7. OVARIAN TUMORS

General considerations

Tumors of the ovary are benign, borderline or malignant. Benign tumors require operative

intervention but do not recur or metastasize, nor do they generally decrease survival. Borderline tumors, in

contrast, are associated with a small risk of recurrence, may have invasive implants and thus may decrease

survival. Malignant tumors recur, metastasize and decrease survival.

Benign ovarian neoplasms do not produce any symptoms that readily differentiate them from

malignant tumors or from a variety of other pelvic diseases. Indeed, one of the most unfortunate features of

benign tumors is that they are indistinguishable clinically from their malignant counterparts.

Although it is not known whether malignant ovarian tumors arise de novo or develop from benign

tumors, there is strong inferential evidence that at least some benign tiunors will become malignant.

7.1. BENIGN TUMORS

Classification

A satisfactory classification of ovarian tumors must precede any discussion of this complex and

variegated group of neoplasm. The following tabulation has proven satisfactoiy in our practice :

A. Cystic tumors

1. Nonneoplastic (functional cysts)

2. Neoplastic serous mucinous dermoid (benign cystic teratoma)

B. Solid tumors

1. Functioning tumors (with characteristics)

2. Endocrinological inert feminizing or masculinizing

Nonneoplastic or functional cysts of the ovary

Among the most frequently found masses involving the adnexa (anatomically, the adnexa consist

of the fallopian tubes, round ligament, ovaries and structures within the round ligament that were formed

from embryologic rests) are the nonneoplastic cysts that are related to the process of ovulation and are

sometimes referred to as functional cysts. They are by far the most common clinically detectable

enlargements of the ovary occurring during the reproductive years.

They are of great significance primarily because they cannot be readily distinguished from true

neoplasms on clinical grounds alone. Among the noneoplastic cysts and hyperplasias of the ovary are:

- functional cysts, both follicular and corpus luteum types;

- theca lutein cysts; pregnancy luteoma;

- sclerocystic ovaries;

- endometriotic cysts.1

If ovulation does not occur, a clear fluid-filled follicular cyst lined by granulosa cells may result

and can reach sizes as large as 10cm in diameter. These cysts usually resolve spontaneously within a few

days to 2 weeks but can persist longer.

When ovulation occurs, a corpus luteum is formed that may become abnormally enlarged through

internal hemorrhage or cyst formation. Such cysts are often associated with variable delays in the onset of

menses and confusion regarding the possibility of an ectopic pregnancy.

Theca lutein cyst result from overstimulation of the ovary by HCG and are characterized by

extensive luteinization of the stroma surrounding the follicle. They are often associated with hydatidiform

moles and choriocarcinoma.

Coipus luteum, follicular and theca lutein cysts are benign, represent an exaggerated physiologic

response of the ovary and, in most instances, involute over time.

Neoplastic tumors

There are three main varieties of these tumors : serous, mucinous, dermoid.

Serous cystadenomas are more common and as a rule do not attain a very large size. Although

most of the inner wall of the cyst may be smooth it may also contain a large number of papillary projections.

Associated fibrosis may lead to the so-called cystadenofibroma.

The serous cyst is usually unilocular, containing a serocitrine, clear fluid. Bilaterality may be in as

10% of patients with serous cystadenomas.

Mucinous cystadenomas may become huge (several have been reported to weigh 100 to 200

pounds). Grossly, they are round or ovoid masses with smooth capsules that are usually translucent and

bluish-whitish gray.

The interior is divided into a number of discrete septa or locules containing generally a clear,

viscid fluid. Of major concern are mucinous cysts that perforate and initiate intraabdominal transformation

of the peritoneal mesothelium to a mucin-secreting epithelium with gradual accumulation in peritoneal

cavity of large amounts of gelatinous material, constituting the pseudomyxoma peritonei!

Incidence of bilaterality in mucinous cysts is no significant.

