Risk reducing oophorectomy for the patient with an elevated risk of ovarian carcinoma may take two forms: the prevention of disease with incidental bilateral oophorectomy at the time of other elective pelvic or abdominal surgery or elective laparoscopic bilateral oophorectomy. In evaluation of the patient with a positive family history of breast and ovarian carcinoma (hereditary breast and ovarian cancer [HBOC] syndrome), one takes into account the age at which the disease develops in the index case(s) as well as the closeness of that relationship to the patient at risk. In the general population, the cumulative risk of developing ovarian cancer is 1.5% (1:70) with a 1% lifetime risk of death from the disease. Relatives with premenopausal HBOC are more likely than those with postmenopausal recurrence of disease to bear a predisposing deleterious mutation. A single first-degree relative confers as much as a fivefold greater risk, while two first-degree relatives with premenopausal disease may increase it to 50%. The association of premenopausal breast and ovarian carcinoma recognized in association with a deleterious BRCA1 or BRCA2 mutation may present as much as a 50% risk of subsequent ovarian carcinoma. Recent analysis of HBOC patients without BRCA1 and BRCA2 mutations has demonstrated that 61% of these patients had a variant allele of KRAS. This KRAS-variant represents a new marker for inherited cancer risk in HBOC families.

Laparoscopic oophorectomy can be easily performed as an outpatient procedure and will reduce, but not eliminate the risk of subsequent “ovarian” carcinoma, as it does not diminish the incidence of primary peritoneal carcinoma. Prior to the time at which prophylactic oophorectomy may be appropriate, the young woman at risk will benefit from the use of ovulation suppression with oral contraceptive therapy. It is in these patients where the prevalence of subclinical ovarian carcinoma is greater, that routine screening with pelvic ultrasound and CA-125 may be appropriate.

Incidental oophorectomy should be performed at the time of other pelvic surgery in the postmenopausal woman. The striking increase in incidence of ovarian carcinoma after menopause, coupled simultaneously
with the decreasing endocrine function of the ovary, makes risk–benefit profile of incidental oophorectomy increasingly favorable with advancing age. As women become cognizant of the difficulty in screening for ovarian malignancy, the surgeon should discuss this option in women undergoing elective pelvic or lower abdominal procedures. Following oophorectomy, patients who have no contraindications to estrogen therapy and have an intact uterus will generally receive short-term course of daily estrogen and progesterone. The progesterone is added to minimize the risk of subsequent endometrial neoplasia and is not needed in the absence of the uterus or active endometriosis.

The evaluation of the pelvic mass in a young premenopausal woman should address both the differential diagnosis that includes assessment risk of malignancy and the possibility of its resection by laparoscopy. Indeed, there are few limitations to laparoscopic surgery: those would include masses that are fixed in the pelvis, typically associated with endometriosis and masses that are so large as to preclude laparoscopic removal without drainage or rupture. Even these limitations are relative, in the sense that fixed masses can often be dissected from the pelvic sidewall with the attached pelvic peritoneum and large cystic masses that have a simple internal architecture may be carefully drained in some limited circumstances where the risk of malignancy is very small.

Preoperative assessment of the patient with a presumed ovarian mass who is considered a candidate for laparoscopic oophorectomy or cystectomy should include the following:

The mobility of the mass at the time of examination under anesthesia may be the strongest predictor of operability. Otherwise, in a premenopausal woman, the obvious laparoscopic appearance of endometriosis may be the most useful intraoperative finding that would suggest that one should proceed with surgical resection in the absence of a freely mobile mass. Biopsy of individual serosal implants for frozen section examination will be reassuring in that regard.

In a young woman with apparent benign disease, a laparoscopic ovarian cystectomy with preservation of the integrity of the majority of ovarian tissue would be the appropriate conservative course of action. Ideally, the cyst should be removed and placed intact into a laparoscopic bag for removal. Typically, one will find residual ovarian tissue to be preserved along the ovarian vessels, though occasionally tumors of very large size do not demonstrate any recognizable residual normal ovarian cortex.

In postmenopausal women where the risk of occult malignancy is greater and the value of preservation of one ovary is lesser, the appropriate course of action is to perform an oophorectomy rather than an ovarian cystectomy, particularly if there is any suspicious appearance to the ovarian mass. Generally speaking, any major degree of fixation of the ovarian neoplasm in the absence of obvious endometriosis should both raise the suspicion of malignancy and increase the likelihood of cyst rupture at the time of laparoscopic intervention.

