The Other Women's Cancers

Sat, 06/10/2006 - 3:22pm

When: May 13, 2010 at the Downtown Library: Multi-Purpose Room

There has been a lot of information about breast cancer, but what about other women's cancers? Each year, 78,000 women in the United States learn they have a gynecologic cancer. Although these gynecologic cancers are often grouped together, they vary widely in their causes, risk factors, detection, treatment and chance of a cure. Carolyn M. Johnston, M.D., Clinical Professor, Department of Obstetrics and Gynecology at the University of Michigan, will focus on types of cancer that affect a woman's reproductive system and discuss her research as principal investigator for Gynecologic Oncology Group (GOG) clinical research trials at the University of Michigan. This event is made possible through Partners In Research grants R03 NS065493 and R03 NS065491-0 and is co-sponsored by The University of Michigan Comprehensive Cancer Center Community Outreach Office, the Michigan Institute for Clinical and Health Research and the UM Taubman Health Sciences Libraries.For more information on glaucoma take a look at our books on the subject. Articles and current research can be explored in our research databases MEDLINE and Health and Wellness Resource Center.

Transcript

[00:00:00.50] [MUSIC PLAYING]
[00:00:22.64] SHANNON RIFFE: My name is Shannon Riffe. I work here in the Community Relations Department, and I would like you to join me in welcoming Associate Director Celeste Choate.
[00:00:33.75] [APPLAUSE]
[00:00:37.65] CELESTE CHOATE: I'll keep this very brief because I know you're here to see our wonderful speaker, Dr. Carolyn Johnston. But because this is a National Institutes of Health grant-sponsored program, I want to give you a little bit of information. Because I know some people came in close to their starting point, they might not have had a chance to read the slide.
[00:00:56.03] What we did is we had the great fortune of being approached by the University of Michigan to say we would like to get a grant with you to talk about clinical research in our community. The University of Michigan has a very strong research program, and it's important for the University and for us as a people collectively to have good research being done across a variety of age groups, races, and sexes, so that drugs and procedures are being tested in ways that will serve all the people. So we thought it was important to talk to the people and talk to the researchers. Get researchers and the general public together and talk about what you know about clinical research, what you'd like to know, and to learn more about clinical research opportunities.
[00:01:39.31] One way to find out more about clinical research is to go to the wonderful website that they have at the University of Michigan called engage. It's available at umengage dot org. You can look for information about different medical conditions, and you can find out if you qualify -- or if someone that you know or love qualifies -- for a clinical research study that you would like to participate in. So I want to let you know that you have that resource available if you are so inclined. We are not here today to browbeat you into participating in research -- just to let you know that opportunities are available to you.
[00:02:12.73] So I mentioned that we have a National Institutes of Health grant. The three parties in that grant are the Ann Arbor District Library, MICHR -- and MICHR is the Michigan Institute for Clinical and Health Research at the University of Michigan -- and the third partner is the University of Michigan Taubman Health Sciences Library. All three of these places are places you can go for good, reliable health information on particular topics. Shannon mentioned the focus groups sign-up and evaluation forms. As this is funded by a grant we need to get data to provide back to the National Institutes of Health, and back to the public to say -- is learning about health research information, clinical research information, in a public library setting like this helpful? Do people learn things? Do you find that you get your questions answered -- or not? So it's really important to us that you take just a moment and complete those forms, and if you are so inclined to participate in the focus group -- which will not ask you personal medical questions, but will ask you about the evening tonight and what you took away from it. So we're not interested in personal health information. We're interested in how this process worked for you, or didn't give you what you were looking for when you came tonight. It's just as important for us to learn what you didn't get, as to what you did take away tonight.
[00:03:26.93] So on that happy note, thank you for coming tonight on this balmy evening. I'm glad that the rain broke free and left us so that we could come tonight and talk with Dr. Carolyn M. Johnston. She's on faculty and provides gynecologic oncologic care at both the University of Michigan and St. Joseph Mercy Hospitals. Her clinical interests include preinvasive disease of the lower genital tract, complex gynecology, gynecologic oncology, and cervical cancer. She's also a board member of the Michigan Cancer Consortium, and the chair of its cervical cancer committee. So please join me in welcoming Dr. Johnston.