Dermoid cyst (benign cystic teratoma) is rarely large, often bilateral and frequent in the younger

individual. On opening the cyst, one frequently finds hair, bone and cartilage as well as a large amount of

greasy fluid.

Microscopically, one may find all types of mature ectoderm, mesoderm and endoderm elements

(gastro-intestinal, nervous, respiratory, thyroid tissue).

Benign solid tumors are usually of connective tissue origin (fibrom, Brenner tumor). They vaiy in

size from very small nodules, found on the surface of the ovary, to very large neoplasms.

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On physical examination these tumors are usually quite firm, slightly irregular in contour and

mobile. The Demons-Meigs syndrome is an uncommon clinical entity in which a benign ovarian fibroma is

seen with ascites and hydrothorax.

Symptoms and diagnosis of benign ovarian tumors

Most neoplasm of the ovary are asymptomatic unless they have been subject to a complication, hi

many instances, the first symptom noted is a palpable pelvic mass or abdominal enlargement.

Pelvic examination remains the best method of identifying an ovarian mass in its earliest stages.

Knowledge of the size, shape, contour and general location within the pelvis helps the physician arrive at the

most likely diagnosis.

Benign tumors are usually smooth walled, cystic, palpable in the lateral vaginal cul-de-sac, mobile,

unilateral, independent of the uterus.

Any mass that is larger than 7 to 8cm in diameter should usually be surgically explored. 95% of

ovarian cysts smaller than 5cm in diameter are nonneoplastic. The transitory existence of functional cysts is

of prime importance in distiguishing them from true neoplasms (tumor disappear in two months).

Most neoplastic ovarian tumors produce few symptoms: sense of pelvic weight or pressure,

abdominal discomfort, urinary tract or intestinal disorders.

Feminizing tumors, that occur before the menarche, are clasically associated with

pseudoprecocious puberty (early breast development, appearance of pubic and axillary hair and vaginal

bleeding).

hi the menstrual years, the symptoms may be : amenorrhea, nausea, gastro-intestinal disturbances,

sensitive breasts, weigh gain and a general lack of well-being.

In the postmenopausal patient, the symptoms are often similar to those of patients of comparable

age who are receiving exogenous hormones (vaginal epithelium matures, the endometrium becomes

proliferative and bleeding may occur).

Gonadal stromal tumor with masculinization is characterized by amenorrhea, breast atrophy,

clitoromegaly, hirsutism.

Complementary investigations, utilized especially in pelvic tumors, are:

- pregnancy test;

- roentgenologic examination of the abdomen (teratoma, calcifications);

- intravenous pyelogram (to detect ureteral displacement or obstruction, which may be

caused by intraligamentary tumors); —> barium enema (if symptomatic);

- pelvic ultrasound (to exclude intrauterine or malignant characteristics of the mass);

- laparoscopy (may be helpful in distinguishing a uterine myoma from an ovarian neoplasm

and in any situation where the source of a pelvic mass is uncertain; laparoscopy may be helpful, but

laparotomy is necessary in the treatment of most adnexal enlargements;

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- usuall laboratory tests in vue of surgical treatment and careful evaluation of general physical

condition.

Differential diagnosis

Although it is not unrealistic to consider every ovarian neoplasm or ovarian mass potentially

malignant, in truth only 20% of all ovarian neoplasms are pathologically malignant. Only occasionally it is

possible to differentiate benign from malignant tumors on the basis of history and physical examination. We

present pelvic findings in benign and malignant ovarian tumors:

benign malignant

unilateral bilateral

cystic solid

mobile fixed

smooth irregular

no ascites ascites

no cul-de-sac nodules presence of cul-de-sac nodules

long time asymptomatic rapid growth rate

All persistent adnexal enlargements must be considered malignant until proved otherwise. Other

aspects which can be differentiated:

♦ pregnancy (intrauterine, ectopic);

♦ myomas of the uterus (especially subserous pedunculated or intraligamentary);

♦ hydrosalpinx;

♦ tubo-ovarian inflammatory mass;

♦ double uterus;

♦ endometriosis (ovarian cystic);

♦ functional cyst;

♦ pelvic kidney;

♦ tuberculous peritonitis (encysted);

♦ ascites (may cause marked enlargement of the abdomen similar to that seen with large cysts);

♦ liver, spleen, kidney or adrenal tumors.

