CONSERVATIVE SURGERY OF OVARIAN CANCER

Guided by:
Dr. Sp.OG

By:
Dr.

PPDS 1 Obstetry and Gynaecology

Medical Faculty of Sebelas Maret University / dr. Moewardi Hospital Surakarta
2015

CHAPTER I
INTRODUCTION
Ovarian cancer is diagnosed in nearly a quarter of a million women globally each
year. It is the eighth most common cancer in women and the seventh leading cause of cancer
death among women, responsible for approximately 140,000 deaths each year. It has the
highest mortality rate of all gynaecological cancers. The prognosis for ovarian cancer patients
is poor, particularly when the disease is diagnosed in its later stages. Symptoms are
ambiguous and often misdiagnosed so the majority of patients are only identifed in the
advanced stages of the disease. Ovarian cancer is therefore often referred to as The Silent
Killer. The current standard of care for ovarian cancer - surgery and chemotherapy - has
remained unchanged for many years and the 5-year US survival rate has improved by only
9% since 1975. Statistics show that just 45% of women with ovarian cancer are likely to
survive for fve years compared to up to 89% of women with breast cancer. In most cases
front-line treatment (with surgery and chemotherapy) does not stop the disease returning.
Most women with advanced ovarian cancer will have a relapse following initial treatment,
usually within 15 months of initial diagnosis. There is a real need for new, more effective
treatment options for women with ovarian cancer. This guide provides an overview of ovarian
cancer, including its incidence, risk factors, symptoms, diagnosis and treatment options.1
Ovarian

cancer

is

the

seventh

most

common

cancer

diagnosis

among

womenworldwide, and the fthmost common cancer diagnosis among women in higherresource regions. The world rate is estimated to be 6.3 per 100 000 women, and is highest in
highresource countries (9.3 per 100 000 women). Primary peritoneal cancer and primary
fallopian tube cancer are rare malignancies but share many similarities with ovarian cancer.
Clinically, these 3 cancers are managed in a similar manner. The main purpose of staging
systems is 2-fold: to provide standard terminology that allows comparison of patients
between centers; and to assign patients and their tumors to prognostic groups requiring
specic treatments. Cancer staging evolves continuously as scientic developments occur,
diagnostic methods improve, and more accurate prognostic information becomes available.
Over the past quarter of a century, several scientic developments have challenged traditional
concepts in ovarian cancer. Initially, it was recognized that ovarian cancer is not a
homogeneous disease, but rather a group of diseaseseach with different morphology and
biological behavior. Approximately 90% of ovarian cancers are carcinomas (malignant
epithelial tumors) and, based on histopathology, immunohistochemistry, and molecular

genetic analysis, at least 5 main types are currently distinguished: high-grade serous
carcinoma (HGSC [70%]); endometrioid carcinoma (EC [10%]); clear-cell carcinoma (CCC
[10%]); mucinous carcinoma (MC [3%]); and low-grade serous carcinoma (LGSC
[b5%]).These tumor types (which account for 98% of ovarian carcinomas) can be
reproducibly diagnosed by light microscopy and are inherently different diseases, as indicated
by differences in epidemiologic and genetic risk factors; precursor lesions; patterns of spread;
and molecular events during oncogenesis, response to chemotherapy, and prognosis. Much
less common are malignant germ cell tumors (dysgerminomas, yolk sac tumors, and
immature teratomas [3% of ovarian cancers]) and potentially malignant sex cord-stromal
tumors (1%2%, mainly granulosa cell tumors). The biomarker expression prole within a
given histotype is consistent across stages. Ovarian cancers differ primarily based on
histologic type.2
Despite great efforts in developing novel screening, diagnosis and therapeutic
strategies, the incidence and mortality of ovarian cancer have not significantly changed in the
last 30 years. It remains the leading cause of death from gynecologic malignancy with a
lifetime probability of developing the disease of 1 in 59. Worldwide, approximately 200.000
women are annually diagnosed with ovarian cancer, and almost 70% of them will be
diagnosed at advanced stage disease. With current treatment modalities, the 5-year survival
rate ranges from 8095% for those with organ-confined or early stage disease (International
Federation of Gynecology and Obstetrics (FIGO) stage I-II); to 30 40% for those women
with advanced disease, FIGO stage III-IV. Thus, ovarian cancer is a challenging and complex
malignancy.Surgical management of ovarian cancer remains as the cornerstone treatment of
this disease. An adequate full surgical staging in women with early stage disease has
demonstrated to improve oncologic outcome. On the other hand, complete surgical
cytoreduction is the only modifiable prognosis factor for patients with advanced disease.
This chapter will describe the rationale and surgical steps for an adequate surgical staging for
women with early stage ovarian cancer, and for obtaining the maximal surgical cytoreduction
in women affected by advanced stage and relapsed disease.3
The standard treatment of ovarian cancer includes upfront surgery with intent to
accurately diagnose and stage the disease and to perform maximal cytoreduction, followed by
chemotherapy in most cases. Surgical staging of ovarian cancer traditionally has included
exploratory laparotomy with peritonealwashings, hysterectomy, salpingo-oophorectomy,
omentectomy, multiple

