Overview of epithelial carcinoma of the ovary, fallopian tube, and peritoneum

Authors:
Lee-may Chen, MD
Jonathan S Berek, MD, MMS
Section Editors:
Barbara Goff, MD
Don S Dizon, MD, FACP
Deputy Editors:
Sandy J Falk, MD, FACOG
Sadhna R Vora, MD

INTRODUCTION — Ovarian cancer is the second most common gynecologic malignancy in developed

countries and the third most common gynecologic malignancy in developing countries (cervical cancer is
the most common) [1]. The majority of ovarian malignancies (95 percent) are epithelial; the remainder arise
from other ovarian cell types (germ cell tumors, sex cord-stromal tumors) (figure 1).
High-grade serous carcinoma, the most common histologic subtype of epithelial ovarian carcinoma, is
regarded as closely related to fallopian tube and peritoneal serous carcinoma, based upon similarities in
histology and clinical behavior. Some experts have proposed that these carcinomas all originate in the
fallopian tubes. Based upon their common features, these carcinomas will be discussed as one clinical
entity and referred to as epithelial ovarian carcinoma (EOC) in this topic review. Distinctions between these
conditions will also be addressed. (See "Pathogenesis of ovarian, fallopian tubal, and peritoneal serous
carcinomas".)

An overview of EOC is presented here. Related topics are discussed in detail separately, including:

●Pathogenesis (see "Pathogenesis of ovarian, fallopian tubal, and peritoneal serous carcinomas")

●Histopathology (see "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Histopathology")
●Epidemiology and risk factors (see "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum:
Epidemiology and risk factors")

●Screening for ovarian cancer (see "Screening for ovarian cancer")

●Clinical features and diagnosis (see "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum:
Clinical features and diagnosis" and "Early detection of epithelial ovarian cancer: Role of symptom
recognition")

●Staging and surgical treatment (see "Cancer of the ovary, fallopian tube, and peritoneum: Staging and
initial surgical management")

●Adjuvant therapy (see "Adjuvant therapy of early stage (stage I and II) epithelial ovarian, fallopian tubal,
or peritoneal cancer" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian
tubal, and peritoneal cancer")

●Posttreatment surveillance and survivorship issues (see "Approach to survivors of epithelial ovarian,

fallopian tubal, or peritoneal carcinoma")

●Relapsed disease (see "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal
cancer: Platinum-sensitive disease" and "Medical treatment for relapsed epithelial ovarian, fallopian tubal,
or peritoneal cancer: Platinum-resistant disease")
HISTOPATHOLOGY — The majority of primary ovarian malignancies (95 percent) are derived from
epithelial cells; the remainder arise from other ovarian cell types (germ cell tumors, sex cord-stromal
tumors) (figure 1) [2]. For epithelial carcinomas, serous is the most common subtype (75 percent of
epithelial carcinomas) [2-4]. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum:
Histopathology".)

Management of borderline ovarian tumors and low-grade ovarian serous carcinoma is reviewed elsewhere.
(See "Management of low-grade serous carcinomas of the ovary" and "Borderline ovarian tumors".)

EPIDEMIOLOGY AND RISK FACTORS — Ovarian cancer is the second most common gynecologic
malignancy in developed countries and the third most common gynecologic malignancy in developing
countries (cervical cancer is the most common) [1]. Ovarian cancer is the second most common
gynecologic malignancy and the most common cause of gynecologic cancer death in the United States
(US) [5].

The average age at diagnosis of ovarian cancer in the US is 63 years old [6]. The age at diagnosis of
ovarian cancer is younger among women with a hereditary ovarian cancer syndrome. The lifetime risk of
developing ovarian cancer is 1.3 percent. A detailed discussion of the epidemiology of EOC can be found
separately. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk
factors", section on 'Epidemiology'.)

An increased risk of EOC is associated with: increasing age, infertility, endometriosis, polycystic ovarian
syndrome, use of an intrauterine device, and cigarette smoking (for mucinous carcinomas) (table 1).
Factors that are associated with a decreased risk include: previous pregnancy, history of breastfeeding,
oral contraceptives, and tubal ligation.