Complications

Torsion of the pedicle

In approximately 15% of cases, ovarian cyst may twist on its pedicle and produce rather acute

initial symptoms. Torsion may be complete or incomplete. When complete torsion occurs, gangrene of the

cyst rapidly results.

Severe nausea and vomiting, rigidity of the lower abdomen appear promptly and if the tumor is on

the right side the simulation to an acute appendicitis is marked. Other differential diagnosis are:

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hemoperitoneum from complicated ectopic pregnancy, intestinal obstruction, peritonitis. Surgery, of course,

is the rule.

Rupture of the cyst

Ovarian cyst may rupture or be associated with intracystic or intraperitoneal bleeding. There may

be acute symptoms with the rapid development of shock as in a ruptured ectopic pregnancy.

Should the rupture of a cyst involve only a single locule, or should bleeding be less severe, the

abdominal symptoms may be mild and transitory.

A benign mucinous cyst rupture may produce pseudomyxoma peritonei.

Supuration

Certain cysts, particularly dermoids, are prone to undergo infection, especially if there is partial

twisting of the pedicle. This will produce symptoms similar to those seen in a pelvic inflammatory disease

(pain, tenderness, rigidity, fever). Without surgical intervention a frank peritonitis may ensue.

Malignant change

This occurs in only 5-10% of the mucinous cysts. The problem is much more serious with the

papillary serous tumors because the histological differentiation between the benign and malignant is often

complex. Malignant degeneration of serous tumors occurs in approximately 25%. Malignant transformation

of dermoid cysts is relatively uncommon (1-3%).

There are some clinical characteristics of malignant change: age more than 40. rapid increase in

volume of a known tumor, benign tumor becomes rigid and fixed, ascites.

Treatment of benign ovarian tumors

A N indicated earlier, small adnexal masses of less than 5-6cm in diameter should be treated

expectantly over the course of two or three months, particularly in a younger woman. Should this not regress

and particularly if it should increase in size, laparotomy must be performed.

Large ovarian cysts are unlikely to be functional and deserve immediate laparotomy as do solid

tumors, which carry a much larger hazard of being malignant.

As to the type of surgery performed, there seems little question that in the average woman who has

completed her family, total hysterectomy with removal of both adnexae is the safest procedure.

Where conservation of one ovary and/or the uterus is desired (to avoid menopausal symptoms or

for further pregnancy) this is permissible if careful inspection (frozen sections and peritoneal washings)

suggests that the lesion is benign. As a rule, complete operation is desirable in the parous woman and after

40 years (the menopause is really a minor problem today now that replacement therapy is available.

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7.2. OVARIAN CANCER

General considerations

Ovarian cancer accounts for only 4% of cancers in women, but it is the leading cause of death

from gynecologic malignancies. This tumor is the seventh most common cancer in women worldwide, after

cancers of the breast, cervix, colon and rectum, stomach, corpus uteri and lung.

One interesting fact about ovarian cancer is that the highest incidence rates are in developed

countries and the lowest rates are in developing countries. In the United States, ovarian cancer is the second

most common gynecologic cancer.

The lifetime risk among women with no history of familial ovarian cancer is estimated to be 1.4%

(1 in 70 women) and that of women with positive family histories is higher.

Ovarian cancer incidence appears to be the highest in North America and Northern Europe and

lowest in Japan and it occurs more commonly in white women. The mean age at diagnosis is 59 years and

the incidence with age and peaks in the eighth decade.

