Incomplete staging surgery as a major predictor of relapse of borderline ovarian tumor.

0.17 MB·English

by  Romeo, Margarita

Romeoetal.WorldJournalofSurgicalOncology2013,11:13
http://www.wjso.com/content/11/1/13 WORLD JOURNAL OF
SURGICAL ONCOLOGY
RESEARCH Open Access
Incomplete staging surgery as a major predictor
of relapse of borderline ovarian tumor
Margarita Romeo1,2*, Francesc Pons3, Pilar Barretina4 and Joaquim Radua5,6
Abstract
Background: Borderline ovarian tumors (BOTs) are a subset ofepithelialovariantumors withlow malignant
potentialbutsignificantriskofrelapse(10%to30%).Unfortunately,surgicalprognosticfactorsforBOTrelapsehavenot
beenclearlyidentified,probablyduetotheuseofheterogeneoussurgicaldefinitionsandlimitedfollow-up.Theaimof
thisstudywastoassesspotentialrelapseriskfactorsusingstandardsurgicaldefinitionsandlongfollow-up.
Methods:AllpatientsdiagnosedwithBOTforaperiodofmorethan10yearsinasingleinstitutionwereincludedin
theanalysis.Completesurgicalstagingwasdefinedasthesetofproceduresthatfollowstandardguidelinesforstaging
surgery(exceptlymphadenectomy),performedeitherwithoneortwointerventions.Fertility-sparingsurgeriesthat
preservedoneovaryandtheuterusbutincludedalltheremainingprocedureswereclassifiedascompletestaging.The
relationshipbetweenpotentialriskfactorsandtimetoBOTrelapsewasassessedbylog-ranktestscorrectedfor
multiplecomparisonsandCoxregression.
Results:Forty-sixpatientswithamedianfollow-upof5.4yearswereincluded,ofwhom91.3%hadbeendiagnosedas
FIGOstageIdiseaseand45.7%hadreceivedcompletestagingsurgery.Fiverelapsesweredetected(10.9%),allofthem
inwomenwhohadbeendiagnosedwithstageIdiseaseandhadreceivedincompletestagingsurgery.Log-ranktests
confirmedtheassociationbetweenincompletestagingsurgeryandshortertimetoBOTrelapse.
Conclusions:CompletestagingsurgeryshouldbeconsideredacornerstoneofBOTtreatmentinordertominimize
theriskofrelapse.
Keywords:Borderlineovariantumor,Relapse,Prognosis,Surgery,Staging,Recurrence,Fertility-sparingsurgery
Background ComparedtoIOTs,BOTsaffectyoungerwomenandare
Borderline ovarian tumors (BOTs), which account for diagnosed at earlier stages, and patients have significantly
15% of epithelial ovarian tumors, are defined by the better survival rates. Approximately 85% of BOTs are
presence of cellular proliferation and nuclear atypia diagnosed at stage I, which confers a 98% overall survival
without an infiltrative pattern or stromal invasion. rate at 5 years [3]. Beyond stage II, the 5-year overall
Histologically,theyaredividedintoserous(50%),mucinous survival is still excellent, around 85% to 92% [2,3].
(45%) and other subtypes (namely endometrioid, clear cell However,upto10%to30%ofpatientswillsufferarelapse
and Brenner). The staging system of the International with locoregional (pelvic or abdominal) disease, and late
Federation of Gynecology and Obstetrics (FIGO) is the relapsesare relatively common(>25% relapses occurafter
same for BOT and for invasive ovarian tumors (IOTs). 5 years) [4-6]. Although most of these recurrences show
Remarkably, BOT’s extra-ovarianimplants can be either borderline histology, up to 30% of them may be IOTs,
noninvasiveorinvasive[1,2]. worseningtheoverallsurvivalofBOTs[7,8].
The standard of care for BOTs is complete comprehen-
sivestagingsurgery,definedastheexplorationoftheentire
abdominal cavity, bilateral oophorectomy, hysterectomy,
*Correspondence:[email protected]
1MedicalOncologyDepartment,InstitutCatalàd’Oncologia-Badalona, infracolic omentectomy, peritoneal biopsies, peritoneal
CarreteradeCanyets/n08916,Badalona,Barcelona,Spain washings, removal of all macroscopic suspicious peritoneal
2MedicalOncologyDepartment,InstitutCatalàd’Oncologia-L’Hospitalet,Gran
Viadel’Hospitalet,199–203,l’HospitaletdeLlobregat,Barcelona08908,Spain lesions and, for mucinous tumors, also appendectomy.