[00:04:02.87] [APPLAUSE]
[00:04:09.18] DR. JOHNSTON: Thank you. So I was asked tonight to speak on all the gynecologic cancers. In an hour and a half it's going to be pretty much a whirlwind. You'll note that I'm speaking on cervical, ovarian, and endometrial. I'm leaving out vulvar and vaginal for obvious reasons -- there's just not enough time. I'm happy to do it another time, but not tonight.
[00:04:33.97] I'm going to give a brief overview of each -- the general epidemiology, the cause if we know it, risk factors, stage, treatment, outcome, sequelae of treatment, and what some of your options are. And then I'll also mention what the research trials are available at both institutions. And I think probably in your handout you have some information -- some website you can go to for more information, along with the engage website.
[00:05:01.84] This is just a figure showing the top 10 cancer types with regards to new cases and deaths. You'll see GYN cancers are not very highly represented. Cancer from the uterus is there. Ovary is there in terms of new cases, but you'll notice ovary moves way up in the list in terms of deaths, and endometrial cancer drops way down.
[00:05:26.85] First I'll talk about the cervix. Most of you know it as the mouth of the womb, the thing that gets the Pap smear done to it, the top of the vagina, the end of the uterus. It's got a skin on the outside, and gland cells on the inside -- two separate cancers.
[00:05:45.99] It's the 2nd or 3rd most common cancer among women worldwide, depending on what year you talk about it. Where I go in Ghana it's the leading cancer because there's no screening. Three quarters of cases occur in the developing world. And you can see that in 500,000 cases more than 50% of them die of disease, whereas in the US -- 11,000 cases, 4,000 die of the disease.
[00:06:12.30] One in 145 women in the US will develop cervical cancer in their lifetime -- so less than 1%. Black women are more likely to get the disease and to die from the disease. And their incidence and mortality rates are about 50% higher. And that's also true for endometrial cancers, but not true for ovary.
[00:06:30.65] Bringing it a little closer to home. Michigan -- the incidence and death rates are slightly less than those in the US in general. And in 2005, 369 women in Michigan developed cancer, and approximately 100 died.
[00:06:47.97] The number of cervical cancer deaths has decreased quite a bit since the 1950s when the Pap smear was introduced. However the 5 year survival has not improved dramatically. So although we screen better for it, we have not figured out better treatments.
[00:07:01.95] The median age of diagnosis is 48, but 50% of the women are between the ages of 35 and 55. It rarely occurs in women who are younger than 20, with the exception of DES-related clear cell cancers -- and DES was stopped being used in 1971, so that's become less of an issue.
[00:07:21.27] Cervical cancers are caused by a very common infection called human papillomavirus. It's the same virus that's associated with genital warts. The prevalence in cervical cancer is about 100% -- if you look hard enough you'll find it. One exception, again, is DES-related cervical cancers, and those are thought to be due to the drugs and not to the virus.
[00:07:43.89] There are more than 100 types of this virus, most are associated with benign diseases. It's not unique to the cervix, it can occur on any skin type. The high-risk types are associated with pre-cancers, and cancers of lots of areas on the body -- the head and neck, the lower genital tract in men and women, the anus, skin diffusely.
[00:08:06.24] The most common types associated with cervical cancers that are high-risk, are 16, 18, 31, 33, and 45. And 16 is the most common, it accounts for most of the cervical cancers throughout the world. And 18 is of importance because it's associated with adenocarcinomas -- or the gland cell cancers that come from the canal of the cervix.
[00:08:30.96] It's a common sexually transmitted disease. The high-risk type is not as common, but look at some of these numbers -- it covers all age groups. 3% to 10% of 11 year olds are affected with the high-risk type, and by the age of 50, 80% of women will have had evidence of the infection. So it's a really common infection, and yet cervical cancer is not common -- it occurs in less than 1%. So don't take home the message that just because the virus is common, cervical cancer is common.
