After the patient has been evaluated preoperatively, exploratory laparotomy is essential for definitive diagnosis and staging. The patient should be advised of the potential for malignancy based on the physical as well as imaging studies, and an explanation given with respect to the possible necessity for carrying out the additional surgical procedures involved in surgical staging. The patient should be prepared optimally with bowel preparation, prophylactic antibiotics, and prophylactic measures against venous thrombosis and embolism.
A key surgical principle is to remove as much tumor as is safely possible. After removal of the ovarian mass or masses and the frozen section reveals a malignant tumor, removal of the uterus and both tubes and ovaries is carried out unless mitigated by the patients reproductive status and extensive preoperative discussions. It is vital that any masses adherent to the pelvic peritoneum be approached by defining the retroperitoneal spaces, identifying the ureters, and removing the peritoneum along with the pelvic masses. This will reduce blood loss, permit more effective removal of the tumor, and reduce the risk of ureteral or blood vessel injury. In addition, omentectomy and removal of all gross cancer is carried out. The omental removal should be at least infracolic, depending on the extent of visible metastases to this structure.
Adherent areas of the primary tumor should be identified for adhesions and external excrescences. Any adhesions to the peritoneum should be biopsied specifically. There is currently an increasing trend to carry out more complete dissections of the pelvic and para-aortic nodes (ie, lymph node dissection rather than sampling), particularly in patients with either early disease or optimal cytoreduction. The presence of extensive residual disease obviates the need for nodal dissection. Following completion of the procedure, an inventory of residual disease, including both the location and size, should be carried out in a systematic fashion and recorded in the operative notes.
Bowel resection during the primary debulking procedure is occasionally indicated if obstructive symptoms are present or complete cytoreduction is enabled. It is uncommon to see a primary ovarian cancer present initially with bowel obstruction, and the presence of ascites may increase the infectious risks of colonic resections.
In patients who have low malignant potential or borderline epithelial tumors, more conservative surgery may be used, especially in patients still desiring reproductive potential. Staging procedures (as described above) may be carried out with preservation of the uterus and the ovary/ovaries after the ovarian masses have been completely removed and the remaining tissue is grossly free of tumor.
Fertility preservation may also be achieved in women with germ cell tumors of the ovary or sex cord-stromal tumors, which are usually unilateral. Unilateral salpingo-oophorectomy is performed with preservation of the uterus and close inspection of the contralateral adnexa. With the effectiveness of multiagent chemotherapy, most of the germ cell tumors, including dysgerminoma, can be managed in a conservative fashion. Retrospective studies have shown no long-term impairment in fertility after conservative surgery followed by adjuvant chemotherapy, and the reliability of tumor markers in many germ cell tumors obviates the need for reassessment laparotomy.
Most epithelial tumors and all germ cell tumors (except grade 1, stage IA immature teratomas) require postoperative adjuvant chemotherapy. Other exceptions might be made in patients with selected grade 1, stage IA epithelial tumors. Clear cell tumors of all grades appear to be more likely to recur or metastasize than other epithelial tumors and may need to be dealt with more aggressively.
The evolving standard for adjuvant treatment of primary epithelial ovarian cancer in this country is paclitaxel (Taxol) combined with cisplatin (Platinol) or carboplatin (Paraplatin). The dose and scheduling options for paclitaxel are still under investigation. Selected early-stage/low-grade epithelial cancers may be treated with three or six courses of chemotherapy, and randomized clinical trials are in progress to define the duration of chemotherapy needed in these patients.
Alkylating agents, such as cyclophosphamide (Cytoxan, Neosar), ifosfamide (Ifex), melphalan (Alkeran), and hexamethylmelamine (altretamine [Hexalen]) can be used for second-line or advanced-disease treatment. In the absence of definitive survival data, individualization in chemotherapy planning may selectively be done based on physician and patient preference.