Some of the geographic differences in the ovarian cancer incidence rates are explained by

intercountry differences in reporting systems, socioeconomic development, fertility rates, patterns of oral

contraceptive use and hysterectomy rates. Because a genetic link has been observed, another possible

explanation is that the prevalence of the gene may be higher in some ethnic groups than in others. More than

75% of cases of ovarian cancer are still diagnosed in advanced stages of the disease.

Risk factors

The causes of ovarian cancer are poorly understood, but several factors have been associated with an

increased or decreased risk of the disease. Age, race, nulliparity, infertility, history of endometrial or breast

cancer and family history of ovarian cancer have been consistently found to increase the risk for invasive

epithelial cancer. Age

The incidence rate of ovarian cancer increases from 15.7 per 100,000 per year in the 40 to 44 age

group to a peak rate of 54 per 100,000 per year in the 75 to 79 age group.

Ovarian cancer is a rare disease before the age of 40, but its incidence increases steeply with age.

The relationship between age at menarche and menopause and the risk of ovarian cancer is

inconclusive. Some studies reported that women experiencing menarche before the age of 18 had a three to

four times higher risk of developing ovarian cancer than those experiencing menarche at older ages.

The data on the association between ovarian cancer risk and age at natural menopause show

similar inconsistencies. Some studies have detected an increased risk of ovarian cancer with increasing age

at menopause that ranges from 1.4 to 4.6.

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Reproductive and menstrual factors

Parity has been associated with a decreased risk for ovarian cancer. The risk of tumor decreases

with each increase in the number of pregnancies. The effects of age at first birth and incomplete pregnancies

(spontaneous abortions) on the risk of ovarian cancer are still unresolved. Some studies showed a protective

effect for incomplete pregnancies similar to that of full term pregnancies.

Breast feeding suppresses ovulation. Women with a history of breast feeding have been reported to

have a lower risk for ovarian cancer (60% reduction in lifetime risk compared with nulliparous women).

Infertility and fertility drugs utilized in treatment of anovulation may cause increased ovulation

and the risk of ovarian cancer.

Exogenous hormones, expressed by combined oral contraceptives, have been shown to reduce the

risk of ovarian cancer and this protective effect is one of the best established and most consistent findings in

the epidemiologic studies of ovarian cancer.

The risk also decreases with increasing duration of oral contraceptive use (11% with each year of

use).

Studies of the association between estrogen replacement therapy and ovarian cancer have not

shown consistent results.

Palpable postmenopausal ovary During the postmenopausal years, when the ovary becomes

smaller (size of 1.5x1x0.5cm) the presence of a palpable ovary must alert the physician to the possibility of

an underlying malignancy (H. Barber).

Family history

At least two well described familial ovarian cancer syndromes exist: the hereditary breast-ovarian

cancer syndrome (BRCA 1 gene, located on the long arm of chromosome 17) and Linch syndrome II

(familial predisposition to ovarian cancer, endometrial and colon cancer without polyposis)

Familial ovarian cancer accounts for less than 5% of all ovarian cancers. For women with a strong

family history of ovarian cancer, management typically includes frequent screening and consideration of

prophylactic oophorectomy after the age of 35 and when childbearing is complete.

Dietary factors

Ecologic studies showed a positive correlation between consumption of animal fat, proteins and

total calories and the incidence of ovarian cancer.

Other risk factors Other risk factors for ovarian cancer that are inconclusive or have been less studied

include the following : obesity, thyroid disease, use of antidepressant, anticonvulsants or psychotropic drugs,

ionizing radiation and occupational exposure to benzene, asbestos or metals.

Pathogenesis

Three hypotheses have been proposed to explain the etiopathogenesis of ovarian cancer:

♦ the incessant ovulation;

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♦ the gonadotropin;

♦ the pelvic contamination.

