Vol. 332 No. 10 DEBULKING SURGERY AND PROGNOSIS IN ADVANCED EPITHELIAL OVARIAN CANCER 629
THE EFFECT OF DEBULKING SURGERY AFTER INDUCTION CHEMOTHERAPY ON THE
PROGNOSIS IN ADVANCED EPITHELIAL OVARIAN CANCER
M
ARIA
E.L.
VAN
DER
B
URG
, M.D., P
H
.D., M
AT
VAN
L
ENT
, M.D., P
H
.D., M
ARC
B
UYSE
, M.B.A., S
C
.D.,
A
NNA
K
OBIERSKA
, M.D., N
ICOLETTA
C
OLOMBO
, M.D., G
IUSEPPE
F
AVALLI
, M.D., A
NGEL
J. L
ACAVE
, M.D.,
M
ARIO
N
ARDI
, M.D., J
OSETTE
R
ENARD
, M.S
C
.,
AND
S
ERGIO
P
ECORELLI
, M.D., P
H
.D.,
FOR
THE
G
YNECOLOGICAL
C
ANCER
C
OOPERATIVE
G
ROUP
OF
THE
E
UROPEAN
O
RGANIZATION
FOR
R
ESEARCH
AND
T
REATMENT
OF
C
ANCER
*
Abstract
Background.
Although the value of primary
cytoreductive surgery for epithelial ovarian cancer is be-
yond doubt, the value of debulking surgery after induction
chemotherapy has not yet been defined. In this random-
ized study we investigated the effect on survival of de-
bulking surgery.
Methods.
Eligible patients had residual lesions meas-
uring more than 1 cm in diameter after primary surgery.
After three cycles of cyclophosphamide and cisplatin,
these patients were randomly assigned to undergo either
debulking surgery or no surgery, followed by further cy-
cles of cyclophosphamide and cisplatin. The study end
points were progression-free survival and overall survival.
At surgery 65 percent of the patients had lesions meas-
uring more than 1 cm. In 45 percent of this group, the le-
sions were reduced surgically to less than 1 cm.
Results.
Of the 319 patients who underwent random-
ization, 278 could be evaluated (140 patients who under-
went surgery and 138 patients who did not). Progression-
free and overall survival were both significantly longer in
the group that underwent surgery (P
0.01). The dif-
ference in median survival was six months. The survival
rate at two years was 56 percent for the group that under-
went surgery and 46 percent for the group that did not. In
the multivariate analysis, debulking surgery was an inde-
pendent prognostic factor (P
0.012). Overall, after ad-
justment for all other prognostic factors, surgery reduced
the risk of death by 33 percent (95 percent confidence in-
terval, 10 to 50 percent; P
0.008). Surgery was not as-
sociated with death or severe morbidity.
Conclusions.
Debulking surgery significantly length-
ened progression-free and overall survival. The risk of death
was reduced by one third, after adjustment for a variety of
prognostic factors. (N Engl J Med 1995;332:629-34.)
From the Rotterdam Cancer Institute, Daniel den Hoed Kliniek, Rotterdam, the
Netherlands (M.E.L.B., M.L.); the International Institute for Drug Development,
Brussels, Belgium (M.B.); the Medical Academy, Gdansk, Poland (A.K.); Ospe-
dale San Gerardo, Monza, Italy (N.C.); the University of Brescia, Brescia, Italy
(G.F., S.P.); the Central Hospital of Asturias, Oviedo, Spain (A.J.L.); the Regina
Elena Cancer Institute, Rome (M.N.); and the European Organization for Re-
search and Treatment of Cancer Data Center, Brussels, Belgium (J.R.). Address
reprint requests to Dr. van der Burg at the Rotterdam Cancer Institute, Daniel den
Hoed Kliniek, P.O. Box 5201, 3008 AE Rotterdam, the Netherlands.
*Other principal investigators who contributed to the study are listed in the Ap-
pendix.
T
HE value of cytoreductive surgery in the manage-
ment of ovarian cancer has been debated for years.
The reasons for cytoreductive surgery are manifold.
Large tumors with relatively poor central blood sup-
plies and the areas with the lowest growth rates are
both rather insensitive to cytotoxic drugs.