The role of radiation therapy in the management of ovarian cancer at the present is limited but helpful in a small group of patients. Phosphorus-32 (32P) isotope has been used intraperitoneally in patients with stage I or early stage II disease after total removal of the primary tumor or in study settings after negative second-looks in advanced disease. The use of external-beam therapy as either whole-abdominal or pelvic irradiation has been used with mixed results, and whole-abdominal radiother- apy (WAR) as adjuvant therapy after cytoreductive surgery has not gained wide acceptance in this country. In the rare patient with isolated localized metastases, external therapy to a localized area may be indicated.
An important feature with respect to ovarian carcinoma is the fact that not all patients who present with obvious findings relating to ovarian cancer, as described in the section above on diagnosis, will actually have a primary ovarian cancer. It has been reported that between 15% and 30% of patients presenting with bilateral pelvic masses actually have metastatic ovarian lesions from another organ. The greatest number come from the breast followed by the colon and finally from the endometrium and other organ sites. Breast examination and mammography as indicated, along with selective preoperative use of barium enema, colonoscopy, upper gastrointestinal series, CT scan, or the CEA tumor marker, may detect the presence of nonovarian primaries.
The second feature is that in young women with adnexal lesions and inconclusive pathologic diagnosis on frozen section, conservative surgery with preservation of the uterus and ovary, if uninvolved, should be considered. One may always return at a later time to carry out additional staging or surgical resection if the diagnosis is definitely cancer.
In pregnant patients with an adnexal lesion, exploration is carried out after the first trimester unless an obvious malignancy is suspected. Treatment of ovarian cancer in pregnant patients should be the same with respect to surgery and thorough staging as in nonpregnant patients. If the patient does not agree to surgery, definitive treatment may have to be delayed until the pregnancy is completed. Platinum-based and multiagent chemotherapy have been used beginning in the second trimester without major reported complications.
Familial Ovarian Cancer
Another area that needs to be considered is the familial ovarian cancer syndromes. Patients with ovarian cancer in their family need a pedigree determination and can then be given a risk profile. With no history of ovarian cancer, the lifetime risk of ovarian cancer is 1 in 70. With one first-degree relative, the risk increases to 1 in 25 to 30. In pedigrees that demonstrate autosomal dominant inheritance for site-specific ovarian cancer, the risk is as high as 40% (50% transmission with 80% penetrance).
During the past few years, efforts have been made to isolate specific genes responsible for various familial ovarian cancer syndromes. Recently, mutations of the BRCA1 gene have been linked to 40% to 50% of early-onset hereditary breast cancers families and 80% to 90% of breast-ovarian cancer families. Somatic BRCA1 mutations have also been found in 10% of sporadic ovarian cancers. The lifetime risks for developing cancer based on BRCA1 mutation are 80% to 90% (breast) and 60% (ovary), as well as a three- to fourfold increased risk of colon and prostate cancer. The strong predictive value of BRCA1 mutation makes BRCA1 testing a potentially useful adjunct in the evaluation of women at risk for ovarian cancer.
Further developments in the molecular analysis of BRCA1 mutations may offer even more precise information for the counseling and management of affected women. Mutations in BRCA1 upstream of exon 13 are associated with a 1:2 breast-ovarian cancer distribution, while mutations downstream from exon 13 are associated with a 5:1 breast-ovarian ratio. A specific BRCA1 mutation, 185delAG, has been identified in 1% of Ashkenazi Jews, and 45% of the cancers that develop in affected women are ovarian, making this ethnic group a particularly important target group for BRCA1 screening and consideration for prophylactic oophorectomy.
In the absence of genetic testing information, prophylactic (bilateral) oophorectomy must be recommended as an indicated procedure to all women from high-risk families after childbearing or the age of 35 to 40 at the latest. In addition to ovarian cancer prevention, prophylactic oophorectomy also offers breast cancer protection in women with breast-ovary and Lynch II family cancer syndromes.
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