Download The Role of Surgery in the Management of Epithelial Ovarian Cancer

Surgery remains key in the diagnosis,
staging, and management of
ovarian cancer.
J. L. Munro. Arctic Whalers. Mixed media on canvas, 24 × 36.
The Role of Surgery in the Management of
Epithelial Ovarian Cancer
Ingrid Ramirez, MD, Hye Sook Chon, MD, and Sachin M. Apte, MD, MS
Background: Epithelial ovarian cancer is the most deadly gynecologic cancer in the United States. Multiple
modalities of therapy are utilized in the management of the disease. The role of surgery remains important in
the treatment of this disease and is described herein.
Methods: Medline and PubMed were utilized to search the English language medical literature up to March
2010. A broad range of studies and quality of data were analyzed, including prospective studies, case control
analyses, and meta-analyses. When possible, the highest level of evidence was reviewed and presented.
Results: For the medically fit patient, optimal cytoreductive surgery positively impacts survival. For some highly
selected patients, there is a role for a minimally invasive approach. In the recurrent setting, factors such as
interval to recurrence and the distribution of disease will determine the utility of secondary cytoreductive surgery.
A subgroup of patients may benefit from palliative surgical procedures in the recurrent setting.
Conclusions: Despite advances in the use of chemotherapy and biologic agents, surgery remains an important
modality in the diagnosis and treatment of ovarian cancer.
Background
Epithelial ovarian cancer (EOC) remains the most deadly
gynecologic cancer in the United States. In 2010, approximately 21,880 new cases and 13,850 deaths occurred.1
There is no proven screening test for this disease. Many
women present with vague symptoms, including abdominal bloating, change in bowel or bladder habits, early satiety, or abdominal pain. For these reasons, many patients
From the Department of Obstetrics and Gynecology at the University of South Florida, Tampa, Florida (IR), and the Department of
Women’s Oncology at the H. Lee Moffitt Cancer Center & Research
Institute, Tampa, Florida (HSC, SMA).
Submitted May 17, 2010; accepted September 9, 2010.
Address correspondence to Sachin M. Apte, MD, MS, Department of
Women’s Oncology, Moffitt Cancer Center, 12902 Magnolia Drive,
MCC-GYNPROG, Tampa, FL 33612. E-mail: [email protected]
No significant relationship exists between the authors and the
companies/organizations whose products or services may be referenced in this article.
22 Cancer Control
present with advanced metastatic disease at diagnosis.
Initial evaluation includes a thorough history and physical examination, imaging studies, assessment of tumor
markers (CA-125), possible biopsies, and/or colonoscopy.
Cytotoxic chemotherapy has an important role in
the treatment of this disease, in the neoadjuvant, adjuvant, and recurrent setting. For the medically fit patient,
surgery also has an important role in the management
of ovarian cancer for diagnosis, primary therapy, and
treatment of recurrent disease.
This paper focuses on the role of surgery in the
management of EOC. Although fallopian tube cancer and
primary peritoneal cancer are not specifically addressed,
these diseases are thought to be similar to EOC and are
treated in a manner identical to EOC.
Terms that should be defined prior to proceeding
include primary cytoreduction, interval cytoreduction,
secondary cytoreduction, neoadjuvant chemotherapy,
January 2011, Vol 18, No.1
and adjuvant chemotherapy. Primary cytoreduction
refers to the initial surgical excision of tumor and tumorinvolved organs prior to chemotherapy. According to the
Gynecologic Oncology Group (GOG), optimal surgical
cytoreduction is defined as residual tumor less than 1
cm. Interval cytoreduction is performed on patients who
have previously received neoadjuvant chemotherapy.
Secondary cytoreduction refers to the surgical management of recurrent ovarian cancer. Cytoreduction and
debulking are terms that are used interchangeably. Neoadjuvant chemotherapy is the administration of chemotherapy prior to cytoreductive surgery. This is reserved
for those patients in whom optimal cytoreduction is not
possible because of either the distribution of disease
or poor performance status. Adjuvant chemotherapy is
administered after surgery in appropriate patients. Patients usually receive 6 cycles of adjuvant platinum and
taxane-based chemotherapy.
Role of Surgery
Surgical evaluation is indicated for most women with
known or suspected EOC. Surgery is generally recommended, provided there are no medical contraindications
and the distribution of disease is deemed resectable on
preoperative evaluation. The goals of the initial surgery
are to obtain a pathologic diagnosis, accurately determine
the extent of disease and, when feasible, optimally cytoreduce the ovarian cancer. For patients with suspected
EOC, the usual differential diagnosis includes uterine,
fallopian tube, primary peritoneal, or metastatic cancers
from the gastrointestinal tract or breast.
Accurate surgical staging is particularly important for
apparent early-stage disease, ie, women with an ovarian
cancer that appears grossly confined to the ovary. Approximately 25% to 30% of women with apparent earlystage disease will be upstaged upon thorough surgical
staging. Treatment is often driven by the surgical stage, as
expressed by the International Federation of Gynecology
and Obstetrics (FIGO) staging system (Table). Precise
surgical staging is critical for the patient in terms of both
therapy and prognosis. Women with a true stage I, welldifferentiated EOC may be observed; however, those
with more advanced disease are generally treated with
chemotherapy. Due to a lack of effective screening and
insidious symptoms, the majority of women will present with advanced disease. In the setting of advanced
disease, the goal of the initial surgical effort is to achieve
optimal cytoreduction. Intraperitoneal chemotherapy
is considered for some patients with advanced disease
who have undergone optimal cytoreductive surgery. A
careful preoperative assessment is mandatory to determine patient fitness for surgery. The surgeon must take
Table. — Carcinoma of the Ovary: FIGO Nomenclature (Rio de Janeiro 1988)
Stage I
Growth limited to the ovaries.
IA
Growth limited to one ovary: no ascites present containing malignant cells. No tumor on the external surface; capsule intact.
IB
Growth limited to both ovaries: no ascites present containing malignant cells. No tumor on the external surfaces; capsules intact.
IC*
Tumor either stage IA or IB, but with tumor on surface of one or both ovaries, or with capsule ruptured, or with ascites present
containing malignant cells, or with positive peritoneal washings.
Stage II
Growth involving one or both ovaries with pelvic extension.
IIA
Extension and/or metastases to the uterus and/or tubes.
IIB
Extension to other pelvic tissues.
IIC*
Tumor either stage IIA or IIB, but with tumor on surface of one or both ovaries, or with capsule(s) ruptured, or with ascites present
containing malignant cells, or with positive peritoneal washings.