Fulllistofauthorinformationisavailableattheendofthearticle
©2013Romeoetal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative
CommonsAttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,and
reproductioninanymedium,providedtheoriginalworkisproperlycited.
Romeoetal.WorldJournalofSurgicalOncology2013,11:13 Page2of7
http://www.wjso.com/content/11/1/13
Unfortunately, only 50% of patients undergo complete collected from medical files. The variables included in
staging. Pelvic and para-aortic lymphadenectomy do the analysis were: age, baseline CA125 and CA199 values,
notincreaseoverallsurvival.Similarly,neitherchemother- type of surgical staging (complete or not), fertility-sparing
apynor radiotherapyare currentlyacceptedas partofthe intention, surgical approach (laparoscopy or laparotomy),
standardcare, since randomized trials havefailed toshow performance of lymphadenectomy, histology subtype
a benefit to survival [2]; chemotherapy is only considered (serous or mucinous), FIGO staging, intraoperative and
incasesofperitonealinvasiveimplants[9]. pathologic cyst rupture, presence and type of peritoneal
The low incidence of BOTs has made it difficult to implants and peritoneal cytology results. Relapse and
establish solid conclusions about their prognosis. survival information was collected after at least 5 years
Numerous studies confirm the association of several offollow-up(31December2008).
pathologic and clinical characteristics with an increased Complete surgical staging was defined as the set of
risk of BOT relapse, namely older age at diagnosis [2], procedures that follow standard guidelines for staging
invasive peritoneal implants (present in 15% to 40% of surgery[9],independentlyofwhethertheywereperformed
BOTs) [10], advanced stage [2,5,8], cyst rupture [11], in one or two interventions (that is, a second procedure
stromal microinvasion [5,12-14] and elevated baseline aftercompletingchildbearing).Fertility-sparingsurgerywas
CA125 [8,15-18]. Invasive peritoneal implants and an defined as a procedure in which the uterus and at least
advanced stage have also been reported to decrease part of one ovary were preserved with the aim of pre-
overallsurvival[2,5,8,10,18,19].However,theprognostic serving fertility. Fertility-sparing surgery that included
impact of surgical procedures, such as fertility-sparing all the procedures of complete surgical staging except
surgery or the surgical approach (that is, laparotomy vs for hysterectomy and unilateral oophorectomy, were
laparoscopy),iscurrentlyinconclusive. considered as complete staging. Histological typing was
Fertility-sparing surgery (or ‘conservative’ surgery) performed according to the World Health Organization’s
showed an increased risk of relapse in some studies system. The staging system was based on the 2006 FIGO
[2,19,20]. The general objective of this approach is the stagesystemforovariancancer[1,2].
preservation of the uterus and the contralateral, non- Baseline CA125 and CA199 values, type of surgery,
affected ovary (or at least part of it) [2], but the specific surgical approach, performance of lymphadenectomy,
definitionoftheprocedure(thatis,includingomentectomy histology subtype, FIGO staging, intraoperative and patho-
ornot)dependsonthesurgicalteam.Moreover,secondary logiccystrupture,presenceofperitonealimplantsandtheir
complete surgery after completing childbearing is a invasiveness and peritoneal washing cytology results were
standard procedure in some institutions but not in included as potential risk factors for relapse. The time to
others. However, overall survival seems unaffected, relapsewasdefinedasthetimefromsurgerytorelapse.
probably because a significant number of these relapses Duetothepresenceofcensorship(forexample,because
exclusively involve the remaining ovary and can be of follow-up failure or deaths from intercurrent disease),
surgicallyrescued[19,20]. the influence of the potential risk factors on the time to
Thefindingsofpreviousstudiesmightalsobeinfluenced relapsewasassessedusingsurvival-analysislog-ranktests,
by the length of their follow-up. A follow-up period above ratherthansimplycomparingtherelapsefrequencies.The
5yearshasbeenclaimed to be crucialinorder to properly falsediscoveryrate(FDR)wasusedtocorrectformultiple
evaluate the relapse rate, due to the high number of late comparisons.Amultivariateanalysisoftheriskofrelapse,
relapses[1,6].Indeed,relapseratesrangefrom5%inseries as a function of the factors found to be statistically
with median follow-up <3 years [21] to 30% in series with significant prognostic factors in the univariate analysis,
medianfollow-up>5years[5-7]. was performed using Cox regression. The data were
The aim of this study was to assess the potential analyzed using the SPSS (SPSS Inc, Chicago, IL) version
associations between the different surgical procedures 17.0statisticalpackage.