Several ovarian cancer susceptibility genes have been identified, primarily BRCA1, BRCA2, and the
mismatch repair genes associated with Lynch syndrome (hereditary nonpolyposis colorectal cancer). A
personal or family history of breast cancer had been thought of as a risk factor for ovarian cancer;
however, BRCA gene mutations appear to account for a significant amount of this increased risk. Genetic
testing for those at high risk of breast or ovarian cancer is discussed elsewhere. (See "Genetic counseling
and testing for those at risk of hereditary breast and ovarian cancer".)

A detailed discussion of the risk factors for EOC can be found separately. (See "Epithelial carcinoma of the
ovary, fallopian tube, and peritoneum: Epidemiology and risk factors", section on 'Risk factors'.)

CLINICAL PRESENTATION — The clinical presentation of EOC may be either subacute or acute. The
majority of women have stage III (disease that has spread throughout the peritoneal cavity and/or that
involves lymph nodes) disease at diagnosis [7]. (See "Epithelial carcinoma of the ovary, fallopian tube, and
peritoneum: Clinical features and diagnosis"and "Epithelial carcinoma of the ovary, fallopian tube, and
peritoneum: Epidemiology and risk factors", section on 'Epidemiology'.)

Most commonly, EOC presents in a subacute fashion (eg, pelvic or abdominal pain, bloating,
gastrointestinal symptoms) in women with either early or advanced disease (table 2). These conditions are
usually evaluated in an outpatient setting. Alternatively, an adnexal mass may be discovered incidentally at
the time of imaging performed for another indication. Symptoms of EOC are discussed in detail separately.
(See "Early detection of epithelial ovarian cancer: Role of symptom recognition".)

Women who present in an acute fashion are typically those with advanced disease who present with a
condition that requires urgent care and evaluation (eg, pleural effusion, bowel obstruction).
DIAGNOSIS — EOC is a histologic diagnosis, based upon pathology evaluation of tissue following surgical
removal of an ovary or fallopian tube or biopsies of the peritoneum. Less frequently, the diagnosis is based
upon tissue or fluid obtained via image-guided biopsy, paracentesis, or thoracentesis.

The evaluation and diagnosis of EOC is discussed in detail separately. (See "Epithelial carcinoma of the
ovary, fallopian tube, and peritoneum: Clinical features and diagnosis".)

STAGING AND TREATMENT — Surgical staging and cytoreduction followed by adjuvant chemotherapy is

the management approach used for most women with EOC. It is thought that optimal cytoreductive surgery
increases the likelihood that chemotherapy will result in long-term disease-free survival.

Staging and surgical treatment — EOC is surgically staged according to the joint 2017 International
Federation of Gynecology and Obstetrics (FIGO)/Tumor, Node, Metastasis (TNM) classification system
(table 3).

Total extrafascial hysterectomy and bilateral salpingo-oophorectomy with pelvic and paraaortic lymph node
dissection is the standard staging procedure for EOC [8]. Cytology is performed of pelvic washings and the
surface of the diaphragm; omentectomy is also performed. Cytoreduction, which may include bowel or
partial hepatic resection, is performed when metastases are evident.

Staging is typically performed via laparotomy or robot-assisted laparoscopy, but vaginal or conventional
laparoscopic approaches are used for some women.

Staging and surgical treatment of EOC is discussed in detail separately. (See "Cancer of the ovary,
fallopian tube, and peritoneum: Staging and initial surgical management".)

Chemotherapy — Most women with early-stage EOC should receive adjuvant chemotherapy, specifically
those with stage IC or II disease, clear cell histology (any grade), or high tumor grade (table 3). Those with
advanced disease (stage III or IV) should also receive adjuvant therapy if they underwent primary surgical
cytoreduction. However, patients who are not good candidates for surgery due to the location and volume
of disease involvement or medical comorbidities at the time of diagnosis may be considered for
neoadjuvant chemotherapy instead. (See "Neoadjuvant chemotherapy for newly diagnosed advanced
ovarian cancer".)

