William G. Nelson, MD, PhD Photo by Joe Rubino

OVARIAN CANCER IS THE 11th most common cancer among women in the U.S. and one of the most dangerous, with about half of women with the disease surviving five years. With no established screening tests, more than half of women with ovarian cancer are diagnosed when the disease has spread far from the ovaries and is difficult to control, even with combinations of surgery and drug treatments. This may be about to change. 

Over the past few decades, evidence has accumulated that shows epithelial ovarian cancer, the most common type, and particularly high-grade serous ovarian cancer, which is fast-growing and life-threatening, may not originate in the ovaries at all. Rather, the earliest cancer precursors and nascent tumors appear to start in the fallopian tubes, hollow organs connected to the uterus that deliver eggs from the ovaries, allowing them to be fertilized, and then transport the fertilized embryos to the uterus.  

The fallopian tubes are about 4 to 5 inches long and approximately half an inch in diameter. One end is anchored in the uterus, while the other end, located near the ovary, contains finger-like structures called fimbriae that aid in capturing egg cells.  

For many years, surgical removal of both fallopian tubes (bilateral salpingectomy) and both ovaries (bilateral oophorectomy) has frequently accompanied removal of the uterus (hysterectomy), a procedure typically undertaken for benign conditions such as uterine fibroids, endometriosis and problematic bleeding.  

Surgery to remove the ovaries results in immediate menopause if the woman is premenopausal, with side effects of hot flashes, sweats and vaginal dryness, and longer-term worries about osteoporosis and cardiovascular complications. Removal of the ovaries, the fallopian tubes or the uterus also results in infertility. For these reasons, pursuing any such surgery requires collaborative decision-making between the care provider (usually a gynecologist) and the patient that factors in risks, benefits, alternatives to surgery and possible fertility preservation options.  

Women with a strong genetic risk for ovarian cancer often elect to pursue risk-reducing surgery to remove their fallopian tubes and ovaries (bilateral salpingo-oophorectomy) after completion of their childbearing years. For women carrying mutant BRCA genes, who are at increased risk for ovarian and breast cancer, this procedure reduces the chance for developing ovarian cancer by about 96%. 

Pathologists—physicians who examine tissues removed during surgery under a microscope—have long recognized that high-grade serous ovarian cancer closely resembles cancers known to arise in the fallopian tubes. As pathologists looked at specimens recovered from risk-reducing bilateral salpingo-oophorectomies performed on BRCA mutation carriers, they noticed what appeared to be cancer precursor lesions called serous tubal intraepithelial carcinomas (STIC) in as many as 0.6% to 7% of cases. The STIC lesions were typically found in the fimbriae near the ovarian surface. Molecular analyses of the STIC lesions and some earlier precursors revealed shared gene defects with high-grade serous ovarian cancers when both were present in the same patient, directly implicating the fallopian tubes as the site of origin of ovarian cancer. 

Researchers are now asking whether women could reduce their risk of high-grade serous ovarian cancer by just having their fallopian tubes removed. Two ongoing clinical trials, called TUBA-WISP II and SOROCk, are attempting to answer this question. The trials are subtly different, but each targets women at high genetic risk for ovarian cancer, and each examines removal of the fallopian tubes with a delay in removing the ovaries. In the meantime, the Society of Gynecologic Oncology and other groups have recommended that women finished with childbearing who undergo hysterectomy, tubal ligation or other pelvic surgery also pursue a salpingectomy, removal of the fallopian tubes, to reduce the risk of high-grade serous ovarian cancer, while leaving the ovaries in place. 

William G. Nelson, MD, PhD, is the director of the Johns Hopkins Kimmel Cancer Center in Baltimore.