and the relapse rate of BOTs. With this aim, all patients
diagnosed with BOTs during an 11-year timeframe in a Results
singleinstitutionwereclassifiedaccordingtostrictsurgical Descriptionofthesample
definitions. Given the results of previous studies, we Forty-six women were diagnosed with BOT between
hypothesized an association between incomplete surgical January 1992 and December 2002. The median time of
stagingandincreasedriskofrelapse. follow-up (from diagnosis to relapse or last date of
follow-up) was 5.4 years (interquartile range: 2.5 to 6
Methods years). Their demographic characteristics are shown
All patients diagnosed with BOTfrom 1 January 1992 to in Table 1.
31 December 2002 in a single institution were included Twenty-five patients (54.3%) received incomplete
in this study. The clinical data from each participant was staging surgery. The main reason that these surgeries
Romeoetal.WorldJournalofSurgicalOncology2013,11:13 Page3of7
http://www.wjso.com/content/11/1/13
Table1Characteristicsofthewholecohort any case. Lymphadenectomies were performed in 21 of
Numberofwomen % the 46 patients (45.7%), all of which included both pelvic
and retroperitoneal areas; the mean number of resected
Mediantimeoffollow-up(years) 5.4
nodeswas12.
Interquartilerange(years) 2.5to6
Most of the patients (91.3%) were diagnosed as FIGO
Meanageatdiagnosis(years±SD) 47.77±16.45
stage I. Peritoneal implants were found in 3 patients
Histology(n=46): (6.7%), none of them invasive. No affected nodes were
Serous 21 45.7 found by the pathologic examinations of any patient.
Mucinous(intestinal+Müllerian) 24 52.2 Adjuvant treatment was not administered to any patient,
according to National Comprehensive Cancer Network
Clear-celltumor 1 2.1
guidelines[9].
CA125orCA199beforesurgery(n=34):
Laparotomy was the most frequent surgical approach
Elevated(>35UNL) 27 79.4
(87%). Intraoperative cyst rupture was observed in only
Normal 7 20.6 2 patients (4.5%), but the relative frequency seemed
Approach(n=46): higher in those women who had received laparoscopy
Laparotomy 40 87.0 (1 out of 6 patients, 16.7%), though this difference did not
reach statistical significance (Fisher’s exact test P > 0.05).
Laparoscopy 6 13.0
No port site metastases were developed in patients
Surgery(n=46):
operatedonbylaparoscopy.
Complete 21 45.7
Three deaths were reported: two in patients free of
Incomplete 25 54.3 recurrence,andonecausedbyinvasivetumorprogression
Lymphadenectomy(n=46): 6.7yearsaftertheinitialdiagnosis(seeTable2).
Pelvic+/−para-aortic 21 45.7 The intention of surgical intervention preserving at
least one ovary and the uterus was not recorded in all of
None 25 54.3
the medical files of patients who underwent this type of
Intraoperativecystrupture(n=44):
surgery. Thus, we were unable to establish whether
Yes 2 4.5
fertility-sparing interventions in women aged 40 to 50
No 42 95.5 who already had children should be considered as
Pathologiccystrupture(n=46): fertility-sparing surgery or whether, conversely, they
Yes 10 21.7 were merely incomplete.
No 36 78.3
Recurrencecharacteristics
Peritonealimplants(n=46):
Five recurrences (10.9%) were detected (Table 2). All
Invasive 0 0.0
patients who eventually relapsed had been considered
Non-invasive 2 4.3 stage I BOT, and none of these patients had received
None 33 71.7 complete surgical staging (their interventions had been
Notdescribedbysurgeon 11 23.9 cystectomies or unilateral adnexectomies). The mean time
for recurrence was 3.3 ± 2.1 years. Laparoscopy had been
Peritonealwashings(n=46):
used in 3 cases (60%). Three relapses were invasive (stage
Positive 0 0.0
IA mucinous IOT in the contralateral ovary, stage IIC
Negative 46 100.0
mucinousIOTandstageIIICserousIOT),whilsttheother
FIGOstaging(n=46): two had borderline histology (one mucinous in the
IA 23 50.0 remaining ovarian tissue and the other serous in the
IB 7 15.2 contralateral adnex). Thus, 3 relapses (60%) involved the
remainingadnexesexclusively,and2(40%)werestageIIor
IC 12 26.1
above.Salvagetreatmentatrelapsewasbasedondebulking
≥II 3 6.5
surgery in all patients but one, in whom a unilateral
Informationnotavailable 1 2.2
salpingo-oophorectomy plus total abdominal hysterectomy
wasperformed.
