nter ve nti o n or t he
o utc o me o bser vati o n. T he e nr oll me nt is c o m petiti ve, a n d t he s u b-ce nter c o or di nat or will
c o ntact t he ce ntral c o or di nat or bef ore t he i ncl usi o n of t he first patie nt i n eac h gr o u p. T he
ce ntral c o or di nat or wil l f oll o w t he ra n d o mizati o n sc he me a n d assi g n t he lar ge e n vel o pes
wit h t he gr o u p n u m bers t o eac h ce nter f oll o wi n g t he or der of c o ntact. Eac h s u b-ce nter
will o pe n t he e n vel o pes acc or di n g t o t he or der of si g ni n g t he i nf or me d c o nse nt f or m, a n d
strictl y f oll o w t he n u m bere d or der of t he e n vel o pes, a n d t he n i nf or m t he partici pati n g
p h ysicia ns of t he assi g n me nt sc he me a n d c o m plete writte n re gistrati o n f or m.
4. 1. 2 All oc ati o n c o nce al me nt mec h a nis m
1) I n t his st u d y, t he s ur gica l pr oce d ures will be selecte d i n a ra n d o mize d ma n ner, a n d t he
C T U
me m bers
will place t he i nter ve nti o n
m o dalit y i n a n e n vel o pe a n d gi ve it t o eac h
ce nter’s c o or di nat or w h o is n ot i n v ol ve d i n t he i m ple me ntati o n of t he i nter ve nti o n or t he
o bser vati o n of t he o utc o me t o ma na ge t he all ocati o n. T he e n vel o pe will be o pe ne d b y t he
i n vesti gat ors
at
eac h
ce nter
f oll o wi n g t he
e nr oll me nt
or der, t o
realize
bli n de d
pre o perati ve ra n d o mizati o n.
2) Data will be e ntere d b y de dicate d st u d y s taff, w ho will be bli n de d t o t he ra n d o mizati o n
all ocati o n a n d s ur gical pr oce d ure.
4. 1. 3 Assi g n me nt i m ple me nt ati o n ( w h o ge ner ates t he seri al n u m bers,
w h o recr uits
t he s u bjects, a n d w h o assi g ns t he m)
1) T he s ur ge o ns will perf or m t he recr uit me nt a n d o btai n i nf or me d c o nse nt, a n d perf or m
t he s ur gical pr oce d ure.
2) T he C T U tea m desi g ns t he ra n d o mizati o n
met h o d a n d ge nerates t he c orres p o n di n g
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 3
e n vel o pes.
3) T he all ocati o n of s ur geries acc or di n g t o t he or der of i nf or me d c o nse nt si g ne d b y t he
st u d y partici pa nts i n eac h ce nter acc or di n g t o t he ra n d o mizati o n
met h o d t o ac hie ve a n
e q ual distri b uti o n of re p orters i n t he o pe n a n d l u m pect o m y gr o u ps.
4) T he ra n d o mizati o n staff will rec or d t he ra n d o mizati o n n u m bers a n d pr oce d ure.
5) F oll o w- u p of eac h patie nt a n d rec or di n g of rele va nt data a n d a d verse e ve nts
will be
perf or me d b y de dicate d f oll o w- u p pers o n nel.
6)
Dat a e ntr y i nt o t he
Re d Ca p data base
will be perf or me d b y de dicate d data e ntr y
pers o n nel.
7) T he C T U a n d t he pri nci pal i n vesti gat or will perf or m statistical a nal ys es.
4. 2 Bli n di n g
4. 2. 1
W h o t o bli n d a n d h o w t o i m ple me nt it
1) T he s pecific pr oce d ure will n ot be k n o w n t o t he s ur gical tea m of eac h ce nter u ntil after
t he patie nts ha ve bee n ra n d o mize d d uri n g t he a d mi nistrati o n p hase of t he i nter ve nti o n.
2)
T he ra n d o mizati o n pr ocess
will n ot be k n o w n t o data e ntr y pers o n nel after t he
o perati o n.
3) Statisticia ns will als o be u na ware of t he ra n d o mizati o n pr ocess.
4) T he ra n d o mizati o n pr ocess is als o u n k n o w n t o t he pers o n nel res p o nsi ble f or e n d p oi nt
e val uati o n.
4. 2. 2 U n bli n di n g
1) T he t otal ra n d o mizati o n f or m
will be ke pt e x cl usi vel y b y t he de dicate d staff at eac h
ce nter, a n d a letter w hic h c o ntai ns i nf or mati o n of t he gr o u p assi g n me nt a n d t he s ur gical
met h o d will be set u p f or eac h gr o u p wit h t he n u m ber.
2) T he u n bli n di n g
will be c o n d ucte d t o re veal t he i n f or mati o n of eac h patie nt
wit h
c orres p o n di n g s ur gical pr oce d ure, o nl y after fi nal data a nal ys es.
3) Si nce t his st u d y d oes n ot i n v ol ve dr u g use, t here is n o e mer ge nc y u n bli n di n g pr ocess
i n place.
V.
Met h o ds of d at a c ollecti o n, m a n a ge me nt a n d a n al ysis
5. 1 D at a c ollecti o n a n d p atie nt rete nti o n
5. 1. 1 Pr ot oc ols f or esti mati n g a n d c ollecti n g o utc o me i n dicat ors, baseli ne a n d ot her trial
data
Base d o n t he st u d y pr ot oc ol a n d data a nal ysis pla n, a case re p ort f or m ( C R F) has b ee n
d e vel o pe d a n d vali date d. Re q uire d fiel ds are set t o e ns ure t he c o m plete ness of ke y data.
