Open Jo urnal of Obstetr ics and Gynecology, 2011, 1, 71-83 OJOG
doi:10.4236 /ojog.2011.13014 Published Online September 2011 (
Published Online September 2011 in SciRes.
Prognostic factors for survival after neoadjuvant
chemotherapy for advanced ovarian cancer: meta-analysis
Malcolm John Farquharson1*, Nadeem Ahmed Siddiqui2
1Department of Obstetrics and Gynecology, Crosshouse Hospital, Ayrshire, UK.
2Department of Gynecological Oncology, Glasgow Royal Infirmary, Glasgow, UK.
E-mai l : *
Received 25 July 2011; revised 20 August 2011; accepted 29 August 2011.
Background: In advanced disease current practice is
staging and primary debulking laparotomy followed
by platinum-based chemotherapy. The effort to achie-
ve ‘optimal debulking’ is associated with a compli-
cation risk of 8% - 63% and a mortality rate of 1% -
6%. Neoadjuvant chemotherapy has been proposed
as an alternative option. Objectives: This meta-analy-
sis aimed to determine prognostic factors influencing
survival in patients with advanced ovarian cancer
following neoadjuvant chemotherapy. Search St rategy :
Clinical trials citing the terms ‘advanced ovarian can-
cer’, ‘ovarian cancer’, ‘neoadjuvant chemotherapy’
and ‘surgery’ were identified by searching Pubmed
and ScienceDirect between January 1st 2000 and
September 30th 2010. Data Collection and analysis:
The trials included used platinum-based chemothe-
rapy a nd i nvolved stage III/IV disease that underwent
neoadjuvant chemotherapy followed by surgery. Prog-
nostic variables were identified for analysis including
number/type of chemotherapy, % stage IV disease, %
max i ma l cy toreductive surg ery a nd w hether a lympha-
denectomy was performed. The % bowel surgery and
ultra-radical surgery was also analysed. Main Results:
Twenty six trials were identified as suitable for anal-
ysis and included 3 non-randomised Phase II studies,
2 retrospective case-control studies, 17 from retros-
pective analysis and 1 RCT. A significant association
betwe en taxane use vs plat inum only (p = 0.019), year
of publication (p = 0.032), % maximal interval cytor-
eduction (p = 0.046) and median overall survival was
identified. No significant survival benefit was dem-
onstrated with number of chemotherapy cycles (p =
0.065), lymphadenectomy (p = 0.813) and % bowel
surgery performed (p = 0.606). Conclusions: The
addition of taxane and % maximal cytoreduction
achieved is associated with improved overall survival.
There is, however no evidence that lymphadenecto-
my, number of chemotherapy cycles or bowel surgery
influences survival.
Keywords: Neoa dj uvant Che mo the ra py; Surviva l;
Advanced Ovarian Cancer; Prognostic Factors
Ovarian cancer is the 2nd commonest gynaecological
malignancy with epithelial tumours accounting for 90%.
In the UK, there are approximately 6500 new cases of
ovarian cancer per year. They are usually discovered at
an advanced stage (FIGO stage III/IV) resulting in the
overall poor prognosis [1]. The 5 year survival rate for
early stage cancer is about 90% whereas the 5 year sur-
vival rate in advanced disease is 10% - 30% [2].
In advanced ovarian disease the standard current prac-
tice is a staging and primary debulking laparotomy
followed by platinum based chemotherapy [3]. Optimal
cytoreduction during initial surgery has become widely
accepted as the most important prognostic indicator.
Over the last 20 years the view on what constitutes
‘maximal debulking’ has changed from leaving no tu-
mour deposit >2 cm to leaving no macroscopic disease
being acceptable. Increasingly more radical surgery is
being performed in an effort to free the patient of macro-
scopic disease [4]. A m et a -analysis of 2637 women from
retrospective non-randomised c ontrol trials de monstrate d
a survival benefit for those patients with advanced di-
sease who had no macroscopic disease or tumour
deposit >2 cm [5].
There has been no evidence that a survival benefit
exists with residual tumour >2 cm and often optimal
debulking is simply not possible due to the extent of the
disease [6]. In this scenario initial surgery may be ques-
tionable if residual tumour <2 cm is not achievable.
The effort to achieve ‘maximal/optimal debulking’ is
associated with a complication risk of 8% - 63% [7].
Mortality following debulking surgery has been reported
from 1% - 6% with a recent systematic review reporting
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
the mean mortality at 2.8% [8]. A laparotomy is a major
operation that requires hospital admission and time for
recovery that may delay the start of chemotherapy. How-
ever two studies have s hown no evidence that a delay in
starting chemotherapy influences the survival rate [9,10].
Neoadjuvant chemotherapy has been proposed as an
alternative option in advanced ovarian cancer. A recent
RCT showed that neoadjuvant chemotherapy was not
infer ior t o primar y debulk ing surger y in ter ms of the s ur-
vival rate [4]. It can be argued that surgery following
chemotherapy may be technically easier than if surgery
was undertaken initially. In addition a prospective study
has shown that there is an improved patient quality of
life and functional status following neoadjuvant chemo-
therapy [11].
The survival benefit and prognosis of upfront surgery
in advanced ovarian cancer is well known and estab-
lished . Howe ver the use of neoadj uvant c hemothe rapy is
less well researched. The aim of this meta-analysis is to
determine the prognostic factors influencing overall sur-
vival rate in patients with advanced ovarian cancer
following neoa djuva nt chemothe rapy.
A meta-analysis was performed based on the recom-
mendations of the Preferred Reporting Items for System-
atic Reviews and Meta-analyses (PRISMA) statement
2.1. Search Strat eg y
A literature search has been carried out using the
National Library of Medicine and National Institutes of
Health (Pubmed) and ScienceDirect for all clinical trials
on the use of neoadjuvant chemotherapy in advanced
ovarian cancer. The following headings and keywords
were used in the literature search; ‘advanced ovarian
cancer’, ‘ovarian cancer’, ‘neoadjuvant chemotherapy’
and ‘surgery’. The search included all English language
articles and was limited to the period of January 1st 2000
to September 30th 2010.
The references of each article were reviewed for any
relevant articles which were subsequently included in the
analysis. The terms have been expanded to include all
subcategories in an attempt to obtain all published trials
that fit the selection criteria.
2.2. Selection Criteria
The trials included have used platinum based chemothe-
rapy and involve advanced epithelial ovarian cancer
stage III/IV that was staged according to the FIGO
classifica tion. The cohorts includ ed must ha ve undergone
neoadjuvant chemotherapy followed by cytoreductive
The excluded trials were those where chemotherapy
regimens other than platinum based were used, early
stage ovarian cancer and no inclusion of the proportion
of patients with stage III or IV disease. Articles were
excluded that did not include the median survival time
(months). Also excluded were articles that did not men-
tion criteria for residual tumour and define what they
considered optimal debulking surgery. Further cohorts
were not included if the number of chemotherapy cycles
administered and the different chemotherapy regimens
were not recorded.