1
In better-
perfused small, residual tumors, the growth rate and
the diffusion of chemotherapeutic agents are higher —
factors that are apt to increase the efficacy of chemo-
therapy. The removal of large tumors also reduces the
likelihood that drug-resistant clones will appear as a
result of spontaneous mutations.
2
Moreover, small tu-
mors require fewer cycles of chemotherapy, thus de-
creasing the probability of drug-induced resistance.
Several nonrandomized studies showed improved
survival of patients with residual tumors less than 1 cm
in diameter after primary surgery, as compared with
patients with larger lesions.
3-5
In a case–control study of
patients with minimal residual disease, Eisenkop et al.
reported that patients whose small lesions were all re-
sected survived significantly longer than patients in
whom such lesions were not resected.
6
On the other
hand, Hacker et al.
7
and Hoskins et al.
8
reported that
despite optimal cytoreduction, the survival of patients
with large intraabdominal metastases before resection
was significantly worse than that of patients with small
initial intraabdominal lesions. These results suggest
that in addition to residual disease after cytoreduction,
intrinsic tumor factors are of prognostic importance.
They also raise the question of whether cytoreduction
has a significant effect on survival among patients with
the same size tumors and the same intrinsic prognostic
factors.
The value of debulking surgery after induction che-
motherapy is even more difficult to assess. Several
studies indicated that patients in whom cytoreduction
was optimal after induction chemotherapy had approx-
imately the same survival rate as patients in whom
cytoreduction was optimal at primary surgery.
9-12
Neijt
et al., however, reported just the opposite.
4,13
Patients
with optimal cytoreduction at intervention surgery had
poorer rates of survival than patients with optimal cy-
toreduction at primary surgery. Moreover, the survival
of patients with optimal cytoreduction at intervention
surgery was the same as that of patients with subopti-
mal cytoreduction. All these studies, however, included
only small numbers of patients with different prog-
noses.
In 1987 the Gynecological Cancer Cooperative
Group of the European Organization for Research and
Treatment of Cancer (EORTC) initiated a randomized
phase 3 study to establish the effect on survival of de-
bulking surgery after induction chemotherapy.
M
ETHODS
Selection of Patients, Study Design, and Evaluation
Methods
From March 1987 to May 1993, 425 patients were enrolled in the
study. Eligible patients had to have biopsy-proved epithelial ovarian
carcinoma with an International Federation of Gynecology and Ob-
stetrics stage of IIb to IV,
14
residual lesions measuring more than
1 cm in diameter, a World Health Organization (WHO) performance
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630 THE NEW ENGLAND JOURNAL OF MEDICINE March 9, 1995
status of 0 to 2,
15
an age of less than 75 years, and adequate bone
marrow and renal function, and they had to have undergone primary
surgery no more than six weeks before treatment began. Clinical re-
sponse was assessed according to the standard WHO response crite-
ria.
15
A complete response was defined pathologically as the absence
of macroscopic and microscopic tumor at surgery. Optimal cytore-
duction was defined as the reduction of all tumor lesions to less than
1 cm in diameter.
The study design is shown in Figure 1. All eligible patients, after
giving informed consent, were registered centrally at the EORTC
Data Center before chemotherapy was begun. The patients received
three cycles of cyclophosphamide at a dose of 750 mg per square
meter of body-surface area, and cisplatin at a dose of 75 mg per
square meter every three weeks. After the third and sixth cycles, a
clinical evaluation was performed consisting of a gynecologic and
general physical examination, computed tomography or sonography
(or both), and measurement of serum CA-125. After the third cy-
cle, patients with tumor progression or a contraindication to sur-
gery were removed from the study. Patients with a clinical response
or stable disease were randomly assigned to undergo debulking
surgery or not to undergo surgery. Randomization was done cen-
trally at the EORTC Data Center after stratification with a mini-
mization technique to account for institution, performance status,
and clinical response.
At surgery, scheduled within 28 days after the third cycle of che-
motherapy, maximal cytoreduction was performed and, if not done
previously, a bilateral salpingo-oophorectomy, hysterectomy, and in-
fracolic omentectomy were carried out when possible. Chemotherapy
was to be resumed within four weeks after surgery. All randomized
patients were scheduled to receive at least six cycles of cyclophospha-
mide and cisplatin unless this therapy was clearly contraindicated.