Stage III
Tumor involving one or both ovaries with histologically confirmed peritoneal implants outside the pelvis and/or positive retroperitoneal
or inguinal nodes. Superficial liver metastases equals stage III. Tumor is limited to the true pelvis but with histologically proven
malignant extension to small bowel or omentum.
IIIA
Tumor grossly limited to the true pelvis, with negative nodes, but with histologically confirmed microscopic seeding of abdominal
peritoneal surfaces, or histologic proven extension to small bowel or mesentery.
IIIB
Tumor of one or both ovaries with histologically confirmed implants, peritoneal metastasis of abdominal peritoneal surfaces, none
exceeding 2 cm in diameter; nodes are negative.
IIIC
Peritoneal metastasis beyond the pelvis > 2 cm in diameter and/or positive retroperitoneal or inguinal nodes.
Stage IV
Growth involving one or both ovaries with distant metastases. If pleural effusion is present, there must be positive cytology to allot a
case to stage IV. Parenchymal liver metastasis equals stage IV.
* In order to evaluate the impact on prognosis of the different criteria for allotting cases to stage IC or IIC, it would be of value to know if rupture of the
capsule was spontaneous, or caused by the surgeon; and if the source of malignant cells detected peritoneal washings, or ascites.
From Heintz APM, Odicino F, Maisonneuve P, et al. Carcinoma of the ovary. Int J Gynecol Obstet. 2006;95(suppl 1):S163. Reprinted with permission
by Elsevier. http://www.sciencedirect.com/science/journal/00207292.
January 2011, Vol 18, No.1
Cancer Control 23
into consideration a variety of factors, such as performance status, nutrition, medical comorbidities, impending bowel obstruction, and patient age. The patient must
undergo a careful and thorough consent process and
must understand the risks, benefits, and radicality of the
possible procedures involved.
Staging Procedure
The staging procedure is usually performed via a vertical incision, and a thorough exploration is performed
to assess the extent of disease. All peritoneal surfaces
and organs are palpated, including the diaphragm, liver,
spleen, gall bladder, small and large intestine, and mesentery. The retroperitoneum is carefully evaluated for
bulky adenopathy. A frozen section is obtained, usually of
a portion of involved omentum or adnexa. An assessment
is made regarding whether a patient can be debulked
optimally. If so, attention should first be placed on the
area of most concern so that it can be rendered free of
disease. Also, potential sites of bowel obstruction must
be carefully evaluated and addressed.
In the absence of gross extra-ovarian disease, multiple
peritoneal biopsies are obtained, along with a pelvic and
para-aortic lymphadenectomy. An omentectomy, hysterectomy, and bilateral salpingo-oophorectomy are also performed. For women with early-stage ovarian cancer, systematic lymphadenectomy is part of the complete staging
procedure. Nearly one-fourth of patients with apparent
early-stage ovarian cancer who undergo this procedure
are upstaged to stage IIIC due to the presence of node
metastases.2 However, in patients with advanced-stage
EOC, the role and benefit of systematic lymphadenectomy
are unclear. In a study of 456 women with advanced
stage III/IV ovarian cancer, no correlation between nodal
status and survival was noted. In addition, nodal status
was not a prognostic factor for optimally cytoreduced
patients with advanced-stage EOC.3 In another trial, 427
women with stage III/IV ovarian cancer were randomized to either systemic lymphadenectomy vs resection of
bulky nodes.4 No statistical difference in the 5-year overall
survival rate (48.5% vs 47%, respectively) was noted. Systemic lymphadenectomy, however, was associated with
increased progression-free survival compared to the nolymphadenectomy arm: 31.2% vs 21.6%. Therefore, the
recommendation is to resect bulky tumor-involved nodes
in advanced-stage ovarian cancer.
Primary Cytoreduction
The cornerstones of the initial management of EOC are
staging and surgical cytoreduction. For patients with
advanced-stage ovarian cancer, the optimal cytoreductive rate has been shown to vary from 17% to 87%.5-16 To
achieve an optimal surgery, a variety of procedures may
need to be performed, such as splenectomy, diaphragm
stripping, partial hepatic resection, partial bladder or
ureteral resection, or bowel resection.
24 Cancer Control
In the 1970s, Griffiths et al17,18 described an association between overall survival and cytoreduction of bulky
disease. In a study of 102 patients with stage II and III
EOC, residual disease 1.5 cm was identified as a poor
prognostic indicator. Hoskins et al19 also reported on the
size of residual disease and overall survival in patients
with stage III ovarian cancer. Patients with suboptimal
cytoreduction ( 1 cm) but with smaller diameter residual disease ( 2 cm) still had an increased overall
survival compared with those who had larger volume
residual disease ( 2 cm). Since then, multiple studies
have consistently shown that the volume of residual
disease remaining after cytoreductive surgery inversely
correlates with survival.5,19-22
The term optimal cytoreduction has recently
become a topic of controversy since the definition has
now evolved to also include maximal cytoreductive
efforts, with the end goal of complete resection of all
visible disease. No residual disease at the completion
of surgery has consistently been shown to result in improved overall survival and progression-free survival.
Although studies have described optimal cytoreduction
by different criteria, for example, 2 cm or 0.5 cm,
to date, no prospective randomized control trials have
defined the degree of residual disease that has the best
clinical outcome.
Based on current retrospective studies, the recommendation for complete resection of all visible disease is
becoming more widely accepted as it has been shown to
improve overall survival.23 Chi et al21 reported that the
amount of residual disease was recognized as a significant
prognostic factor. In that study, 465 patients with stage
IIIC EOC who had undergone primary cytoreductive
surgery were identified from a prospective database.
The amount of residual disease was categorized into
five distinct groups: no gross residual, gross 0.5 cm,
0.6–1.0 cm, 1–2 cm, and 2 cm residual. The median
overall survival rates in the five groups were as follows:
106 months for no gross, 66 months for gross 0.5 cm,
48 months for 0.6–1.0 cm, 33 months for 1–2 cm, and 34
months for 2 cm. In a study of 3,126 patients, du Bois
et al24 also demonstrated improved overall and progression- free survival with complete resection. The patients
with complete resection had a median survival of 99.1
months, whereas the median survival for patients with
0.1 to 1 cm and 1 cm residual disease was 36.2 and
29.6 months, respectively.
The findings from the above studies reiterate the
importance of optimal cytoreduction at the time of
primary surgery for EOC. In addition, although the
GOG defines optimal cytoreduction as residual disease of
1 cm, data from more recent studies suggest that
overall and progression-free survival are improved to a
greater extent when maximal cytoreduction is achieved.