2.3. Studies Identified
A total of 333 potentiall y relevant studie s were iden tified
based on the above search criteria. After screening the
titles and abstracts, 291 studies were excluded for the
following reasons: (1) unrelated to subject (n = 115), (2)
review article s (n = 96), (3) non ovarian patients (n = 60),
(4) case reports (n = 15), (5) preclinical trials (n = 5).
Further assessment of these studies for more detailed
information identified 16 ineligible studies due to intra-
peritoneal or intra-arterial chemotherapy (n = 8), no me-
dian overall survival (n = 5), no residual tumour criteria
(n = 2) and the use of adjuvant chemotherapy (n = 1).
Finally 26 studies were identified as suitable for inclu-
sion in the meta-anal ysis (Figure 1).
2.4. Extraction of Data
The baseline characteristics of patients were recorded
incl uding the medi an and range of age, the hi stolo gy and
grade of disease and the number of patients within each
cohort. The percentage of patients with stage III/IV
disease were recorded as well as a breakdown of Stage
III A, B a nd C if inc lude d. T he residual tu mour criteria o f
each study was identified and maximal cytoreduction
was con sidered to have occurred if residual disease mea-
sured less than 1cm in largest diameter.
Additional information included the study design and
the year of study. The staging procedure used to diagnose
and determine severity were collected and also the pre-
operative disease severity including the main site of
Other information included percentage of patients
achieving maximal debulking within the cohort, rate of
bowel surgery performed, whether or not lymphadenec-
tomy was performed and the site of the residual disease
following debulking surgery. The percentage of patients
in each cohort who did not go on to have cytoreductive
surgery following neoadjuvant chemotherapy was re-
corded and the outcomes of these patients.
Whether ultra radical surgery was done or not among
the cohorts was collected in addition to what procedures
were performed.
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Figure 1. Studies identified—flow diagram.
The chemotherapy administered and number of cycles,
including the percentage taxane use verses platinum onl y
chemotherapy, were collected. The overall median sur-
vival and progression free survival in months was re-
The region in which the cohort was undertaken was
recorded for comparison within the analysis.
2.5. S tatistica l Analysis
Sub-a nal ysis was done on a number of prognostic factors
including the extent of debulking surgery, percentage
stage IV disease, whether or not lymphadenectomy was
performed and age with respect to survival benefit. In
addition the pre-operative severity, percentage of bowel
resection performed, site of residual tumour and percen-
tage of ultra-radical surgery performed among the co-
horts was analysed. A comparison of maximal debulk-
ing and the median overall survival rates between re-
gional centres was also analysed.
Statistical methods included simple linear regression
models to analyse the data with bubble charts corre-
sponding to the number of patients in each cohort and p
< 0.05 was considered statistically significant. The analy-
sis was carried out using Mini Tab 16, a statistical soft-
ware package.
3.1. Clinical Characteristics
A total of 26 studies were identi fied follo wing the liter a-
ture search as meeting the inclusion criteria and suitable
fo r me ta -a nalysis. The clinical characteristics of the stud-
ies are outlined in Tables 1 a nd 2. Three cohorts were
from non-randomised Phase I studies; 3 cohorts were
from non-randomised Phase II studies; 2 cohorts were
from retrospective case control studies; 17 were from
retrospective analysis and 1 was a randomised control
trial. The mean number of patients in each cohort was 64
(median = 46.5, range = 17 - 334).
The majority of the studies had serous histological
type with a mean percentage of 70.4% (range = 25.9% -
95%) with the remainder including mucinous, endo-
metrioid, undifferentiated, unspecified adenocarcinoma
and clear cell histology types.
The percentage grade 3 and 4 was identified in 17 of
the 26 cohorts and the mean percentage Grade 3 and 4
was 64.6% (range = 27% - 9 0 . 9% ). Me d ia n s urvi va l t ime
ranged from 18 to 52 months with the mean of all the
cohorts as 32.1 months. Progression free survival rates
were recorded in 16 of the 26 cohorts and the mean was
16.5 months (range = 12 - 25.4 months).
The residual tumour criteria which was the optimal re-
sidual disease following debulking surgery ranged from
<1 cm to <2 cm between cohorts. Between 2000 - 2005
the residual tumour criteria was <2 cm in 62% of cohorts
compared to 31% between 2006-2010. During the pe-
riod 2006-2010, the residual tumour criteria was >1 cm
in 69% of cohorts.
3.2. Neoadjuvant Chemotherapy
The mean number of pre-operative chemotherapy cycles
received prior to surgery between the cohorts was 3.6
(range = 2.5 - 6). All cohorts used platinum based che-
motherapy and twenty three cohorts used taxane as part
of the chemotherapy regime. The mean percentage of
patients receiving taxane per cohort was 77.6% with a
range of 0% to 100%.
Simple linear regression shows an increase of 3.7
months in the median survival time for every single in-
crease in chemotherapy cycle. The Pearson correlation
was r = +0.37. However there was a non-significant
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Table 1. Study charact er istics.
Author Year of
(n) Median
age Range
of age
ogy %
% Stage
B + C
No. of
% Max
% no
[13] 2001 54 63 33 - 78 76 / IIIC-85 14.8 >2 cm 4 57.4 72.2 42.6 20 / 22
2001 45 58.5 49 - 68 73.3 60 IIIC-46.7 53.3 >2 cm 3 68.9 75.6 / 0 13.9 18
2001 31 61 49 - 77 93.6 83.9 IIIC-100 0 >2 cm 3 100 83.9 / 3.2 / 42
2002 20 65 40 - 77 95 65 IIIC-85 15 >1 cm 4 0 60 40 0 / 24.7
2002 65 60.3 48 - 73 63.1 / IIIC-78.4 21.5 >1 cm 3.8 21.5 41.5 / 31 / 22
2003 48 57 35 - 74 79 55 IIIC-83 17.2 >2 cm 3 100 100 58.7 0 23 28
[19] 2003 45 68 28 - 80 62.2 / IIIC-80 20 >2 cm 4 77.7 68.9 / 13.3 12 29
[11] 2003 17 54.6 47 - 62 41.2 35.3 IIIC-23.6 76.5 >2 cm 3 100 58.9 / 23.6 13.3 22.9
[20] 2003 73 60 / 73 78.1 IIIC-100 0 >2 cm 3 57.6 71.2 71.2 15 20 27
[21] 2005 25 64 52 - 75 76.7 / IIIC-77 23.3 >1 cm 4 60 76 83 16.7 21 32
Leb [22] 2005 61 63 36 - 88 59 / III-90.3 3.3 >2 cm 3 100 80.3 / 0 / 41.7
2005 27 58.7 54 - 63 25.9 / IIIC-40.7 59.3 >1 cm 3 0 48.1 66.6 33.3 22 25
Avrila [24] 2005 33 60 34 - 76 87.9 90.9 IIIC-69.7 30.3 >1 cm 3 69.7 66.7 / 10.8 / 26.8
[25] 2006 98 61 / 71.4 73.2 III A -6.1,
26.5 >1 cm 3 94 85.7 / 0 / 33
Leea [26] 2006 18 45 36 - 66 72.2 83.3 IIIC-88.9 11.1 >2 cm 3 100 77.8 77.8 0 15 53
[27] 2006 213 64.8 / 39.4 / III-77.5 22.6 >2 cm 3 0 62.9 / 0 13.3 23.7
Deob [28] 2006 82 49.9 32 - 72 / / IIIC-72 28 >1 cm 4 34.3 71.9 0 9.8 25.4 33.8
Leb [29] 2006 58 64 36 - 88 74.3 81 III-89.7 3.4 >1 cm 3 100 55.2 / 0 / 41.5
Houb [30] 2007 63 64.1 52 - 76 80.9 80.9 IIIC-46 53.9 >1 cm 6 58.7 95.3 / 3.2 16 46
Rafiib [31] 2007 22 59 33 - 79 71 27 III-81.9 18 >1 cm 6 100 77.3 54.6 53.2 / 45.5
Rosab [32] 2007 42 66 38 - 86 / / III-69 30.9 >2 cm 5 50 38 / 0 / 35
[33] 2008 24 59.8 / 79.2 66.7 IIIC-87.5 12.5 >2 cm 3 84 36.3 91.6 18.2 18 25
[34] 2008 29 54 42 - 70 68.9 58.6 IIIC-69 31 >1 cm 3 68.9 68.9 37.9 / 13 34
[35] 2009 88 64 39 - 80 92 71.6 IIIC-73 27.3 >1 cm 2.5 100 75 52.3 5.7 12.4 26.3
Bilicib [36]
2010 52 62 33 - 77 76.9 48.1 IIIC-98 1.9 >1 cm 4 94.2 83 / 0 13.3 47.5
2010 334 63 33 - 81 58.1 38.9 IIIC-75.7 24.3 >1 cm 3 87.9 80.6 39.1 / 12 30
aPhase I study; bRet rospective analysis; cRetrospective case-control study; dPha se II study; eRandomised control trial.