peritoneal

biopsies,

and

possible

pelvic

and

para-aortic

lymphadenectomy. In the early 1990s, pioneers in laparoscopic surgery used minimally

invasive techniques to treat gynecologic cancers, including laparoscopic staging of early

ovarian cancer and primary and secondary cytoreduction in advanced and recurrent disease in
selected cases. Since then, the role of minimally invasive surgery in gynecologic oncology
has been continually expanding, and today advanced laparoscopic and robotic-assisted
laparoscopic techniques are used to evaluate and treat cervical and endometrial cancer.
However, the important ques-tion about the place of the minimally invasive approach in
surgical treatment of ovarian cancer remains to be evaluated and answered.4
Conservative and functional surgery is increasingly used in surgical oncology, the aim
being to preserve the function of organs and to reduce radical resection. The development of
new surgical procedures in oncological gynaecological surgery is a perfect example of this
evolution. Although radical surgery remains the `gold standard' in the treatment of ovarian
and cervical cancer, a conservative approach can be considered in patients with early-stage
disease, in order to preserve their fertility function. These procedures were proposed in
selected patients, depending on histological sub-types and prognostic factors. Ovarian cancers
are classified as epithelial and non-epithelial tumours. Conservative treatment of nonepithelial ovarian tumours, particularly germ cell tumours, has been considered for some time
as a standard surgery in young patients (Creasman et al., 1979; Schwartz, 1984; Brewer et al.,
1999). Published data relating to conservative surgery in borderline and invasive epithelial
ovarian cancer are more recent however.5

CHAPTER II

SURGICAL STAGING OF OVARIAN CANCER2,8,9,10

Approximately 25% of newly diagnosed ovarian cancer will be early stage disease.
Prognosis is good with survival rates ranging from 80 % to 95 % when recommended
treatment is followed. These patients are initially managed by comprehensive surgical
staging, which is relevant not only for identifying women with truly early stage disease, but

also

to select patients who will be candidates for adjuvant chemotherapy.

Adequate surgical staging procedures include: exploration of abdomen/pelvis,

peritoneal washings, bilateral salpingo-oophorectomy, hysterectomy, peritoneal biopsies of

Cul-de-sac, pelvic walls, paracolic gutters, diaphragm, suspicious areas, omentectomy,

appendectomy, as well as pelvic and para-aortic node dissection up to the renal veins.
(TABLE 1). These procedures are needed to find hidden disease in nearly 18% of women,
which has implications in the prognosis and subsequent patient treatment. Surgeon expertise
is crucial given that it was correlated with under-staged ovarian cancer. Several studies
demonstrated that over 30% of patients operated by general gynecologists or general
surgeons were upstaged by gynecologist oncologists by finding disease on pelvic-aortic
lymph nodes, diaphragm biopsies and omentum. Moreover, as it has been demonstrated,
inadequate initial surgical staging leads to a higher risk of developing recurrent disease
despite receiving adjuvant chemotherapy. Thus, if the operative risk is not too high, all
patients should be routinely re-staged before starting chemotherapy.

Table . Surgical staging procedures for early stage ovarian cancer

Surgical staging procedures
Midline vertical incision is the recommended surgical approach for initial
management of suspected early stage ovarian cancer. The incision is firstly made from the
pubis to the umbilicus and then progressed to xifoid appendix, if surgical staging is indicated
following the frozen section diagnosis. The abdominal-pelvic cavity is opened and visualized.
If free fluid is present, a minimum sample of 100 cc should be obtained for cytological
examination. Peritoneal washing from paracolic gutters, pelvis and abdominal cavity should
be done in the absence of ascites. It is estimated that over 30% of patients with stage I
disease have tumoral cells on cytological examination. Careful inspection and palpation is
preformed to detect extra-ovarian implants in a systematic way: starting by right paracolic
space, advancing the hand to the right kidney, suprahepatic space, the right diaphragm,
right hepatic lobe, gallbladder, Morrisons pouch, left hemi-diaphragm, left hepatic lobe,

spleen, stomach, transverse colon, left kidney and left paracolic space. The lesser sac is
entered on the left side of the gastrocolic ligament. Both surfaces of the mesentery should
be examined and retroperitoneal vascular areas should be palpated as well. The result of this
comprehensive procedure should be properly described.
The ovaries need to be examined for capsule rupture or external excrescences. The
affected ovary must then be removed for frozen section. Although the influence on the
prognosis of the intraoperative rupture of malignant ovarian tumors is controversial,[12]
adnexal masses should be removed intact. If malignancy is confirmed in the frozen
section, full surgical staging, as previously described, must be performed by the extension
of

the

incision up

to xifoid

appendix. Contralateral

oophorectomy

and

total

hysterectomy is completed due to the possibility of synchronous cancer.

Even though controversial, random peritoneal biopsies are indicated in early-stage
disease. A retrospective study demonstrated that less than 4% of patients with ovarian cancer
were upstaged due to positive peritoneal biopsies. No patient, however, had a change in
treatment recommendations based on these biopsies.[13] Infracolic omentectomy should be
performed from the hepatic to splenic flexure. During dissection, the lesser sac is
developed dissecting the posterior and anterior layer of the transverse mesocolon, while
preserving the middle

colic artery. The omentum

is

removed and

the pedicles are

sequentially sutured ligated. Appendectomy is only reserved for mucinous histology.

