International Medical Conference Endometriosis 2025:
Endometriosis 2025: Your Mother Should Know, Your Doctor Should Know Better!
Review of Recent Increased Risk of Endometriosis and Ovarian Cancer: How Real Is It? - Farr Nezhat, MD
In academician, a dedicated educator and a prolific writer who has a profound impact on his field. His interests include the pathophysiology of ovarian cancer, specifically the malignant transformation of endometriosis. Dr. Farha is a clinical professor of OB GYN, it's Vail Corneal Medical College and the director of the division and fellowship in minimally invasive gynecologic surgery and robotics at NYU. He was honored with the Endometriosis Foundation of America's Heritage Award in 2016 for his lifelong commitment and his work in treating and investigating the relationship between endometriosis and cancer. Dr. Farad, we are eagerly looking for your insightful lecture about the recent increase in endometriosis related cancers. Thank you.
Thank you very much. Introduction. Thank you very much my dear friend Tam Kin and Dr. Dan Martin, my great friends for many years and it is pleasure to be among you this distinguished audiences. So I think they at the session and Martin asked me to give this talk review of recent increase in risk of end y young cancer high realities. I think this word of resent is accidentally put here. So I think the reason is that there should be review of the increase in risk of endometrial cancers because I think based on one article that we discussed about in JAMA that the incidence is reported to the higher than we were expecting. So that's some clarification about this title. So a little bit background about myself as Dr. Rich and Dr. Serkin this morning mentioned about the himself. I am a GI oncologist before I go to my fellowship in New York in Mount Sinai Hospital, I had worked with my brothers Carolyn Aina for 10 years and when I decided to do Y oncology the first thing I noticed that there is a lot of similarity with OY on cancer and endometriosis.
So I became interested in subject and I started publishing about it and these are some of my publications that I refer to you and during these years I try not only learn myself to help my patients also share my experiences with my colleagues and with my friends. So that is the background of myself and this talk. So the purpose of my talk is to briefly review with you the endometrial lung cancer, a little bit discussion about the pathogenesis of this transformation that what we know so far and I try to spend most of my turn on clinical implication that you take something to your practices and take care of your patients. So you all have been exposed to this discussion about the problem with endometriosis and I don't have to go over it, but now the issue that definitely we know endometriosis is a risk factor for malignant transformation that is definitely shown.
There's no discussion about it. So since Samsung more than 100 years ago suggested there is a malignant transformation endometriosis, now we have epidemiological that I discussed about it more and molecular biology and histological EVs that there is malignant transformational endometriosis to cancer. Also there is a coexistence of endometriosis at the time of the diagnosis of ovarian cancer. So this, you have to keep this in mind. The most common histology that we discuss about it more is endometrioid and clear cell carcinoma, but there are some other rare and also low grade sero carcinoma that there are more evidences. But there are data that other types of rare condition like adeno sarcoma or even TMP could become from endometriosis to make your mind easier when endometrium you could have adenocarcinoma and endometrial adenocarcinoma. Also we could have high GCE carcinoma and cardio SAR carcinoma to make it that ease endometrium and endometriosis is similar to glan and the like the endometrium so it could become malignant.
So this 2025, we have about 20,000 OI cancer diagnosed in this country. We have unfortunately more than 12,000 death. The lifetime risk is one in 70, one woman in 70 could develop cancer and the average age is 63. It seems end endometriosis cancer arise from cancer are women are few years young. Now when we talk at ovarian cancer, first let's clarify what we are talking about based on the cell origin we have germ cell tumor and six stronger tumor. These are the 10% and they are always coming from the ovaries always is a mass. Most of them are in earlier stage because they become big. Patient has symptoms. Either you could feel it or they have symptoms. They go to the physician and they find, but this is not difficult to diagnose them. Most of them they have tumor markers and they respond to treatment variable.
The problem is epi epithelial type of tumors that there are majority of them and there are two type I want to remember this type one and two that later on we talk about one of the studies what are the type one and type two. Type two are the most of them and they got high gu sero carcinoma. Now we are realizing they are not coming from the ovary. Majority of them actually they are coming from fallopian tubes and from ated end and the cells they grow, they drop gradually in the peritoneal cavity. They don't have any OY masses and all of a sudden the patient that has been exam six months ago and she was fine, now she has come with the ascites and oral caking. These tumor are the majority of the epithelial type of ovarian cancer. These type are very aggressive and molecular characteristic of this tumor are different than type one that we discussed about more.