The preferred chemotherapy regimen is a platinum-based combination (which may be used in the adjuvant
or neoadjuvant setting). However, treatment options differ based on extent of disease at staging.

For women with early-stage disease, we prefer carboplatin and paclitaxel administered every three weeks

for six cycles. However, it is reasonable to individualize the number of cycles based upon patient risk
factors and the tolerance of therapy. In this case, we prefer a minimum of three cycles be administered.
(See "Adjuvant therapy of early stage (stage I and II) epithelial ovarian, fallopian tubal, or peritoneal
cancer".)

For women with advanced EOC, the options depend on the surgical outcomes. (See "First-line
chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and peritoneal cancer".)

●For women with optimally cytoreduced EOC (ie, <1 cm residual disease at the completion of surgery), we
prefer a regimen that includes intraperitoneal (IP) carboplatin or cisplatin, intravenous (IV) paclitaxel, and IP
paclitaxel chemotherapy over IV therapy alone. We administer treatment for a total of six cycles.
●For women with suboptimally cytoreduced EOC (ie, ≥1 cm residual disease), we administer a platinum-
based doublet such as carboplatin plus paclitaxel IV for six cycles. These patients are not candidates for IP
therapy.

PROGNOSIS — Approximately 80 percent of patients with early-stage disease are recurrence-free at five

years. However, the majority of women with advanced-stage ovarian cancer will relapse. Among those with
relapsed disease, mortality is high. The one-, two-, and five-year survival rates by stage for ovarian and
fallopian tube carcinoma are shown in the tables (table 4 and table 5).

In an analysis of almost 1900 stage III ovarian cancer patients treated with primary surgery and six cycles
of platinum/paclitaxel, the major prognostic factors associated with improved outcome were younger age,
low volume of residual disease, good performance status, and serous histology [9]. Others have reported
that patients with residual tumor burden less than 1 cm in diameter without debulking did better than those
who required debulking to achieve this residual tumor burden. Among patients who achieve optimal
debulking, those with less advanced disease at initial surgery did better than those with more advanced
disease [10,11]. The importance of debulking is discussed elsewhere. (See "Cancer of the ovary, fallopian
tube, and peritoneum: Staging and initial surgical management", section on 'Cytoreduction'.).

Younger patients are more likely to have a favorable prognosis because they are more likely to have
tumors of less aggressive histology and lower grade, and better baseline performance status [12,13]. In a
database study of over 5000 patients, 294 of whom were <40 years, those who were <40 years had a
median overall survival of 75 months, versus 46 months among those ≥40 years [12].

The volume of residual disease is the only major prognostic factor that the surgeon can address. As such,
resectability is, in part, influenced by the experience, judgment, and effort of the surgeon [14].

The biologic characteristics of ovarian cancer may help predict the patient's prognosis and her response to
medical and surgical therapies. As an example, preliminary studies into these characteristics have found an
association with relapse or survival with the decline in cancer antigen (CA) 125 after surgery and cancer
cell expression of nuclear maspin expression [15,16]. In addition, a 2013 meta-analysis found that high
expression of the progesterone receptor (PR) was associated with improvement in overall survival (hazard
ratio [HR] 0.88, 95% CI 0.82-0.95). However, while elevated levels of human epidermal growth factor
receptor 2 (HER2) predicted worse survival (HR 1.41, 95% CI 1.05-1.89) [17], expression of estrogen
receptors was not significantly associated with outcomes.

Retrospective studies have suggested that women upstaged to stage IIIC based on nodal involvement
alone may have a better prognosis than IIIC patients with gross intraabdominal disease larger than 2 cm,
even if optimally cytoreduced [18,19]. These results require confirmation.

Women with BRCA gene mutations, particularly BRCA2, appear to have a somewhat better prognosis than
noncarriers. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Epidemiology and risk
factors", section on 'BRCA gene mutations'.)