These findings of increased overall survival with maximal
cytoreduction have led many to advocate for complete
January 2011, Vol 18, No.1
resection with the end goal of no residual disease.
However, maximal cytoreduction may be associated
with significant perioperative morbidity, as aggressive
surgical techniques such as diaphragmatic stripping may
have to be employed to obtain an optimal cytoreduction.
Nevertheless, surgery by either optimal cytoreduction or
maximal cytoreduction before chemotherapy has been
shown consistently to improve survival in patients with
advanced EOC. In addition to the improved survival with
cytoreduction, surgery improves some of the symptoms
associated with advanced-stage EOC, such as bloating,
abdominal distention, or abdominal pain.
Adjuvant Chemotherapy
After primary cytoreductive surgery, adjuvant platinum
and taxane-based chemotherapy is used in the majority
of women with advanced ovarian cancer. Optimal debulking is thought to maximize the efficacy of chemotherapy. Chemotherapeutic drugs exert their maximum
effects on small tumors that are well perfused and therefore mitotically active. Large tumor size is associated
with poor perfusion, a greater chance of sublethal cellular damage, and the emergence of multidrug-resistant
clones. Chemotherapy can be administered by intravenous or intraperitoneal routes. In EOC, the peritoneum
is the focus of tumor metastasis. The intraperitoneal
route allows for direct exposure to chemotherapeutic agents and has been shown to increase overall and
progression-free survival in advanced ovarian cancer
compared with intravenous chemotherapy.25-27 In a
recent study by Armstrong et al,27 429 optimally debulked patients were randomized to receive intravenous
paclitaxel followed by either intravenous cisplatin on
day 2 (intravenous group) or intraperitoneal cisplatin
on day 2 and intraperitoneal paclitaxel on day 8 (intraperitoneal group). Among 415 eligible patients, the
median progression-free survival and overall survival in
the intraperitoneal group vs the intravenous group were
23.8 vs 18.3 months and 65.6 vs 49.7 months. However,
intraperitoneal chemotherapy is associated with more
side effects and thus has a higher discontinuation rate.
Nonetheless, in this study, despite the discontinuation
rate (only 42% of the patients in the intraperitoneal
group completed the assigned six cycles), a survival
benefit was shown. Most of the complications with
intraperitoneal chemotherapy were catheter related,
such as infection, leakage near the port, access difficulties, blocked catheter, and leakage of fluid through the
vagina.28 Other adverse events included abdominal
pain, nephrotoxicity, fatigue, hematologic disorders, and
neuropathy. Despite these adverse effects, intraperitoneal chemotherapy should be considered for adjuvant
chemotherapy in optimally cytoreduced patients with
advanced-stage ovarian cancer, as it has consistently
been shown to confer a clinical advantage with increased overall survival.
January 2011, Vol 18, No.1
Suboptimal Debulking
Achieving optimal debulking is not always feasible. Limiting factors may include extensive upper abdominal or
retroperitoneal disease, large tumor burden in bowel
mesentery, or porta hepatis. Selection criteria often used
to determine which patients cannot be optimally cytoreduced include presence of stage IV disease, massive
ascites, bulky omental disease with splenic involvement,
and suprarenal lymphadenopathy. If optimal debulking
is not possible, then the operation is generally limited to
a bilateral salpingo-oophorectomy and/or omentectomy
to prove the site of origin and to address potential sites
of bowel obstruction.
Clinical models have been developed to try to identify those patients who will have a low probability of
optimal cytoreductive surgery. Computed tomography
(CT) scans have been evaluated to determine their predictive value in identifying unresectable disease. Nelson
et al29 assessed the likelihood of resectability based on
CT findings. The CT findings predictive of unresectability included the presence of an omental cake extending
to the spleen, a diaphragm coated by tumor extending
to the liver serosa, lesions 2 cm in the suprarenal
para-aortic lymph nodes and porta hepatis, parenchymal liver disease, pulmonary metastases, and enlarged
pericardial lymph nodes. With these criteria, the likelihood of resectability was accurately predicted in 23 of
24 patients. Bristow et al30 also used CT radiographic
features for predicting the outcome of cytoreductive
surgery in advanced ovarian cancer. The authors identified 13 radiographic features corresponding to certain
anatomic locations that have traditionally made optimal
cytoreductive surgery difficult, such as extensive upper
abdominal disease. Forty-one patients with stage III/IV
EOC who had undergone primary surgical cytoreduction were identified. Their preoperative CT scans were
reviewed and, based on certain radiographic features and
performance status, the patients were assigned a score.
In this study, a Predictive Index score 4 was indicative of poor likelihood to undergo optimal cytoreduction. However, more recent studies have contradicted
these findings.31 Axtell et al32 analyzed preoperative CT
scans from 65 patients with stage III/IV ovarian cancer
who had undergone primary cytoreduction. Fourteen
radiologic criteria were chosen as possible pertinent
predictors of suboptimal cytoreduction, including largevolume ascites, pleural effusion, diffuse peritoneal thickening, omental caking, omental extension to spleen or
stomach, suprarenal lymph nodes 1 cm, infrarenal or
inguinal lymph nodes 2 cm, and tumor implants 2
cm (located on bowel mesentery, peritoneum, diaphragm,
liver, or porta hepatis). Only diaphragmatic disease 2
cm and large bowel mesentery implants 2 cm were
noted to be statistically significant predictors of suboptimal cytoreductive outcome. However, the utility of this
finding is limited because half of the patients with Cancer Control 25
2-cm disease in the diaphragm and large bowel actually
underwent optimal cytoreduction. In addition, when
these criteria were applied to two previously published
patient cohorts (patients who underwent primary cytoreduction at Johns Hopkins Medical Institute30 and the
Mayo Clinic33), the sensitivity, specificity, and accuracy
of these positive predictors were all noted to decrease.
CT scans should thus be used with caution when trying
to identify those patients who are not likely to achieve
optimal cytoreduction. Clinical judgment must be exercised when deciding whether to proceed with primary
cytoreductive surgery, as no clinical model has yet accurately predicted disease resectability.