T he C R F will be c o m plete d b y trai ne d i n vesti gat or at eac h site, a n d eac h e nr olle d case
has t o c o m plete t he C R F, w hic h will be re vie we d b y t he i n vesti gat or a n d ha n de d o ver t o
data ma na ger f or data e ntr y a n d ma na ge me nt at eac h site.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 4
5. 1. 2 I m pr o ve patie nt e n ga ge me nt a n d c o m pleti o n of f oll o w- u p, i ncl u di n g o utc o me data
t o be c ollecte d f or patie nts w h o wit h dra w or c ha n ge treat me nt met h o ds
1)
Detaile d
patie nt
orie ntati o n b y st u d y tea m
me m bers at eac h ce nter
d uri n g t he
recr uit me nt p hase t o ac hie ve f ull y i nf or me d patie nts.
2) T he st u d y tea m me m bers will pr o vi de l o n g-ter m re m ote c o n diti o n assess me nt ser vices
a n d relate d i nf or mati o n c o ns ultati o n ser vices f or all st u d y patie nts.
3) Patie nts will be f oll o we d u p re g ularl y b y de dicate d staff t o re d uce t he rate of l oss t o
f oll o w- u p.
4) T he f oll o w- u p s yste m will re g ularl y re mi n d t he s u bjects of t he f oll o w- u p ti me a n d t he
f oll o w- u p ite ms acc or di n g t o t he f oll o w- u p n o des.
5. 2 D at a m a n a ge me nt (e ntr y, c o di n g, e ncr y pti o n a n d st or a ge)
5. 2. 1 E ntr y a n d c o di n g pr ot oc ols:
A data base f or data ma na ge me nt a n d e ntr y is desi g ne d base d o n t he fi nalize d C R F f or m.
T his st u d y uses Re d Ca p, w hic h was de vel o pe d b y a pr ofessi o nal C R O data ma na ge me n t
tea m, a n d t he pr oject data e ntr y a n d ma na ge me nt will be ha n dle d b y de dicate d pers o n nel.
To e ns ure t he acc urac y of t he data, d o u ble e ntr y s h o ul d be perf or me d b y t w o researc h
me m bers i n de pe n de ntl y,
a n d
bli n d
verificati o n
a n d
statistical
a nal ysis
s h o ul d
be
perf or me d after s oft ware verificati o n a n d
ma n ual err or c orrecti o n. T he data base will be
l oc ke d after acc urac y c o nfir mati o n. T he l oc ke d data files t he n
will be s u b mitte d t o a n
i n de pe n de nt t hir d- part y statistical tea m f o r a nal ysis. T he statistical a nal ysis pla n ( S A P) is
de vel o pe d b y t he statistical tea m d uri n g t he st u d y s u bject i ncl usi o n pr ocess, a n d fi nalize d
after re peate d disc ussi o ns
wit h t he i n vesti gat or tea m, a n d u pl oa de d t o t he cli nical trial
re gistr y we bsite bef ore t he last patie nt data c ollecti o n is c o m plete d at t he st u d y re gistr y
we bsite, or s u b mitte d f or p u blicati o n wit h t he pr ot oc ol.
5. 2. 2 Data st ora ge a n d access
All i nf or mati o n o n researc h s u bjects is c ollec te d a nd st ore d i n l oc ke d ca bi nets b y
de dicate d pers o n nel, a n d access t o it is o nl y p ossi ble wit h t he rele va nt vie wi n g pri vile ges.
5. 3 St atistic al met h o ds
5. 3. 1 O utc o me st atistic al met h o ds
Statistical a nal ysis of t he st u d y will be u n derta ke n b y t he C T U of t he C hil dre n’s H os pital
of
F u da n
U ni versit y. I nter ve nti o ns be ga n at t he st u d y desi g n sta ge, base d o n ke y
scie ntific q uesti o ns, clear desi g n pr ot oc ols, a n d statistical a nal ysis met h o ds base d o n t he
pr o perties of t he p ri mar y outc o me i n dicat ors,
w here b y sa m ple sizes
were calc ulate d
base d o n e x pecte d effects.
After st u d y i ncl usi o n be gi ns u ntil t he last patie nt data
c ollecti o n is c o m plete d, a detaile d S A P is
writte n a n d u pl oa de d t o t he
Cli nical Trials
Re gistr y
we bsite. T he f oll o wi n g is a n o ver vie w of t he statistical a nal ysis strate g y a n d
met h o ds.
All a nal ys es will be perf or me d o n a n i nte nti o n-t o-treat (I T T) basis, e x ce pt f or se nsiti vit y
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 5
a nal ysis t hat will be perf or me d acc or di n g t o per- pr ot oc ol ( P P) treat me nt.
