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Ovarian Cancer

Ovarian cancer is the second most common gynecologic malignancy, but the most common cause of death among women who develop gynecologic cancer, and it is the fifth most common cancer in females.

The majority (90 percent) of primary ovarian tumors derive from epithelial cells, although they can also arise from germ cell tumors, sex cord-stromal tumors, and mixed cell type tumors.

Clinical manifestations

Most ovarian cancers are diagnosed between the ages of 40 and 65. Symptoms of early stage disease are often vague. Acute symptoms due to ovarian rupture or torsion are unusual. As a result, 75 to 85 percent of cases of ovarian cancer are advanced at the time of diagnosis. More advanced disease is typically associated with abdominal distention, nausea, anorexia, or early satiety due to the presence of ascites and omental or bowel metastases.

Most women have nonspecific symptoms, such as lower abdominal discomfort or pressure, gas, bloating, constipation, irregular menstrual cycles/ abnormal vaginal bleeding, low-back pain, fatigue, nausea, indigestion, urinary frequency, or dyspareunia.

Physical examination

Palpation of an asymptomatic adnexal mass during a routine pelvic examination is the usual presentation for ovarian cancer. The presence of a solid, irregular, fixed pelvic mass on pelvic examination is highly suggestive of an ovarian malignancy. However, endometriomas and tubo-ovarian abscesses are benign tumors that may be fixed, while cystadenofibromas and tubo-ovarian abscesses are benign masses that feel irregular. The diagnosis of malignancy is almost certain if a fixed, irregular pelvic mass is associated with an upper abdominal mass or ascites.

Differential Diagnosis of Adnexal Masses in Women

Extraovarian mass
Ectopic pregnancy
Hydosalpinx or tuboovarian abscess
Paraovarian cyst
Peritoneal inclusion cyst
Pedunculated fibroid
Diverticular abscess
Appendiceal abscess
Ovarian mass
Simple or hemorrhagic physiologic cysts (eg, follicular, corpus luteum)
Endometrioma
Theca lutein cysts
Benign or malignant neoplasms (eg, epithelial, germ cell, sex-cord)
Metastatic carcinoma (eg, breast, colon, endometrium)

Diagnostic evaluation

The finding of a pelvic mass usually requires surgery for definitive histologic diagnosis. Tumor markers (eg, serum CA 125) and ultrasound examination can help distinguish between malignant and benign pelvic masses.

A complete pelvic examination and assessment of cervical cytology should be performed preoperatively. Routine hematologic and biochemical assessments should be obtained prior to surgery. Ultrasonography for diagnosis of ovarian malignancy has a sensitivity of 62 to 100 percent and a specificity of 77 to 95 percent.

It is reasonable to pursue a period of observation in a premenopausal woman with an adnexal mass if the mass is not clinically suspicious on ultrasonography. Adnexal masses that are mobile, purely cystic, unilateral, less than 8 to 10 cm in diameter, and have smooth internal and external contours by ultrasound are highly unlikely to be malignant and can be followed for two months; the majority of physiologic cysts will regress during this time.

Exploration is indicated if there is no resolution within two months. However, women who have solid, fixed, irregularly shaped, or large masses should undergo surgery. A mass that increases in size or does not regress must be presumed to be neoplastic and should be removed surgically.

The threshold for surgical intervention is lower in postmenopausal women; those with cysts greater than 3 cm should undergo exploratory surgery, laparotomy, or laparoscopy.

Tumor markers. CA 125: The preoperative evaluation of a woman with suspected ovarian cancer should include measurement of the CA 125 concentration. The serum CA 125 (normal <35 U/mL) is elevated (>65 U/mL) in 80 percent of women with epithelial ovarian cancer. It is also increased in patients with other malignancies, including endometrial cancer and certain pancreatic cancers; in endometriosis, uterine leiomyoma, and pelvic inflammatory disease; and in approximately 1 percent of healthy women.

Staging

Surgery is necessary for diagnosis, accurate staging and optimal cytoreduction, and is crucial for the successful treatment of EOC. Ovarian malignancies are surgically staged according to the 2002 revised American Joint Committee on Cancer (AJCC) and International Federation of Gynecologic Oncologists (FIGO) joint staging system, as long as the patient is an appropriate surgical candidate.

Definitions of the Stages in Primary Carcinoma of the Ovary

Growth is limited to the ovaries

Growth is limited to one ovary; no ascites present containing malignant cells; no tumor on the external surface; capsule is intact

Growth is limited to both ovaries; no ascites present containing malignant cells; no tumor on the external surfaces; capsules are Intact.

Tumor is classified as either stage IA or IB but with tumor on the surface of one or both ovaries; or with ruptured capsule; or with ascites containing malignant cells present or with positive peritoneal washings.

Growth involves one or both ovaries with pelvic extension

Extension and/or metastases to the uterus and/or tubes

Extension to other pelvic tissues

Tumor is either stage IIA or lIB but with tumor on the surface of one or both ovaries; or with capsule ruptured; or with ascites containing malignant cells present or with positive peritoneal washings.

Tumor involves one or both ovaries with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis equals stage III; tumor is limited to the true pelvis but with histologically proven malignant extension to small bowel or omentum.

Tumor is grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces.

Tumor involves one or both ovaries with histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2cm in diameter; nodes are negative.

Abdominal implants greater than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes.

Growth involves one or both ovaries with distant metastases; if pleural effusion is present, there must be positive cytology findings to assign a case to stage IV; parenchymal liver metastasis equals stage IV.

Procedure

The staging procedure is usually approached through a laparotomy incision. Any free fluid in the cul-de-sac is submitted for cytologic evaluation. Washings of the peritoneal cavity are obtained by instilling and removing 50 to 100 mL of saline. The affected adnexa should be removed intact and a frozen section obtained to determine or confirm the diagnosis. Thorough surgical staging should be carried out in the absence of obvious stage IV disease. Preservation of the uterus and a normal appearing contralateral adnexa is an option in women desirous of maintaining future fertility.

All intraperitoneal surfaces should be carefully inspected and suspicious areas or adhesions should be biopsied. If there is no evidence of disease, multiple intraperitoneal biopsies should be performed, including from the cul-de-sac, both gutters, bladder peritoneum, and bowel mesentery.

The diaphragm is evaluated by either biopsy or cytologic smear. A complete omentectomy should be performed.

The retroperitoneal spaces are explored to dissect the pelvic and paraaortic lymph nodes. Any enlarged lymph nodes should be resected and submitted separately for histopathologic evaluation.

For patients with advanced disease, optimal cytoreduction (debulking) should be attempted at the time of initial surgery. The majority of women with EOC (except for those with stage I disease) will require surgery and chemotherapy.

Treatment of ovarian cancer

Cytoreductive surgery improves response to chemotherapy and survival of women with advanced ovarian cancer. Operative management is designed to remove as much tumor as possible. When a malignant tumor is present, a thorough abdominal exploration, total abdominal hysterectomy, bilateral salpingo-oophorectomy, lymphadenectomy, omentectomy, and removal of all gross cancer are standard therapy.

Adjuvant therapy

Patients with stage IA or IB disease (who have been completely surgically staged) and who have borderline, well- or moderately differentiated tumors do not benefit from additional chemotherapy because their prognosis is excellent with surgery alone.

Chemotherapy improves survival and is an effective means of palliation of ovarian cancer. In patients who are at increased risk of recurrence (stage I G3 and all IC-IV), chemotherapy is recommended. Sequential clinical trials of chemotherapy agents demonstrate that cisplatin (or carboplatin) given in combination with paclitaxel is the most active combination identified.

2011-08-25