So we start from OV cancer, we come to the histology now we become epithelial type of tumor from the endometrial clear cell called missionaries low grade high grade. Now we are coming to molecular profile of this tumor. So more and more we are going to the molecular characteristic of this tumor. So high RP 53 and B barrack mutation and type one. Most of them are low grade endometrial clear cell Al Aries and as Dr. Cell are balloon this morning mentioned endometriosis. There are molecular alteration exactly the same type of the alteration that endometriosis we have in this type one end OY cancer K-R-A-S-P-R-A-P 10 radio one. So there is some commonality between the endometriosis cells and type one epithelial OI and cancer mostly end endometrioid and keeo cell carcinoma. So it keep these things in mind and we talk about it later. So epidemiological study, I just few of them I go over it and one of them is famous from by peers Arian Cancer Association course that they looked at 13 ovarian cancer case control study in the patient that they have self-reported endometriosis is not diagnosed by laparoscopy or histologically self-reported endometriosis and they look at the histology grade stage and the bottom line was that showed patient that they had endometriosis compared to control group.
They had almost three and a half percent higher chance of the killer cell carcinoma, two and a half percent endometrioid adenocarcinoma, even low grade sero CEUs but not ous and high grade carcinoma. So this is one of the epidemiological study, another one which was reported by Herman from Netherland and they looked at the more than 130,000 case of the histological diagnosed and endometriosis compared to more than 132,000 control group that they had the benign DER neighbors moles and they look at the incidence of the ovarian cancer, the incidence relative ratio was 4.7 by adjusted age of 7.18. But if they exclude the cases that they diagnosed in the first year, they found there was no significant differences overall compared to control group. However, again, the significant relative risk state for endometrioid and killer cell carcinoma. So these numbers keep in mind that the chance of the endometrioid and killer cell carcinoma is higher in patients with endometriosis.
This is the meta-analysis which was published by Leo. Again, they looked at several studies and they look at the relative risk of the killer cell carcinoma and endometrial carcinoma and again you could see that the risk is higher and this is another metaanalysis which was published in 2021 and they looked at the several studies metaanalysis and you could see the clear cell carcinoma in five studies show that a standard relative risk is 3.4% and endometrioid is 2.3% for seros it's not significantly higher. OSI is not significantly higher and the borderline is not higher. So so far everything has shown that in the MET and ke cell carcinoma, the incidence are higher until this paper came last year that this is from United States, from Utah, that they looked at the almost 80,000 patient endometriosis and one to five match control group. They look at the few things compared to the other studies.
First of all they look at the overall risk of the cancer and look at the type one and type two that I mentioned to you. Type one was endometrial and killer cell carcinoma, low grade and type two was high GCE carcinoma. Also they looked to see if peritoneal superficial end endometriosis, deep infected endometriosis and AYA endometrioma has any effect and that overall they showed that the incidences is increases overall is 9.7% for type one 19% and type two 3.7%. Well this paper was very interesting at another interesting part was that they showed that the incidents in two time of the follow-up was higher when it was less than five years and then after five to 15 years the incident is low and then becomes gradually goes up. So this paper at the end, they recommend that because this incident is higher than what was reported.
So they recommended that you should do certain surveillance in the patient with endometriosis and maybe we should do surgeries in this type of the patient. Well two commentaries was written about this suggestions and this data and two letters to the editors, one of them by Dr. Stacey that she's here and her colleague and one of them with Dr. Paula Verini that we just listened to his talk and both of them they raised some question that is completely valid. One of them is that some of these risk is absolute risk is much less than whatever reported the incidence of relative risk because if the patient the first year was of the diagnosis and endometriosis had y cancer, there was no enough time that endometriosis could cause ovarian cancer. So you have to adjust the data. The other thing is that we know that the diagnosis of endometriosis is very challenging.
Now you have heard this morning on for past two years, they say between seven to 10 years delay of the time of the diagnosis. So we don't know when was the individual was diagnosed. The other thing we don't know how many of these people that have used hormonal suppressive therapies. Again you happy hearing about suppressive therapy for treatment. We don't know how many of these people they had genetics predisposition like BRCA one, BCA three mutations. So none of those areas was addressed on that paper. However, whatever it is clear that we know endometriosis is a risk factor for cancer especially for certain histology and that is maybe the risk is not as high as that we discussed later as BRCA mutation. So we should be aware of it. So briefly, what is the pathogenesis of this malal transformation and listening to Dr. Berlin this morning and Dr.
Bini this morning, the endometriosis is a hallmark of endometriosis, estrogen dependent inflammatory chronic disease the same way that an exposed endometrium like PCOS or obese patient, they could develop end endometrial cancer the same way the patients they could and opposed estrogen could cause proliferation, abnormal proliferation in inflammation. Again the hallmark. The same vein we have in patient with asbestosis, they could have lung cancer, patient with hepatitis could hepatoma the same way. This inflammation plays a role also. Again, Dr. Lin was mentioned high iron concentration in the peritoneal cavity could cause stress and that could produce abnormal mutations of the cells and also there is dysregulation, macro RNAs and finally environmental and the diets that could be a factor. For example, we know C cell carcinoma is more common in Korea or maybe in China. So all this combination could be the reason for this malignant transformation.