One of our previous publications has addressed the clinical significance of cyst rupture on prognosis and supports the concept that the measurable adverse effect of cyst rupture may well be related to a delay in intervention after the event occurs. Alternatively, the presence of occult invasion of adjacent soft tissues may account for adhesion and rupture. Hence, more advanced disease may have been present than clinically recognized; cyst rupture then representing a manifestation of extra-ovarian spread and potential residual locally metastatic disease at the site of rupture. Immediate intervention and wide excision of surrounding soft tissue in the presence of rupture of a potentially malignant cyst, proven by frozen section, might be considered reasonable on that basis. However, as most of these patients now would be treated with chemotherapy in that event, the need for immediate surgical intervention is limited to being certain that all potential local sites of extension are excised. Assessment of occult distant spread is better handled with complete surgical staging in the hands of someone skilled in that procedure.

Patients with early invasive cancer diagnosed at the time of laparoscopy or laparotomy
require the same intensive staging procedure (Table 1) irrespective of the route of access. In the absence of overt metastatic disease, a minimally invasive approach to surgical staging can be considered, either laparoscopically or with a robotic-assisted approach. The patient should undergo a preoperative mechanical bowel prep, if only to facilitate visualization of the pelvic and abdominal viscera. The surgeon should be prepared to carry out a definitive staging and carefully examine (but not necessarily biopsy) the contralateral ovary as well, particularly if conservative management is warranted. The consistent difficulty for laparoscopic or robotic-assisted staging is gaining access to para-aortic nodes at the level of the renal vein and particularly those nodes that lie posterior to the left renal vein.

Some gynecologic oncologists still prefer an open approach to these nodes for the patient with a poorly differentiated ovarian lesion; others feel that if one is truly going to treat with chemotherapy on the basis of a high-grade primary lesion alone, that resection of nodes appearing normal on computed tomography (CT) scan or at surgical exploration be unnecessary. This latter view remains controversial for patients advanced disease, though not so for patients with limited ovarian disease. Analysis from the SEER database in the United States indicates inferior survival among those patients who do not undergo systematic lymphadenectomy. A multicenter review of patients with extensively staged localized disease further supports this approach with an excellent outcome among patients undergoing comprehensive surgical staging. In a prospective European trial for advanced ovarian cancer, there was no difference in long-term outcome between patients having selective removal of enlarged pelvic and abdominal lymph nodes and those having complete pelvic and para-aortic lymphadenectomy. Clearly, however, it was important to remove any macroscopically enlarged lymph node, if that represented the largest site of residual disease.

Conventional wisdom dictates that, even in young women, the use of a vertical midline or paramedian incision should be a prerequisite for the adequate staging of a patient with possible ovarian carcinoma, to explore diaphragmatic surfaces, biopsy suspicious upper abdominal lesions, and carry out para-aortic node dissection. However, with healthy, slender young women, consideration of a more cosmetically favorable transverse incision frequently arises in patients at relatively low risk for invasive carcinoma. My personal preference is not to pursue that conventional approach for such patients, but to be conservative in the choice of incision.

Tumor resection and extent of disease evaluation are two components of the surgical procedure that are integral to management of the patient with an apparently localized ovarian lesion. Staging is carried out in accordance with the protocol delineated by the FIGO and requires the following:

This comprehensive staging procedure is necessary for the accurate assessment of risk for recurrence and the need for postoperative chemotherapy. Essentially all patients with disease involving the ovarian surface and beyond are candidates for chemotherapy. Patients with high-grade lesions confined to the ovary or those with less aggressive lesions who are found to have cyst rupture, particularly if associated with dense pelvic adhesions, are also candidates for chemotherapy. Alternatively, some young women of childbearing age may undergo conservative therapy with preservation of reproductive function (Table 2). The primary tumor must be of low histologic grade and rigorously staged. These patients should undergo completion of the definitive surgical procedure following conclusion of childbearing.

At the present time, adjuvant chemotherapy has no role in treatment of well-differentiated early invasive epithelial malignancies confined to the ovary with no surface involvement. The data regarding grade 2 tumors do not clearly indicate a benefit for adjuvant chemotherapy and only with grade 3, stage IA tumors as well as for more advanced lesions, is there a role for adjuvant treatment. As the success with pregnancy following chemotherapy of other malignancies is well supported in the literature, it is reasonable to consider this possibility in carcinoma of the ovary as well. Patients with stage IA, G3 and all with unilateral stage IC disease should receive adjuvant platinum and taxane-based chemotherapy along with preservation of a normal contralateral ovary. Patients with stage IB disease, or more advanced disease with contralateral ovarian involvement may require bilateral oophorectomy. A careful deliberation with the patient and her family and clearly defined informed consent is critical to this course.