were considered ‘incomplete’ was the understaging of the At the date of last control, the three women with
abdomen, including the lack of infracolic omentectomy, relapse confined to adnexes were free of disease, the
theincompleteexplorationoftheentireabdominalcavity, woman with invasive stage IIIC relapse was alive with
and the paucity of peritoneal biopsies and peritoneal disease and the woman with invasive stage IIC relapse
washings. There was no residual macroscopic disease in haddied because ofdisease.
hR
ttpom
://weo
wet
wa
.wl.
jsW
oo
.corld
m/cJou
onternal
no
t/11/1/1fSurgica
3l
O
n
c
o
Table2Descriptionofthefiverecurrences lo
g
y
Ageat FIGOstaging Intraoperative/ Approach Kindofoperation Serummarker Yearsfrom Natureof Recurrencesite Treatmentfor Lastcontrol Timeof 2
diagnosis pathologic (noneofthemhad atdiagnosis firstsurgery relapses relapse status follow-up 01
3
cystrupture anyre-resection) torecurrence (years) ,
1
1
1 34.53 IA No LSC Adnexectomy CA199=7939 1.4 IOTmucinous contralateral debulking Freeofdisease 6.06 :1
3
intestinal ovary,IA
Negwashings CA125=4387
2 35.63 IC No/Yes LT Adnexectomy 2 BOTserous contralateral USO+TAH Freeofdisease 10.14
ovary
Negwashings
3 20.30 IC No/Yes LSC Cystectomy 2 BOTmucinous sameovary debulking Freeofdisease 5.80
intestinal
Negwashings
4 62.62 IC Yes LSC Adnexectomy CA125=554 6.2 IOTserous pelviclymph debulking+ Alivewithdisease 9.66
nodeIIIC chemotherapy
Negwashings
5 38.42 IA No LT Adnexectomy 4.7 IOTmucinous positiveascites, debulking Deadofdisease 6.69
intestinal IIC
Negwashings
BOT,borderlineovariantumor;IOT,invasiveovariantumor;LSC,laparoscopy;LT,laparotomy;USO+TAH,unilateraloophorectomyplustotalabdominalhysterectomy.
P
a
g
e
4
o
f
7
Romeoetal.WorldJournalofSurgicalOncology2013,11:13 Page5of7
http://www.wjso.com/content/11/1/13
Relapseprognosticfactors
The time to relapse was found to be significantly lower
in those patients who had undergone incomplete staging
surgery (χ2=5.507, degrees offreedom –df- =1,uncor-
rected P = 0.019, FDR-corrected P = 0.038), in those
patients operated on by laparoscopy (χ2 = 8.072, df = 1,
uncorrected P = 0.004, FDR-corrected P = 0.024), and in
those patients without lymphadenectomy (χ2 = 5.862,
df = 1, uncorrected P = 0.015, FDR-corrected P = 0.038).
TheomnibustestofaCoxregressionusingthesesurgical
factors was statistically significant (χ2 = 10.281, df = 3,
P = 0.016), thus rejecting the joint hypothesis that the
coefficients are all zero. Individual tests for the regression
coefficients were not statistically significant (Wald = 0.003
to0.612,df= 1,P> 0.05), thoughthiscould potentially be
due to collinearity as these three surgical factors were not
independent (χ2 = 5.217 to 15.146, df = 1, P = 0.001 to
0.030)(Figure1).
No significant differences were found depending on
Figure1Time-to-relapseanalysisinpatientswithcomplete
the histology type, FIGO or the presence of pathologic
andwithincompletestagingsurgery.
cystrupture.Thepresenceofintraoperativecystruptures,
positive peritoneal washing or peritoneal implants could
notbeincludedinthe analysisduetothelowfrequencies operatedonbylaparoscopy(comparedtolaparotomy),and
of these events (2, 0 and 3 respectively). CA125 and inpatientswhohadnotundergonelymphadenectomy.