Retropetitoneal lymph node dissection
The incidence of lymph-node involvement in patients with disease confined to the
ovary is 5% in only pelvic nodes, 9% in aortic nodes and 6% in both pelvic and aortic nodes.
Systematic lymphadenectomy as part of surgical staging of apparent early stage ovarian
cancer is associated with a statistically significant increase in median operative time, median
blood loss, and the proportion of patients undergoing blood transfusions. Systematic
lymphadenectomy, however, significantly improves progression-free survival (PFS) rates,
without a statistically significant impact on overall survival (OS). Lymphatic drainage of
the ovaries is known to follow the gonadal blood supply that reaches the renal vein, on the
left side, and the inferior vena cava, on the right side. Pelvic lymphadenectomy should
include removal of nodes

from paravesical and pararectal spaces,

including bilateral

common iliac nodes. Aortic nodes should be removed from aortic bifurcation to the renal
veins.

Minimally invasive surgery for surgical staging ovarian cancer

Over the last years, laparoscopy has gained an important role for the management of
suspected adnexal masses. High-volume centers have reported their experience in performing
a comprehensive surgical staging by using minimally invasive surgery. Nezhat et al.
reported a case series of 36 patients with early stage invasive ovarian carcinoma managed by
laparoscopy. They showed 100% OS rate with a mean duration of follow-up of 55.9 months.
Chi et al. conducted a case control study by staging 20 patients with early ovarian cancer with
laparoscopy compared with 30 patients staged with laparotomy. There were no differences in
the omental specimen size or number of lymph nodes removed. Blood loss and hospital stay
were lower for the laparoscopy group, with longer operating time. There were no conversions
to laparotomy or other intraoperative complications in the laparoscopy group.
Despite laparoscopic staging of early ovarian cancer seems to be a safe and feasible
procedure performed by expert surgeons, the possibility of cyst rupture or port-site
metastases remain controversial. The immediate effect of tumor rupture is that a
patient with a potentially curable disease will require additional adjuvant chemotherapy.
Preoperative evaluation is essential, as well as the surgical experience and the quality of
laparoscopic instruments. Even though there are no specific recommendations, adnexal
masses up to 5-6 cm could be reasonably managed by laparoscopy.
The etiology of port-site metastases is uncertain. Several hypotheses include tumor
cell entrapment, direct spread from the trocar in which instruments are exchanged, and the
chimney effect, which suggests that tumor cells travel along the sheath of the trocars
with the leaking gas. Port-site metastases have been reported in 1% to 2% of patients with
ovarian cancer. However, <5% of port metastases are clinically detected and these sites are
likely to respond to chemotherapy.
Robotic surgery has emerged as an innovative minimally invasive approach in the
field of gynecology. The da Vinci Surgical System (Intuitive Surgical, Inc, Sunnyvale,
California, USA) offers several advantages over conventional laparoscopy including threedimensional view, greater dexterity, and tremor filtration. Most of the data regarding the
application of robotic technology for ovarian cancer staging are included in the literature
used in the assessment for its implementation in other gynecologic malignancies, such as
cervical and endometrial cancer. Data are still scarce but promising.

Laparoscopic Surgical Staging of Early Ovarian Cancer

Since its advent in the early 1990s, laparoscopic surgical staging for early ovarian
cancer has been explored as an option with the potential to offer women equivalent cancer
control and survival as provided by laparotomy but with the clear benefits of minimally
invasive surgery. A limited but expanding body of literature suggests aggressive surgical
staging can be performed with equivalent tissue assessment compared with laparotomy.
Given the lack of randomized, controlled trials, the risks and benefits of such a procedure
remain ambiguous. This review summarizes the current body of literature regarding the role
of laparoscopy in upfront surgical staging of ovarian cancer. disease.
Complete surgical staging for early ovarian cancers has clear benefits for disease
management and has been recommended by the International Federation of Obstetrics and
Gynecology (FIGO). Surgical staging for ovarian cancer originally necessitated an
exploratory laparotomy to perform the various procedures advised by FIGO: hysterectomy
and salpingo-oophorectomy, pelvic and paraaortic lymph node dissections, omentectomy,
peritoneal washings, and peritoneal biopsies. With the modernization of equipment and
technique in the late 1980s and early 1990s, surgical pioneers began to use laparoscopic
surgery for the treatment of gynecologic cancers with more regularity and success. In 1990,
the first report of partial surgical staging of an early ovarian cancer appeared. By 1994,
Querleu and LeBlanc had published the first report on laparoscopic surgical staging of nine
early ovarian cancers. A decade and a half later, published studies on laparoscopic surgical
staging of early ovarian cancer are small in size and relatively scarce. Questions still remain
regarding its performance compared with a traditional laparotomy and its proper application
to diverse populations of patients. This review examines the current research on surgical and
oncologic outcomes after laparoscopic staging of early ovarian cancer, and provides an
overview of the laparoscopic techniques feasibility, benefits, possible risks, and future
directions with the aim of standardizing and advancing its use in staging of early ovarian
cancer.
Several potential benefits of laparoscopic staging for early ovarian cancer are
currently supported by conflicting or anecdotal data in the literature. These potential benefits
include a lower overall cost of treatment, higher patient and surgeon satisfaction, and
improved fecundity after fertilitysparing staging procedures. Laparoscopic staging may offer
improved cost containment, both from a medical system and societal perspective. Several