In addition, the above clinical models did not take
into account the surgeon as an independent predictive
factor of surgical outcome. In a study by Aletti et al,34
certain preoperative and intraoperative factors were
analyzed to identify a correlation with optimal residual
disease. The variables analyzed were patient age, performance status, CA-125 level, ascites volume, carcinomatosis, diaphragm and mesentery involvement, and surgeon
tendency. Only performance status, carcinomatosis, and
surgeon tendency were independently associated with
optimal cytoreduction. These findings were consistent
with the belief that resectability of tumor is highly dependent on surgical skills. This study also demonstrated that
any proposed model to preoperatively identify patients
unlikely to have optimal cytoreduction must take into
account surgeon tendency as a predictive factor.
Preoperative CA-125 level also has been evaluated as
a predictor for primary optimal cytoreduction in patients
with advanced ovarian cancer. Despite initial positive
results from Chi et al35 regarding the preoperative predictability of CA-125 for optimal cytoreduction, the same
group recently reported that there was no threshold
CA-125 level that accurately predicted cytoreductive
outcome after their change in surgical paradigm that
incorporated extensive upper abdominal procedures to
attain optimal debulking.36 It is a general consensus that,
currently, CA-125 level does not appear to be a significant
predictor of tumor resectability.
In addition to cytoreduction and surgeon skill, a
patient’s specific tumor biology likely plays a role in resectability of disease and survival. The reasoning is that
certain tumor cells have the ability to escape cell repair
mechanisms, making them inherently more aggressive.
For example, the “biological aggressiveness” of certain
tumors may decrease long-term survival due to tumordependent characteristics, such as rapid development
of chemoresistance, despite optimal cytoreduction. A
study by Hacker et al37 showed that large-volume ascites
or large tumor burden ( 10 cm), despite cytoreduction,
was a poor prognostic factor. Heintz et al38 found that
ascites, large tumor diameter, and peritoneal carcinomatosis were poor prognostic factors despite cytoreduction.
The above studies support the idea that initial tumor
26 Cancer Control
burden may be in itself an indicator of tumor biological
aggressiveness.
The majority of women will receive adjuvant chemotherapy after suboptimal debulking. Whether these
women would benefit from another attempt at debulking
is unclear. A report by van der Burg et al39 described
the findings of a European Organisation of Research and
Treatment of Cancer (EORTC) study in which 278 evaluable patients with suboptimal tumor debulking (residual
tumor 1 cm) were randomly assigned, after three cycles
of cyclophosphamide and cisplatin, to either undergo a
secondary attempt at debulking or continue with another
three cycles of chemotherapy. Those with progressive
disease after neoadjuvant chemotherapy were excluded
from the study. The secondary attempt at debulking was
performed on 140 patients and was well tolerated: 65%
of patients had residual disease 1 cm after neoadjuvant
chemotherapy, and optimal cytoreduction was achieved
in 45% of patients in this group. Median survival time was
26 months for those undergoing a secondary attempt and
20 months for those in the non-secondary attempt group
(P = .04). Overall, after adjustments were made for all
other prognostic factors, surgery reduced the risk of death
by 33% (95% confidence interval, 10% to 50%; P = .008). A
second study showed results contradictory to the EORTC
study. In GOG 152, Rose et al40 reported on 425 patients
with advanced EOC who had been suboptimally debulked
(residual tumor 1 cm) at primary surgery, received
three cycles of paclitaxel and cisplatin chemotherapy, and
then were randomized to secondary attempt at debulking
or no surgery followed by chemotherapy in both groups.
Patients receiving secondary attempt at debulking had a
median survival time of 32 months compared with 33
months for those receiving chemotherapy alone. There
was no difference in progression-free survival time (10.5
and 10.8 months, respectively). Unlike the EORTC trial,
GOG 152 had inclusion criteria for a maximal surgical
effort at the time of primary surgery. It is apparent that
patients who have had a maximal but suboptimal primary
cytoreductive surgical effort do not benefit from a secondary attempt at debulking. Therefore, women who
have undergone an attempted cytoreduction by a surgeon
trained in the aggressive management of this disease are
unlikely to benefit from a second attempt for debulking
surgery after chemotherapy.
Neoadjuvant Chemotherapy Followed by
Interval Debulking Surgery
For patients with suspected advanced ovarian cancer, the
general recommendation is for primary surgical cytoreduction followed by chemotherapy. However, when this
is not advisable, patients are usually treated initially with
neoadjuvant platinum and taxane-based chemotherapy
prior to cytoreductive surgery. These patients may have
significant pre-existing medical comorbidities or severe
malnutrition and thus be at high risk for perioperative
January 2011, Vol 18, No.1
morbidity or mortality. Patient age, poor performance
status, and complexity of surgery are associated with perioperative morbidity. Stage of disease, volume of ascites,
and serum albumin levels are also correlated with morbidity.41,42 In addition, the distribution of disease is an important determinant in choosing whether patients should
be treated with neoadjuvant chemotherapy. Patients with
massive ascites, large bilateral pleural effusions, extensive
retroperitoneal lymphadenopathy, disease involving the
porta hepatis, or bulky intraparenchymal liver disease
may benefit from neoadjuvant chemotherapy. Such patients should have a biopsy-proven diagnosis prior to
chemotherapy. Provided that the patients have a favorable response to chemotherapy and their performance
and nutritional status improves, they should generally be
considered for interval debulking surgery.
Neoadjuvant chemotherapy has previously been considered for those who are believed to have extensive
disease that precludes them from obtaining maximal cytoreductive surgery. Results from a GOG study on patients
with stage IV EOC noted that, postoperatively, only 8% of
patients had been cytoreduced to microscopic residual
disease.23 In numerous retrospective and prospective
case-control studies, neoadjuvant chemotherapy followed
by interval debulking has been shown to be associated
with decreased morbidity when compared to initial cytoreductive surgery in advanced ovarian cancer.43-48 Neoadjuvant chemotherapy also identifies those patients with
chemosensitive disease who can then undergo optimal
cytoreduction, while at the same time identifying those
patients with chemoresistant disease who will have a
poor outcome regardless of treatment, therefore avoiding the morbidity associated with cytoreduction in this
subset of patients.49 With regard to overall survival, it
seems that when neoadjuvant chemotherapy followed
by interval debulking is compared with initial cytoreductive surgery, the overall survival rates are similar.44,45,50,51
In a retrospective trial of 172 patients with advanced
EOC, 109 patients were treated with primary debulking
surgery and 63 patients were treated with neoadjuvant
chemotherapy.48 Interestingly, in this trial, an improved
overall survival was noted in patients with stage IV disease
who received neoadjuvant chemotherapy (31 months)
compared with those who underwent primary debulking
surgery (20 months). Nonetheless, the majority of data
demonstrate similar overall survival rates.