CA199 values were not included because the values were Complete surgical staging has been reported to be an
missinginmostofthepatientswhosufferedarelapse. important local relapse predictive factor for nearly all
There was no difference in survival between patients tumors, and complete staging including the removal of
who had received complete staging surgery and patients all macroscopic implants has been demonstrated to
who had not (mean survival: 9.6 vs 9.5 years, χ2 = 0.324, improve overall survival in patients with IOTs [24,25].
df=1,P=0.569). However, the benefits of complete staging in patients
withBOTscouldbepotentiallylimitedbecause:a)itmight
Discussion not modify the decision regarding adjuvant treatment as
Despite their excellent prognosis, BOTs are not a minor this is not the standard care; and b) most recurrences can
health problem as 10% to 30% of patients relapse and be salvaged. However, incomplete staging may prevent the
one third of relapses can be in form of IOTs, thus possibility of detecting more aggressive disease, which
impairing overall survival [7,8]. Moreover, BOTs affect could be surgically removed or be a reason to deliver
younger women than IOTs and often require surgery chemotherapy.Inarecentseriesof233patientswithBOTs
entailing infertility. Unfortunately, surgical prognostic without re-staging procedures, those patients who had
factors for long-term relapse outcomes have not been undergone complete staging suffered fewer relapses than
clearly established, probably due to the use of different those with incomplete staging (5.1% vs 12.3%), although
surgical definitions or to the short follow-up periods of this difference was not statistically significant in the
some ofthereportedseries. multivariate analysis [8]. National Comprehensive Cancer
This article presents an analysis of prognostic factors Network guidelines [9] and other authors [2] have
for BOT relapse in a series with a median follow-up >5 recommended the same complete staging procedure as is
years and using the standard definition of complete performed on patients with IOTs. Remarkably, all patients
comprehensive surgical staging, even in those cases who suffered a relapse in our series had previously under-
where fertility-sparing surgery had been performed. The goneincompletesurgicalstaging.
proportion of patients who suffered a relapse (10.9%) The FIGO staging classification for ovarian neoplasms is
and the mean time from surgery to recurrence (3.3 ± based on surgical findings and it can only be determined
2.08 years) in the series presented here are similar to withcompletesurgicalstaging.Inoursample, thepercent-
those reported in other long-term follow-up series age of patients with stage I disease or peritoneal implants
[5,6,8,10,21-23]. The main finding was that incomplete (91.3%and4.3%respectively)andthosereceivingcomplete
staging surgery significantly increased the risk of relapse. surgical staging (45.7%) were in agreement with figures
The relapse risk was also found to be higher in patients reported in the literature [2,5,8,22,23]. Taking into account
Romeoetal.WorldJournalofSurgicalOncology2013,11:13 Page6of7
http://www.wjso.com/content/11/1/13
the number of stage I cases among patients in this series suchasFIGOstaging.However,thesmallsamplesizealso
withincompletesurgery,asignificantnumberofBOTsthat implies that the relationships detected between relapse
had been diagnosed as stage I should be better defined as incidence and surgical factors should probably be very
presumedstageI.Thisstudysuggeststhatahighernumber strong. Second, the low numbers in some subgroups
of complete staging procedures might result in detecting precluded the exploration of some of the potential prog-
more cases with peritoneal implants and thus, that the nosticfactorssuchasbaselineserummarkersatdiagnosis,
incidence of stage I tumors in the literature might be intraoperative cyst rupture, peritoneal washings and the
slightlyoverestimated.Thefactthatasignificantnumberof presence of implants. Fortunately, the FIGO stage may
relapses appear in the peritoneum reinforce this idea indirectly include the effects of some of these factors.
[3,5,8,23]. The five relapses in our sample occurred for Third, the three surgicalfactors analyzed(type ofsurgery,
presumedstageIpatients:theperitonealoneswereinvasive surgical approach and performance of lymphadenectomy)
while two of the three patients who had relapses in the were not independent (χ2 = 5.217 to 15.146, df = 1, P =
remaining adnexes had borderline histology. The three 0.001to0.030),soitcannotberuledoutwhichoneorones
patientswith adnexes-confined relapsewere freeofdisease might be truly related to relapses and which might not.