So we know the patient that had long history of endometriosis patient that they have large end endometrioma or prolonged exposure to an estrogen, even an opposed estrogen of the hysterectomy and BS o if the patient has had end endometriosis that was not resected has been shown to be causes malignant transformation and also patient with infertility have higher chance of ovarian cancer. So these are the facts that we know majority of malignant transformation are on the ovary when about 20% of them are extra ovarian on the bowel fallopian tube, even abdomen wallan scar endometriosis could cause malignant transformation. So if you keep those pathogens of the transformation high level of the estrogen and also the inflammation that explains why majority of the cancers coming from the endometriosis are on the ovary because there's a high level of the estrogen there because as Dr. Poland mentioned in the endometriosis lesion the IS activities much higher than regular circulation.
So there's a high level of the estrogen on the endometrial implant. So what is a clinical implication? I just want to go two short case is a 38-year-old patient with a hyster of severe endometriosis that in the past she has infertility, she has multiple RUI and IVF and she had bilateral in four centimeter and five centimeters. She got Lupron, didn't get better and finally she was referred to me because the end was getting bigger and also she had the fibroid. I do my own ultrasound in my office all the time When I did the ultrasound, this is a certain nodule that I noticed it in her ovary and I consult him that if it is cancer, what do you want me to do? This patient was very adamant, don't take my ovary out, wake me up and we discuss about it. So I scoped the patient and that nodule is a nodule for the laparoscopy, which we took a biopsy and was adenocarcinoma so it was adenocarcinoma.
She didn't want to be removed. So I took a biopsy of different area. I took that tube out and from the pathologist showed that she has these two big grade one in the met adenocarcinoma and because she wanted to get pregnant, we sent her for one more cycle of the IVF and she got one more cycle of the IVF. And interestingly enough they couldn't get eggs from the good ovary. They got some eggs from the ovary that had cancer. Then she got six course of chemotherapy and then she came back to me. I went back and took that ovary out. I stage her and then watch her and after one year that she was in ed, they transferred that egg and she got pregnant and she had this baby and now it is 10 years that she's doing fine and we published this paper. So what I want him to say that majority of endometrial adenocarcinoma coming from endometriosis fortunately are low grade and the patient will do well.
However, if the patient has endometrioma, you have to watch that endometrioma to be sure doesn't have any solid component. And if her solid component she has to be referred to be taken care of, this is another patient that is not as a history as better than the first one. She's 57. She has history of the endometriosis and infertility for several years she never got pregnant and went into menopause and she was fine. Then she started having pain for a couple of years with vague abdominal pain and they thought she has all endometriosis, didn't have a scar tissue, you let her go. And finally one day she came back with abdominal distention and ascites. So she was referred to me, can you play the movie? So her CAT scan, you could see her CAT scan and when I did laparoscopy on her, I do laparoscopy to all of my ovarian cancer.
You could see she had disseminated carcinomatosis everywhere you could see ascites is liver look in her pelvic area. This is all disseminated cancer. And this is when you took a biopsy. This was clear cell carcinoma disseminated in spite of the debulking and aggressive chemotherapy. Unfortunately she died. So one side they have early endometrioid and they do very well. However, if it is clear cell carcinoma, you do not recognize them. And the killer cell carcinoma do not respond to chemotherapy very well. So you have to, unfortunately they don't do well. I have a few more minutes than so that's all I want to see. My last slide is that lifetime of the lifetime of the risk of general population is 1.4. For BRCA one BRC two mutation is 30%. And this group of the patient will recommend prophylac, Ingle, ectomy and even lynch syndrome. This group, there is some guideline of the certain age with the Pringle ectomy for endometriosis.
If the risk is two three 4% higher does not justify to do ectomy at the present time and only covering these people, covering these people, washing these people carefully is very important. And the last slide I want to show you is that endometriosis is very challenging as you have been sitting here every day and you have to be cognizant about it. I am a general oncologist. We have about 100,000 cancer in this country a year and we have 65 fellowship program. And endometriosis is very common disease only few program including KIN program that has a fellowship to teach young physicians in endometriosis. We need to have a society to educate our physicians about endometriosis. That is that we reason, we formed a society called American and Global Congress of Endometriosis. We have our first annual meeting this year in March in Atlanta, DR. Session, Dr. Martin and some other people here are part of it. And we encourage all of the young physician to be get involved because we all are patient. We all are sisters, mothers. Our future generation to increase awareness about this disease and you all have here is very complex disease and challenging and we need more attention to it. Thank you very much.