trend towards increased survival with increasing number
of chemotherapy cycles (p = 0.065) (Figure 2).
There was a statistically significant association be-
tween percentage taxane use and the overall survival rate
(p = 0.019) (Figu re 3). For every 10% increase in taxane
use there was a 1.27 month increase in the survival rate.
There was a strong correlation r = +0.46.
3.3. % Stage IIIC and IV
The majority of the cohorts were stage IIIC disease with
a range of 23.6% - 100% and a mean of 74.5%. One co-
hort broke the staging down into stage IIIA, B and C
with 6.1%, 17.3% and 50% respectively present within
the cohort .
The mean percentage of patients with Stage IV disease
per cohort was 24.1% with a range from 0% - 76.5%.
Two cohorts involved 100% Stage IIIC and did not have
any patients with stage IV disease within the cohort.
Analysis showed that for every 10% increase in stage IV
disease there was a 1.8 month decrease in the overall
survival rate. Simple linear regression showed a non-
significant trend towards decreased survival with in-
creasing % stage IV disease (p = 0.065) (Figure 4).
There was a negative correlation r = 0.37.
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Table 2. Results from studies included in the meta-anal ysis.
Author Staging proce dure Pre-op disea se sev erity Ultra-radical sur gery
Residual tumour si te Nationality
Ansquer [13] Laparoscopy (61%),
Laparotomy (39%) /
Diaphragm stripping - 5.6%,
Splenectomy - 3.7%,
Cholecystectomy - 1.9%,
Partial pancre atic
resection - 1.9%
Peritoneum - 33.3% ,
liver seros a - 26.7%,
subdiaphragmatic -
colon serosa - 20%,
small bowel - 13.3%,
spleen serosa - 8.9%,
douglas - 22.4%
Europe -
Kayikc iog [14] CT + Biopsy
Upper abdominal
disease - 55. 6% 0% 2.2 /
Europe -
Kuhn [ 15 ] Laparoscopy / / 29 /
Vrscaj [16]
Laparoscopy or
La p arotomy
/ 0% 0 /
Europe -
Ushijima [17] / / / / / Asia - Japan
Morice [18] Laparoscopy (21%),
Laparotomy (72%)
CT + Biopsy (7%) / Diaphragm stripping - 16%,
Splenectomy - 5%,
Permanent enterostomy - 5% 19 / Europe -
Ma zzeo [19]
CT + Biopsy
/ / / / Europe -
Chan [11] CT sc a n
Pleural effusion - 41%,
Liver mets - 23.6%,
Lung mets - 5.9%,
Ch est wall m ets - 5.9%
/ 11.8 / Asia - China
Fanfani [20] Laparotomy (100%)
Upper abdominal disease -
9.8%, Portal t riad di sease -
Diaphragm disease - 32.4%
/ / / Europe -
Loizzi [21] / / / / /
Europe -
Le [22] CT + US S-guided
Upper abdominal disease -
6.6%, solely pelvic disease -
42.6% / /
pelvis - 27.9%,
upper abdomen - 18%,
pelvi s + upper abd om en
- 27.9%
N.America -
Hegazy [2 3]
/ Bladder resection - 5.6%,
Splenectomy - 5.6% 16.7 / USA
Avril [24] Laparoscopy (100%) / / / / USA
Everett [25] / / / 16.3 / USA
Lee [26]
Laparotomy or
CT-g ui de d biopsy
/ 0% 5.6 / Asia -
S. Kor e a
Inciura [27] CT scan / / / / Europe -
Deo [28]
CT + cytology ( 75 %) ,
(25%) / / 7.4 / Asia - India
Le [29]
CT + USS-guided
/ / 3 .4 /
N.America -
Hou [30] CT + c ytology Only pleural eff us ion - 53.9%,
disease limited to
abdomen - 46%
Splenectomy - 0%,
Pancreatectomy - 0%,
Gallbladder resection - 1.6%,
Liver resection - 0%,
Appendectomy - 3.2%
4.8 / USA
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Rafii [31] / / / 2.9 /
Europe -
Rosa [32] / / / / / Europe - UK
[33] Lapa rotomy (100%) / / / / Asi a -Iran
Suprasert [34] /
Pelvis - 51.7%,
Abdomen - 13.8%,
Abdom en + pel vis - 34.5%,
Lung mets - 20.7%,
Liver mets - 6.9%,
Splenic mets - 3.4%
/ 3 .4 / Asia - Thai-
Polcher [35]
Laparotomy (18.2%)
/ Upper abdo surgical proce-
dures - 30.1% 36.1 / Europe -
Bilic i [ 36 ] CT + biops y,
Laparotomy or
Laparoscopy / / / / Europe -
Vergo te [4] Laparotomy (3.6%),
Laparoscopy (34.7%) / Splenectomy - 4% 8.7
Diaphragm - 26.4%,
liver seros a - 10.2%,
omentum - 13.6%,
intestines - 22%,
peritoneal - 25.8%,
pelvis - 22.4%,
spleen - 3.4%
Figure 2. Survival time against % taxane use.
Figure 3. Survival time against No. of chemotherapy cycles.
Figure 4. Surviva l time against % stage IV disease.
3.4. Year of Publication and Median Cohort Age
13 of the 26 cohorts (50%) were published between 2001
- 2005 with the remaining 13 cohorts between 2006-2010.