Preliminary data from an EORTC trial (protocol
55971), a randomized study of neoadjuvant chemotherapy followed by interval cytoreduction vs primary cytoreduction in stage IIIC/IV EOC patients, suggested that
neoadjuvant chemotherapy is comparable to primary
cytoreductive surgery.52 The overall survival rates were
similar: 30 and 29 months, respectively. In addition,
patients assigned to the neoadjuvant arm had decreased
mortality and morbidity. Another randomized control
study, Chemotherapy or Upfront Surgery (CHORUS), is
January 2011, Vol 18, No.1
currently underway in the United Kingdom. This trial
will also be comparing neoadjuvant chemotherapy with
primary cytoreductive surgery.
One theoretical disadvantage with neoadjuvant chemotherapy is the potential for developing chemoresistance, which in turn makes tumor cells less responsive
to chemotherapy following interval debulking surgery.
Although no specific number of cycles of chemotherapy
has been identified as the ideal number in neoadjuvant
chemotherapy, most patients receive an average of three
to four cycles.
One limitation with neoadjuvant chemotherapy is
that the data supporting its association with survival
rates are based on retrospective reviews, meta-analyses,
and uncontrolled prospective reviews. These data lack
controls for patient population and compare different
chemotherapy regimens, again without well-matched
control groups. Because of a lack of good evidence and
the small number of randomized controlled trials analyzing neoadjuvant chemotherapy, primary optimal cytoreductive surgery remains the recommendation for the
management of advanced EOC.
Use of Minimally Invasive Surgery
Laparoscopic management of ovarian cancer is feasible,
but it is not for routine clinical use and should be utilized
judiciously. It can be utilized in the surgical management
of apparent early-stage ovarian cancer, in assessing resectability of advanced disease prior to laparotomy, and also
in second-look procedures.
Laparoscopic staging for EOC has been generally
performed in young women who have had surgery for
a suspected benign adnexal mass that is found to be
malignant intraoperatively. Several studies suggest that
laparoscopy is safe and feasible in the surgical management of apparent early-stage ovarian cancer.53-56 In a
study comparing laparoscopic treatment of gynecologic
malignancies with traditional laparotomy for early-stage
ovarian cancer, Tozzi et al57 demonstrated acceptable
survival rates with decreased morbidity and shorter hospitalization: 91.6% with disease-free survival and overall
survival of 100% at 46 months. Staging was performed
according to FIGO guidelines, including pelvic lymphadenectomy and infrarenal para-aortic lymphadenectomy.
Because a diagnosis of early-stage ovarian cancer is less
common, data comparing the overall survival rate associated with laparoscopy vs laparotomy are limited. The
advantages of laparoscopy in patients with early-stage
ovarian cancer also include faster recovery with early
return of bowel function and a shorter hospital stay.
Laparoscopy can also be a useful tool when deciding
whether to proceed with primary cytoreductive surgery
or neoadjuvant chemotherapy in advanced EOC. In a
study of 87 patients who underwent diagnostic laparoscopy, 53 were deemed resectable.58 Of these 53 patients,
96% were optimally cytoreduced. Laparoscopy seems
Cancer Control 27
to be an acceptable method for assessing disease resectability. Operative time of 120 to 240 minutes has been
reported with laparoscopic staging of ovarian cancer.59
Complications include vascular and gastrointestinal injuries, and another concern is the formation of port site
metastases, particularly in the setting of carcinomatosis.
The etiology and true incidence remain unclear.60
Another concern in the laparoscopic management
of ovarian cancer is that in many instances, the mass is
ruptured while trying to remove it. Ovarian cyst rupture
has been reported in 12% to 25% of patients undergoing
laparoscopy,61,62 and rupture may cause intra-abdominal
dissemination, thus worsening prognosis. Indeed, several
studies have suggested that cyst rupture should be avoided
as it may increase recurrence rate and worsen survival.63,64
The ovarian mass should be placed in a laparoscopic bag
and retrieved through the umbilical port or through a
colpotomy, while taking care to avoid any spillage.
Second-Look Surgery
Second-look surgery, via either laparotomy or laparoscopy,
is a procedure to determine the disease status in an asymptomatic ovarian cancer patient who has no clinical evidence of disease and has completed the planned number
of chemotherapy cycles. The procedure was used initially
to determine the endpoint for chemotherapy, given the
concerns for leukemogenic therapy. Second-look surgeries
via laparoscopy are associated with decreased blood loss
and shorter hospital stays.65,66 The value in laparoscopy
lies mostly in its positive predictive value; if unresectable
residual disease is identified, then a laparotomy can be
avoided. However, its negative predictive value is limited
because complete exploration is usually restricted by significant adhesions.67 Thus, after a negative second-look
laparoscopy, some will proceed with laparotomy.
Second-look surgery involves a thorough evaluation
of peritoneal surfaces and organs and mesentery, with liberal use of biopsy. In women with a history of advancedstage disease with apparent complete response to therapy,
50% will have microscopic residual disease on second
look. Despite this information, it has not been demonstrated that women who receive additional therapy based
on this pathologic confirmation survive longer than those
who receive additional therapy that is based on clinical
information. Clinical information may include cancerrelated symptoms, physical findings, or recurrence seen
on imaging. Although second-look surgery is the most
accurate means of determining response to therapy, there
is no clear survival benefit. Even with a negative second
look, the patient has a 30% to 50% chance of recurrence.
For these reasons, second-look procedures are generally
not performed outside of a clinical trial setting.68,69
Secondary Cytoreduction Surgery
Some women with recurrent ovarian cancer are candidates for secondary cytoreductive surgery. Due to a lack
28 Cancer Control
of large randomized trials, conclusive data are limited regarding the benefits of secondary cytoreductive surgery.
A patient with a rapid, multifocal recurrence is unlikely to
obtain any clinical benefit from surgery. Secondary cytoreduction should be considered for the subgroup of patients
with progression-free interval of 12 to 18 months from
completion of adjuvant chemotherapy, localized recurrence amenable to complete cytoreduction, potentially
chemosensitive disease, and good performance status.70-75
As with primary debulking, resection to no gross residual disease is the most important prognostic factor.76-78
Patients with optimal secondary cytoreduction ( 1 cm)
survived for 16 to 60 months, compared to 8 to 27 months
for those patients with residual diseases 1 cm. However,
the benefit of surgery, compared to chemotherapy alone, is
unclear because of a lack of data. As with primary surgery,
the biology of the cancer is certainly another confounding
factor. Although data are limited, a subgroup of patients
may be candidates for tertiary debulking, based on similar
selection criteria used for secondary debulking.
