Ovarian cancer often arises from precursor endometriosis




LAS VEGAS – Gynecologists, general surgeons, and primary care physicians now share an unprecedented opportunity to put a major dent in the incidence of ovarian cancer, according to Dr. Farr R. Nezhat.

Mounting evidence suggests that identification and complete surgical removal of endometriosis reduce the risk of several histologic types of ovarian cancer. So when a woman visits her primary care physician for pelvic pain or vaginal bleeding that might be due to endometrial pathology, or a general surgeon finds asymptomatic endometriosis during pelvic surgery, these encounters provide an opportunity for preventive intervention, explained Dr. Nezhat, professor of ob.gyn. and director of minimally invasive surgery and gynecologic robotics at Mount Sinai Medical Center, New York.

Dr. Farr R. Nezhat

Dr. Farr R. Nezhat

The latest thinking about the pathophysiology of ovarian cancer, he noted, is that there are two different types of the malignancy. One type, which likely arises from endometriosis as the precursor lesion, is characterized by low-grade serous, clear cell, and endometrioid carcinomas, which tend to present at an earlier stage and are more indolent. They are associated with mutations in the PTEN, BCL2, and ARID1A genes.

A pooled analysis of 13 ovarian cancer case-control studies conducted by investigators in the Ovarian Cancer Association Consortium made the point that women with endometriosis are at increased risk of specific subtypes of the malignancy. The analysis, which included 7,911 women with invasive ovarian cancer, 1,907 others with borderline ovarian cancer, and more than 13,000 controls, concluded that women with a self-reported history of endometriosis had a 3.05-fold increased risk of clear cell invasive ovarian cancer, compared with controls, a 2.04-fold increased risk of endometrioid ovarian cancer, and a 2.11-fold greater likelihood of low-grade serous ovarian cancer.

In contrast, no association was apparent between endometriosis and the risk of high-grade serous or mucinous invasive ovarian cancer or borderline tumors. Thus, the pathogenesis of low- and high-grade serous ovarian cancers may differ (Lancet Oncol. 2012;13:385-94).

Dr. Nezhat cited as another influential study a Swedish national registry case-control study involving all Swedes with a first-time hospital discharge diagnosis of endometriosis during 1969-2007. The cases in this study were all 220 Swedish women diagnosed with epithelial ovarian cancer at least 1 year after their endometriosis was diagnosed. Each was matched with two controls with no ovarian cancer diagnosis before the date of the case’s cancer diagnosis.

This was the first published study to demonstrate that treatment of endometriosis has a salutary impact on subsequent risk of ovarian cancer. Complete surgical removal of all visible endometriotic tissue was associated with a 63% reduction in the risk of ovarian cancer in a univariate analysis and a 70% relative risk reduction in a multivariate analysis. One-sided oophorectomy involving the endometriosis-involved ovary was similarly associated with a 58% risk reduction for ovarian cancer in a univariate analysis and an 81% reduction in risk in a multivariate analysis (Acta Obstet. Gynecol. Scand. 2013:92:546-54).

An earlier study in which Dr. Nezhat was senior author highlighted that different histologic types of early-stage ovarian carcinoma feature distinctive patterns of clinical symptoms. The study included 76 consecutive patients with FIGO stage I ovarian carcinoma, of which 54 – that is, more than two-thirds – were nonserous, which is a much higher proportion than is seen in women diagnosed with stage III and IV disease.

Most patients with serous papillary carcinoma in this series presented with an asymptomatic pelvic mass. In contrast, most of those with endometrioid or clear cell carcinoma presented with pelvic pain or abnormal vaginal bleeding with or without a pelvic mass (Fertil. Steril. 2007;88:906-10).

Endometrioisis is a pervasive condition. Dr. Nezhat said the endometriosis patients he considers to be at possible increased risk for ovarian cancer include those with longstanding endometriosis, a history of infertility, endometriosis diagnosed at an early age, as well as those with ovarian endometriomas. Eventually it will be possible to pin down more precisely the ovarian cancer risk of an individual with endometriosis through screening for genetic mutations, but the evidence base isn’t yet sufficient to introduce this into everyday practice, he said.

One audience member said it’s her practice and that of many of her gynecologic colleagues that when they incidentally find a patient has asymptomatic endometriosis, for example, during surgery for ectopic pregnancy, they will often leave it in place, even if it is quite severe. Is it time to rethink that practice and instead remove all visible endometriosis, even if the patient is asymptomatic? she asked.

“The short answer is, Yes,” Dr. Nezhat replied. “The most important thing is that when you do surgery, remove it all or else do biopsies to make sure you’re not leaving early ovarian cancer behind. Draining endometriomas is not adequate.”


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