5. 3. 2 A n al ysis of pri m ar y o utc o me d at a
a) T his st u d y is n o n-i nferi orit y trial desi g n, a n d t he pri mar y o utc o me is t he rate of O S at 5
years. T he h y p ot hesis is as f oll o ws:
H y p ot hesis: Let π 1 de n ote t he rate of O S at 5 years i n t he o pe n s ur ger y gr o u p, a n d let π 2
de n ote t he rate
of
O S at
5
years i n t he
mi ni mall y i n vasi ve s ur ger y
gr o u p, t he
n o n-i nferi orit y mar gi n = 8 %. T he n ull h y p ot hesis is H 0: π 1 – π 2 ≥
vers us t he alter n ati ve
h y p ot hesis is H 1: π 1 – π 2 < .
b) T he c ur ves of O S at 5 years
will be esti mate d usi n g t he Ka pla n- Meier
met h o d. T he
l o gra n k test will be use d t o test t he a b o ve h y p ot hesis, t he 5- year O S rate differe nce a n d
its 9 5 % c o nfi de nce i nter val ( CI) f or t he c o m paris o n bet wee n t he t w o gr o u ps
will be
esti mate d. T he
mi ni mall y i n vasi ve s ur ger y
will be c o nsi dere d n o n-i nferi or t o t he o pe n
s ur ger y if t he o ne-si de d 9 5 % u p per li mit is less t ha n ,
w here = 8 %, t he pre deter mi ne d
n o n-i nferi orit y mar gi n .
c) C o variate a dj uste d a nal ysis:
A n a nal ysis of t he pri mar y o utc o me a dj usti n g f or t he bl o o d l oss d uri n g o perati o n,
o perati ve
d urati o n,
a n d
p ost o perati ve
pai n
sc ore
will
be
perf or me d
usi n g
C o x
pr o p orti o nal hazar ds re gressi o n m o del. T he hazar d rati o of 5- year O S a n d 9 5 % CI will be
esti mate d.
d) S u b gr o u p a nal ysis:
We
will stratif y b y t u m o ur sta gi n g, a n d perf or m
C o x pr o p orti o nal hazar ds re gressi o n
m o del t o esti mate t he hazar d rati o a n d 9 5 % CI of t he 5- year O S.
e) Se nsiti vit y a nal ysis:
A se nsiti vit y a nal ysis of t he pri mar y o utc o me will be perf or me d usi n g t he P P strate g y.
5. 3. 3 Sec o n d ar y o utc o me a n al ysis
a) T he rate of P F S at 5 years:
C o x pr o p orti o nal hazar ds m o del will be use d t o esti mate t he hazar d rati o a n d 9 5 % CI f or
t he effect of treat me nt o n t he 5- year P F S rate.
b) A nal ysis of c o nti n u o us o utc o mes:
T he c o nti n u o us o utc o mes i ncl u de o perati ve d urati o n, a nest hesia ti me, bl o o d l oss d uri n g
o perati o n, p ost o perati ve pai n sc ore a n d p ost o perati ve h os pital sta y. T he o utc o mes
wit h
n or mal distri b uti o n will be s u m marise d usi n g
mea n a n d sta n dar d de viati o n ( S D), w hile
t he
o utc o mes
wit h
n o n- n or mal
distri b uti o n
will
be s u m marise d
usi n g
me dia n a n d
i nter q uartile.
T he
differe nces i n t he
o utc o mes a n d
9 5 %
CIs
will
be a nal ys e d
b y
ge neralise d li near
m o del ( G L M)
wit h treat me nt as fi xe d
effect a n d
wit h
n or mal
distri b uti o n a n d i de ntit y li n k f u ncti o n.
c) A nal ysis of bi nar y o utc o mes:
T he i ntra o perati ve c o m plic ati ons, p ost o perati ve c o m plicati o ns, o ne- m o nt h a n d o ne- year
p ost o perati ve q ualit y of life a n d se x ual life will be treate d as bi nar y o utc o mes, a n d will
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 6
be s u m marise d b y n u m ber ( %) of partici pa nts
wit h t he e ve nt. T he differe nces i n t he
o utc o mes a n d 9 5 % CIs will be a nal ys e d b y G L M wit h treat me nt as fi xe d effect a n d wit h
bi n o mial distri b uti o n a n d i de ntit y li n k f u ncti o n.
d) I nteri m a nal ysis
T he O' Brie n Fle mi n g met h o d will be use d t o c o n d uct a n i nteri m a nal ysis t hree years after
t he st u d y. If t he st u d y has c o n d ucte d o nl y o nce i nteri m a nal ysis, t he α le vel will be set as
0. 0 4 8 i n t he fi nal a nal ysis.
4. Safet y a nal ysis
A d verse e ve nts ( A E s) will be s u m marise d usi n g t he n u m ber of A Es, t he n u m ber ( %) of
partici pa nts wit h A Es b y gr o u ps.
5. All a nal ys es
will be perf or me d
wit h a t w o-si de d si g nifica nce le vel
of 0. 0 5 a n d
c o n d ucte d usi n g S A S s oft ware, versi o n 9. 4 ( S A S I nstit ute).
5. 3. 4
Defi niti o n of
n o n-c o m pli a nt
p o p ul ati o n, a n d a n al ysis a n d
m a n a ge me nt of
missi n g d at a
All data will be
m o nit ore d b y a n i n de pe n de nt data
m o nit ori n g c o m mittee c o nsisti n g of
s ur gical e x perts, e pi de mi ol o gists, R C T e x perts, statisticia ns a n d s ur ge o ns.
5. 3. 5 St atistic al a n al yses
All statistical a nal ys es will be perf or me d wit h a t w o-si de d si g nifica nce le vel of 0. 0 5 a n d
c o n d ucte d usi n g S A S s oft ware, versi o n 9. 4 ( S A S I nstit ute).