A statistical significance was identified between the year
of publication and the overall survival rate (p = 0.032)
(Figu re 5). Analysis showed that for every year increase
in publication there was a 1.46 month increase in the
overall survival rate. There was a positive corre- lation r
= +0.42.
The mean percentage maximal cytoreduction ac hieved
between 2000 - 2005 was 69.5% compared to 69.8%
between 2006-2010.
The mean of the median age was 60.4 years among the
cohorts (range = 45 - 68 years). On further analysis no
statistical significance was found between median age
and the overall survival rate (p = 0.312) (Figure 6).
There was a negative correlation r = 0.21.
3.5. Maximal Cytoreductive Surgery
The distribution amongst cohorts in terms of definition
of maximal debulking was as follows: <2 cm in 46.2%
and <1 cm in 53.8%. The mean percentage of maximal
cytoreductive surgery for all cohorts was 69.7%, with a
range fro m 36.3% to 10 0%. A statistical significance was
found between percentage maximal cytoreductive sur-
ger y and the o verall s urvival rate (p = 0.046) (Figure 7).
On further analysis it showed that for every 10% increase
in % maximal cytoreductive surgery there was a 2.28
month increase in the overall survival rate. There was a
strong positive Pearson correlation r = +0.40.
3.6. Lymphadenectomy
Lymphade necto my was recorded in 12 of the 26 cohorts.
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Figure 5. Survival time against year of publication.
Figure 6. Survival time agai nst median age of patien ts.
Figure 7. Survival time against % maximal cytoreduction
In the remaining 14 cohorts it was unclear whether lym-
phadenectomy was performed or not as part of the de-
bulking s urgery.
The mean percentage of lymphadenectomy performed
among the 12 cohorts was 55%, with a range from 0% to
91.6%. No statistical significance was found between the
percentage lymphadenectomy performed and the overall
survival rate (p = 0.813) (Figure 8). There was a weak
positive correlation r = +0.07.
3.7. Comparison between Centres
The cohort studies were from a broad range of countries
from Europe, Asia and North America. Twelve of the
cohorts were from Europe, 7 were from Asia, 6 were
from North America and the recent randomised control
trial from Vergote et al. [4] was an international paper.
The mean o f the o ver all s urvi val r ate was 3 1.9 month s in
Figure 8. Survival time against % of Lymphadenectomy
performed among the cohorts.
Europe, 29.8 months in Asia and 35.6 months in North
America (Figure 9).
The percentage of maximal cytoreduction achieved
between the centres was 72.4% in Europe, 61.6% in
Asia and 71.8% in North America (F igure 10).
Lymphadenectomy was performed in 7 of the 12 Euro-
pean cohorts (58%), in 3 of the 7 Asian cohorts (43%)
and in 1 of the 6 North American cohorts (17%).
3.8. Bowel Resection and Ultra Radical Surgery
The percentage of bowel resections performed among the
cohorts ranged from 0% - 36.1%. Sixteen of the 26 co-
horts recorded whether bowel resection was performed
or not. Two studies differentiated bowel resection as
large or small bowel and one study identified the site of
resection as a rectosigmoid resection. The mean bowel
resection rate was 9.8% between cohorts.
Further analysis showed t hat for every 10% increase in
percentage bowel surgery there was a decrease of 1.4
months in the overall survival rate. There was no statis-
tically significant relationship found between the median
overall survival rate and percentage bowel surgery per-
formed (p = 0.606). There was a weak correlation r =
The mean percentage maxima l cyto reduct ion ac hieve d
among the cohorts that performed bowel surgery was
74.2% compared to the remaining cohorts that did not
mention or perform bowel surgery of 62.5%. There was a
higher percentage of Stage IV disease of 28.7% in the
cohorts that performed bowel surgery compared to
16.7% in those cohorts that did not perform the surgery.
Nine of the 26 cohorts mentioned if ultra radical de-
bulking surgery was performed. Six of the nine studies
actually performed ultra radical surgery. A variety of pro-
cedures were performed amongst the cohorts including
splenectomy, cholecystectomy, diaphragm stripping, per-
manent enterostomy, bladder resection, liver resection,
appendicectomy and pancreatectomy. One study just
mentioned upper abdominal surgical procedures and did
not specify the individual procedures. The rate of sple-
nectomies performed ran ged from 0% - 5.6%, with a mean
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Figure 9. Survival between the centres.
Figure 10. % Maximal cytoreduction achieved between
the cen tres.
of 3.7%. Diaphragmatic stripping ranged from 5.6% to
The percentage maximal debulking ranged from
48.1% - 100% in the cohorts that performed ultra radical
surgery with a mean of 78.5%. In the cohorts that per-
formed ultra radical surgery the mean overall survival
rate was 29.6 months with a range from 22 to 46 months.
3.9. St aging Procedure
Twenty cohorts out of 26 mentioned the method of stag-
ing used to establish the diagnosis and severity of the
disease. The methods included laparoscopy, laparotomy,
CT + biopsy, CT + ultrasound guided biopsy, CT + cy-
tology and CT scan only. The majority of cohorts used
either laparoscopy or laparotomy with 12 out of 20 and
11 out of 20 cohorts respectively using this method of
staging. One cohort used CT scan for staging but was
unclear if a biopsy or cytology was performed. The re-
maining six cohorts did not mention the staging proce-
3.10. Pre -Operative Severity
Only 6 out of the 26 cohorts mentioned the severity of
disease prior to neoadjuvant chemotherapy and debulk-
ing surgery 5 of these 6 cohorts involved some degree of
upper abdominal disease. The percentage of upper ab-
dominal disease ranged from 6.6% to 55.6%. 2 cohorts
recorded the presence of lung metastasises (5.9% and
20.7%). 1 cohort recorded the presence of portal triad
disease (12.8%). 2 cohorts differentiated between the
presence of abdominal disease and pelvic disease.
The cohort that had 55.6% upper abdominal disease
achieved maximal debulking in 75.6%. No ultra radical
surger y was note d as b ei ng pe rfo r med. T he median o ve r-
all survival ra te in thi s cohort was 18 mon ths, whi ch wa s
the lowest survival rate amongst the cohorts, compared
to a mean overall survival rate between the cohorts of
32.1 months. There were 2 cohorts that mentioned the
presence of lung metastasises, the cohort with 5.9% of
lung met a stasi se s p re se nt a c hi e ve d ma xi mal de b ul ki n g i n
58.9% and the overall survival rate was 22.9 months.
This co mpared to the other cohort with lung metasta sises
present in 20.7 % that had maximal debulking achieved in
68.9% and the overall survival rate was 34 months.
The % stage IV disease between these cohorts was
76.5% and 31% respectively. Ultra radical surgery was
not noted as being performed in either of these cohorts.
3.11. Residual Tumour Site
The residual tumour site following neoadjuvant chemo-
therapy and debulking surgery was recorded in only 3 of
the 26 cohor ts. One of these cohorts ide ntified the site of
residual tumour as pelvis, abdomen or pelvis + abdomen
and the remaining 2 cohor ts id e ntified the specific s ite .