The decision to continue or discontinue treatment after the sixth cy-
cle was based on the policy of the center. Patients with a complete
clinical response preferably had a “second-look” operation regardless
of whether they had undergone debulking surgery. After therapy pa-
tients were seen every two months during the first two years and in-
definitely thereafter according to each center’s policy. The end points
of the study were overall survival and progression-free survival.
Statistical Analysis
An accrual target of 440 randomized patients was specified in the
protocol in order for the study to have an 80 percent probability of
detecting a 30 percent reduction in the risk of death, with the use of
a two-tailed log-rank test at the conventional 5 percent level of sig-
nificance.
16
No formal statistical rules were specified in the protocol
for interim analyses, which were performed once a year according to
EORTC policy.
17
A difference in survival first emerged in September
1991 (P
0.006). This difference was confirmed by further interim
analyses in October 1992 (P
0.016), February 1993 (P
0.028), and
April 1993 (P
0.012), at which time the group decided to stop en-
rolling patients in the study. Follow-up was continued on all random-
ized patients.
Survival was calculated from the day chemotherapy was begun un-
til death, regardless of the cause of death. Progression-free survival
was calculated from the day chemotherapy was begun to the time of
progression or death. All randomized patients with some follow-up
information were included in the analyses of survival and progres-
sion-free survival, which were performed strictly according to the
intention-to-treat principle. Survival and progression-free survival
curves were calculated for each treatment group with Kaplan–Meier
estimates
18
and compared with the log-rank test.
19
Stratified analyses
and Cox regression analyses were performed to adjust treatment
comparisons for all known prognostic factors.
20
R
ESULTS
Recruitment and Demographic Characteristics of the
Patients
Of the 425 patients enrolled in the study, 319 pa-
tients underwent randomization. One hundred six pa-
tients did not undergo randomization for the following
reasons: 39 had disease progression, 22 had a contrain-
dication to surgery, 17 were still receiving induction
chemotherapy, 11 died, 10 declined to participate in the
study, 4 were found to be ineligible, and 3 were lost to
follow-up.
At the time of the analysis follow-up data were avail-
able on 278 of the 319 randomized patients: 140 pa-
tients who were assigned to undergo debulking surgery
and 138 who were assigned not to undergo surgery. All
known prognostic characteristics were well balanced
between the two treatment groups (Table 1). The pa-
tients ranged in age from 32 to 74 years, with a median
age of 59 years in both groups.
Treatment Received
Treatment data were available for all 278 patients.
Ninety-three percent of the patients (130 patients) as-
signed to undergo surgery had had surgery, and 100
percent of the patients (138 patients) assigned not to
undergo surgery had had no surgery. In both groups 84
percent of the patients received at least six cycles of cy-
Figure 1. Design of the Study.
Enrollment
3 Cycles of
cyclophosphamide
cisplatin
Evaluation
Debulking
surgery
Complete response,
partial response, or
stable disease
Randomization
Progressive
disease
Removal
from
study
Overall survival
Progression-free survival
End points:
No debulking
surgery
3 Cycles of
cyclophosphamide
cisplatin
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Vol. 332 No. 10 DEBULKING SURGERY AND PROGNOSIS IN ADVANCED EPITHELIAL OVARIAN CANCER 631
clophosphamide and cisplatin. A reduction in the dose
or postponement of chemotherapy was necessary in 36
percent and 48 percent of the patients who had had
surgery and in 37 percent and 49 percent of the pa-
tients who had not undergone surgery, respectively. The
length of time from cycle 4 to cycle 6 was similar in
both treatment groups (P
0.42), lasting a median of
seven weeks in each. The median overall duration of
treatment from cycle 1 to cycle 6 was 21 weeks for the
patients who had had surgery and 17.5 weeks for the
patients who had not had surgery.
The reasons for stopping chemotherapy after ran-
domization and before the sixth cycle in the group that
had undergone surgery and in the group that had not
were as follows: progressive disease in 5 and 3 percent,
respectively; toxic reactions in 3 and 2 percent, respec-
tively; refusal to continue chemotherapy in 4 and 5 per-
cent, respectively; and unknown in 4 and 6 percent,
respectively. Consolidation chemotherapy after the
sixth cycle was given to 36 percent of the patients who
had undergone surgery and 51 percent of those who
had not had surgery. A second-look operation was per-
formed in 52 patients who had undergone surgery and
51 patients who had not.