VI. Q u alit y of life q uesti o n n aire
6. 1 P atie nt-re p orte d cli nic al o utc o me assess me nt sc ale P R O 1 4 7 ( V 1. 0) f or Cer vic al
C a ncer
T he researc h tea m de vel o pe d its o w n scale assess me nt relate d t o patie nt re p orte d
o utc o mes i n cer vical ca ncer,
w hic h is base d o n t he patie nt 's pers pecti ve t o assess t he
o utc o me after s ur ger y. Cer vical ca ncer is t he f o urt h m ost c o m m o n ca ncer i n w o me n, a n d
its i nci de nce has bee n o n t he rise i n rece nt years, es peciall y i n y o u n ger patie nts. Si nce t he
uter us is l ocate d i n t he ce ntral pel vis, da ma ge t o pel vic fl o or tiss ues b y s ur ger y ma y ca use
a variet y of c o m plicati o ns s uc h as uri nar y, i ntesti nal, va gi nal a n d l o wer li m b d ysf u ncti o n,
w hic h ca n n ot be acc uratel y assesse d b y c o n ve nti o nal scales.
C o nsi deri n g t he hi g h
s ur vi val rate of patie nts
wit h earl y-sta ge cer vical ca ncer, it is es peciall y i m p orta nt t o
st u d y t he s h ort-ter m a n d l o n g-ter m treat me nt effects f or patie nts.
Acc or di n g t o t he
U. S.
F o o d a n d
Dr u g
A d mi nistrati o n ( F D A), patie nt re p orte d
o utc o me ( P R O), a
meas ure of a n y as pect of a patie nt's healt h stat us t hat c o mes directl y
fr o m t he patie nt, is a vali d patie nt-ce ntere d,
m ultifacete d
mea ns of e val uati n g treat me nt
o utc o mes (s uc h as s y m pt o m i m pr o ve me nt or relate d f u ncti o n ) t hat is
wi del y use d i n
cli nical practice a n d trials.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 7
T he researc h tea m has de vel o pe d t he Patie nt-re p orte d Cli nical O utc o me Assess me nt
Scale P R O 1 4 7 ( V 1. 0) f or cer vical ca ncer base d o n t his c o nce pt. T his scale is base d o n
t hree d o mai ns i ncl u di n g dail y life, ps yc h ol o gical a n d s ocial life,
wit h 1 4 7 q uesti o ns
c o veri n g 1 3 latit u des: uri nar y d ysf u ncti o n ( U RI), b o wel d ysf u ncti o n ( B O W), pel vic
or ga n pr ola pse ( P O P), l oss of o varia n f u ncti o n ( O V A), l y m p hatic d ysf u ncti o n ( L Y M),
ne ur ol o gical d ysf u ncti o n ( N E U), se x ual d ys f uncti o n ( S E X), a n xiet y ( A N X) de pressi o n
( D E P), sti g ma ( S H A), life beliefs ( B E L), s ocial s u p p ort ( S U P), a n d dail y life ( LI F) t o
assess patie nt pr o g n osis.
At prese nt, o ur scale has bee n scree ne d, a n d c o m plete d t he
e x pert re vie w, a n d n o w is i n t he pil ot st u d y p hase. S o far, t here are a b o ut 1 0 0 patie nts
ha ve c o m plete d t he s ur ve y, a n d t he i nf or mati o n is ver y usef ul f or f ut ure c o m plicati o n
ma na ge me nt a n d s ur gical efficac y assess me nt.
6. 2 Ge neric q u alit y of life q uesti o n n ai re
Ot h er selecte d q ualit y of life q uesti o n naires relate t o p ost o perati ve s y m pt o ms (e. g.,
pai n) as well as disease-s pecific a n d ge neral healt h-relate d q ualit y of life. T hese s ur ve ys
are self-a d mi nistrate d a n d pr o vi de a n u n dersta n di n g of t he patie nt’s q ualit y of life, a n d
will ta ke less t ha n 3 0 mi n utes t o c o m plete.
T he c urre nt scale use d f or st u d y f oll o w- u p is
mai nl y t he E O R T C
Q ualit y of Life
Meas ure me nt Scale Q L Q C 3 0 ( V 3. 0) scale, w hic h is i nte n de d f or m ost o nc ol o g y pa tie nts
a n d is a u ni v ersal scale. Fr o m a s yst e matic re vi e w i ncl u di n g 1 5 6 st u dies, Cas per Ta x et al.
f o u n d t hat t he E ur o pea n Or ga nizati o n f or Researc h a n d Treat me nt of Ca ncer, Q ualit y of
Life
Q uesti o n naire, Cer vical Ca ncer
M o d ule ( E O R T C
Q L Q- C X 2 4) a n d t he F u ncti o nal
Assess me nt of
Ca ncer T hera p y f or
Cer vical
Ca ncer ( F A C T- C x) are t he o nl y cer vical
ca ncer-s pecific i nstr u me nts t o
date.