The incessant ovulation theory postulates that repeated minor trauma to the epithelial surface of

the ovary caused by continuous ovulation increases the likelihood of ovarian cancer. This hypothesis

suggests that factors which suppress ovulation (parity, oral contraceptives, lactation) reduce the risk of

ovarian cancer.

The gonadotropin hypothesis considers that the exposure of the ovary to continuous, high

circulating levels of pituitary gonadotropin increases the risk of malignancy.

The pelvic contamination theory suggests that carcinogens may come in contact with the ovary

after passage through the genital tract.

Classification

The student of ovarian pathology is often confused by the prodigious variation in histologic

structure, and biologic behaviour. Currently, the most popular and practical scheme of classification is based

on the histogenesis of the ovary:

I. Neoplasms derived from coelomic epithelium (serous, mucinous,

endometrioid etc);

II. Neoplasms derived from germ cells (teratoma, dysgerminoma, gonadoblastoma);

III. Neoplasms derived from specialized gonadal stroma (granulosa-theca cell tumors,

arrhenoblastoma, gynandroblastoma, lipid cell tumors);

IV. Neoplasms derived from nonspecific mesenchyme (fibroma,

sarcoma);

V. Neoplasms metastatic to the ovary (gastro-intestinal tract, breast,

endometrium, lymphoma).

The histologic type of tumor varies with age. Most tumors in postmenopausal patients are of

epithelial origin. Common epithelial tumors, which account for about 90% of all ovarian cancers, arise from

the surface epithelium of the ovary.

Serous carcinomas are the most common histologic type of ovarian malignancy accounting for

about 50% of all epithelial ovarian cancers. Mucinous tumors represent the second most common type of

epithelial ovarian malignancy.

The pathogenesis of epithelial ovarian cancer is unknown. Theoretically, malignant ovarian

neoplasms may arise de novo from benign lesions or from changes in tumors of low malignant potential.

The primary mode of dissemination of epithelial ovarian cancer is by implantation on peritoneal

surfaces, pelvis, right paracolic space to the right hemidiaphragm, pleural surfaces. Involvement of .the

omentum is extremely common (more than 80 %). Implantation on the serosa of the small intestine is also

common. Ascites frequently accompanies peritoneal metastases.

Other ways of dissemination can be:

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0 direct local extension (cul-de-sac and bladder peritoneum, uterus, fallopian tubes and

rectosigmoid colon);

0 hematogenous spread (especially as a late manifestation); 0 lymphatic metastases (pelvic or para-

aortic nodes).

Clinical evaluation. Diagnosis. Staging classification.

The high mortality rate of ovarian cancer is due primarily to the difficulty in detecting the disease

in early stages. If diagnosed when the cancer is confined to the ovary (stage I), the 5 year survival rate

approaches 80% compared with only 19% for stage IV disease. Unfortunately, fewer than 25% of cases are

stage I at diagnosis. The disease tends to be asymptomatic until it is well advanced.

Early symptoms are often nonspecific, such as vague abdominal discomfort, nausea, dyspepsia,

which may be present for several months before the diagnosis. Such complaints are usually not recognized

as anything more than "middle-age indigestion".

A high index of suspicion is warranted in all women between the ages of 40 and 70 who have

persistent gastrointestinal symptoms that cannot be diagnosed. The possibility of ovarian cancer is often

dismissed.

As the ovarian tumor enlarges, it causes compression of surrounding pelvic structures, resulting in

such symptoms as constipation, urinary frequency or pelvic pressure. Menstrual irregularity is also

occasionally associated.

Of course, malignant tumors may undergo changes similar to benign tumors including torsion,

hemorrhage or rupture which may result in acute abdominal pain, constituting a surgical emergency.

As ascites develops or the tumor metastasizes, abdominal distension becomes more pronounced.

Pain is usually a late complication and is seen with early disease only when associated with a torsion,

rupture or infection.

Pelvic examination remains the most reliable means of detecting early disease. Any ovary palpated

in a patient 3 or more years after menopause should raise a high index of suspicion of an early ovarian

neoplasm.