Surgery for Bowel Obstruction
Some patients with recurrent ovarian cancer will develop
small and/or large bowel obstruction. Palliative surgery
in this setting is controversial and requires skilled patient
selection. Patients are often end-stage and malnourished,
with substantial chemoresistant tumor burden. The
causes of obstruction are often multifactorial and include
mechanical blockage, dense mesenteric infiltration, carcinomatosis, and adhesions. Possible palliative procedures
include bowel resection, colostomy, or intestinal bypass.
On occasion, the bowel and mesentery may be so heavily
involved by cancer that only a gastrostomy tube can be
used for decompression. Even with palliative methods
to remove obstruction, the reobstruction rate is 10% to
50%.79 Despite these data, a subset of patients will benefit
from palliative surgery. Jong et al80 noted factors associated with successful palliation, which included absence
of the following: 3 liters of ascites, multifocal obstruction, palpable bulky tumors, and preoperative weight
loss 9 kg. Others, however, have failed to elucidate
specific factors predicting successful palliation.81 This
likely shows the importance of individualizing the approach to a patient with a terminal bowel obstruction.
In patients with a malignant bowel obstruction who
are not surgical candidates, percutaneous gastrostomy,
hydration, and hospice should be considered.
Conclusions
EOC remains the most deadly gynecologic cancer in the
United States. Despite significant progress in chemotherapy and biologic therapy, surgery remains an important
modality in the treatment of this disease. Despite the
benefits of surgical intervention, the specific biology of
a patient’s disease is central to her response to chemotherapy, duration of remission, and ultimate survival.
January 2011, Vol 18, No.1
References
1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J
Clin. 2010;60(5):277-300.
2. Maggioni A, Benedetti Panici P, Dell’Anna T, et al. Randomised study
of systematic lymphadenectomy in patients with epithelial ovarian cancer
macroscopically confined to the pelvis. Br J Cancer. 2006;95(6):699-704.
3. Parazzini F, Valsecchi G, Bolis G, et al. Pelvic and paraortic lymph
nodal status in advanced ovarian cancer and survival. Gynecol Oncol. 1999;
74(1):7-11.
4. Panici PB, Maggioni A, Hacker N, et al. Systematic aortic and pelvic
lymphadenectomy versus resection of bulky nodes only in optimally debulked
advanced ovarian cancer: a randomized clinical trial. J Natl Cancer Inst.
2005;97(8):560-566.
5. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of
maximal cytoreductive surgery for advanced ovarian carcinoma during the
platinum era: a meta-analysis. J Clin Oncol. 2002;20(5):1248-1259.
6. Piver MS, Lele SB, Marchetti DL, et al. The impact of aggressive debulking surgery and cisplatin-based chemotherapy on progression-free survival in stage III and IV ovarian carcinoma. J Clin Oncol. 1988;6(6):983-989.
7. Young RC, Chabner BA, Hubbard SP, et al. Advanced ovarian adenocarcinoma. A prospective clinical trial of melphalan (L-PAM) versus combination chemotherapy. N Engl J Med. 1978;299(23):1261-1266.
8. Smith JP, Day TG Jr. Rewiew of ovarian cancer at the University of
Texas Systems Cancer Center, M.D. Anderson Hospital and Tumor Institute.
Am J Obstet Gynecol. 1979;135(7):984-993.
9. Delgado G, Oram DH, Petrilli ES. Stage III epithelial ovarian cancer:
the role of maximal surgical reduction. Gynecol Oncol. 1984;18(3):293-298.
10. Neijt JP, ten Bokkel Huinink WW, van der Burg ME, et al. Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v
CP) in advanced ovarian carcinoma. J Clin Oncol. 1987;5(8):1157-1168.
11. Wharton JT, Edwards CL. Cytoreductive surgery for common epithelial tumours of the ovary. Clin Obstet Gynaecol. 1983;10(2):235-244.
12. Redman JR, Petroni GR, Saigo PE, et al. Prognostic factors in advanced ovarian carcinoma. J Clin Oncol. 1986;4(4):515-523.
13. Heintz AP, Hacker NF, Berek JS, et al. Cytoreductive surgery in ovarian
carcinoma: feasibility and morbidity. Obstet Gynecol. 1986;67(6):783-788.
14. Piver MS, Lele SB, Marchetti DL, et al. Surgically documented response to intraperitoneal cisplatin, cytarabine, and bleomycin after intravenous cisplatin-based chemotherapy in advanced ovarian adenocarcinoma.
J Clin Oncol. 1988;6(11):1679-1684.
15. Potter ME, Partridge EE, Shingleton HM, et al. Intraperitoneal chromic
phosphate in ovarian cancer: risks and benefits. Gynecol Oncol. 1989;32(3):
314-318.
16. Eisenkop SM, Spirtos NM, Montag TW, et al. The impact of subspecialty training on the management of advanced ovarian cancer. Gynecol
Oncol. 1992;47(2):203-209.
17. Griffiths CT. Surgical resection of tumor bulk in the primary treatment
of ovarian carcinoma. Natl Cancer Inst Monogr. 1975;42:101-104.
18. Griffiths CT, Parker LM, Fuller AF Jr, et al. Role of cytoreductive
surgical treatment in the management of advanced ovarian cancer. Cancer
Treat Rep. 1979;63(2):235-240.
19. Hoskins WJ, McGuire WP, Brady MF, et al. The effect of diameter
of largest residual disease on survival after primary cytoreductive surgery in
patients with suboptimal residual epithelial ovarian carcinoma. Am J Obstet
Gynecol. 1994;170(4):974-979; discussion 979-980.
20. Eisenkop SM, Friedman RL, Wang HJ. Complete cytoreductive surgery is feasible and maximizes survival in patients with advanced epithelial
ovarian cancer: a prospective study. Gynecol Oncol. 1998;69(2):103-108.
21. Chi DS, Eisenhauer EL, Lang J, et al. What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian carcinoma
(EOC)? Gynecol Oncol. 2006;103(2):559-564. Epub 2006 May 22.
22. Winter WE 3rd, Maxwell GL, Tian C, et al. Prognostic factors for
stage III epithelial ovarian cancer: a Gynecologic Oncology Group Study. J
Clin Oncol. 2007;25(24):3621-3627.
23. Winter WE 3rd, Maxwell GL, Tian C, et al. Tumor residual after surgical cytoreduction in prediction of clinical outcome in stage IV epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2008;26(1):
83-89. Epub 2007 Nov 19.