Results of Debulking Surgery
Surgical data were available on 127 of the 130 pa-
tients who underwent debulking surgery. At laparoto-
my, 83 of the 127 patients (65 percent) had tumors that
exceeded 1 cm in diameter and 44 patients had tumors
that had been reduced to less than 1 cm by chemother-
apy (Table 2). In 37 of the 83 patients (45 percent) with
lesions measuring more than 1 cm, the tumors were re-
duced by surgery to a diameter of less than 1 cm. In the
other 46 patients an attempt was made to perform
maximal cytoreduction, but lesions measuring more
than 1 cm had to be left behind. The ovaries were re-
sected in 32 of 41 patients (78 percent) whose ovaries
were still in situ. Overall, 81 of the 127 patients (64 per-
cent) had residual lesions of less than 1 cm after de-
bulking surgery.
No lethal or serious complications were observed af-
ter debulking surgery. The intraoperative complications
consisted of bowel injury in 3 percent of the patients
and bladder injury in 2 percent. Twenty-two percent
lost more than 500 ml of blood. The postoperative
complications consisted of fever (temperature of more
than 38.5
°
C on more than two days) in 4 percent, ileus
for more than five days in 1 percent, urinary tract in-
fection in 4 percent, wound infection in 2 percent, deep
venous thrombosis in 1 percent, and lung embolism in
2 percent. These complications were similar in kind
and severity to those observed at primary surgery.
Clinical Response
The overall rate of clinical response after the sixth
cycle of chemotherapy was 84 percent for the group
that underwent debulking surgery and 70 percent for
the group that did not undergo surgery; the rate of
complete response was 70 percent and 35 percent, re-
spectively. The disease progressed in 8 percent of the
patients who underwent debulking surgery and 12 per-
cent of those who did not.
Before second-look surgery, 79 percent of the pa-
tients who had undergone debulking surgery had a
complete clinical response, as compared with 59 per-
cent of the patients who did not have debulking surgery.
Second-look surgery in the patients who had undergone
debulking surgery and in those who had not revealed
similar rates of complete response (37 percent vs. 33
percent), partial response (28 percent vs. 37 percent),
*FIGO denotes International Federation of Gynecology and
Obstetrics.
Table 1. Characteristics of the Patients.
C
HARACTERISTIC
D
EBULKING
S
URGERY
(N
140)
N
O
D
EBULKING
S
URGERY
(N
138)
percent
WHO performance status
03434
14851
21815
FIGO stage*
IIb 6 4
III 71 75
IV 23 21
Histologic type
Serous 59 56
Mucinous 8 4
Endometrioid 7 10
Clear cell 1 4
Unclassified 25 26
Tumor grade
189
22732
36154
Unknown 4 5
Tumor size
1–2 cm 6 4
2–5 cm 25 20
5–10 cm 20 24
10 cm 28 32
Unknown,
2 cm 21 20
No. of lesions
1–5 35 35
6–10 22 15
10 43 50
Ovary in situ
Yes 29 31
Unknown 18 18
Peritoneal carcinomatosis
Yes 46 43
Unknown 23 23
Ascites 78 72
Response after 3 cycles of
cyclophosphamide and
cisplatin
Complete response 18 17
Partial response 54 55
Stable disease 28 28
Table 2. Results of Debulking Surgery after Three
Cycles of Cyclophosphamide and Cisplatin.
L
ARGEST
L
ESIONS
BEFORE
D
EBULKING
S
URGERY
T
OTAL
L
ARGEST
L
ESIONS
AFTER
D
EBULKING
S
URGERY
NO
MACROSCOPIC
1 cm
1 cm
No macroscopic
lesions
22 22 0 0
1 cm 22 7 15 0
1 cm 83 19 18 46
Total 127 48 33 46
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632 THE NEW ENGLAND JOURNAL OF MEDICINE March 9, 1995
stable disease (2 percent vs. 6 percent), disease pro-
gression (8 percent vs. 6 percent) and microscopic dis-
ease (15 percent vs. 10 percent), and similar percentag-
es of patients whose response could not be evaluated
(10 percent vs. 8 percent). The size of the tumors be-
fore cytoreduction and after cytoreduction at second-
look surgery is shown in Table 3.