E O R T C- Q L Q- C X 2 4
a p pears t o
be t he
m ost
c o m m o nl y use d i nstr u me nt t o assess Healt h Relate d Q u alit y of Life ( H R Q o L) i n patie nts
wit h cer vical ca ncer, a n d t he de vel o pers of t he E O R T C
Q L Q- C X 2 4 pr o p ose d i n t heir
st u d y t hat n o test-retest a nal ysis was perf or me d a n d res p o nse o ver ti me. B ot h scales are
si m ple a n d u ni versal, b ut ca n o nl y disti n g uis h bet wee n patie nts
wit h earl y vers us
a d va nce d disease a n d t h ose w h o are recei vi n g vers us n ot recei vi n g treat me nt. H o we ver,
w het her t he efficac y of differe nt treat me nts (e. g., s ur ger y vers us c he m ot hera p y) or
differe nt s ur gical a p pr oac hes (e. g., la par osc o pic ra dical h ysterect o m y vers us a b d o mi nal
ra dical h ysterect o m y) ca n be disti n g uis he d has n ot bee n re p orte d. It i n dicates t hat
E O R T C- Q L Q- C X 2 4 has s o me li mitati o ns i n t he e val uati o n of efficac y.
VII.
Met h o ds of D at a
M o nit ori n g
7. 1 St u d y m o nit ori n g
7. 1. 1 Tri al S afet y C o m mittee
A n i n de pe n de nt Trial Safet y
C o m mittee ( T S C)
will be esta blis he d t o re vie w t he
safet y a n d efficac y data c ollecte d d uri n g t he st u d y.
T he
T S C
will be c o m p osed o f
i n di vi d uals w h o are i n de pe n de nt of t he st u d y a n d n ot directl y or i n directl y i n v ol ve d i n t he
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 8
a d mi nistrati o n of t he st u d y.
Me m bers will i ncl u de t he f oll o wi n g i n di vi d uals.
T w o g y n ec ol o gic o nc ol o gists n ot i n v ol ve d t he trial.
T w o statisticia ns n ot i n v ol ve d i n t he trial.
Me m bers of t he G y n ec ol o gic O nc ol o g y C o m mittee ( S ha n g hai
Me dical Ass ociati o n
O bstetrics a n d
G y n ec ol o g y
Secti o n, S ha n g hai P h ysicia ns
Ass ociati o n
O bstetrics a n d
G y n ec ol o g y Secti o n)
7. 1. 2 Tri al
M a n a ge me nt C o m mittee
A Trial
Ma na ge me nt C o m mittee ( T M C) will be esta blis he d f or t his st u d y t o re vie w a n d
o versee data a n d a nal ysis. T he T M C will be c o m p ose d of t he
mai n ce nter st u d y lea der,
t he s u b-ce nter lea ders, a n d t he st u d y statisticia n, a n d will n ot ha ve a c o nflict of i nterest
wit h t he f u n di n g pr o vi der. T he ma na ge me nt c o m mittee will meet e ver y f o ur m o nt hs, a n d
after eac h
meeti n g, t he c o m mittee will rec o m me n d t hat t he st u d y c o nti n ue acc or di n g t o
t he pr ot oc ol or rec o m me n d m o dificati o ns t o t he pr ot oc ol base d o n t he res ults of t he data
re vie w.
7. 1. 3 D at a
M o nit ori n g C o m mittee
A Data
M o nit ori n g C o m mittee ( D M C) will be esta blis he d t o i n de pe n de ntl y re vie w a n d
o versee data a n d a nal ysis. T he D M C d oes n ot ha ve a c o nflict of i nterest wit h t he f u n di n g
a ge nc y.
7. 2 I nteri m A n al ysis
T he et hics c o m mittee has t he ri g ht t o ter mi nate t he st u d y
w he n t he n u m ber of deat hs
reac hes a critical le vel or
w he n t he differe nce i n pr o gressi o n-free s ur vi val or o verall
s ur vi val bet wee n t he t w o gr o u ps is si g nifica nt; t he et hics c o m mittee has t he ri g ht t o
ter minate t h e st u d y w he n t here is a vi olati o n of et hics d uri n g t he pr o gress. To e ns ure t he
c o m plia nce of t he patie nts, partici pa nts i n t his st u d y will be gi ve n pri orit y f or treat me nt at
o ur h os pital, a n d t here will be de dicate d staff f or p ost f oll o w- u p a n d data c ollecti o n.
7. 3 Q u alit y C o ntr ol
T he st u d y pr ocess will be cl osel y f oll o we d b y t he pr oject s p o ns or, t he s u b PIs of eac h
st u d y ce nter, t he C R O
ma na ger, a n d t he s ur gical tea m. Data q ualit y is
m o nit ore d b y t he
i n de pe n de nt D M C, CR O p r oject ma na ger, a n d t he s ur gical tea m.
Cli nical
o bser vati o n
a n d
f oll o w- u p:
s ur gical treat me nt
pla n,
s ur ger y-relate d
i n dicat ors, i ntra o perati ve
a n d
p ost o perati ve
c o m plicati o ns,
p ost o perati ve
pat h ol o g y
rec or ds, p ost o perati ve a dj u va nt treat me nt i ncl u di n g ra di ot hera p y a n d c he m ot hera p y d ose
a n d ti me, n u m ber of c o urses a n d a d verse reacti o ns; f oll o w- u p
will be c o n d ucte d e ver y
t hree
m o nt hs f or 2 years after s ur ger y; t he n e ver y 6
m o nt hs fr o m year 3 t o year 5 after
s ur ger y.
Meas ures t o e ns ure patie nts' c o m plia nce: patie nts partici pati n g i n t his st u d y will be
gi ve n pri orit y i n o ur h os pital f or treat me nt, a n d p ost- o perati ve f oll o w- u p
will als o be
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
3 9
assi g ne d.
