Fallopian tube excision prevents ovarian cancer

 A recent article in the NY Times strongly suggested that ovarian cancer is very largely a result of a cancer spreading from the fallopian tubes: (see https://www.nytimes.com/2026/07/28/health/ovarian-cancer-fallopian-tubes.html ), and thanks to Steve Leiner for bringing that to my attention. it turns out, unbeknownst to me, that this focus on fallopian tubes has been known and promulgated for more than 20 years. Below is from a brief Viewpoint in JAMA that summarizes this issue, along with a more extensive review of some recent articles: see ovarian ca dec with salpingectomy JAMA2023 in dropbox, or doi:10.1001/jama.2023.6979

Details and Commentary:

-- 20,000 women are diagnosed with ovarian cancer in the US annually. 80% have high-grade serous carcinomas, almost all with no known cancer risk factors, and these patients overwhelmingly present with widely metastatic disease at symptom onset and die within 5 years of diagnosis

    -- ovarian cancer is the fifth-leading cause of cancer mortality among US women

-- screening efforts have been ineffective. For example, the large PLCO study (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) enrolled 78,215 women who had annual CA-125 blood tests and transvaginal ultrasound vs usual care for 3-5 years; 496 women were diagnosed with ovarian cancer over a period of more than 2 decades and the results were that this screening was no better than usual care https://pubmed.ncbi.nlm.nih.gov/29156299/ , https://prevention.cancer.gov/research-areas/networks-consortia-programs/plco_

    -- CA-125 is nonspecific but is increased in 80-90% of serous ovarian tumors, CA19-9 is associated with mucinous tumors in >50%, and with serous tumors in 11-15%

-- the 2018 USPSTF evidence report and symptomatic review found that of 4 trials (including PLCO) with 293,587 women, studies assessing CA-125 levels, transvaginal ultrasound, and both together found that "no trial found a significant difference in ovarian cancer mortality with screening"

    -- two of the largest trials in their evaluation (which included PLCO) found that 1% of the women had surgery for suspected ovarian cancer that was not found on pathological exam (false positive screen) and there were major complications in 3% to 15% of those having surgery, thereby giving ovarian cancer screening a level "D" recommendation (ie, don't do it): https://pubmed.ncbi.nlm.nih.gov/29450530/ and https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/ovarian-cancer-screening

--there has been accumulating evidence noted in this recent JAMA Viewpoint that over that past 20 years "high-grade serous carcinoma primarily originates from microscopic precancers in the fimbriated ends of fallopian tubes, rather than from the ovary itself. Unfortunately, the fallopian tube cannot be visualized using clinical-grade imaging, and there is no blood test to detect the early, yet rapidly spreading, peritoneal metastasis characteristic of high-grade serous carcinoma"

    -- there was a 2022 Canadian study that found that having salpingectomy (either removing the fallopian tubes during hysterectomy, or instead of just having tubal ligation for sterilization) was associated with "no high-grade serous carcinoma in 25,889 women" between 2008-2017 and followed until 2018: see ovarian ca opportunistic salpingectomy JAMA2022 in dropbox or doi:10.1001/jamanetworkopen.2021.47343

        -- these patients were considered to have had "opportunistic salpingectomy" since the full salpingectomy was not for any specific medical reason. unclear though why the surgeons who chose full salpingectomy did so for those patients...(this could present a bias to this retrospective analysis)

        -- the women assessed had mean age of 39, no difference between patients by income, both groups had about 2 live births, there was no difference in oral contraceptive use, or its duration

            -- there was, however, a difference comparing those with hysterectomy/tubal ligation vs opportunistic salpingectomy respectively in: BRCA variants in 0.11% vs 0.10%; endometriosis 7.15% vs 12.8%; uterine leiomyoma 11.7% vs 25.0%; benign uterine or ovarian neoplasm 0.7% vs 1.4%; abnormal bleeding 21.6% vs 36.3%; PID 1.9% vs 2.9%. hydrosalpinx 0.4% vs 0.8% and polycystic ovary syndrome in 0.1% vs 0.19%. [ie, almost all who had the opportunistic salpingectomy did have higher rates of these conditions]

        -- the anticipated projection in general was that there would have been 5.27 (range 1.78-19.28) serous cancers and 8.68 (range 3.36-26.58) epithelial ovarian cancers in these women

            -- BUT, they found zero serous ovarian cancers, and 5 or fewer epithelial ovarian cancers

        -- also, the age-adjusted expected number of breast cancers was 22.1 vs 23 observed; and for colorectal cancers it was 9.35 expected vs 8 observed, essentially no difference between the groups