A pelvic or pelvic-abdominal mass is palpable in most patients with ovarian cancer. There are no

pathognomonic findings on physical examination that distinguish a malignant from a benign tumor.

Benign ovarian tumors tend to be cystic, smooth, unilateral and mobile.

Malignant tumors tend to be solid, nodular, bilateral, immobile or fixed.

The finding of ascites suggests malignant tumor but may also be found in Meig's syndrome.

Although ascites may be distinguishable from a pelvic-abdominal mass by percussion (central tympany

associated with ascites, central dullness and lateral tympany associated with a mass) this distinction is not

always possible. Ascites without the presence of a pelvic mass should lead one to consider liver disease or

other primary malignancies (colon, pancreas, stomach or breast).

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Examination of the upper abdomen in patients with advanced disease may reveal hepatomegaly,

massive omental involvement.

Careful chest auscultation and percussion may aid in the diagnosis of pleural effusions.

The differential diagnosis of a pelvic mass includes benign ovarian tumors, functional cysts,

endometriosis, pelvic inflammatory disease. Common nongynecologic causes include diverticular disease,

tumors of the colon or appendix, retroperitoneal tumors, metastatic cancer and a pelvic kidney.

Laboratory tests

Routine blood studies, including a complete blood count, differential blood count, platelet count

and chemistry survey, should be part of the preoperative evaluation.

A serum CA 125 determination is recommended because an estimated 80% of patients with

epithelial ovarian cancer have an abnormal value at diagnosis. CA 125 is the most extensively studied

antigen and is the expression of cells derived from embryonal coelomic epithelium and

Mullerian duct. Serum CA 125 levels are greater than 35U/ml in 80% of women with nonmucinous

epithelial ovarian cancer.

CA 125 levels may be elevated in a significant proportion of women destined to develop ovarian

cancer sometimes years prior to the onset of clinical disease.

Recent work has concentrated on the evaluation of new tumor markers that may be complementary

to CA 125: CA 15-3, TAG 72.3.

Radiographic studies are realised in different teritories : abdominal (calcifications, indication of

associated ascites or intestinal obstruction), chest (pleural effusions, pulmonary metastases), excretory

urography, barium enema (to eliminate the diagnosis of conditions such as diverticular disease, cancer of the

colon, inflammatory bowel disease or involvement of the rectosigmoid by ovarian cancer).

Sonography is used to differentiate benign from malignant ovarian tumors. Malignant tumors are

generally multiloculated, more solid or echogenic, larger than 5cm, with thick septae and solid nodules.

Ascites is easily detected, mesenteric or peritoneal involvement may also be noted.

CT has a superior ability to detect disease in the liver, retroperitoneum and omentum. When

indicated, fine-needle aspiration under CT guidance may be performed.

MRI may be used but it is not determined if it is superior to CT or US.

Lymphography may be used to delineate lymph node involvement but is not been used routinely.

Other categories of investigations may be: Pap smear, cystoscopy, cytology of peritoneal lavage,

Iaparoscopy.

The primary care physician needs to be alert to the possibility of an ovarian malignancy in all

women with intact ovaries who present with abdominal or pelvic complaints. The primary care physician

can also play an important role in identifying patients at high risk for ovarian cancer and in helping patients

understand the risks and benefits of the various screening methods, prevention strategies and treatment

options. Staging

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Stage of disease is determined by the extent of tumor at the initial diagnosis. The staging

classification for ovarian cancer is a surgico-pathologic system, last modified by FIGO in 1985. An

exploratory laparotomy is often necessary to diagnose ovarian cancer, since ovarian masses may also be

caused by benign cysts, by other primary ovarian tumors or by metastases to the ovary from a primary

gastrointestinal or breast cancer.

Laparotomy permits a careful examination of all serosal surfaces, biopsies of grossly involved

areas, collection of ascites or peritoneal washings for cytologic studies.