3.12. Percentage of No Debulking Surgery
24 of the 26 cohorts noted the percentage of patients that
did not go on to have debulking surgery following neo-
adjuvant chemotherapy. The percentage not receiving
debulking surgery ranged from 0% - 53.3% with a mean
of 9. 5%. In ten c oho rts d eb ulking surge ry was performed
on all the patie nts. The cohor t that had 53.3 % of patients
not going on to receive debulking surgery had a median
over all survi val rate of 45 .5 mont hs, the highest survi val
rate among the cohorts. The percentage maximal de-
bulking was 77.3% in this cohort and 18% of the patients
had stage IV disease. No ultra radical surgery was done
on this cohort.
3.13. Outcome Following No Debulking Surgery
Only 7 cohorts recorded the outcome in those patients
that did not go on to have debulking surgery following
neoadjuvant che mot herap y. T hese ha ve bee n listed in the
following table ( Table 3). The most common outcome in
4 of the 7 cohorts was disease progression following
neoa djuva nt chemothe rapy.
A n umber of prognostic factors were analysed in relation
to the median overall survival rate. The analysis found
that the greater percentage of maximal cytoreductio n
achieved among the cohorts was associated with an im-
proved overall survival rate (p = 0.046). For every 10%
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Table 3. Ou t co me s following no debulking surgery.
Author Outcome following no debulking sur gery
Ansquer [13] 4 pati en ts di ed before 3 cycles o f chemo
Kuhn [ 15 ] 1 patient had a PE
Ushijima [17] 2 patients did not receive c hemo due to poor prognosis, 18 received chemo, 3 refused surgery - all died
Ma zzeo [19 ] 1 patient had IHD, 1 refused surgery + died, 3 had d isease progr ession
Loizzi [21] 5 patients had dis ease progressi on + died within 6 month s
Hou [30] 1 patient due to co -morbidities - remained disease free, 1 had dis ease progression and died within 9 months
Ghaemmaghami [33] 4 patients had disease progression
increase in percentage optimal debulking there was a
2.28 month increase in the survival rate. This is consis-
tent with a number of studies and it is now commonly
accepted that optimal debulking surgery is the single best
prognostic indicator for overall survival.
The addition of taxane to the chemotherapy regime
was also found to improve the overall survival (p =
0.019). For every 10% increase in taxane use there was a
1.27 month increase in the overall survival rate. However
there was no association between the number of chemo-
therapy cycles and survival rates which differed from a
pre vious me ta -anal ysi s b y B ri s to w et a l. that found a sig-
nificant association [37].
The percentage stage IV disease did show the expected
decrease in the overall survival rate with an increase in
the percentage stage IV disease but this was not a signi-
ficant trend. This may have been because the remaining
patients had e xte nsive sta ge III C disea se whic h is a ssoci -
ated with a poor survival rate and therefore survival rates
between stage I IIC and IV may not be dissimilar.
For every year increase in publication there was a sta-
tistically significant increase in the overall survival rate
(1.46 months). The mean percentage maximal cytoreduc-
tion was similar between 2000-2005 and 2006-2010
(69.5% and 69.8%) but the definition of optimal debulk-
ing as <1 cm became much more acceptable. With 38%
of cohorts defining optimal debulking as <1 cm between
2000-2005 and 69% between 2006-2010. This change in
definition of optimal debulking combined with similar
cytoreduction rates is a possible reason for the improved
survival ra t es over time.
The mean of the median age was 60.4 years among the
cohorts. There was a negative correlation (r = 0.21) be-
tween age a nd the overall survival rate but not a statisti-
cally significant association (p = 0.312). A more useful
meas ureme nt woul d ha ve bee n the perfo rmanc e stat us o f
patients as this is more likely to be associated with a poor
survival rate than increased age.
In comparing centres, there was a better overall sur-
vival rate in North America (35.6 months) than both
Europe (31.9 months) and Asia (29.8 months). The per-
centage optimal cytoreduction achieved was similar in
Europe (72.4%) and North America (71.8%) but much
lower in Asia (61.6%). This would be a possible explana-
tion for the improved survival rates in North America
and Europe compared to Asia but it is difficult to com-
ment further as there were relatively few cohorts and not
an equal distribution betwee n re gio ns.
A wide va r ie t y of sta gi ng p roc edures were used among
the cohorts. Laparoscopy and laparotomy were the most
common procedures performed with 14 out of the 20
cohorts using either procedure.
Pre-operative severity and residual tumour site were
poorly recorded among the cohorts with only 6 of the 26
cohorts and 3 of the 26 cohorts respectively recording the
relevant data. I t is therefore d ifficult to analyse due to the
limited data. There was a wide range of upper abdominal
disease pre-operatively (6.6% - 55.6%) and the cohort
with 55.6% of abdominal disease was associated with the
lowest overall survival rate of 18 months.
Resid ual tu mour s ite follo wi ng d ebul kin g su rgery can-
not be reliably analysed as so few cohorts recorded this
information. It would have been interesting to compare
the pre-operative severity with both the optimal debulk-
ing achieved and the overall survival rate. Also to be able
to correlate the cohorts that had a poor optimal debulking
percentage with the site of residual tumour. We know
that upper abdominal disease is associated with a re-
duced likelihood of achieving complete cytoreduction.
The percentage of patients who did not go on to have
debulking surgery ranged from 0% - 53.3%. The reason
why debulking surgery was not performed was not rou-
tinely mentioned among the cohorts. The cohort with
53.3% of patients not goi ng o n t o ha ve d e b ulki ng s urgery
had a high ove rall surv ival rat e o f 45.5 months. Ho wever
this may have been because 77.3% in the cohort achie-
ved maximal debulking and only 18% had stage IV dis-
ease. The outcome of patients who had no debulking
surgery was poorly recorded with only 7 cohorts noting
the outcome.
The percentage of bowel resection performed among
the cohorts did not correspond to an increase in survival
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
rates. There was in fact a decrease in the survival rate of
1.4 months for every 10% increase in bowel resection
but this was not statistically significant (p = 0.606).
However in the cohorts that performed bowel resections
there was a greater percentage of optimal debulking
achieved (74.2%) compared to the cohorts that did not
perform bowel surgery (62.5%). There was also a much
higher percentage of Stage IV disease amo ng the c ohor ts
that performed bowel surgery (28.7%) compared to those
that did not (16.7%). The greater percentage of Stage IV
disease in some cohorts meant that there were a greater
number of patients with widespread and extensive dis-
ease. Bowel resection may have been necessary in some
cohorts more than others in an effort to achieve optimal
debulking. This may be a possible explanation for why
there was a slight decrease in the survival rate in those
cohorts that performed bowel surgery as a greater num-
ber of patients had extensive disease before debulking
surgery was attempted. It is also unclear whether a spe-
cialist or a general surgeon performed the bowel surgery
within the cohorts.
Most experts believe that the less residual disease pre-
sent a fter surgery the better the overall survival rate. The
question still remains how radical and aggressive should
surgeons be in an effort to achieve ‘optimal’ debulking.