[00:09:01.57] The longer the infection stays around the more likely you are to get dysplasia -- or pre-cancer -- or to get cancer.
[00:09:09.36] And dysplasia, CIN, SIL -- for any of you that have had those issues -- is the precursor lesion to cervical cancer. It's much more common than invasive cancer. I'll learn these button eventually. The immediate precursor lesion to cervical cancer is called CIS -- or carcinoma in situ, or CIN 3. And that, if untreated, will progress to cervical cancer -- but for the most part does not.
[00:09:41.93] And this is just a schema sort of telling what we think about how cervical cancer develops. If you have a high-risk HPV infection, you can either keep that infection -- most people get rid of it due to your immune system. If you keep it, then you get cervical dysplasia or pre-cancer. If your immune system isn't working because you're on steroids, or you're HIV positive, or you've had a transplant -- that acts here, makes the cervical dysplasia more likely to progress to cervical cancer. Other factors enter here -- tobacco, birth control pills, estrogen.
[00:10:19.78] Is it preventable? Definitely. You can detect and treat pre-cancers before they become cancer, and that's with regular Pap smear screening. You can prevent the pre-cancers with the HPV vaccine. You can use condoms to reduce the acquisition of HPV. You cannot smoke. You can avoid behaviors such as having sex at an early age, having sex with multiple partners, having a partner who has multiple partners.
[00:10:46.90] And I need to put this comment in because it comes up time and time again when we talk to women. A pelvic exam is not a Pap smear. Just because a speculum is put in your vagina, and someone's looking at your cervix, doesn't mean they've done a Pap smear. So if you're uncertain, ask, because it's important that you get regular screening with regards to Pap smears.
[00:11:06.59] The American College of Obstetrics and Gynecology recommends that all women should have their first Pap test beginning at age 21. And then between ages 21 to 29, every other year. Many of us would disagree with that -- we think it should be yearly -- but nonetheless that's the recommendation. Low-risk women, once they're past the age of 30, can get screened less frequently if they've had normal Pap smears. And above the age of 30, you should also expect to get HPV testing with your Pap smears. Once you reach the age of 65 or 70, and you've had 3 or more normal Pap smears and you have no history of cancer -- different groups debate whether or not Pap testing can be discontinued, and that's an individual factor. Pap testing is not recommended if you've had a hysterectomy that was done for benign disease, as long as you don't have any history pre-cancer or cancer. Otherwise you continue to get a Pap smear every year.
[00:12:03.78] 50% of women with cervical cancer have not had a recent Pap smear, and yet most of these people have had some sort of encounter with a healthcare professional in the last six months. So the failure's on both parts -- we're not necessarily delivering, and people maybe aren't necessarily asking for it. So you need to be aware of that as well. About one third of people with cervical cancer will have had a recently normal Pap smear. And that's more common in the gland cell cancers -- the ones that are from the canal. They're also more likely to have false negative, meaning the Pap smear was actually interpreted as negative but not in there, and more rapidly progressive disease.
[00:12:44.52] The infection is usually asymptomatic. Most people don't have symptoms, so you don't know you're passing it on to somebody else. So it's best to try to reduce your risk of acquiring it, and probably the best option available right now -- besides the behavior changes, which quite frankly aren't very practical -- is the HPV vaccine. I'm guessing most of us in the room are too old for it. There are two types out there. One protects against two high-risk types of HPV, as well as two low-risk types. And the other protects against two high-risk types. It's to be given to boys and girls ages 9 to 26, but it's recommended that you start routinely at age 11 to 12. You can start as early as age 9, and you can play catch up, up into the teens. It's not currently approved for women over the age of 26. It works best if you got it before you get the infection, so it's ideal to get it early -- and 7% of 13 year olds in Michigan are sexually active, I think, so you have to get it early. And the vaccine doesn't protect against all cancer-causing types of HPV -- it may not be universally protective, so you still need Pap testing routinely, you still need exams.