POSTTREATMENT SURVEILLANCE — Following all first-line treatment for EOC, monitoring should

include routine history and physical, assessment of cancer antigen (CA) 125 (or other tumor markers if they
were elevated on initial presentation), and other testing if clinically indicated (eg, imaging or laboratory
assessments) [20]. The specific schedule of posttreatment surveillance evaluations is discussed
elsewhere. (See "Approach to survivors of epithelial ovarian, fallopian tubal, or peritoneal carcinoma",
section on 'Posttreatment surveillance'.)
CA 125 surveillance — Following patients longitudinally by CA 125 may help identify patients for surgical
treatment at recurrence and thereby increase the likelihood of an optimal cytoreduction. However, there is
no clear impact of serial CA 125 measurements on overall survival. (See "Approach to survivors of
epithelial ovarian, fallopian tubal, or peritoneal carcinoma", section on 'Role of CA 125 surveillance'.)

No role for routine imaging — Standard imaging techniques, including ultrasound, computed tomography
(CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), have limited sensitivity
to detect recurrent EOC [21]. There are some data to support the use of PET/CT to detect early recurrent
disease, but we do not perform surveillance imaging studies in asymptomatic women given lack of
evidence for a survival benefit. This is discussed in more detail elsewhere. (See "Approach to survivors of
epithelial ovarian, fallopian tubal, or peritoneal carcinoma", section on 'No role for routine imaging'.)

RELAPSED DISEASE — Despite initial therapy, the majority of women with advanced-stage ovarian
cancer will relapse and require additional treatment. The likelihood for recurrence depends on many
factors, including distribution of disease at initial presentation, success of initial surgical cytoreduction (ie,
the presence of any residual disease), the rapidity of cancer antigen (CA) 125 resolution, and treatment
response after primary therapy. However, a predictive marker for recurrence has not been prospectively
verified.

The approach to treatment depends upon the amount of time that has elapsed between the completion of
platinum-based treatment and the detection of relapse, known as the platinum-free interval (PFI). This is
because the PFI correlates with progression-free survival (PFS), overall survival (OS), and response to
subsequent treatment (both with platinum and nonplatinum agents as well as cytoreduction).

●Patients with a PFI of six months or longer are considered to have chemotherapy-sensitive disease (often
also termed "platinum-sensitive"). (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or
peritoneal cancer: Platinum-sensitive disease".)

●Patients with a PFI of less than six months are considered to have chemotherapy-resistant disease (often
also termed "platinum-resistant"). Of this group, those patients who progress while on platinum-based
therapy are often referred to as having "platinum-refractory" disease. The management of these patients is
discussed separately. (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal
cancer: Platinum-resistant disease".)

ISSUES IN SURVIVORS

Fertility preservation — Fertility preservation options are limited for women with EOC, since most cases
are diagnosed at an advanced stage and hysterectomy and bilateral salpingo-oophorectomy is part of
staging and surgical treatment. Fertility-preserving surgery (ie, unilateral salpingo-oophorectomy) is
typically reserved for women with stage IA EOC or those with borderline ovarian tumors who desire future
childbearing. (See "Cancer of the ovary, fallopian tube, and peritoneum: Staging and initial surgical
management", section on 'Fertility preservation'.)

Other posttreatment issues — Issues pertaining to survivorship for women previously treated for EOC
are not as well studied as they are for many other cancers. This may be in part due to an overall poor
prognosis and small population of affected individuals. A detailed discussion of issues in EOC survivors,
including medical and psychosocial effects (eg, gastrointestinal toxicity, neurologic effects, menopause
management, and sexual dysfunction), can be found separately. (See "Approach to survivors of epithelial
ovarian, fallopian tubal, or peritoneal carcinoma".)
SUMMARY

●Surgical staging and cytoreduction followed by adjuvant chemotherapy is the management approach
used for most women with epithelial ovarian carcinoma (EOC). It is thought that optimal cytoreductive
surgery increases the likelihood that chemotherapy will result in long-term disease-free survival. In some
cases, including women who are not good candidates for radical cancer surgery, chemotherapy is
administered first (neoadjuvant chemotherapy), with surgery performed following the chemotherapy.
(See "Adjuvant therapy of early stage (stage I and II) epithelial ovarian, fallopian tubal, or peritoneal
cancer" and "First-line chemotherapy for advanced (stage III or IV) epithelial ovarian, fallopian tubal, and
peritoneal cancer" and "Neoadjuvant chemotherapy for newly diagnosed advanced ovarian cancer".)