If optimal cytoreduction is achieved this does not how-
ever mean the patient will have a similar survival rate
than a patient who initially had disease less than 1cm
without cytoreduction. This is supported by Hoskins et al.
who showed that patients with large volume disease with
optimal debulking did not have a similar survival rate to
those patients who presented with small volume disease
[38]. It has been suggested that large volume disease may
have a more aggressive pathology than small volume
disease and this requires further study.
In this meta-analysis, ultra radical surgery was per-
formed in six cohorts in an effort to achieve optimal de-
bulking. Only 9 cohorts recorded if ultra radical surgery
was performed or not. A wide range of procedures were
performed including splenectomies, liver resections and
pancreatectomies. The percentage achieving maximal
debulking among the cohorts that performed ultra radical
surgery ranged from 48.1% to 100% with a mean of
The mean over all s urvival r ate a mong the coho rts tha t
had ultra radical surgery was 29.6 months which is below
the overall mean of all cohorts of 32.1 months. The range
of overall survival rates among these cohorts was 22 - 46
months. The reason for the one study that had a survival
rate of 46 months was unclear as no patient had a sple-
nectomy, pancreatectomy or liver resectio n in this coho rt
however optimal debulking was achieved in 95.3% of
patients. The overall survival rate of 29.6 months could
be less than the mean of all the cohorts as the effort to
achieve optimal debulking may be associated with ex-
tensi ve mor b idity. T he post-operative complications were
not recorded from the cohorts and this would have been
useful to compare morbidity associate d with ultra radica l
surgery and lymphadenectomy. The data regarding ultra
radical surgery is however difficult to interpret and ana-
lyse as it was performed in so few studies and further
research needs to be done to establish any benefit.
This meta-analysis has not looked at the use of CA-
125 monitoring in terms of resectability and prognosis,
however a number of studies have suggested it may be a
useful indicator. It is widel y accepted that C A-125 levels
decrease during first line che motherap y and is associated
with a better pr ognosis [39]. A st udy by Bilici et a l. [36]
showed that following neoadjuvant chemotherapy, a sta-
tistically significant decrease in CA-125 levels was de-
termined and this is consistent with similar studies fol-
lowing ad juvant che motherapy.
CA-125 levels have failed to be precise and reliable in
determining the resectability of advanced ovarian cancer.
Ho weve r st ud ies ha ve s hown t hat a CA -125 that does not
normalise following neoadjuvant chemotherapy is asso-
ciated with a worse outcome. An alternative more reli-
able method may be the use of laparoscopy routinely to
establish the severity of disease prior to undertaking de-
bulking s urgery.
CT scan criteria for determining the resectability of the
tumour has been reported to be a reliable indicator. Qay-
yum et el found that pre-operative CT and MRI were
equally accurate in detecting inoperable disease with a
positive predictive value of 94% and a negative predic-
tive value of 96% [40]. There is however no uniformly
accepted CT scan criteria for predicting resec ta bility.
The ascites volume has been shown by Kuhn et al. [15]
to have an influence on the survival rate and tumour re-
sectability. The ascites volume is often associated with
extensive and diffuse peritoneal disease and the mea-
surement of ascites volume alongside other investiga-
tions may well be useful in the prediction of tumour re-
This meta-analysis did not show a statistical signifi-
cant association between lymphadenectomy and the
overall survival rate (p = 0.813) however less than half
the cohorts recorded whether lymphadenectomy was per-
formed or not. This was consi stent wit h a RCT by Pa nici
et al. that noted an improved progression free survival
but no t ove rall sur vi val i n wome n fol lo win g a systematic
lymphadenectomy [41].
A much reported hypothesis is that lymph node invol-
vement in ovarian cancer is chemoresistant and is often
termed a ‘sanctuary’ site with regards to its response to
chemotherapy. A possible explanation for this resistance
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
from Eisenkop et al. is that retroperitoneal nodal metas-
tases have a reduced blood supply compared to intra-
abdominal disease and this results in lower levels of cy-
totoxic age nts re ach ing t he no d es [4 2] . It is unclear if the
poor prognosis of patients with positive lymph nodes is
due to the tumour’s aggressiveness or that nodal in-
volvement is resistant to che motherapy [43].
Lymphadenectomy is commonly performed outside
the UK however wi thi n t he U K very fe w ce ntr e s p er form
the procedure routinely. The recent pre-publication from
the National Institute for Health and Clinical Excellence
(NICE) (Guideline February 2011) does not mention the
role of systematic lymphadenectomy in advanced ova-
rian cancer which suggests it may be a while before the
procedure becomes common practice within the UK
The recent study by Vergote et al. [4] in September
2011 was the first randomised control trial comparing
primary debulking surgery followed by chemotherapy
versus neoadjuvant chemotherapy followed by debulking
surgery. The study concluded that neoadjuvant chemo-
therapy followed by interval debulking was not inferior
to the standard primary debulking surgery in the treat-
ment of advanced ovarian cancer. However both groups
had little or no upp er abdominal surgery performed. This
may have been a coincidence with relatively few patients
requiring the surgery or due to the aggressiveness of the
debulking surgery. Either way this will have influenced
the overall survival rate compared to other studies where
there are a higher percentage of upper abdominal surgery
often associated with a poorer prognosis.
The study also had a wide variability between the rate
of optimal and complete cytoreduction. With the range
for complete cytoreduction at primary debulking be-
tween 3.9% and 62.9%. This again would be expected to
influence the overall survival rate.
The number of cohorts included in this meta-analysis
made a multiple linear regression analysis difficult so
there was the potentia l for interactio ns between variables.
There will have been a degree of selection bias but there
was a strict inclusion criteria. However the criteria for
neoadjuvant chemotherapy administration varied across
the cohorts with some studies using CT imaging and
other cohorts using laparoscopy or laparotomy to assess
the disease severity and need for chemotherapy.
The studies included in the meta-analysis were not all
of the highest quality. There was only one randomised
control study done on the subject and therefore a system-
atic review including only randomised control trials was
not possible.
Additional prognostic factors that may have influ-
enced survival rates were not examined and these in-
cluded preoperative CA-125 levels, ascitic volume and
performance status. In further studies it would be inter-
esting to record post-operative co mplication s withi n eac h
cohort to compare whether the aggressiveness of debulk-
ing surgery is associated with additional morbid ity.
This meta-analysis has shown a number of important
prognostic factors that influence survival rates in patients
that have had neoadjuvant chemotherapy followed by
debulking surgery. The recent RCT by Vergote et al. has
shown that neoadjuvant chemotherapy is not inferior to
the traditional primary cytoreduction. Therefore it is
likely that neoadjuvant chemotherapy will have an in-
creasing role in the future management of advanced
ovarian cancer. The results from the CHORUS trial are
awaited to see if they support these findings. Further
research will need to address the issue of identifyi ng pa-
tients that are suitable for neoadjuvant chemotherapy or
primary cytoreduction. This may be a combination of CT
findings, pre-operative CA-125 levels, ascitic volume or
performance status that can predict the resectability of
the disease.
MJF is the first and main author of the manuscript. MJF
conceived and designed the manuscript and analysed the
data. NAS contributed to interpretation of the data and
assisted in the preparation of the article.
This is a review of the literature, so no ethical approval
was required. No funding source was involved.