International Federation of Gynecologic Oncologists (FIGO) staging system for epithelial cancer

of the ovary

STAGE TUMOR CHARACTERISTICS

I tumor limited to the ovaries

IA one ovary, no ascites, intact capsule

IB both ovaries, no ascites, intact capsule

IC ruptured capsule, capsular involvement, positive peritoneal washings or

malignant ascites

II ovarian tumor with pelvic extension

IIA pelvic extension to uterus or tubes

IIB pelvic extension to other pelvic organs (bladder, rectum) or vagina

IIC pelvic extension plus findings indicated for IC

III tumor outside the pelvis or with positive nodes

IIIA microscopic seeding outside the true pelvis

IIÏB * gross deposits (implants) none exceeding 2cm in diameter, node negative

IIIC abdominal implants greater than 2cm, positive retroperitoneal or

inguinal nodes

IV distant organ involvement, including liver parenchyma or pleural space

Early detection of ovarian cancer

The mortality from ovarian cancer has changed little in the last 30 years. The overall five-year

survival for this disease is variably quoted between 20 and 30%. Ovarian cancer has a higher mortality than

all the other gynecological malignancies combined. Thus, the need for the development of tests to aid the

early detection of ovarian cancer is important.

The time course of the progression of early disease is an important aspect that is poorly understood

but is crucial to the design of any protocol for the early detection of ovarian cancer.

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It can be seen that target screening of high risk populations, although important on an individual

basis, is unlikely to have a significant impact on ovarian cancer statistics. Over 90% of cases of ovarian

cancer are sporadic tumors and need to be detected by screening techniques. Several methods have been

tested for ovarian cancer screening.

Pelvic examination is currently the standard for screening. It has a sensitivity of 67% for detecting

a 4x6cm mass. Therefore, the pelvic examination alone is of limited value as a screening tool for the

detection of early ovarian cancer.

Tumor markers are substances which include enzymes, hormones, nonspecific inflammatory

proteins and placental and fetal antigens. They may reflect an alteration in ovarian function or surface

molecular structure or a general response to malignancy. Since the original description of tumor-associated

antigens in ovarian cancer over 30 years ago, over 100 potential tumor-associated markers have been

reported in the literature.

The most extensively studied ovarian cancer-associated antigen is CA-125, a high molecular

weight glycoprotein of which intense expression is found in more than 80% of epithelial ovarian cancers.

CA -125 has been used in three different situations:

=> follow-up of patients with ovarian cancer;

=^> preoperative evaluation of benign versus malignant neoplasms;

=> ovarian screening (in postmenopausal women, a value greater than 35U/ml is highly suggestive

of malignant process).

Transvaginal ultrasonography can detect early morphologic changes accompanying oncogenesis (size,

papillary projections from the cyst wall and cyst complexity). Most recently, transvaginal color Doppler

blood flow studies were suggested as a highly accurate way to screen women for ovarian cancer.

Transvaginal screening is optimal in postmenopausal women in whom ovarian volume does not

vary on a physiologic basis. Routine screening for ovarian cancer in the general population is not

recommended by the American College of Obstetrics and Gynecology.

Screening is recommended for some very high risk patients (advanced age and family history of

ovarian cancer). The current recommendation for those patients is annual rectovaginal examination, serum

CA-125 and TVS until childbearing is complete or the woman reaches 35 years of age. At that point,

prophylactic oophorectomy is recommended.

Treatment of ovarian cancer

Early stage disease

For older women who have completed childbearing, standard surgical management includes total

hysterectomy and bilateral salpingo-oophorectomy

A complete surgical staging operation must be performed to identify the significant proportion of

patients who will harbor occult metastatic disease. This surgical staging should include a through abdominal

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exploration with biopsies and cytologic washings from multiple sites, omentectomy and sampling of the

pelvic and paraaortic lymph nodes.