VIII . Defi niti o n a n d tre at me nt of a d verse e ve nts
8. 1 Defi niti o n of a d verse e ve nts
T he
A d verse E ve nt ( A E) is a n a d verse
me dical e ve nt t hat occ urs after a patie nt or a
s u bject i n a cli nical trial recei ves a dr u g, b ut is n ot necessaril y ca usall y relate d t o t he
treat me nt.
A n y a d verse me dical e ve nt t hat occ urs i n t his trial fr o m t he ti me t he patie nt si g ns t he
i nf or me d c o nse nt a n d recei ves t he treat me nt u ntil 1 m o nt h after t he e n d of t he treat me nt,
re gar dless of
w het her it is ca usall y relate d t o t he s ur ger y perf or me d, is j u d ge d as a n
a d verse e ve nt, i ncl u di n g s y m pt o ms, si g ns, dia g n osis, a n d a b n or mal la b orat or y tests.
8. 2 O bser v ati o n, rec or di n g a n d tre at me nt of a d verse e ve nts
O bser vati o n a n d rec or di n g: t he i n vesti gat or s h o ul d caref ull y o bser ve a n y a d verse e ve nts
occ urri n g i n t he patie nt d uri n g t he st u d y, a n d re q uire t he patie nt t o tr ut hf ull y reflect t he
c ha n ges i n c o n diti o n after treat me nt a n d a v oi d eliciti n g q uesti o ns. Pa y atte nti o n t o
a d verse reacti o ns or u na ntici pate d t o xicities (i ncl u di n g s y m pt o ms, si g ns a n d la b orat or y
tests) w hile o bser vi n g si de effects. Re gar dless of w het her t he a d verse e ve nt is relate d t o
t he s ur ger y perf or me d, it s h o ul d be rec or de d i n detail i n t he C R F, i ncl u di n g t he ti me of
occ urre nce of t he a d verse reacti o n, s y m pt o ms, si g ns, e xte nt, d urati o n, la b orat or y test
i n dicat ors, treat me nt met h o ds, pr ocess, res ults, f oll o w- u p ti me, etc. T he c o m bi ne d use of
dr u gs s h o ul d be rec o r de d i n detail f or a nal ysis of a d verse e ve nt a n d test dr u g c orrelati o n,
a n d t he rec or d s h o ul d be si g ne d a n d date d.
Me dical treat me nt of patie nts:
W he n a d verse reacti o ns are re p orte d, t he i n vesti gat or
s h o ul d ta ke necessar y treat me nt
meas ures acc or di n g t o t he c o n diti o n, s uc h as d ose
a dj ust me nt, te m p orar y i nterr u pti o n of
me dicati o n, etc., a n d deci de w het her t o ter mi nate
t he trial. T he occ urre nce of seri o us a d verse e ve nts, t he u nit u n derta ki n g t he pil ot st u d y
m u st i m me diatel y ta ke t he necessar y
meas ures t o e ns ure t he pr otecti o n of t he safet y of
t he s u bject.
T he first safet y a nal ysis
will
be c o n d ucte d after
2 0
patie nts
ha ve c o m plete d
treat me nt. T S C will re vie w all safet y data c ollecte d d uri n g t he st u d y t wice a year.
I X. C ost- be nefit A n al ysis
We
will als o assess t he s u bjects' h o use h ol d i nc o me a n d s o urces of s ur gical treat me nt
c osts, rec or d t heir healt h i ns ura nce rei m b urse me nt rates, a n d e val uate t he i m pact of
differe nt healt h i ns ura nce rates o n patie nts' h o use h ol d b ur de n.
X. Re vie w
T he
mai n ce nter at t he
O bstetrics a n d
G y n ec ol o g y
H os pital of F u da n
U ni versit y
will
cl osel y
m o nit or t he st u d y. T he
m o nit or
will
mai ntai n a n effecti ve u n dersta n di n g of t he
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
4 0
st u d y t hr o u g h
o bser vati o n, re vie w
of
st u d y rec or ds
a n d
s o urce
d oc u me nts,
a n d
disc ussi o ns wit h i n vesti gat ors a n d staffs a b o ut t he c o n d uct of t he st u d y. T he mai n ce nter
or its desi g nee
will caref ull y
m o nit or all as pects of t he st u d y t o e ns ure t hat t he st u d y
c o m plies wit h a p plica ble g o ver n me nt re g ulati o ns re gar di n g c urre nt g o o d cli nical practice
a n d c urre nt sta n dar d o perati n g pr oce d ures.
I n vesti gat ors
a n d i nstit uti o ns i n v ol ve d i n t he
st u d y
will
all o w trial-relate d
m o nit ori n g, re vie w, I nstit uti o nal
Re vie w
B oar d (I R B)
or
H u ma n
Researc h
Et hics
C o m mittee ( H R E C) re vie ws a n d re g ulat or y i ns pecti o ns t hr o u g h direct access t o ra w
data/ d oc u me nts.