Survival and Progression-free Survival
At the time of the analysis, 75 percent of the patients
had been followed for more than 2.2 years, 50 percent
for more than 3.5 years, and 25 percent for more than
4.3 years. The maximal follow-up was 5.6 years. Both
overall survival and progression-free survival were sig-
nificantly longer (P
0.01) for the patients who under-
went debulking surgery. In addition, the three most re-
cent interim analyses had shown a significant benefit of
surgery. The difference in survival was more substan-
tial when patients with stage IV disease were excluded
(P
0.003 for overall survival and P
0.002 for pro-
gression-free survival).
The median survival was 26 months for the patients
who underwent debulking surgery and 20 months for
those who did not. The proportion of patients alive at
two years was 56 percent in the former group and 46
percent in the latter group (Fig. 2). Overall, surgery re-
duced the unadjusted risk of death by 31 percent (the
hazard rate, or the risk of death at any given moment).
The beneficial effect of surgery on survival was consis-
tent throughout the observation period. Figure 3 shows
the survival curves for the patients who did not under-
go debulking surgery and for the patients who did un-
dergo debulking surgery according to the size of resid-
ual lesions at the time of surgery. Patients whose lesions
measured less than 1 cm before cytoreduction survived
significantly longer (median, 41.6 months; P
0.001)
than patients whose lesions measured more than 1 cm
after debulking surgery (median survival, 19.4 months);
survival in the latter group was similar to overall
survival in the group that did not undergo debulking
surgery (median survival, 20.0 months). Patients with
optimal cytoreduction (whose remaining lesions meas-
ured less than 1 cm) also survived significantly longer
(median survival, 26.6 months; P
0.04) than patients
with suboptimal cytoreduction.
The median progression-free survival was 18 months
for the patients who had debulking surgery and 13
months for the patients who did not have debulking
surgery. The percentage of patients alive and free of
progressive disease at two years was 38 percent in the
former group and 26 percent in the latter (Fig. 4).
Figure 5 shows the progression-free survival curves
for the patients who did not have debulking surgery and
for the patients who did have debulking surgery, accord-
ing to the size of the residual lesions at the time of sur-
gery. The progression-free survival of patients whose
lesions were less than 1 cm in diameter before cytore-
duction was significantly longer (median, 24.1 months;
P
0.001) than that of patients with suboptimal cytore-
duction (median survival, 12.1 months); results for the
latter were similar to the progression-free survival seen
in the group that did not have debulking surgery (me-
dian survival, 12.9 months). Likewise, the progression-
free survival of patients with optimal cytoreduction was
significantly longer (median survival, 23.3 months;
P
0.003) than the progression-free survival of pa-
tients with suboptimal cytoreduction.
Adjusted and Multivariate Analyses
Table 4 shows the effect of adjusting the compari-
son of survival between the two treatment groups for
all known prognostic factors. The 31 percent reduc-
tion in the risk of death derived from the unadjusted
comparison (95 percent confidence interval, 8 to 49
percent) remained qualitatively unchanged by all ad-
justments for prognostic factors (risk reductions rang-
ing from 29 to 36 percent). The relative benefit of sur-
gery was remarkably consistent across all subgroups
of patients (data not shown). When all prognostic fac-
tors were taken into account simultaneously in a Cox
regression model, the reduction in the risk of death
due to surgery was 33 percent (95 percent confidence
interval, 10 to 50 percent; P
0.008). When the pop-
ulation of patients was subdivided into two equal
groups on the basis of the multivariate risk, there was
*No information was available for nine patients.
Table 3. Size of the Tumors before Cytoreduction and after
Cytoreduction at Second-Look Surgery.
S
IZE
OF
T
UMOR
D
EBULKING
S
URGERY
(N
52)
N
O
D
EBULKING
S
URGERY
(N
51)
BEFORE
CYTO
-
REDUCTION
AFTER
CYTO-
REDUCTION
BEFORE
CYTO-
REDUCTION
AFTER
CYTO-
REDUCTION
no. of patients
No macroscopic
lesions
27 37 22 30
1 cm 13 9 5 6
1 cm 7 1 20 11
Unknown* 5 5 4 4
Figure 2. Survival of Patients with Advanced Epithelial Ovarian
Cancer According to Whether They Underwent Debulking
Surgery.
P 0.012 for the comparison between the groups by the
log-rank test.