in the follow-up, while the two patients who suffered an However, incompleteness of surgery may probably be the
extra-ovarianrelapsewerenot.Thisisconcordantwiththe main relapse risk factor, since: a) lymphadenectomy is not
study of Wu et al., in which nearly all invasive relapses considered to be a relevant prognostic factor for BOT; b)
occurredintheperitoneum,whilemostrelapseswithBOT the relationship between laparotomy and completeness of
histologyoccurredintheadnexes[8].Wehypothesizethat staging procedures could be explained by the insufficient
complete surgical staging could minimize peritoneal and laparoscopic skills during the 1992 to 2002 period; and c)
invasiverelapse. all patients suffering relapses in our series were incom-
In our series, relapse risk was also found to be signifi- pletelystaged.Finally,asmentionedearlier,thisstudycould
cantly higher in patients who had not undergone lympha- not separately assess the influence of fertility-sparing
denectomy.Itmustbenoted,however,thatthisassociation surgeryintheprognosisofBOT.
may be confounded by the fact that lymphadenectomies
were usually performed in the context of complete staging
Conclusions
and laparotomy, an association that might reflect the
In summary, this study, though small, stresses the
everydayworkatgynecologicservicesuntilthelate1990s,
importance of complete staging of BOTs in order to
whenthenumberofsystematiclymphadenectomiesbegan
prevent peritoneal relapse, some of which may be invasive.
todeclinefor patientswithBOTs[26].Indeed, lymphade-
Moreover, complete staging enables clinicians to discover
nectomy is no longer recommended for BOT treatment
thepresenceofinvasiveimplants,whichmaybeanindica-
because lymph node positivity has not been proved to
tion of the need for adjuvant chemotherapy. Based on the
affect overall survival when adjusted for FIGO staging, as
findings of this study, we suggest performing complete
reported in published retrospective series or analyses of
comprehensive staging surgery in patients diagnosed
largedatabases[18,27-29].
with BOT. In young patients who desire to preserve
Laparotomy was also associated with decreased risk of
their fertility, as well as sparing the uterus and one ovary,
relapse. However, this association could again be related
wewouldsuggestcarefullyexploringtheabdominalcavity
to the accrual period (1992 to 2002), as laparotomy was
andconsideringperitonealabdominalstagingsurgery.
the selected approach in 87% of cases. Nowadays,
Further investigations are encouraged inorder to better
surgeons have improved their laparoscopy skills and a
clarify the specific roles of the different predictive factors
complete staging procedure with lower morbidity is
forrelapseinlong-termfollow-ups(>5years).
feasible with this approach, although the frequency of
understaging and cyst ruptures still remains high with
this technique [2,22,23]. In our series, intraoperative cyst Abbreviations
BOT:Borderlineovariantumor;FDR:Falsediscoveryrate;FIGO:International
ruptures seemed more frequent in women operated on
FederationofGynecologyandObstetrics;IOT:Invasiveovariantumor.
by laparoscopy (16.7%) than in those operated on by
laparotomy (4.5%), like the percentages reported in 2005
Competinginterests
by Fauvet et al. [22]. Of interest, this group found the Theauthorshavenocompetingintereststodeclare.
same relapse rate between patients who had undergone
laparotomyorlaparoscopy[22]. Authors’contributions
Some limitations of this study must be highlighted. Theauthors’contributionswereasfollows:MRandJRdesignedthestudy;
First, its sample size was relatively small, a condition MRandFPretrievedthedata;MRandJRconductedthestatisticalanalyses.
Alloftheauthorswereinvolvedindraftingthemanuscriptorcritically
whichmayhavereducedthepowertodetectrelationships
revisingitandgavefinalapprovaloftheversiontobepublished.Allauthors
between relapse incidence and factors other than surgery, readandapprovedthefinalmanuscript.
Romeoetal.WorldJournalofSurgicalOncology2013,11:13 Page7of7
http://www.wjso.com/content/11/1/13
Acknowledgements borderlineovariantumors:multivariateanalysisofaFrenchmulticentre
WethankDrC.BalañáfortheirsupportandMrF.J.Pérezforhisadviceon study.EurJSurgOncol2010,36(11):1066–1072.
statistics. 17. LenhardMS,NehringS,NagelD,MayrD,KirschenhoferA,HertleinL,Friese
K,StieberP,BurgesA:PredictivevalueofCA125andCA72–4inovarian
Authordetails borderlinetumors.ClinChemLabMed2009,47(5):537–542.