24. du Bois A, Reuss A, Pujade-Lauraine E, et al. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined
exploratory analysis of 3 prospectively randomized phase 3 multicenter
trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d’Investigateurs
Nationaux Pour les Etudes des Cancers de l’Ovaire (GINECO). Cancer.
2009;115(6):1234-1244.
25. Markman M, Bundy BN, Alberts DS, et al. Phase III trial of standarddose intravenous cisplatin plus paclitaxel versus moderately high-dose carboplatin followed by intravenous paclitaxel and intraperitoneal cisplatin in
small-volume stage III ovarian carcinoma: an intergroup study of the Gynecologic Oncology Group, Southwestern Oncology Group, and Eastern Cooperative Oncology Group. J Clin Oncol. 2001;19(4):1001-1007.
26. Alberts DS, Liu PY, Hannigan EV, et al. Intraperitoneal cisplatin
January 2011, Vol 18, No.1
plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer. N Engl J Med.
1996;335(26):1950-1955.
27. Armstrong DK, Bundy B, Wenzel L, et al. Intraperitoneal cisplatin
and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34-43.
28. Walker JL, Armstrong DK, Huang HQ, et al. Intraperitoneal catheter
outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study. Gynecol Oncol. 2006;100(1):27-32.
29. Nelson BE, Rosenfield AT, Schwartz PE. Preoperative abdominopelvic computed tomographic prediction of optimal cytoreduction in epithelial
ovarian carcinoma. J Clin Oncol. 1993;11(1):166-172.
30. Bristow RE, Duska LR, Lambrou NC, et al. A model for predicting
surgical outcome in patients with advanced ovarian carcinoma using computed tomography. Cancer. 2000;89(7):1532-1540.
31. Salani R, Axtell A, Gerardi M, et al. Limited utility of conventional
criteria for predicting unresectable disease in patients with advanced stage
epithelial ovarian cancer. Gynecol Oncol. 2008;108(2):271-275.
32. Axtell AE, Lee MH, Bristow RE, et al. Multi-institutional reciprocal
validation study of computed tomography predictors of suboptimal primary cytoreduction in patients with advanced ovarian cancer. J Clin Oncol.
2007;25(4):384-389.
33. Dowdy SC, Mullany SA, Brandt KR, et al. The utility of computed
tomography scans in predicting suboptimal cytoreductive surgery in women
with advanced ovarian carcinoma. Cancer. 2004;101(2):346-352.
34. Aletti GD, Gostout BS, Podratz KC, et al. Ovarian cancer surgical resectability: relative impact of disease, patient status, and surgeon. Gynecol
Oncol. 2006;100(1):33-37.
35. Chi DS, Venkatraman ES, Masson V, et al. The ability of preoperative serum CA-125 to predict optimal primary tumor cytoreduction in stage III
epithelial ovarian carcinoma. Gynecol Oncol. 2000;77(2):227-231.
36. Chi DS, Zivanovic O, Palayekar MJ, et al. A contemporary analysis
of the ability of preoperative serum CA-125 to predict primary cytoreductive
outcome in patients with advanced ovarian, tubal and peritoneal carcinoma.
Gynecol Oncol. 2009;112(1):6-10.
37. Hacker NF, Berek JS, Lagasse LD, et al. Primary cytoreductive surgery for epithelial ovarian cancer. Obstet Gynecol. 1983;61(4):413-420.
38. Heintz AP, Van Oosterom AT, Trimbos JB, et al. The treatment of
advanced ovarian carcinoma (I): clinical variables associated with prognosis.
Gynecol Oncol. 1988;30(3):347-358.
39. van der Burg ME, van Lent M, Buyse M, et al. The effect of debulking surgery after induction chemotherapy on the prognosis in advanced
epithelial ovarian cancer. Gynecological Cancer Cooperative Group of the
European Organization for Research and Treatment of Cancer. N Engl J Med.
1995;332(10):629-634.
40. Rose PG, Nerenstone S, Brady MF, et al. Secondary surgical cytoreduction for advanced ovarian carcinoma. N Engl J Med. 2004;351(24):24892497.
41. Aletti GD, Dowdy SC, Podratz KC, et al. Relationship among surgical
complexity, short-term morbidity, and overall survival in primary surgery for
advanced ovarian cancer. Am J Obstet Gynecol. 2007;197(6):676.e1-677.
42. Aletti GD, Santillan A, Eisenhauer EL, et al. A new frontier for quality
of care in gynecologic oncology surgery: multi-institutional assessment of
short-term outcomes for ovarian cancer using a risk-adjusted model. Gynecol Oncol. 2007;107(1):99-106.
43. Vergote I, De Wever I, Tjalma W, et al. Neoadjuvant chemotherapy
or primary debulking surgery in advanced ovarian carcinoma: a retrospective
analysis of 285 patients. Gynecol Oncol. 1998;71(3):431-436.
44. Schwartz PE, Rutherford TJ, Chambers JT, et al. Neoadjuvant chemotherapy for advanced ovarian cancer: long-term survival. Gynecol Oncol.
1999;72(1):93-99.
45. Hegazy MA, Hegazi RA, Elshafei MA, et al. Neoadjuvant chemotherapy versus primary surgery in advanced ovarian carcinoma. World J
Surg Oncol. 2005;3:57.
46. Lee SJ, Kim BG, Lee JW, et al. Preliminary results of neoadjuvant
chemotherapy with paclitaxel and cisplatin in patients with advanced epithelial ovarian cancer who are inadequate for optimum primary surgery. J
Obstet Gynaecol Res. 2006;32(1):99-106.
47. Giannopoulos T, Butler-Manuel S, Taylor A, et al. Clinical outcomes
of neoadjuvant chemotherapy and primary debulking surgery in advanced
ovarian carcinoma. Eur J Gynaecol Oncol. 2006;27(1):25-28.
48. Hou JY, Kelly MG, Yu H, et al. Neoadjuvant chemotherapy lessens
surgical morbidity in advanced ovarian cancer and leads to improved survival in stage IV disease. Gynecol Oncol. 2007;105(1):211-217.
49. Ansquer Y, Leblanc E, Clough K, et al. Neoadjuvant chemotherapy
for unresectable ovarian carcinoma: a French multicenter study. Cancer.
2001;91(12):2329-2334.
50. Jacob JH, Gershenson DM, Morris M, et al. Neoadjuvant chemotherapy and interval debulking for advanced epithelial ovarian cancer. Gynecol
Oncol. 1991;42(2):146-150.