Probability of Survival
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0
1
23
4
5
6
NO. AT RISK
Surgery
No surgery
140
138
118
100
61
47
31
20
17
6
6
1
Years
Surgery (85 deaths)
No surgery (97 deaths)
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Vol. 332 No. 10 DEBULKING SURGERY AND PROGNOSIS IN ADVANCED EPITHELIAL OVARIAN CANCER 633
no evidence that the relative benefit of debulking sur-
gery was different for the high-risk and the low-risk
patients.
DISCUSSION
Our study establishes the effect of tumor reduction
on progression-free and overall survival, which were
both significantly prolonged in patients randomly
assigned to undergo debulking surgery. The median
progression-free survival and overall survival were in-
creased by five and six months, respectively. Moreover,
the beneficial effect of surgery on progression-free and
overall survival was consistent throughout the observa-
tion period (with a median follow-up of 3.5 years).
However, much longer follow-up is clearly needed be-
fore the curative value of debulking surgery can be as-
sessed.
The majority of the studies in the literature com-
pared the survival of patients after optimal cytoreduc-
tive surgery with the survival of patients after subopti-
mal cytoreduction.
3-5,9-11
All these studies are hampered
by the unavoidable and serious bias inherent in the
comparison of patients with different prognostic fac-
tors. Only one other prospective randomized study has
addressed the question of the value of cytoreduction.
21
In the interim analysis there was no significant differ-
ence in survival between the group that underwent sur-
gery (median survival, 23 months) and the group that
did not (median survival, 16 months). Only 34 patients
in each group were evaluated, however.
In our study patients with lesions of less than 1 cm
at debulking surgery before or after cytoreduction sur-
vived longer than patients with larger residual lesions
(Fig. 3). Nonetheless, the survival of patients with re-
sidual lesions of more than 1 cm after surgery — the
patients with the poorest prognosis — was not signifi-
cantly different from the survival of the patients who
did not undergo debulking surgery. The fact that sur-
vival was similar in these two groups means either that
patients with suboptimal cytoreduction did benefit from
cytoreduction or that there were patients in the group
that did not undergo debulking surgery who might have
benefited from cytoreductive surgery. Qualitatively, the
same observations were made for progression-free sur-
vival (Fig. 5).
We also attempted to identify a group of patients
who did not benefit from debulking surgery. In the mul-
tivariate analysis, the benefit of surgery remained sig-
nificant even after adjustment for all other known prog-
nostic factors (33 percent reduction in the risk of death,
P 0.008). When the patients were subdivided into
high-risk and low-risk groups on the basis of either in-
dividual prognostic factors or the multivariate risk,
there was no difference in the relative benefit of surgery
between the two groups. Thus, we could not identify a
subgroup of patients who clearly did not benefit from
Figure 3. Survival of Patients with Advanced Epithelial Ovarian
Cancer Who Did Not Have Debulking Surgery and Patients Who
Had Such Surgery, According to Whether the Lesions Were Less
Than 1 cm in Diameter before Cytoreduction, Less Than 1 cm
after Cytoreduction (Optimal), or More Than 1 cm after Cytore-
Probability of Survival
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0
1
2
3
4
5
6
Years
1 cm before (n 44; 20 deaths)
Optimal (n 37; 21 deaths)
Suboptimal (n
46; 36 deaths)
No surgery (n
138; 97 deaths)
duction (Suboptimal).
Figure 4. Progression-free Survival of Patients with Advanced
Epithelial Ovarian Cancer According to Whether They Under-
Probability of Progression-
free Survival
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
01
234
5
6
NO. AT RISK
Surgery
No surgery
140
138
88
69
36
25
19
12
9
4
5
1
Years
Surgery (progression in 91)
No surgery (progression in 104)
went Debulking Surgery.
P 0.013 for the comparison between the groups by the
log-rank test.
Figure 5. Progression-free Survival of Patients with Advanced
Epithelial Ovarian Cancer Who Did Not Have Debulking Surgery
and Patients Who Had Such Surgery, According to Whether the
Lesions Were Less Than 1 cm in Diameter before Cytoreduction,
Less Than 1 cm after Cytoreduction (Optimal), or More Than
1 cm after Cytoreduction (Suboptimal).
Probability of Progression-
free Survival
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
0
1
2
3
4
5
6
Years
1 cm before (n 44; progression in 22)
Optimal (n
37; progression in 21)
Suboptimal (n 46; progression in 38)
No surgery (n
138; progression in 104)
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