            -- these negative results for breast and colorectal cancers are used to reinforce their findings about salpingectomy, since the epidemiology of ovarian cancer has been found to have a link between both breast and colorectal cancers: https://pubmed.ncbi.nlm.nih.gov/15051584/. this relationship between these cancers was largely attributed to familial and genetic issues leading to these cancers

--  another important link here is that ovarian cancer may explain much of the otherwise unknown origin of many peritoneal cancers, further supporting the importance of eliminating the fallopian tubes when possible

    --serous carcinoma accounts for approximately 60% of all PC (peritoneal carcinomatosis) cases and is typically associated with advanced ovarian or fallopian tube cancer; PC is diagnosed as primary peritoneal carcinoma in 10%–15% when the cause of the peritoneal cancer is not identified: https://onlinelibrary.wiley.com/doi/10.1002/cam4.71043

    -- in fact, primary peritoneal cancer without a clear source is typically treated as if it were ovarian or fallopian tube cancers: "Ovarian epithelial cancer, fallopian tube cancer, and primary peritoneal cancer form in the same type of tissue and are treated the same way", since they are all Müllerian-origin malignancies per https://www.cancer.gov/types/ovarian/patient/ovarian-epithelial-treatment-pdq; also see the NCCN (National Comprehensive Cancer Network) Guidelines Version 4.2026, which confirms this primary peritoneal cancer approach.

-- another report commented: "as many as 80% of tumors that were classified as high-grade serous carcinomas of the ovary or peritoneum may have originated in the fimbrial end of the fallopian tube. Therefore, the incidence of fallopian tube cancers may have been substantially underestimated. These new data support the view that high-grade serous ovarian, fallopian tube, and peritoneal cancers should be considered collectively, and that the convention of designating malignancies as having an ovarian origin should no longer be used, unless that is clearly the origination site": doi.org/10.1002/ijgo.13878

-- so, how could we implement preventative guidelines based on the opportunistic salpingectomy results?

    -- women who elect to have their fallopian tubes tied should be informed of the above findings and strongly consider having their complete tubes resected

    -- similarly, women who are getting hysterectomies should have the option of having their tubes resected

    -- the broadest group of clinicians to reach for opportunistic salpingectomy is general surgeons, since they often do lots of abdominal surgeries (hernias, gall bladder, GI surgery, etc), and they already typically take out appendices to prevent appendicitis in the future as well as the rare appendiceal cancers. BUT:

        -- for non-gynecologists to be able to do this, general surgeons would need to learn the procedure from gynecologists, be able to code for opportunistic salpingectomy, and have third-party payer coverage for the procedure

        -- and gynecologists should be able to bill for salpingectomy in menopausal women with history of tubal ligation, since this surgery cannot be coded as a sterilization

-- Are there benefits to leaving the ovaries in when women do have pelvic surgery? and what about the use of hormone replacement therapy (either estrogen alone or with a progestin)?

        -- there are documented health benefits in leaving the ovaries in place in post-menopausal women: women aged 40-80 have increased life expectancy with their ovaries intact than if they have elective oophorectomy (they are especially found to have decreases in coronary heart disease), but also osteoporotic hip fracture, stroke, and breast cancer: https://pmc.ncbi.nlm.nih.gov/articles/PMC3514564/

            -- there is no clear benefit of having elective oophorectomy (EO) at any age

                -- the statistics: those having EO <65yo have increased risk of dying from coronary artery disease by age 80 from 15.95% down to 7.75% baseline risk; women >65yo have increased risk of dying from osteoporotic hip fracture from 4.96% to baseline risk of 3.38% (though this number does not reach statistical significance).

                 -- women with EO and treated continuously with estrogen therapy have been found to have decreased risk of death from coronary artery disease as well as for lung cancer at all ages (not sure what the connection is here, and the results of other studies are mixed: https://pubmed.ncbi.nlm.nih.gov/19995648/)

                -- also, diminished cognitive function has been found to be associated with decreased serum estradiol levels; a study found that women with a serum estradiol decrease of >50% at 6 months after oophorectomies had worse cognitive function when compared to women who had estradiol levels that decreased <50%

                -- and, hormone replacement therapy (HRT) may help this. in the past there has been significant controversy on this, but there is a pretty strong argument of HRT benefit from studies: https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/1741892

                     -- estradiol is better than conjugated equine estrogen (premarin) as estrogen replacement therapy; estradiol has significantly lower cardiovascular risk; and transdermal estradiol has the fewest adverse effects since it bypasses hepatic metabolism and does not induce clotting factors

                     -- however HRT should only be prescribed if there are no contraindications: history of estrogen-sensitive cancer, breast cancer, coronary heart disease, stroke, venous thromboembolism, liver disease, unexplained vaginal bleeding; and these conditions should be reassessed annually if on HRT