This paper was submitted as part of an e-dissertation in May 2010 for
the Edinburgh Surgical Sciences Qualification (ESSQ). The ESSQ is a
3 year distance learning programme leading to a Masters in Surgical
Sciences (
[1] P o mel , C., Barton, D.P.J., McNeish, I. and Shepherd, J.
(2008) A statement for extensive primary cytoreductive
surgery in advanced ovarian cancer. An International
Journal of Obstetrics and Gynaecology, 115, 808-810.
[2] Hariprasad, R., Kumar, L. and Kapoor, A. (2007)
Neoadjuvant chemotherapy for advanced ovarian cancer-
editorial. Indian Journal of Medical & Paediatric Oncology,
28, 4-5.
[3] Scottish Intercollegiate Guidelines Network (SIGN)
(2003) Epithelial ovarian cancer, Clinical Guideli ne 75.
[4] Vergot e, I., Trope, C.G. and Armant, F. (2010) Neoad-
juvant chemotherapy or primary surgery in stage IIIC or
IV ovarian cancer. The New England Journal of Medi-
cine, 363, 943-953. HHUUdoi:10.1056/NEJMoa0908806UU
[5] Allen, D.G., Heintz, A.P. and Touw, F.W. (1995) A
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
meta-anal ysis of residual diseas e and survival in st age III
and IV carcino ma of th e ovar y. European Journal of Gyna-
ecologic Oncology, 16, 349-356.
[6] Morrison, J., Swanton, A., Collins, S. and Kehoe, S.
(2007) Chemotherapy versus surgery for initial treatment
in advanced ovarian epithelial cancer. Cochrane Data-
base of Systemat ic Reviews, 4, CD005343.
HHUUdoi:10.1002/14 651858.CD005343.pub2UU
[7] V enesmaa, P. and Ylikorkala, O. (1992) Morbidity and
Mortality associated with primary and repeat operations
for ovarian cancer. Obstetrics & Gynecology, 79, 168-
[8] Gerest ein, C.G., Damhuis, R.A., Burger, C.W. and Kooi,
G.S. (2009) Postoperative mortality after primary cytor-
eductive surgery for advanced stage epithelial ovarian
cancer: A systematic review. Gynecologic Oncology, 114,
[9] Aletti, G.D., Long, H.J., Podratz, K.C. and Cliby, W.A.
(2007) Is time to chemotherapy a determinant of prog-
nosis in advancedstage ovarian cancer? Gynecolog ic
Oncology, 104, 212-216.
[10] Gadducci, A., Sartori, E., Landoni, F., et al. (2005) Rel-
ationship between time interval from primary surgery to
the start of taxaneplus platinum-based chemotherapy and
clinical outcome of patients with advanced epithelial
ovarian cancer: Result s of a multicenter retrospective Ita-
lian study. Journal of Clinical Onc ology, 23, 751-758.
[11] Chan, Y.M., Ng, T.Y., Ngan , H.Y. and Wong, L.C. (2003)
Quality of life in women treated with neoadjuvant chem-
oth erapy for advanced o varian cancer: A prospecti ve lon-
gitudinal study. Gynecologic Oncology, 88, 9-16.
[12] Moher, D., Liber ati , A., Tetzlaff, J. and Altman, D.G. (2009)
PRISMA group. preferred reporting items for systematic
reviews and meta-analyses: The PRISMA statement. British
Medicine Journal, 339, b253 5.
[13] Ansquer, Y., Leblanc, E., Clough, K., Morice, P., Daupl at,
J., Math ev et, P., et al. (2001) Neoadjuvant chemotherap y for
unresectable ovarian carcinoma. Cance r, 91, 2329-2334.
HHUUdoi:10.1002/10 97-0142(20010615)91:12<2329: :AID-CN
[14] Kayikciog, F., Kose, M.F., Boran, N., Caliskan, E. and
Tulunay, G. (2001) Neoadjuvant chemotherapy or primary
surgery in advanced epithelial ovarian carcinoma. Inter-
national Jour nal of Gynecological Cancer, 11, 466-470.
[15] Kuhn, W., R ut ke, S., Späthe, K., Schmalfeld t, B., Flo rack,
G. and Von, H.B. (2001 ) Neoadjuvant chemotherapy
followed by tumor debulking prolongs survival for pa-
tients with poor prognosis in International Federation of
Gynecolo gy and Obst etrics stage IIIC ovarian carcin oma.
Cancer, 92, 2585-2591.
HHUUdoi:10.1002/10 97-0142(20011115)92:10<2585: :AID-CN
[16] Vrščaj, M.U. and Rakar, S. (2002) Neoadjuvant chemo -
therapy for advanced epithelial ovarian carcinoma: A
retrospective case-control study. European Journal of
Gynaecolocal Oncology, 23, 405-410.
[17] Ushijima, K., Ota, S., Komai, K., Matsuo, G., Motoshima,
S., Honda, S., et al. (2002) Clinical assessment of neo a-
djuvant chemotherapy and interval cytoreductive surgery for
unresectable advanced ovarian cancer. International Surgery,
87, 185-190.
[18] Morice, P., Dubernard, G., Rey, A., Atallah, D., Pautier,
P., Po mel , C., et al. (2003) Results of interval debulking
surgery compared with primary debulking surgery in
advanced stage ovarian cancer. Journal of the American
Colloge of Surgeons, 197, 955-963.
[19] Mazzeo, F., Berlière, M., Kerger, J., Squifflet, J., Duck,
L., D’Hondt, V., et al. (2005) Neoadjuvant chemoth-
erapy in patients with primarily unresectable, advanced-
stage ovarian cancer. Gynecolocal Oncology, 23, 7445-
[20] Fanfani, F., Ferrandina, G., Corrado, G., Fagotti, A.,
Zahut, H.V., Mancuso, S., et al. (2002) Impact o f interval
debulking surgery on clinical outcome in primary
unresectable FIGO stage IIIC ovarian cancer patients.
Oncology, 65, 316-322. HHUUdoi:10.1159/000074644UU
[21] Loi z zi, V., Cormi o, G., Rossi, C.A., Di, G.A.R., Cucco vill o,
A. and Selvaggi, L. (2005) Neoadjuvant chemotherapy in
advanced ovarian cancer: A cas e-control study. International
Journal of Gyne cological Cancer, 15, 217-223.
[22] Le, T., Faught, W., Hopkins, L. and Fung, M.F.K. (2005)
Primary chemotherapy and adjuvant tumor debulking in the
management of advanced-stage epithelial ovarian cancer.
International Journal of Gyneco log ical Can ce r, 15, 770-775.
[23] Hegazy, M.A.F., Hegazi, R.A.F., Elshafei, M.A., Setit,
A.E., Elshamy, M.R., Eltatoongy, M., et al. (2005) Neoa-
djuvant chemotherapy versus primary surgery in advan-
ced ovarian carcinoma. World Journal of Surgery Oncology,
3, 57-64. doi:10.1186/1477-7819-3-57UU
[24] Avril, N., Sassen, S., Schmalfeldt, B., Naehrig, J., Rutke ,
S., Weber, W.A., et al. (2005) Prediction of response to
neoadjuvant chemotherapy by sequential F-18-fluor-
odeoxyglucose positron emission tomography in patients
with advancedstage ovarian cancer. Jouanl of Clinical
Oncology, 23, 7445-7453.