1MedicalOncologyDepartment,InstitutCatalàd’Oncologia-Badalona, 18. CamatteS,MoriceP,AtallahD,PautierP,LhommeC,Haie-MederC,
CarreteradeCanyets/n08916,Badalona,Barcelona,Spain.2Medical DuvillardP,CastaigneD:Lymphnodedisordersandprognosticvalueof
OncologyDepartment,InstitutCatalàd’Oncologia-L’Hospitalet,GranViade nodalinvolvementinpatientstreatedforaborderlineovariantumor:an
l’Hospitalet,199–203,l’HospitaletdeLlobregat,Barcelona08908,Spain. analysisofaseriesof42lymphadenectomies.JAmCollSurg2002,
3MedicalOncologyDepartment,HospitaldelMar-ParcdeSalutMar,Passeig 195(3):332–338.
Marítim25-29,Barcelona08003,Spain.4MedicalOncologyDepartment, 19. ParkJY,KimDY,KimJH,KimYM,KimYT,NamJH:Surgicalmanagementof
InstitutCatalàd’Oncologia-Girona,Av.Franças/n.17007,Girona,Spain. borderlineovariantumors:theroleoffertility-sparingsurgery.Gynecol
5King’sCollegeLondon,16DeCrespignyPark,LondonSE58AF,United Oncol2009,113(1):75–82.
Kingdom.6FIDMAGResearchUnit,CIBERSAM,C/Dr.AntoniPujadas,38,Sant 20. UzanC,KaneA,ReyA,GouyS,DuvillardP,MoriceP:Outcomesafter
BoideLlobregat,Barcelona08830,Spain. conservativetreatmentofadvanced-stageserousborderlinetumorsof
theovary.AnnOncol2010,21(1):55–60.
Received:11June2012Accepted:13January2013 21. DesfeuxP,CamatteS,ChatellierG,BlancB,QuerleuD,LécuruF:Impactof
Published:23January2013 surgicalapproachonthemanagementofmacroscopicearlyborderline
ovariantumors.GynecolOncol2005,98:390–395.
22. FauvetR,BoccaraJ,DufournetC,PonceletC,DaraiE:Laparoscopic
References managementofborderlineovariantumors:resultsofaFrench
1. HeintzAP,OdicinoF,MaisonneuveP,QuinnMA,BenedetJL,CreasmanWT, multicenterstudy.AnnOncol2005,16(3):403–410.
NganHY,PecorelliS,BellerU:Carcinomaoftheovary.FIGO26thAnnual 23. RomagnoloC,GadducciA,SartoriE,ZolaP,MagginoT:Managementof
ReportontheResultsofTreatmentinGynecologicalCancer.IntJ borderlineovariantumors:resultsofanItalianmulticenterstudy.Gynecol
GynaecolObstet2006,95(Suppl1):S161–S192. Oncol2006,101(2):255–260.
2. KadronI,LeunenK,VanGorpT,AmantF,NevenP,VergoteI:Management 24. DuBA,QuinnM,ThigpenT,VermorkenJ,VallLundqvistE,BookmanM,
ofborderlineovarianneoplasms.JClinOncol2007,25:2928–2937. BowtellD,BradyM,CasadoA,CervantesA,EisenhauerE,FriedlaenderM,
3. ZanettaG,RotaS,ChiariS,BonazziC,BratinaG,MangioniC:Behaviorof FujiwaraK,GrenmanS,GuastallaJP,HarperP,HogbergT,KayeS,Kitchener
borderlinetumorswithparticularinteresttopersistence,recurrence,and H,KristensenG,MannelR,MeierW,MillerB,NeijtJP,OzaA,OzolsR,Parmar
progressiontoinvasivecarcinoma:aprospectivestudy.JClinOncol2001, M,PecorelliS,PfistererJ,PovedaA,etal:2004consensusstatementson
19(10):2658–2664. themanagementofovariancancer:finaldocumentofthe3rd
InternationalGynecologicCancerIntergroupOvarianCancerConsensus
4. UzanC,KaneA,ReyA,GouyS,PautierP,LhommeC,DuvillardP,MoriceP:
Howtofollowupadvanced-stageborderlinetumours?Modeof Conference(GCIGOCCC2004).AnnOncol2005,16(Suppl8):viii7–viii12.