                     -- and 80% of woman have bothersome vasomotor symptoms that can last more than 10 years, leading to hot flashes, night sweats, sleep disturbance, cognitive complaints, depression and anxiety, and vaginal dryness. those who are <60yo or within 10 years of their final menstruation typically benefit well from the estrogen. this finding is found in analysis of the Women's Health Initiative, which initially found in their 2002 analysis that risks exceeded benefits:https://pmc.ncbi.nlm.nih.gov/articles/PMC117494/) but are confirmed in further analysis of this initial WHI study: https://jamanetwork.com/journals/jama/fullarticle/2839211; and the benefits are now included in the recommendations of the North American Menopause Society: see hormone replacement therapy DrugAging2023 in dropbox, or https://doi.org/10.1007/s40266-023-01043-3, 

-- the largest ovarian cancer screening study with 202,562 women followed 16.3 years did find that annual multimodal screening with CA125 and second line transvaginal ultrasound, annual transvaginal ultrasound screening alone or no screening revealed a significant ovarian cancer stage shift to more stage 1 and stage 2 disease (early cancers) and fewer of the advanced stage 3 and stage 4 cancers in the multimodal screening group. But there was no difference in in the number of women who died and included finding no difference in the reduction of both ovarian and tubal cancer deaths (see ovarian cancer population screening Lancet2021 in dropbox, or https://doi.org/10.1016/S0140-6736(21)00731-5 . this finding of a stage shift suggests that the screening was helpful. however women who were 50-74yo were excluded. how does that fit into the above argument that tubal carcinoma is the main driver of ovarian carcinoma?

    -- this study did have 16.3 years of follow-up, reinforcing that short-term studies (as in some of the above ones) may miss cancer development, and longer-term studies are likely to find more cancers

    -- this study did not include patients with bilateral oophorectomy, undercutting the researchers being able to see if fallopian tube cancers were associated with ovarian cancer

    -- we do not know how the types of cancer that were determined: did those diagnosed as ovarian cancer deaths have their initial cancer in the tubes? given the above studies, it would seem that a detailed assessment would have revealed some tubal cancer involvement in a pretty large number of women with ovarian cancer. and there was no information about the co-occurrence of both tubal and ovarian cancers...

            -- but,  but, but, a major issue that undercuts the results of this study: the surface area of the fimbriated end of the tube is very large, and the area of the precancerous cells is very small. though the estimates do vary, some evaluations estimate that <1% of the fimbriated end is actually assessed histopathologically to determine a final diagnosis. all of this means that the pathological differentiation of a fallopian source of the cancer vs an ovarian one is suspect...

    -- and the findings in this study of a "stage shift" to less advanced cancers detected is really just a surrogate marker for mortality, and a not great one at that: what appears to be a cancer under the microscope may not be an actual clinical cancer that adversely affects the ultimate prognosis (as is found in many different cancers). so, though stage shift is a reasonable marker to assess, the actual physiology of what happens in real life may well be discordant from what the pathologists see under the microscope

        -- a 2025 ovarian cancer review found that early ovarian cancer (stage 1-2) is associated with a 5-year life-expectancy of 70-95% (a pretty wide range), whereas those with later stages (stage 3-4) have a 5-year life expectancy over the range of 10-40% (also a wide range): doi:10.1001/jama.2025.9495. these wide ranges support the above conclusion that stage shift is not a reliable prognosticator

so, what does this all mean?

-- it seems pretty clear from this study, as well as many in other medical/scientific fields, that we always need to remain skeptical of our prior understandings/beliefs and continue to reassess them

-- the evidence seems to be pretty solid that there is an important role of the fimbriated end of the fallopian tube in the development of a large percent of highly fatal ovarian cancers

    -- reliably identifying serous tubal intraepithelial carcinoma in the tube (stage 0, in situ disease) is difficult. we really have no blood or imaging tests for early detection

-- which all means that surgical removal of the entire fallopian tubes would be our current best approach. This should be offered to patients in conjunction with other gynecological procedures (tubal ligations becoming tubal removal; hysterectomies, other pelvic surgeries to include the option of "opportunistic salpingectomy")

    -- and this would be best if other surgeons could be trained and appropriately compensated for elective fallopian tube removal and have the systems that allow them to do this (like doing the incidental appendectomies that they are already doing).

    -- of course, any surgical intervention, including opportunistic salpingectomy, should only be done with patient understanding and consent

-- but, at this time, opportunistic salpingectomy appears to be our best approach at primary prevention of the typically devastating ovarian cancer...

geoff

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