studies on laparoscopic surgical staging for endometrial cancer, a similar procedure to

laparoscopic staging of early ovarian cancer, report lower overall hospital costs for
laparoscopy compared with laparotomy. It is unclear whether patients return to work faster
after laparoscopic ovarian cancer staging, especially if adjuvant chemotherapy is required.
Further cost analyses on the laparoscopic management of early ovarian cancer are needed, but
in general, laparoscopic techniques tend to decrease hospital stay, decrease complications,
and improve patient postoperative performance status, all of which tend to increase hospital,
patient, and societal cost-effectiveness. Numerous reviews indicate that systematic research is
also needed to assess both patient and surgeon satisfaction with laparoscopic surgical staging.
Anecdotal evidence suggests that the increased visibility and precision afforded by a
laparoscopic approach, as well as shorter patient recovery time, provide more satisfactory
outcomes for surgeons trained in the technique. Similarly, reduced postoperative pain, shorter
recovery time, and more aesthetic results support the anecdotal existence of patient
preference for laparoscopic staging when the procedure is available. Laparoscopic staging
may offer reproductive benefits to premenopausal women seeking fertility preservation in the
setting of a unilateral ovarian malignancy. Fertility sparing, or conservative laparoscopic
staging, entails pelvic and para-aortic lymph node dissection, omentectomy, and unilateral
salpingo-oophorectomy with the preservation of the uterus as well as the contralateral ovary
and tube that do not appear to contain cancer. Muzii and colleagues conducted a prospective
study of 27 unexpected ovarian cancer patients who underwent fertility-saving laparoscopic
surgical staging. They reported two term pregnancies and two instances of spontaneous
abortion after 20-month follow-up. Laparoscopic staging has been indicated as preferable to
laparotomy for fertility-sparing surgeries due to the smaller number of adhesions caused by
laparoscopy and avoidance of laparotomy, known to decrease fecundity. However, several
studies have reported recurrence in patients who underwent a more conservative, fertilitysparing laparoscopic staging.
Comparison of laparoscopy and laparotomy for the management of early-stage ovarian
cancer
In laparoscopic surgery, a 10-mm 0o laparoscope was introduced at the umbilical site
after pneumoperitoneum was established. Under direct vision, 3 ancillary trocars were
positioned: one 12-mm suprapubic trocar for extraction of the retrieved lymph nodes and two
5-mm trocars at the lower abdomen lateral to the epigastric arteries. After employing this 4trocar system, pelvic procedures including hysterectomy, bilateral salpingo-oophorectomy,

and pelvic

lymphadenectomy were performed. Next,

in order to perform para-aortic

lymphadenectomy and omentectomy, the laparoscope was moved to and placed on the 12mm suprapubic trocar, and an additional pair of 5-mm trocars was introduced 2 cm inferior to
the costal margin and immediately medial to the left and right midclavicular line. At the
beginning of both laparoscopy and laparotomy staging, parietal and visceral peritoneal
surfaces were carefully inspected, including the diaphragm, liver, gallbladder, small bowel
and mesentery, rectosigmoid colon, pouch of Douglas, paracolic gutters, and abdominal wall.
In the case of laparotomy, the peritoneum and organs in the abdomen and pelvis were
palpated as well. In laparoscopic surgery, aside from the use of high-energy devices
including either LigaSure

(Covidien, Boulder, CO, USA) or PowerBlade

(LiNA,

Copenhagen, Denmark) that were used in particular for paraaortic lymphadenectomy, all
procedures were performed with conventional laparoscopic instruments such as straight forceps, a suction and irrigation device, monopolar scissors, and a bipolar electrocoagulator.
The retrieved lymph nodes were extracted from the intraperitoneal cavity by using an
Endopouch. To reduce the risk of port site metastasis, incision sites were irrigated with large
amounts of saline and povidoneiodine solution after removal of the trocars.
In both laparoscopy and laparotomy, postoperative manage-ment was similar

in

terms of diet resumption and antibiotic use. Patients were allowed to drink water after they
passed gas from the bowel, and thereafter, a liquid, soft, and normal regular diet was given
on a daily basis until the patients had no complaints of gastrointestinal symptoms. Early
ambulation was encouraged. In all patients, 3 kinds of antibiotics were used for at least 3
postoperative days; frst- or secondgeneration cephalosporin was administered intravenously;
aminoglycoside, intramuscularly; and metronidazole, intravenously.
Our results have provided evidence that laparoscopic surgery might be adequate
and feasible for the treatment of early-stage (FIGO I or II) ovarian cancer with comparable
surgical outcomes and oncological