[25] Everett, E.N., French, A.E., Stone, R.L., Pastore, L.M.,
Jazaeri, A.A., Anderson, W.A., et al. (2006) Initial
chemotherapy followed by surgical cytoreduction for the
treatment of stage III/IV epithelial ovarian cancer. Am-
erican Jouranl of Obstetrics and Gynecol ogy, 195, 568-
576. HHUUdoi:10.1016/j.ajog.2006.03.075UU
[26] Lee, S., Kim, B., Lee, J., Park, C., Lee, J. and B ae, D.
(2006) Preliminary results of neoadjuvant chemotherapy
with paclitaxel and cisplatin in patients with advanced
epith eli al o varian cancer who are i nad equat e for o pt imu m
primary surgery. Journal of Obstetrics and Gynecology,
32, 99-106.
[27] Inciura, A., Simavicius, A., Juozaityte, E., Kurtinaitis, J.,
Nadi sau sk iene, R., S ved as, E., et al. (2006) Comparison of
adjuvant and neoadjuvant chemotherapy in the man-
agement of advanced ovarian cancer: A retrospective study
of 574 pa tients. Biomed Central, 6, 153.
HHUUdoi:10.1186/14 71-2407-6-153UU
[28] Deo, S.V.S., Goyal, H., Shukla, N.K., Rain a, V., Kuma r, L.,
M. J. Farquharson et al . / Open Journal of Obstetrics and Gynecology 1 (2011) 71-83
Copyright © 2011 Sci Res. OJOG
Srinivas, G., et al. (2006) Neoadjuvant chemotherapy fol-
lowed by surgical cytoreduction in advanced epithelial ova-
rian cancer. Indian Journal of Cancer, 43, 117-121.
HHUUdoi:10.4103/00 19-509X.27933UU
[29] Le, T., Alshaikh, G., Hopkins, L., Faught, W. and Fung,
M.F.K. (2006) Prognostic significance of postoperative
morbidities in patients with advanced epithelial ovarian
cancer treated with neoadjuvant chemotherapy and delayed
primary surgical debulking. Annuals of Surggical Oncology,
13, 1711-1716.
[30] Hou, J.Y., Kelly, M.G., Yu, H., McAlpine, J.N., Azodi,
M., Rut herford, T.J., et al. (2007) Neoadjuvant chemo-
therapy lessens surgical morbidity in advanced ovarian
cancer and leads to improved survival in stage IV
disease. Gynecological Oncology, 105, 211-217.
[31] Rafi i, A., Deval, B., Geay, J.F., Chopin, N. and Paoletti,
X., P ar aiso, D., et al. (2007) Treatment of FI GO stage IV
ovarian carcinoma: Results of primary surgery or interval
surgery after neoadjuvant chemotherapy: A retrospective
study. International Journal of Gynecological Cancer, 17,
777-783. HHUUdoi:10.1111/j.1525-1438.2007.00905.xUU
[32] Rosa, D.D., Ton, N.C., Clamp, A., Mullamitha, S., Lau,
S., Clayton, R., et al. (2007) The neoadjuvant approach in
the treat ment of patien ts with ad vanced epit helial ovarian
carcinoma. Clinical Oncology, 19, 125-128.
[3 3] Ghaemmaghami, F., Kari mi-Zar chi , M., Modares-Gilan i, M.,
Mousavi, A. and Behtash, N. (2008) Clinical outcome of
Iranian patients with advanced ovarian cancer with neoa-
djuvant chemotherapy versus primary debulking surgery.
Asian Pacific Journal of Cancer Prevention , 9, 719-724.
[34] Supraser t, P., Tiyanon, J. and Kietpeerakool, C. (2008)
Outcome of interval debulking in advanced ovarian
cancer patients. Asian Pacific Journal of Cancer Prev-
ention, 9, 519-524.
[35] Pölch er, M., Mahner , S., Ortman n, O., Hilfrich, J., Di edri ch,
K., B r eitbach, G., et al. (2009) Neoadjuvant chemotherapy
with docetaxel in advanced ovarian cancera prospective
multicenter phase II trial (PRIM OVAR). Oncologu
Reports, 22, 605-613.
[36] Bilici, A., Salep ci, T., Dane, F., Gu mu s, M., Ustaalioglu,
B.B.O., Seker, M., et al. (2010) Neoadjuvant chemo-
therapy followed by interval cytoreductive surgery in
patien ts with unresectable, advanced stage epitheli al ova-
rian cancer: A single centre experience. Archives of Gy-
necology and Obs tetics, 282, 417-425.
[37] Bristow, R.E. and Chi, D.S. (2006) Platinum-based neoa-
djuvant chemotherapy and interval surgical cytor-eduction
for advanced ovarian cancer: A meta-analysis. Gyneco-
logical Oncology, 103, 1070-1076.
[38] Hoskins, W.J., Bundy, B.N., Thigpen, J.T. and Omur a,
G.A. (1992) The influence of cytoreductive surgery on
recurrence-free interval and survival in small-volume
stage III epithelial ovarian cancer: A gynaecologic on-
cology group study. Gynecological Oncology, 47, 159-
166. HHUUdoi:10. 1016/0090-8258(92 )90100-WUU
[39] Pecorelli, S., Odicino, F. and Favalli, G. (2002) Interval
debulking surgery in advanced epithelial ovarian cancer.
Best Pra ctice and Research Clin ic al Obstetrics and Gyn-
aecology, 16, 573-583.
[40] Qa yyum, A., Coakley, F.V., Westphalen, A.C., Hricak,
H., Okuno, W.T. and Powell, B. (2005) Role of CT and
MR imaging in predicting optimal cytoreduction of newly
diagnosed primary epithelial ovarian cancer. Gyneco-
logical Oncology, 96, 301-306.
[41] Panici, P.B., Maggioni, A., Hacker, N., Landoni, F.,
Acker-Mann, S., Campagnutta, E., et al. (2005) S ys -
tematic aortic and pelvic lymphadenectomy versus res-
ection of bulky nodes only in optimally debulked ad-
vanced o varian can cer: A ran domized clinical trial. Jour-
nal of the National Cancer Inst itue, 97, 560-566.
[42] Eisenkop, S.M. and Spirtos, N.M. (2001) The clinical
significance of occult macroscopically positive retrop-
eritoneal nodes in patients with epithelial ovarian cancer.
Gynecol ogical Oncology, 82, 143-149.
[43] Kim, H.S., Ju, W., Jee, B.C., Kim, Y.B., Park, N.H. and
Song, Y.S. (2010) Systematic lymphadenectomy for
survival in epithelial ovarian cancer: A meta-analysis.
International Journal of Gynecological Cancer, 20, 520-
528. HHUUdoi:10.1111/IGC.0b013e3181d6de1dUU
[44] National Institute for Health and Clinical Excellence
(NICE) (2011) Ovarian cancer: Full guideline for pre-
publication check.