XI. Et hics a n d Disse mi n ati o n
1 1. 1 Et hic al a p pr o v al
A t otal of 1 1 0 4 patie nts will be recr uite d i n si x ce nters: O bstetrics a n d G y n ec ol o g y
H os pital of F u da n U ni versit y, Z h o n gs ha n H os pital affiliate d t o F u da n U ni versit y, Xi n h ua
H os pital affiliate d t o S ha n g hai Jia o To n g U ni versit y Sc h o ol o f
Me dici ne, Re nji H os pital
affiliate d t o
S ha n g hai Jia o
To n g
U ni versit y
Sc h o ol of
Me dici ne,
Taiz h o u
H os pital
Affiliate d Ca ncer
H os pital of t he
U ni versit y of C hi nese Aca de m y of Scie nces, a n d t he
First
Affiliate d
H os pital of
We nz h o u
Me dical
U ni versit y.
All patie nts
will be f ull y
i nf or me d of t he p ur p ose,
met h o ds, be nefits a n d p ote ntial ris ks of t his cli nical trial a n d
si g n t he i nf or me d c o nse nt f or m.
T he st u d y pr ot oc ol has bee n se nt t o eac h s u b-ce nter a n d has bee n re vie we d a n d
a p pr o ve d b y t he et hics c o m mittees of res pecti ve h os pitals.
1 1. 2 St u d y pr ot oc ol m o dific ati o n pl a n
T he mai n o bjecti ve of t his st u d y is t o o bser ve P F S a n d O S after cer vical ca ncer s ur ger y.
T he patie nt sa m ple size is lar ge a n d t he e nr oll me nt ti me is l o n g, s o it nee ds t o ta ke m ore
t ha n 3 years t o c o m plete t he e nr oll me nt.
Maj or s ur ger y, p ost o perati ve treat me nt a n d
i nitial f oll o w- u p c o ul d be c o m plete d d uri n g t his peri o d. It is e x pecte d t hat i nitial
o utc o mes ca n be gi n t o be pr o d uce d after 3 years. H o we ver, t u m or f oll o w- u p will re q uire
at least 5 years t o o btai n c o m plete a n d c o m pre he nsi ve data, es peciall y f or P F S a n d O S.
Pre vi o us si milar st u dies ha ve ta ke n a b o ut 1 0 years t o reac h a fi nal a n d c o n vi nci n g
c o ncl usi o n. After t he i nitial 3 years of f u n di n g f or t his st u d y, t here is still n u mer o us a n d
l o n g-ter m
w or kl oa ds t hat nee d t o be c o m plete d. As a res ult, it is e x pecte d t hat re g ular
f oll o w- u p a n d a nal ysis
will be nee de d f or se veral years after t he c urre nt gra n d e n ds.
T heref ore, we h o pe t hat t he ti me fra me f or t he use of f u n ds a n d t he ti me fra me f or t he
p u blicati o n of res ults ca n be e xte n de d t o facilitate t he l o n g-ter m i m ple me ntati o n of t he
pr oject a n d t he fi nal i nter pretati o n of t he researc h res ults. If t he pr oject d oes n ot c o m plete
t he st u d y
o bjecti ves
or t he tas k
acce pta nce c o ncl usi o n is false, t he
pr oject lea d
or ga nizati o ns s h o ul d ret ur n t he o utsta n di n g f u n ds.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
4 1
1 1. 3 I nf or me d c o nse nt
All patie nts ha ve bee n f ull y i nf or me d of t he p ur p ose,
met h o ds, be nefits a n d p ote ntial
ris ks of t his cli nical trial a n d s h o ul d si g n t he i nf or me d c o nse nt f or m (see A p pe n dices f or
details).
Writte n i nf or me d c o nse nt s h o ul d be o btai ne d fr o m eac h patie nt bef ore e nr oll me nt. A
te m plate of i nf or me d c o nse nt
will be pr o vi de d b y t he
mai n ce nter. Pri or t o recr uit me nt
a n d e nr oll me nt, eac h pr os pecti ve patie nt
will be gi ve n details of t he st u d y a n d e n o u g h
ti me t o un dersta n d t he a p pr o ve d i nf or me d c o nse nt f or m. T he i n vesti gat or will i nf or m t he
patie nt of t he st u d y p ur p ose, t he ra n d o mizati o n pr oce d ure a n d t he f oll o w- u p sc he d ule.
T he i n vesti gat or will disc uss t he p ote ntial be nefits a n d ris ks. T he i n vesti gat or will i nf or m
t he
patie nt t hat
her
me dical rec or ds
will
be re vie we d
b y t he
S he n ka n g
H os pital
A d mi nistrati o n Ce nter a n d H os pital De part me nt.
Patie nts
will
be i nf or me d
b y t he i n vesti gat or t hat t he y
are free t o
decli ne
part ici pati o n, a n d if t he y c h o ose t o partici pate, t he y
ma y wit h dra w at a n y ti me wit h o ut
affecti n g f urt her me dical care.
T his st u d y has c o m plie d wit h t he Re g ulati o ns of t he Pe o ple's Re p u blic of C hi na o n
H u ma n
Ge netic
Res o urces
Ma na ge me nt i n t he c ollecti o n, st ora ge a n d utilizati o n of
bi ol o gical s peci me ns a n d ge netic res o urces (see A p pe n dices f or details).
XII. C o nfi de nti alit y
All me dical rec or d, rele va nt la b orat or y data, c o m plete d C R F f or ms, a n d pr ot oc ol-relate d
d oc u me n ts will be ke pt i n a s pecial l oc ke d ca bi net f or eac h st u d y partici pa nt, a n d access
t o t he m will be gra nte d o nl y after pr o vi di n g rele va nt per missi o ns.