safety

to

laparotomy, while achieving the same

comprehensive staging. Recent advances in surgical techniques have led to the increasing
utility of minimally invasive surgery, even in oncology. However, it is challenging for
surgeons to use a laparoscopic approach for ovarian cancer, as the tumor may have
metastasized throughout the peritoneal cavity at presentation. Any peritoneal surface
suspected of harboring metastasis should be excised or biopsied, which is difficult with
laparoscopy because of loss of the tactile sense and the need for profcient laparoscopic skill.
Nevertheless, several studies

indicating the advantages of

laparoscopic surgery over

laparotomy in earlystage ovarian cancer have been published recently. On the other hand,

several issues have been raised regarding laparoscopic staging of ovarian cancer. The main
concerns are the increased risks of intraoperative tumor rupture, disease recurrence, and
trocar-site metastasis, as well as reduced surgical adequacy and accuracy. The rate of tumor
rupture or spillage during surgery may be afected by the surgical tech-nique. Port-site
metastasis is another major risk of laparoscopic surgery. The incidence ranges widely, 1%16%.

CHAPTER III
CONSERVATIVE SURGERY OF OVARIAN CANCER5,6,7
Ten to twenty percent of ovarian cancers occur before the age of 40 years. THe 5year survival of patients with Stage IA, grade 1, epithelial ovarian cancer treated
conservatively is 90%. Malignant ovarian germ cell tumors (MOGCTs) represent
approximately 5% of all ovarian neoplasms observed in Europe and North America. Germ
cell tumors represent most (80%) of the pre-adolescent malignant ovarian neoplasms;
the mean age at diagnosis is 16-20 years and they may occasionally be diagnosed
during pregnancy or the puerperium. In the literature, a 5-year survival rate of 90-100%
has been reported with the use of the new combination chemotherapy regimens. Sex
cord-stromal tumors (SCSTs) are rare neoplasms that account for approximately 3-5%
of ovarian malignancies and the majority of them are functioning tumors with clinical
manifestations. These are characterized by 85-100% long-term survival rates for Stage
IA tumors, and a propensity for late recurrences. The juvenile form of granulose cell
tumors occurs before the age of 30 in 97% of cases, and is often associated with
precocious puberty. Almost all tumors are present at Stage I. Sertoli-Leydig cell tumors
account for less than 0.5% of all ovarian tumors and 75% of these neoplasms are diagnosed
in women younger than 40 years of age. Preservation of reproductive ability has
become an important issue in the treatment of young patients with malignant ovarian
tumors, that may be cured and lead normal lives. A variety of studies have tried to
document the impact of conservative treatment aimed at preserving ovarian function and
reproductive ability, little information has been available regarding survivors attitudes and
emotions, and their choice to have children.6
The term conservative surgery for ovarian cancer indicates a surgical procedure that
allows the removal of the ovarian tumour together with adequate staging procedures, while
preserving the patients reproductive potential. Ideally fertility potential should be preserved
without compromising cure rates. Conservative surgery has been shown to be onocologically
safe in certain histological subtypes of ovarian cancers such as malignant ovarian germ cell
tumours, granulaosa cell tumours, borderline ovarian tumour and early stage, lowintermediate grade, invasive epithelial ovarian cancer. Malignant ovarian germ cell tumours
(MOGCT) are rare but curable even in advanced stages of disease. Appropriate surgical

treatment for patients where fertility needs to be preserved consists of staging laparotomy
with unilateral salpingo-oophorectomy (USO). Conventionally, adjuvant chemotherapy is
recommended in all cases except stage-IA dysgerminoma and stage IA grade-1 immature
teratoma. Borderline ovarian tumour (BOT) represents 10- 20% of epithelial ovarian cancers.
The mean age at diagnosis of BOT is 10 years younger than that of invasive EOC and 1/3rd
of BOTs are diagnosed in patients aged less than 40 years. Conservative surgery is the
standard of care in these cases. Although such treatments increase the rate of recurrences (1535% depending on the type of surgery i. e. oophorectomy vs ovarian cystectomy) however
this does not adversely impact survival as most recurrences are of borderline type and can
easily be treated with surgery. Nearly 15% of invasive epithelial ovarian cancer (EOC)
occurs in women younger than 40 years. The role of conservative surgery in invasive EOC is
less well defined. The prognosis for patients who develop a recurrence after fertility- sparing
surgery remains poor. Therefore, initial selection of candidates for fertility-sparing surgery
should be done carefully. The patient and the family should be extensively counseled. The
patient should be aware of slightly increased risk for recurrence associated with conservative
surgery. Furthermore, patient needs to be assessed for the realistic probabilities of achieving
conception on the basis on their age, history, and infertility evaluation. Most authors agree
that conservative surgery can be offered to patients with stage Ia and grade 1-2, non clearcell
EOC. A comprehensive surgical staging is mandatory because occult extra-ovarian metastases
can occur in a significant proportion of women with apparent early-stage disease. Opposite
adnexal should be carefully evaluated however; random biopsies or bisection of normal
looking ovary is not indicated. The optimal interval between completion of cancer treatment
and conception must be carefully determined by a multidisciplinary team including
oncologists and obstetrician. The general recommendation is to wait for one to two years after
completion of treatment before attempting conception. However, delaying conception for too
long has the risk of premature ovarian failure in these patients with low oocyte reserve. The
reproductive outcomes of fertility-sparing treatment are promising and majority of patients
can expect spontaneous conception. However, 10-20% patients will fail to conceive naturally
and will require assisted reproduction technology (ART) to achieve a pregnancy, especially
in-vitro fertilization (IVF). Although some retrospective studies in the past have reported
increased risk of EOC in patients undergoing ART, more recent literature does not support
this observation and ART is believed to be oncologically safe. A normal pregnancy outcome
can be expected in most cases although a few studies have reported slightly increased risk of
congenital malformation and miscarriages in ovarian cancer patients treated with surgery and