25. DuBA,ReussA,Pujade-LauraineE,HarterP,Ray-CoquardI,PfistererJ:Role
diagnosisofrecurrenceinalargeseriesstageII-IIIserousborderline
tumoursoftheovary.AnnOncol2011,22(3):631–635. ofsurgicaloutcomeasprognosticfactorinadvancedepithelialovarian
cancer:acombinedexploratoryanalysisof3prospectivelyrandomized
5. LongacreT,McKenneyJ,TazelaarH,etal:Ovarianseroustumorsoflow
phase3multicentertrials:bytheArbeitsgemeinschaftGynaekologische
malignantpotential:outcomebasedstudyof276patientswithlong
termfollowup.AmJSurgPathol2005,29:707–723. OnkologieStudiengruppeOvarialkarzinom(AGO-OVAR)andtheGroupe
d’InvestigateursNationauxPourlesEtudesdesCancersdel’Ovaire
6. SilvaE,GershensonD,MalpicaA,etal:Therecurrenceandtheoverall
(GINECO).Cancer2009,115(6):1234–1244.
survivalratesofovarianserousborderlineneoplasmswithnon-invasive
26. GershensonDM:Contemporarytreatmentofborderlineovariantumors.
implantsistimedependent.AmericalJournalofPathology2006,
30(11):1367–1371. CancerInvest1999,17(3):206–210.
27. McKenneyJK,BalzerBL,LongacreTA:Lymphnodeinvolvementinovarian
7. GershensonDM,SilvaEG,Tortolero-LunaG,LevenbackC,MorrisM,Tornos
seroustumorsoflowmalignantpotential(borderlinetumors):
C:Serousborderlinetumorsoftheovarywithnoninvasiveperitoneal
implants.Cancer1998,83(10):2157–2163. pathology,prognosis,andproposedclassification.AmJSurgPathol2006,
30(5):614–624.
8. WuTI,LeeCL,WuMY,HsuehS,HuangKG,YehCJ,LaiCH:Prognosticfactors
28. DjordjevicB,MalpicaA:Lymphnodeinvolvementinovarianserous
predictingrecurrenceinborderlineovariantumors.GynecolOncol2009,
114(2):237–241. tumorsoflowmalignantpotential:aclinicopathologicstudyofthirty-six
cases.AmJSurgPathol2010,34(1):1–9.
9. Ovarian,fallopiantubeandprimaryperitonealcancers1:NCCNclinical
29. LesieurB,KaneA,DuvillardP,GouyS,PautierP,LhommeC,MoriceP,Uzan
practiceguidelinesinoncology2013.http://www.nccn.org/professionals/
C:Prognosticvalueoflymphnodeinvolvementinovarianserous
physician_gls/pdf/ovarian.pdf.
borderlinetumors.AmJObstetGynecol2011,204(5):438.e1–7.
10. MoriceP,CammatteS,ReyA,AtallahD:Prognosticfactorsforpatients
withadvancedstageserousborderlinetumorsoftheovary.AnnOncol
2003,14:592–598. doi:10.1186/1477-7819-11-13
Citethisarticleas:Romeoetal.:Incompletestagingsurgeryasamajor
11. VergoteI,DeBJ,FylesA,BertelsenK,EinhornN,SeveldaP,GoreME,KaernJ,
predictorofrelapseofborderlineovariantumor.WorldJournalof
VerrelstH,SjovallK,TimmermanD,VandewalleJ,VanGM,TropeCG:Prognostic
SurgicalOncology201311:13.
importanceofdegreeofdifferentiationandcystruptureinstageIinvasive
epithelialovariancarcinoma.Lancet2001,357(9251):176–182.
12. SilverbergSG,BellDA,KurmanRJ,SeidmanJD,PratJ,RonnettBM,
CopelandL,SilvaE,GorsteinF,YoungRH:Borderlineovariantumors:key
pointsandworkshopsummary.HumPathol2004,35(8):910–917.
13. McKenneyJK,BalzerBL,LongacreTA:Patternsofstromalinvasionin
ovarianseroustumorsoflowmalignantpotential(borderlinetumors):
areevaluationoftheconceptofstromalmicroinvasion.AmJSurgPathol
2006,30(10):1209–1221.
14. RenJ,PengZ,YangK:Aclinicopathologicmultivariateanalysisaffecting
recurrenceofborderlineovariantumors.GynecolOncol2008,110(2):162–167.
15. AyhanA,SedaE,GuvenS,KucukaliT:Recurrenceandprognosticfactors
inborderlineovariantumors.GynecolOncol2005,98:439–445.
16. PonceletC,FauvetR,YazbeckC,CoutantC,DaraiE:Impactofserum
tumormarkerdeterminationonthemanagementofwomenwith