●Ovarian cancer is the second most common gynecologic malignancy and the most common cause of
gynecologic cancer death in the United States. The average age at diagnosis of ovarian cancer in the
United States is 63 years old. The age at diagnosis of ovarian cancer is younger among women with a
hereditary ovarian cancer syndrome (BRCA gene mutations or Lynch syndrome). The lifetime risk of
developing ovarian cancer is 1.3 percent. (See 'Epidemiology and risk factors' above.)

●The majority of primary ovarian malignancies (95 percent) are derived from epithelial cells; the remainder
arise from other ovarian cell types (germ cell tumors, sex cord-stromal tumors) (figure 1). Serous
carcinoma, the most common histologic subtype of EOC, is similar in histology and clinical behavior to
fallopian tube and peritoneal carcinomas. It has been proposed that ovarian and peritoneal carcinomas
originate in the fallopian tubes. (See 'Histopathology' above.)

●Risk factors for EOC include: increasing age, infertility, and endometriosis (table 1). Women with ovarian
cancer susceptibility genes are at the highest risk of ovarian cancer, including BRCA gene mutations and
Lynch syndrome. Factors that are associated with a decreased risk include: previous pregnancy, history of
breastfeeding, oral contraceptives, and tubal ligation. (See 'Epidemiology and risk factors' above.)

●The clinical presentation may be either subacute or acute. Most commonly, the presentation is subacute
(eg, pelvic or abdominal pain, bloating) or an adnexal mass is discovered incidentally (table 2). An acute
presentation may occur in women with advanced disease and includes pleural effusion or bowel
obstruction. (See 'Clinical presentation' above.)

●EOC is a histologic diagnosis. Pathology evaluation is performed following surgical removal of an ovary or
fallopian tube or biopsies of the peritoneum. (See 'Diagnosis' above.)

●EOC is surgically staged according to the joint 2017 International Federation of Gynecology and
Obstetrics (FIGO)/Tumor, Node, Metastasis (TNM) classification system (table 3). Total hysterectomy and
bilateral salpingo-oophorectomy with pelvic and paraaortic lymph node dissection is the standard staging
procedure. (See 'Staging and surgical treatment' above.)

●Most women with EOC require adjuvant treatment, specifically those with stage IC or II disease; those
with stage III or IV disease who are candidates for primary surgical cytoreduction; and those with clear cell
histology (any grade) or high tumor grade (table 3). However, patients who are not good candidates for
surgery may be considered for neoadjuvant chemotherapy instead. (See 'Chemotherapy' above.)

●Major prognostic factors associated with improved outcomes among patients with resected EOC include
younger age, low volume of residual disease, good performance status, and serous histology (table 4).
(See 'Prognosis' above.)
●Posttreatment surveillance includes routine history and physical, assessment of cancer antigen (CA) 125
or other tumor markers if they were elevated on initial presentation, and other testing if clinically indicated
(eg, imaging or laboratory assessments). The specific schedule of posttreatment surveillance evaluations is
discussed elsewhere. (See "Approach to survivors of epithelial ovarian, fallopian tubal, or peritoneal
carcinoma", section on 'Posttreatment surveillance'.)

●Despite initial therapy, the majority of women with advanced-stage ovarian cancer will relapse and require
additional treatment. The approach to treatment depends upon the amount of time that has elapsed
between the completion of platinum-based treatment and the detection of relapse, known as the platinum-
free interval (PFI). (See "Medical treatment for relapsed epithelial ovarian, fallopian tubal, or peritoneal
cancer: Platinum-sensitive disease" and "Medical treatment for relapsed epithelial ovarian, fallopian tubal,
or peritoneal cancer: Platinum-resistant disease".)