chemotherapy.

The

cryopreservation,

role

oocyte

of

newer

reproductive

cryopreservation,

embryo

techniques

e.g.

cryopreservation

ovarain

tissue

needs

further

exploration in selected cases of ovarian cancer. The role of completion surgery i.e. removal
of the uterus and adnexal at the completion of fertility is debatable. Completion of surgery
can be reasonably deferred until menopause if the patient agrees to careful follow-up.
Management of young women with ovarian cancer should be individualized; the risk of
conservative therapy should be balanced against the disadvantages of more radical treatment.
Usually a multidisciplinary approach with close collaboration among gynecologic oncologist,
obstetrician and perinatologist is required to have successful oncologic and obstetric
outcomes.7
A. Borderline ovarian tumours5
The definition of borderline ovarian tumour (BOT) is related to the histological
characteristics of the ovarian tumour, and not to the peritoneal implants. Four characteristics
are used to define the BOT: (i) epithelial proliferation with the formation of papillary
configuration; (ii) a definable demonstration of atypical epithelial activity; (iii) mild or
moderate atypicality of the nuclei (these three characteristics are essential to differentiate a
BOT from ovarian cystadenoma); and (iv) the absence of stromal invasion (which makes the
clear difference with invasive carcinoma). Peritoneal implants are associated in 1040% of
cases with BOT, and are either non-invasive in 80% (without stromal invasion) or invasive in
20%. A non-invasive implant was defined as a glandular or papillary proliferation, but with
no stromal invasion. Peritoneal non-invasive implants can be subdivided into either epithelial
type (with a predominance of epithelial elements) or desmoplastic type (in which the
epithelial elements lay in a predominant inamed, desmoplastic stroma). Invasive implants
are defined by a proliferation in the peritoneum with a stromal invasion. If biopsies or
resection of peritoneal implants are too superficial, the degree of invasion could not be
accurately determined, and such implants should be considered as `non-specified' implants. In
order to avoid this situation, large biopsies or resection of peritoneal implants should be
performed during the surgical procedure. Therefore, the pathological examination is a crucial
step to: (a) confirm the diagnosis of BOT (and peritoneal implants); (b) identify prognostic
factors; and (c) specify the optimal treatment. In order to carry out an adequate sampling, at
least one section should be taken for each centimetre of the greatest dimension of the tumour,
and the totality of peritoneal implants should be examined. In patients with non-invasive
implants, complete surgical reduction of peritoneal lesions is the only treatment that may

improve survival. Although the prognosis of patients with non invasive implants is good,
evolution into a more aggressive disease may occur in one-third of cases when invasive
peritoneal implants are detected. In such cases, adjuvant treatment should be considered.
A new entity of patients with peritoneal implants associated with borderline tumour
designated as micropapillary serous carcinoma (MPSC) was recently described, in order to
identify a subgroup of patients with poor prognosis. MPSC is more commonly associated
with invasive implants, and in the present study the presence of MPSC in implants was an
adverse prognostic factor. By contrast, others reported that the evolution of patients with noninvasive implants associated with MPSC was similar to that of patients with non-invasive
implants without MPSC. In a recent report, it was confirmed that the presence of
micropapillary pattern is not an unfavourable prognostic factor.
Modalities of conservative surgery and clinical outcomes
The standard treatment of BOT is total abdominal hysterectomy and bilateral
salpingo-oophorectomy, peritoneal cytology, omentectomy and multiple peritoneal biopsies.
These procedures allow an adequate staging to be performed and eventually for an adjuvant
therapy to be proposed in those patients with invasive peritoneal implants. Although the
prognosis of BOT is excellent, late recurrence (after 5 or 10 years) has been observed.
Conservative surgery is defined as preservation of the uterus and at least a part of one ovary,
in order to preserve fertility. As borderline ovarian tumours arise in a young population, for
which preservation of fertility is a major concern, the analysis of conservative management
data is crucial in these patients. An analysis of published data relating to the conservative
management in BOT has proved difficult, mainly because most of the series reported are
retrospective and the length of follow-up is too short (<5 years) to evaluate the exact rate of
recurrence. Furthermore, the rate of recurrence among patients who have been adequately
staged has been seen to vary among series and to depend upon the centre of treatment.
Indeed, this variability might explain the different values of recurrence rate that have been
obtained. The risk of relapse, which is increased after this type of surgery, is estimated at
between 0 and 20%, but is less than that after cystectomy (from 12 to 58%). Hence, it is more
likely that some of these lesions are in fact new primary tumours rather than recurrences of
the initial BOT.
In order to reduce the risk of recurrence after cystectomy, recommended that a
complete pathological analysis of the margins be carried out in order to rule out any
microscopic invasion. Pathological interpretation of section margins in case of cystectomy is