XIII. Decl ar ati o n of C o m peti n g I nterests
T he pr ot oc ol desi g ner a n d all st u d y partici pa nts ha ve n o rele va nt ties or i nterests
wit h t he ma n ufact urers of t he c orres p o n di n g dr u gs, de vices, etc. a n d f u n d pr o vi ders.
XI V. D at a C ollecti o n
Rele va nt e x peri me ntal data a n d basic i nf or mati o n a b o ut t he st u d y s u bjects
will be
c ollecte d a nd fille d o ut b y t he s ur gical tea m, a n d f oll o w- u p i nf or mati o n will be c ollecte d
b y t he f oll o w- u p staff a n d e nter i nt o t he Re d Ca p s yste m b y desi g nate d researc h staff,
w hic h were accessi ble t o t he pr oject tea m
me m bers b ut di d n ot k n o w t he c orres p o n di n g
i nf or mati o n.
Eac h i n vesti gat or a n d or ga nizati o ns i n t his st u d y nee d t o si g n t he " Pr oject
Data
S u b missi o n
U n derta ki n g" (see A p pe n dices f or details), a n d c o m mit t o t he sta n dar dize d
o perati o n of data c ollecti o n, s u b m issi on a n d discl os ure.
O B & G Y  o f  F u d a n  U n i v e r s i t y

A  m ulti c e nt er  n o ni nf eri or  r a n d o mi z e d c o ntr oll e d  st u d y c o m p ari n g  t h e effi c a c y  of  l a p ar os c o pi c v ers us  a b d o mi n al  
r a di c al h yst er e ct o m y  f or c er vi c al  c a n c er  ( St a g e I B 3 a n d  II A 2)
4 2
X V. Affili ati o n a n d P ost-test C are
T he s ur gical pr oce d ures perf or me d i n t his pr ot oc ol are t h ose t hat ha ve bee n i n use f or
m ore t ha n
1 0
years
a n d
meet i nter nati o nal
N C C N
g ui deli ne sta n dar ds,
wit h
n o
o perati o nal a b n or malities a n d n o c orres p o n di n g ter ms attac he d.
X VI. Disse mi n ati o n P olic y
T he i ntellect ual pr o pert y ri g hts of t his st u d y, i ncl u de pate nts, c o p yri g hts, tra de mar ks,
c o p yri g hts of c o m p uter s oft ware, tec h nical secrets, a n d tra de secrets t hat a bi di n g b y t he
la w. Ne w i ntellect ual pr o pert y ri g hts ge nerate d i n t he c o urse of t his st u d y bel o n g t o t he
mai n ce nter, w hic h is res p o nsi ble f or declari n g a n d e nj o yi n g pri orit y, a n d t he s u b-ce nters
are ra n ke d acc or di n g t o t heir c o ntri b uti o n. I ntellect ual pr o pert y ri g hts res ulti n g fr o m t he
i n de pe n de nt
c o m pleti o n
of t he
researc h
w or k
ma y
be
o w ne d
b y
eac h
ce nter
i n de pe n de ntl y.
N o part y s hall discl ose t o ot her parties
wit h o ut t he c o nse nt of t he
c olla b orati n g part y.
T he mai n ce nter has t he ri g ht t o use all t he i nf or mati o n a n d data, a n d t he s u b-ce nters
ha ve t he ri g ht t o use t he i nf or mati o n a n d data of t heir ce nter.
T he
mai n ce nter is
res p o nsi ble f or statistical pr ocessi n g a n d a nal ysis,
writi n g s u m mar y re p orts a n d pa pers.
T he a ut h ors hi p will be deter mi ne d b y t he mai n ce nter, base d o n t he c o ntri b uti o n ( n u m ber
of vali d cases e nr olle d), a n d t he res ults will be s hare d. F or c ollecti ve data a n d c ollecti ve
res ults, t he mai n ce nter will be t he first a ut h or a n d c orres po n di n g a ut h or, a n d s u b-ce nters
will be assi g ne d c o-first a ut h or or c o-c orres p o n di n g a ut h or or c o-a ut h or base d o n t heir
c o ntri b uti o ns. T he p u blicati o n of eac h ce nter's res pecti ve data
will be si g ne d b y eac h
ce nter.
Res ults p u blis he d se paratel y b y s u b-ce nters are re q uire d t o i ncl u de t he
mai n
ce nter as a c o-c orres p o n di n g a ut h or. T he s u b-ce nter ca n n ot p u blis h t he res ults relate d t o
t his st u d y i n a n y f or m u ntil t he mai n ce nter has p u blis he d t he
mai n res ults of t his st u d y.
All
p ers o n nel
of
eac h
ce nter
ca n n ot
d u plicate
or
cr oss-re p ort t his
pr oject.
T he
" T hree- Year
Acti o n Pla n
Maj or
Cli nical
Researc h Pr oject" a n d t he pr oject a p pr o val
n u m ber are i n dicate d.
X VII. A p pe n dices
1. I nf or me d C o nse nt F or m
2. C o m mit me nt t o t he Re g ulati o ns of t he Pe o ple's Re p u blic of C hi na o n H u ma n Ge netic
Res o urces
Ma na ge me nt
3. C o m mit me nt t o S u b mit Pr oject Data
4. State me nt of n ot i n v ol vi n g t he use of hi g hl y pat h o ge nic micr o or ga nis ms
O B & G Y  o f  F u d a n  U n i v e r s i t y