In young women with early ovarian cancers who wish to preserve the potential for childbearing, a

number of possibilities exist. If the patient has a cancer likely to be cured by surgery alone (stage 1A) it is

appropriate to preserve the uterus and the opposite tube and ovary, provided this ovary has been found free

of tumor by wedge biopsy and frozen section.

Most authorities agree that women who have had conservative surgery for epithelial ovarian cancer

should undergo removal of their remaining reproductive organs when they have completed childbearing.

Patients with stage I, well differentiated tumors, have a 5 year survival rate of 95%. For patients

with grade 3 tumors, clear cell histologic type, or possibly dense adherence and large volume ascites

postoperative therapy is indicated because of the higher risk of recurrence. The most popular current

adjuvant therapy for stage I high risk disease is platinum based chemotherapy.

Advanced stage disease

Unfortunately, the typical patient with ovarian cancer presents with advanced stage III or IV

disease, with large pelvic masses, ascites and upper abdominal masses.

Agressive cytoreductive surgery remains standard surgical management for patients with metastatic

ovarian cancer. Its goal is to reduce the amount of tumor as much as possible (the concept of the "maximum

surgical effort").

The standard cytoreductive procedure for patients with disseminated ovarian cancer consists of

abdominal hysterectomy, bilateral adnexectomy and omentectomy. In the course of attempting to resect as

much tumor as possible, other procedures may be necessary, such as resection of the colon, small intestine, a

portion of urinary tract, the spleen, diaphragmaytic metastases, retroperitoneal lymph nodes.

Optimal residual disease has come to denote minimal residual disease no greater than 1 to 2cm in

diameter. The removal of large tumor masses may enhance the response to subsequent chemotherapy.

Since the mid-1980s, the most popular chemotherapy regimen for advanced ovarian cancers has

been the combination of CISPLATIN and CYCLOPHOSPHAMIDE, Other combinations include

CARBOPLATIN and DOXORUBICIN.

One of the most promising new drugs has been PACLITAXEL (TAXOL), perhaps the most active

agent since cisplatin for patients with ovarian cancer.

The optimal length of chemotherapy remains to be determined. It appears that there is no

advantage to treatment with more than 6 cycles of an intensive chemotherapy regimen.

Radiation therapy techniques include intraperitoneal radioactive gold or chromium phosphate and

external beam therapy to the abdomen and pelvis. Several institutions abandoned the use of irradiation as

postoperative therapy in patients with bulky residual epithelial cancers of the ovary.

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These same institutions continued to test the applicability of irradiation in patients with minimal

residual disease after surgery.

Surgical re-exploration after completion of a planned program of chemotherapy to attempt to

detect residual disease, referred to as second look laparotomy has been a part of many treatment programs

for ovarian cancer.

The findings at SLL clearly correlate with survival and this has served as an important end point in

the evaluation of both surgical and chemotherapeutic interventions.

In practice, a SLL includes multiple washings for cytology, a thorough exploration of the

abdominal cavity, removal of any remaining internal reproductive organs, biopsy of any suspicious areas

and biopsy of retroperitoneal lymph nodes.

Other innovative approaches to the first-line postoperative treatment of advanced ovarian cancer

have included such treatments as concomitant chemotherapy and radiotherapy in patients with minimal

residual disease.

Intraperitoneal chemotherapy in patients with minimal residual disease consists in introduction of

dose-intensity strategies using either autologous bone marrow rescue or peripheral stem cell support.

Utilization of hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor or

granulocyte colony-stimulating factor) into clinical trials has enabled clinicians to ameliorate some of the

myelosuppressive effects of chemotherapy.

Other agents and modalities that are receiving considerable attention include biologic therapy

using:

—» autologous tumor-infiltrating lymphocytes;

—> monoclonal antibodies;

—> hormonal agents (GnRH analogues).

Innovative therapies using information from molecular biologic and genetic studies are also

rapidly emerging.

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