At the time of diagnosis, ovarian carcinoma presents with the greatest tumor burden of any solid tumor; a kilogram or more of tumor may be distributed in the pelvis and upper abdomen, along with several liters of ascites. Although the epithelial ovarian tumors are considered quite responsive to primary chemotherapy with response rates in the 80% to 90% range in untreated individuals, the dominant variable predictive of long-term survival is the amount of residual disease present at the conclusion of the initial surgical procedure. The validity of less than total excision in the presence of obvious metastatic disease appears to violate basic tenets of surgical oncology and has often been questioned. Nonetheless, it has been subjected to careful scrutiny over the last three decades and has been consistently documented as the dominant prognostic factor in studies of patient survival, whether treatment involves chemotherapy or radiation therapy. Essentially, every clinical study has documented that the extent of residual disease even outweighs surgical stage in its prognostic importance.

Griffiths, in an NCI monograph, demonstrated that patients with bulky intra-abdominal spread of ovarian cancer who underwent extensive cytoreduction to minimal residual disease had the same median survival time as those patients who had the same amount of minimal residual disease, but did not require extensive surgical cytoreduction. We have similarly examined the outcome of patients requiring multiple resections at the time of primary surgery, and have contrasted that with the outcome of patients requiring much more limited resection (Fig. 4). As long as the amount of residual disease remained the same at the conclusion of surgery, there was no difference in survival, whether the patient had a simple hysterectomy, bilateral salpingo oophorectomy and gastrocolic omentectomy, or, in addition, splenectomy, transverse colon resection, rectosigmoid resection, small bowel resection and resection of enlarged pelvic and para-aortic nodes. The theoretical explanation employed to support this observation is that surgical cytoreduction removes bulky tumor that is either constitutively drug resistant, or one that is resistant because of poor drug penetration into a large tumor mass. In addition to this effect, reduction from a 5-cm tumor mass to a 0.5-mm tumor mass represents a seven log tumor cell reduction, from 10¹¹ cells to 10⁴ cells, decreasing the amount of chemotherapy needed for tumor control based on first-order kinetics of cell kill. This threshold effect may further be explained in theory by the elimination of cells that carry extreme drug resistance (Fig. 5).

There is a threshold, however, above which surgical resection does not incrementally improve survival; that appears to be a largest residual tumor mass of 1.0 to 1.5 cm. Resection of disease to that level, or below does improve survival time and there is a further increment in survival with every additional decrement in residual disease, down to the microscopic level. Traditionally, resection to a largest residual mass of
1.5 cm or less has been termed “optimal” cytoreduction, in the sense that resection to this level or below to improves survival. As the Latin root for “optimal” is “best,” one should reserve that term for complete cytoreduction. The appropriate term for cytoreduction to the threshold level or below is “adequate,” as it is adequate for improvement in survival. In common use, however, the reasonable compromise is to call complete cytoreductive surgery “complete,” anything else is “incomplete,” either optimal, or suboptimal. As noted in Figure 6, patients who underwent complete cytoreduction had a 5-year survival in excess of 75%, while patients who had macroscopic residual disease, but <1 cm in size had about a 30% survival and patients with residual disease >1 cm but <2 cm had only a 15% 5-year survival. This retrospective study from the Mayo Clinic underscores the primacy of complete cytoreductive surgery in the surgical management of this disease.

The success of cytoreductive surgery is dependent upon the metastatic pattern of the tumor spread as well as the experience of the surgeon. Rarely is the pelvis the site of residual disease after incomplete cytoreduction. The challenge to the gynecologic oncologist is the resection of metastases to the upper abdomen. Common sites of surgical failure are the root of the small bowel mesentery, nodal disease above the celiac axis involving the lesser curve of stomach and the left lobe of liver, and perihepatic disease on the right as well as peripancreatic disease involving the C-loop of the duodenum. Although there may be an element of patient selection for surgical exploration, the proportion of patients who undergo “adequate” cytoreductive surgery should be in the 80% to 90% range; approximately half of these patients should have no more than 2 to 3 mm residual disease. Bristow has demonstrated that institutions with a high-frequency of optimal cytoreduction also have improved survival when compared with institutions that do not have such a level of surgical success (Fig. 7).