very difficult however, especially if morcellation or fractionation of the tumour occurs during
surgery.
In order to reduce the rate of relapse in the remaining ovary, some authors carry out
an initial complete staging surgery with routine ovarian biopsies in the spared ovary. It
appears that macroscopic inspection is sufficient, and biopsies should be performed only
when a macroscopically suspicious lesion is identified.
The high rate of relapse implies that the optimal treatment in patients with
intraoperative diagnosis of BOT is unilateral adnexectomy, and this reduces the risk of
relapse. Cystectomy should be performed only in cases of bilateral tumour (with
oophorectomy in the contralateral tumour) and/or in patients with only one ovary (previous
history of adnexectomy). In case of relapse on the remaining ovary under borderline form,
another conservative management (cystectomy) may be proposed in these patients, in order to
preserve fertility.
Survival of patients after conservative surgery
Is this increased risk of relapse after conservative surgery affecting the survival of
patients? All recurrent diseases on the ovary were BOT, and none of the patients treated
conservatively died as a result of the tumour. Furthermore, all recurrent diseases were
diagnosed using follow-up procedures (based on clinical examination, systematic
ultrasonography and/or the blood markers CA 125 or 19.9). These data appear to confirm
that, even though the risk of relapse is substantial after conservative treatment of BOT,
patient survival is not altered by the use of this approach. Hence, conservative surgery could
be safely performed in young patients treated for BOT, and then carefully followed-up.
Limits of conservative surgery
Whether all young patients with BOT are eligible for conservative treatment is also a
matter of debate. Although such procedures could be safely offered in patients with earlystage disease, few published data exist relating to conservative management in BOT with
peritoneal implants. Another question is whether it is possible to propose such surgical
management in patients with invasive peritoneal implants. Considering the aggressiveness
and bad prognosis of BOT with invasive peritoneal implants, it seems logical to propose
conservative therapy only to BOT patients with no invasive implants.

Practical management at the time of surgical procedure

If a young patient is treated for a suspicious adnexal tumour (elevated blood markers
and/or `suspicious' ultrasonography), the surgical procedure should ideally be performed in a
centre where a frozen section analysis is available. If the tumour is unilateral, and if the
diagnosis of BOT is raised intraoperatively at the time of frozen section analysis, a unilateral
adnexectomy should be performed with peritoneal cytology, multiple peritoneal biopsies and
omentectomy. In case of a bilateral ovarian tumour, a unilateral adnexectomy and a
contralateral cystectomy may be proposed.
It is possible however that frozen section analysis is either not available, is not
performed (because the macroscopic aspect of the cyst was not suspect), or misdiagnoses the
BOT. The diagnosis was not made during surgery by using the frozen section, but has been
achieved during the postoperative routine pathological examination. In most of these patients,
as only cystectomy was carried out during the initial surgery, it may then have been necessary
to reoperate when the initial surgery was a cystectomy. There are two possibilities here: (i) a
restaging surgery (including completion of unilateral oophorectomy, peritoneal washings,
multiple peritoneal biopsies and eventually an omentectomy); and (ii) a careful follow-up
(based on clinical examination, ultrasonography and blood markers) in order to reconsider a
new surgical approach only in case of ovarian tumour recurrence. The decision of which
approach should be used must be made through discussion with the patient. However, it was
noted that recurrent disease on the spared ovary is often a borderline tumour and does not
affect patient survival. Hence, on a practical basis, the present authors do not perform a
restaging surgery in patients initially treated at other centres, provided that those patients
agree to the follow-up procedure and if the normality of the abdominopelvic cavity is clearly
stated in the initial operative report. Re-staging surgery is performed however when
inspection of the abdominopelvic cavity is not described on the initial operative report; this
surgery can be carried out using a laparoscopic approach.
Fertility results after conservative surgery
Pregnancies have been reported in patients with BOT treated conservatively. Despite
the use of conservative management in BOT, some of these patients will experience
infertility. However, whether ovarian stimulation or IVF should be proposed to them remains
the subject of debate, especially as other studies have incriminated hyperstimulation in the
genesis of BOT and ovarian cancer. Bilateral salpingo-oophorectomy should be performed in
patients with bilateral massive BOT and/or a BOT relapse on the remaining ovary, and for

whom preservation of a part of one ovary is not feasible. It is possible that, in the near future,
cryoconservation of ovarian tissue could be proposed in such cases. However, this technique
has not yet been evaluated in this precise indication, and as yet no pregnancies have been
achieved in humans.
An additional question is whether re-operation should be performed in order to
remove the remaining ovary in patients where fertility is no longer an issue and who have
conceived after conservative treatment of BOT. Furthermore, these recurrent diseases
(borderline type in most cases) could be easily curable by use of a simple surgical procedure.
Hence, the present authors consider that systematic removal of the spared ovary is not
mandatory, on

condition

that

patients

undergo

regular

follow-up

examinations.

