With regard to prophylactic oophorectomy; there have been publications in the literature, most notably from Buffalo, suggesting that prophylactic oophorectomy in women with positive family histories was indicated. But if you look at their own data published in 1993 in Cancer, what you find is that after prophylactic oophorectomy – and they had a total of 324 women who underwent prophylactic oophorectomy because of positive family histories – their incidence of primary peritoneal neoplasia at a median follow-up of six years was already 1.8% which exceeds the risk in the general population for ovarian carcinoma, and begins to approach the risk in patients with positive family histories. So it would appear that what we are doing here is removing only a small portion of the tissue at risk. Most of the tissue at risk, that is the coelomic epithelium that lines the peritoneal cavity is left in place. The risk of other problems after oophorectomy will increase. So as of right now the only group for which prophylactic oophorectomy is recommended for serious consideration is in those who have hereditary syndromes. And the recommendation was to consider that beginning at age 35 and later. And that came from the Ovarian Cancer Consensus Conference held in August 1994 at the National Cancer Institute. But that was based, as the conference report said, on no data, merely speculation that this would work. So as of right now there is really no truly scientifically defined role for prophylactic oophorectomy. There is a consensus role for those with hereditary syndromes.

Screening for ovarian carcinoma; if you read luminary medical journals like Cosmopolitan and Redbook you will find that screening is something you really ought to be doing for your ovarian cancer patient. What those journals recommend is a combination of pelvic examination by the physician once a year, serial CA125’s annually, and annual transvaginal sonography. But the actual figures on the use of these show that, first of all, pelvic examination has no impact. We know that from numerous studies. When you combine transvaginal sonography and CA125 done in a serial fashion, the positive predictive value for finding ovarian carcinoma is 26.8%, which is really quite good. But, most of those cases are going to be stage III at diagnosis. The positive predictive value for stage I and stage II disease is 9.8% and by most standards a value of greater than 10% is required before you can label an approach as a valid screening test. Not only that, but the studies that have been done to date show that for every one laparotomy that you do for ovarian carcinoma, you are going to do somewhere between 14 and 39 for benign causes that did not require exploration. So there really is a downside for screening for ovarian carcinoma. So at least for right now screening is not recommended, there is no scientific basis for using the combination of transvaginal sonography and CA125 to screen for ovarian carcinoma. There is an ongoing randomized trial that we hope will at least in part answer this question.

Pathologically, coelomic epithelial carcinomas of the ovary fit into four broad categories; serous, endometrioid, mucinous and clear cell. You will note that the two most common types are serous and endometrioid and that’s fortunate, because the two poor-risk types are mucinous and clear cell carcinomas. These two tumors have a much poorer prognosis than the serous and the endometrial types. If you look just at patients with stage III and stage IV disease what you find is less than 10% of the patients have either mucinous or clear cell carcinomas. Almost 90% will have either serous or endometrioid tumors. We don’t know what to do differently for the mucinous and clear cell tumors, currently, to hopefully impact greater on their outcome. So right now that histology has very little impact on how you are going to manage the patient clinically, except to know that the patient is at much greater risk for death due to disease if they have a mucinous or clear cell carcinoma. The only part of histology that really makes a difference in our approach to the tumors is if the pathologist identifies a particular ovarian cancer as being a borderline ovarian carcinoma. That is, it appears to be a well-differentiated tumor with no underlying stromal invasion. These tumors have an excellent prognosis, even if you simply observe them, do nothing to treat them other than an attempt at surgical resection. And even those with intraabdominal spread, that is stage III disease, have an 80% survival at five years. In a large study done by the GOG, no stage I ovarian borderline tumor has occurred as yet at ten years of follow-up. So the treatment for borderline tumors is resection if possible, and then no further treatment until the tumor declares itself as a more aggressive tumor. At that point you would introduce systemic therapy.