Strategies to reduce incidence of ovarian cancer

Updates on surgery to reduce incidence of ovarian cancer, along with the role of screening and oral contraceptives, were the key points of a presentation at the 2018 Annual ACOG Meeting in Austin.

In January 2015, ACOG issued a Committee Opinion indicating that prophylactic salpingectomy may offer clinicians an opportunity to prevent ovarian cancer in their patients. Since then, in the United States, there has been a major push to perform salpingectomy at the time of hysterectomy for benign indications or tubal ligation as a way to significantly decrease risk of ovarian cancer.

“For years, we have thought that ovary cancer is undetectable as it advances,” said John Schorge, MD, associate editor of Obstetrics & Gynecology. “Yet, over the past decade or so, in prophylactically removing the tubes and ovaries in high-risk women, we have found a number of microscopic fallopian tube cancers. Hence, the thinking has changed to the fallopian tube being the site for the majority of what is generally referred to as ovarian cancer.”

A Finnish population-based study (Falconer, et al) of roughly 250,000 women in the Journal of the National Cancer Institute (JNCI) in 2015 found a 50% decrease in risk of ovarian cancer among many women who had undergone bilateral salpingectomy.

Dr. Schorge is encouraged by such studies because traditionally, removing the ovaries as a risk-reducing procedure had significant health risks related to inducing early menopause. “The current thinking is that the ovaries function with hormone production to some degree and provide health benefits up until about age 65,” Dr. Schorge told Contemporary OB/GYN.

Screening for ovarian cancer, however, has been historically challenging. “In fact, for a while, we did not believe there was any precursor on the ovarian surface, so it was difficult to intervene before it had turned into advanced ovarian cancer,” he said.

Many screening studies involving thousands of patients have evaluated ultrasound and various blood tests, “none of which showed a dramatic benefit or reduced mortality,” said Dr. Schorge. “It may be that we were looking in the wrong place all of these years-that most of the ovarian cancers arise from the fallopian tube instead of the ovarian surface. This represents a different paradigm.”

In any event, screening has been “generally disappointing,” according to the presenter. “I am also skeptical about any new screening technique, despite the lay press touting on a routine basis a new promising blood test or a new innovation. They never seem to pan out.”

It is not surprising, therefore, that the U.S. Preventive Services Task Force, the National Comprehensive Cancer Network and the FDA “have all recommended against routine screening in the general population,” said Dr. Schorge, a gynecologic oncologist at Tufts University School of Medicine in Boston.

Oral contraceptives are one of the proven fertility-preserving methods for preventing ovarian cancer. “We used to think that every month when a woman ovulated, an egg would rupture through the ovarian surface and then the body would need to repair that surface,” said Dr. Schorge. “Those ruptures and repairs were believed to lead to some errors over the course of time and a predisposition to ovarian cancer. But when a woman goes on a birth control pill, there is no ovulation or repair. This is the mechanism of action which we previously thought prevented ovarian cancer.”

However, due to the current understanding that most ovarian cancers originate from the fallopian tubes, “this thinking has to be reset,” said Dr. Schorge. “It is not clear why the birth control pill prevents ovarian cancer, but it does.”

Women at high risk for ovarian cancer are generally BRCA1 or BRCA2 mutation carriers. “There are clinical trials ongoing to simply remove the fallopian tubes and leave the ovaries in these women,” said Dr. Schorge. “We do not know if that strategy is as effective as removing both the tube and the ovary but we should know more when these studies are completed.”

In recent years, researchers have found strong p53-positive sites at the fimbriated ends of the fallopian tubes of both BRCA-positive and BRCA-negative women. Dr. Schorge said that cells from these sites can float off the fallopian tube and are potentially detectable via Pap smear, making them a possible target for screening. 

Meanwhile, both mortality and incidence of ovarian cancer have been slightly decreasing over the past few years, whereas endometrial cancer has been increasing substantially. “However, it is not known for sure why we are seeing a decrease in ovarian cancer,” said Dr. Schorge.  “But it is thought and hoped that opportunistic salpingectomy is a big contributor to decreasing the risk.”

Disclosures:

Dr. Schorge reports no relevant financial disclosures.

References:

Falconer H, Yin L, Grönberg H, et al. Ovarian cancer risk after salpingectomy: a nationwide population-based study. J Natl Cancer Inst. 2015 Jan 27;107(2). pii: dju410.