Oophorectomy is then proposed only in case of relapse, although some patients prefer to
undergo an oophorectomy after completing their fertility desire, for psychological reasons.
B. Epithelial ovarian cancer
Indications of conservative surgery
The differential criterion between epithelial ovarian cancer (EOC) and BOT is
invasion of the ovarian stroma. The standard surgical procedure in EOC is radical
(hysterectomy with bilateral salpingo-oophorectomy).
Initially, conservative treatment for EOC was proposed, though the study inclusion
criteria for patients included: fertility desire; close follow-up; stage IA disease; wellencapsulated tumour without adhesions; lymphatic channels and/or the mesovarium free of
tumour; and negative peritoneal washings. Histological type plays a major role in these
inclusion criteria, and so only serous, mucinous and endometrioid EOC may be considered
for conservative management. Patients with clear cell and anaplastic EOC must not be
considered for conservative treatment, because of the high risk of relapse on the remaining
ovary.
Furthermore, recent series seem to suggest that a conservative treatment can be safely
proposed in more advanced epithelial ovarian cancer without affecting patient survival.
Surgical procedure for conservative surgery
This conservative surgery must be considered only after an adequate surgical staging
that must include peritoneal washings, excision of any suspicious peritoneal lesion, multiple
peritoneal biopsies, omentectomy, and endometrial curettage. A pelvic and para-aortic lymph
node dissection (PALND) must also be carried out. The modalities of PALND have recently

been discussed; some authors have proposed limiting the PALND to the same side of the
tumour, in case of very early EOC.
A systematic biopsy of the remaining ovary has been proposed, but it was also
considered by this author that contralateral microscopic involvement existed in 12% of cases
of EOC. Nevertheless, systematic biopsies of contralateral ovarian cancer can induce
infertility by provoking postoperative adhesions with the remaining ovary.
In consequence, routine biopsy on the contralateral ovary is not recommended if
preoperative vaginal ultrasonography did not reveal deep parenchymous abnormalities in the
ovary contralateral to the tumour, and if it appears macroscopically normal during the
surgical procedure.
Fertility results
Such a laparoscopic approach, which reduces the risk of postoperative adhesions and
mechanically induced infertility, might explain the difference observed in fertility results in
favour of the Italian series. Restaging surgery is both feasible and safe using a laparoscopic
approach. However, the harmless nature of this surgery in patients with ovarian cancer
remains the subject of debate, and restaging surgery using midline laparotomy remains the
current the `gold standard'. In case of persistent infertility, there have been no published
recommendations of either ovarian stimulation or IVF but our own opinion is not to use these
procedures in patients with a previous history of ovarian cancer. Oral contraception can be
used in those patients who do not wish to become pregnant immediately.
A case of relapsing EOC 10 years after conservative treatment was recently reported
in a patient with a previous history of infertility. With regard to the possibility of long-term
relapse in EOC, radical surgery must be considered when fertility is no longer an issue, with
removal of the remaining ovary in order to reduce the risk of tumour recurrence in the spared
ovary.

CHAPTER IV
CONCLUSIONS
Despite concerns regarding the ability to explore the full extent of peritoneal ovarian
cancer cells, the literature confirms that laparoscopic surgical staging of early ovarian cancer
is a feasible and adequate procedure associated with multiple established and potential
benefits. Although concern still exists regarding recurrence and survival rates in patients
staged by laparoscopy, most of the retrospective literature reports survival rates of
approximately 90% at follow-up, rates similar to that observed in patients staged by
laparotomy. Although prospective trials on laparoscopic staging of early ovarian cancer will
be a challenge to conduct due to the low prevalence of ovary-confined ovarian cancers, this
level of data will be required to understand how laparoscopy impacts cancer recurrence and
mortality for this specialized population. Given these clear limitations, proper patient
selection and counseling, in addition to careful surgical technique, remains the mainstay of
successful laparoscopic staging.
Although laparoscopic surgery can provide better visualization and magnification of
small lesions, it still has limitations in its access to critical areas such as the hepatophrenic
ligament, lesser sac, porta hepatis, splenophrenic ligament, and hidden space in the folded
intestine. In a selective patient population, laparoscopic staging surgery performed by a
skilled surgeon has at least equivalent surgical and oncological outcomes for the treatment
of early-stage ovarian cancer, similar to laparotomy.
Conservative treatment provides good results for fertility, and does not affect the
survival of patients with borderline ovarian tumour. This approach should be considered for
young women desiring fertility, even if peritoneal implants are discovered at the time of the
initial surgery. In case of infertility, the use of assisted reproduction techniques may be
suggested to patients with stage I BOT, with a limited number of stimulation cycles. In
patients with epithelial ovarian cancer, conservative surgery of an ovary and the uterus can
only be considered in adequately stratified patients with serous, mucinous or endometrioid
tumour, excellent prognostic factors (stage IA, grade 1 or perhaps 2) and a careful follow-up.
Removal of the ovary should be carried out when childbearing is complete.

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