51. Everett EN, French AE, Stone RL, et al. Initial chemotherapy followed
by surgical cytoreduction for the treatment of stage III/IV epithelial ovarian
cancer. Am J Obstet Gynecol. 2006;195(2):568-574; discussion 574-576.
Cancer Control 29
52. Weinberg LE, Rodriguez G, Hurteau JA. The role of neoadjuvant
chemotherapy in treating advanced epithelial ovarian cancer. J Surg Oncol.
2010;101(4):334-343.
53. Ghezzi F, Cromi A, Uccella S, et al. Laparoscopy versus laparotomy
for the surgical management of apparent early stage ovarian cancer. Gynecol Oncol. 2007;105(2):409-413.
54. Chi DS, Abu-Rustum NR, Sonoda Y, et al. The safety and efficacy of
laparoscopic surgical staging of apparent stage I ovarian and fallopian tube
cancers. Am J Obstet Gynecol. 2005;192(5):1614-1619.
55. Park JY, Kim DY, Suh DS, et al. Comparison of laparoscopy and
laparotomy in surgical staging of early-stage ovarian and fallopian tubal cancer. Ann Surg Oncol. 2008;15(7):2012-2019.
56. Nezhat FR, Ezzati M, Chuang L, et al. Laparoscopic management of
early ovarian and fallopian tube cancers: surgical and survival outcome. Am
J Obstet Gynecol. 2009;200(1):83.e1-6.
57. Tozzi R, Köhler C, Ferrara A, et al. Laparoscopic treatment of early
ovarian cancer: surgical and survival outcomes. Gynecol Oncol. 2004;93(1):
199-203.
58. Angioli R, Palaia I, Zullo MA, et al. Diagnostic open laparoscopy in
the management of advanced ovarian cancer. Gynecol Oncol. 2006;100(3):
455-461.
59. Childers JM, Lang J, Surwit EA, et al. Laparoscopic surgical staging
of ovarian cancer. Gynecol Oncol. 1995;59(1):25-33.
60. Ramirez PT, Wolf JK, Levenback C. Laparoscopic port-site metastases: etiology and prevention. Gynecol Oncol. 2003;91(1):179-189.
61. Havrilesky LJ, Peterson BL, Dryden DK, et al. Predictors of clinical
outcomes in the laparoscopic management of adnexal masses. Obstet Gynecol. 2003;102(2):243-251.
62. Canis M, Botchorishvili R, Manhes H, et al. Management of adnexal
masses: role and risk of laparoscopy. Semin Surg Oncol. 2000;19(1):28-35.
63. Bakkum-Gamez JN, Richardson DL, Seamon LG, et al. Influence
of intraoperative capsule rupture on outcomes in stage I epithelial ovarian
cancer. Obstet Gynecol. 2009;113(1):11-17.
64. Vergote I, De Brabanter J, Fyles A, et al. Prognostic importance of
degree of differentiation and cyst rupture in stage I invasive epithelial ovarian
carcinoma. Lancet. 2001;357(9251):176-182.
65. Abu-Rustum NR, Barakat RR, Siegel PL, et al. Second-look operation
for epithelial ovarian cancer: laparoscopy or laparotomy? Obstet Gynecol.
1996;88(4 Pt 1):549-553.
66. Casey AC, Farias-Eisner R, Pisani AL, et al. What is the role of reassessment laparoscopy in the management of gynecologic cancers in 1995?
Gynecol Oncol. 1996;60(3):454-461.
67. Clough KB, Ladonne JM, Nos C, et al. Second look for ovarian cancer: laparoscopy or laparotomy? A prospective comparative study. Gynecol
Oncol. 1999;72(3):411-417.
68. Cannistra SA. Cancer of the ovary. N Engl J Med. 2004;351(24):25192529.
69. Chu CS, Rubin SC. Second-look laparotomy for epithelial ovarian
cancer: a reappraisal. Curr Oncol Rep. 2001;3(1):11-18.
70. Munkarah AR, Coleman RL. Critical evaluation of secondary cytoreduction in recurrent ovarian cancer. Gynecol Oncol. 2004;95(2):273-280.
71. Güngör M, Ortaç F, Arvas M, et al. The role of secondary cytoreductive
surgery for recurrent ovarian cancer. Gynecol Oncol. 2005;97(1):74-79.
72. Onda T, Yoshikawa H, Yasugi T, et al. Secondary cytoreductive surgery for recurrent epithelial ovarian carcinoma: proposal for patients selection. Br J Cancer. 2005;92(6):1026-1032.
73. Berek JS, Bertelsen K, du Bois A, et al. Advanced epithelial ovarian
cancer: 1998 consensus statements. Ann Oncol. 1999;10(suppl 1):87-92.
74. Salani R, Santillan A, Zahurak ML, et al. Secondary cytoreductive
surgery for localized, recurrent epithelial ovarian cancer: analysis of prognostic factors and survival outcome. Cancer. 2007;109(4):685-691.
75. Chi DS, McCaughty K, Diaz JP, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinumsensitive epithelial ovarian carcinoma. Cancer. 2006;106(9):1933-1939.
76. Tebes SJ, Sayer RA, Palmer JM, et al. Cytoreductive surgery for
patients with recurrent epithelial ovarian carcinoma. Gynecol Oncol. 2007;
106(3):482-487.
77. Santillan A, Karam AK, Li AJ, et al. Secondary cytoreductive surgery
for isolated nodal recurrence in patients with epithelial ovarian cancer. Gynecol Oncol. 2007;104(3):686-690.
78. Benedetti Panici P, De Vivo A, Bellati F, et al. Secondary cytoreductive surgery in patients with platinum-sensitive recurrent ovarian cancer.
Ann Surg Oncol. 2007;14(3):1136-1142.
79. Feuer DJ, Broadley KE, Shepherd JH, et al. Surgery for the resolution
of symptoms in malignant bowel obstruction in advanced gynaecological and
gastrointestinal cancer. Cochrane Database Syst Rev. 2000;(4): CD002764.
80. Jong P, Sturgeon J, Jamieson CG. Benefit of palliative surgery for bowel
obstruction in advanced ovarian cancer. Can J Surg. 1995;38(5):454-457.
81. Pothuri B, Vaidya A, Aghajanian C, et al. Palliative surgery for bowel
obstruction in recurrent ovarian cancer: an updated series. Gynecol Oncol.
2003;89(2):306-313.
30 Cancer Control
January 2011, Vol 18, No.1