[00:14:02.83] Risk factors for cervical cancer. Early age at first intercourse, multiple partners, partners with multiple partners, tobacco, HPV infection, history of an abnormal Pap smear, history of cervical cancer or pre-cancer, a long time between your Pap smears, history of other cancers -- vulva, vagina -- intravenous drug use, any immunosuppression, in utero DES exposure. Not only increase your risk of clear cell cancer of the cervix when you were younger, but for a lifetime also increases your risk of the routine type of cancer of the cervix that we think of as squamos cell cancer. Having a lot of kids and oral contraceptive use.
[00:14:45.49] Symptoms. Any kind of abnormal bleeding. Bleeding after trauma -- so after intercourse, in between periods, after menopause -- is abnormal and should be brought to attention. Bloody, watery discharge is a frequent complaint, usually of more advanced disease. Back pain, leg swelling, bladder and bowel complaints -- those are usually signs of more advanced disease, as things spread sort of north to the bladder and south to the rectum. Nonetheless they're common symptoms.
[00:15:16.38] Of the subtypes, the kind that you'll most often encounter or hear about are the skin type -- from the outside of the cervix -- and the gland cell type or the adenocarcenoma -- from up inside the cervix. The others are relatively rare. You should just know that cancer can spread from anywhere in the body to the cervix -- the most common places are from the uterus to the cervix, and from the rectum up to the cervix.
[00:15:38.60] Diagnosis is always a biopsy. You can't look at it and say it's cancer, you can't make a diagnosis on a Pap smear. You have to have a piece of tissue for the pathologist to look at. The rest of the work up -- you can expect a chest x-ray to look to make sure there's nothing in the lungs. You can expect a CT scan, probably of the abdomen and pelvic area, to make sure that there's no blockage of the tubes that go from the kidneys to the bladder, called the ureters -- looking for lymph nodes as well. We use PET scans now. They're very good for looking for enlarged lymph nodes -- they're better than the CT scan. Blood work to check the function of other organs. And if there are bladder symptoms -- blood in your urine, problems urinating, blood in your stool -- you'll get a scope to look in either one of those areas.
[00:16:24.80] Stage defines where the disease is relative to the cervix. It determines treatment options, it determines what symptoms you're probably presented with, prognosis, and likelihood of recurrence.
[00:16:37.36] Just briefly, Stage 1 confined to the cervix. 2 -- to the upper vagina, or slightly outside of the cervix. 3 -- all the way to the edge of the body to your hip bones. 4 -- to the bladder or bowel, or to the lungs and the rest of your body. 5 year survival is very good for Stage 1, and not so good for Stage 4 -- and that's a general theme about most cancers. Squamous cell cancer and adenocarcinoma -- although the adenocarcinoma may present at a later stage, at the same stage they're both treated the same and do just as well.
[00:17:21.43] An overview of early stage, which is confined to the cervix. Treatment options are hysterectomy, removing just the cervix, radiation and chemotherapy -- and they're all equally effective. We help to guide selection for those. An exception of that is microinvasion, or cancer that barely invades into the cervix. Those people can be treated with what's called a cone biopsy. It literally looks like an ice cream cone. The center part of your cervix is cored out, and that leaves the uterus and the cervix, and it preserves fertility. In later stages radiation and chemotherapy, palliative care, or clinical trials are the real options.
[00:18:06.30] When women are young, we encounter the difficulty of people not having finished childbearing. So some people want to try to retain fertility, and sometimes we can offer that option. Other people are not ready to be rendered menopausal by the treatment -- having your ovaries removed or being radiated. So there are some techniques we can use to improve quality with regards to those. In terms of preserving fertility, we now can refer people -- if there's time, if the cancer's early enough -- for either egg retrieval or embryo storage. The delay takes about a month and a half -- by the time you get an appointment, get the ovaries stimulated, and retrieve the eggs. But possible. We also can preserve fertility by maintaining the uterus and ovaries by the cone biopsy that I talked about, if the cancer's early enough. And by what's called radical tracheloectomy, which removes the cervix, the tissue around the cervix, the upper vagina, lymph nodes in the pelvis, but leaves the body of the uterus -- so you can still carry a child. If you're trying to preserve ovary function, surgery's going to do it a lot better than radiation. Two doses of radiation pretty much zaps the ovaries to being non-functional.
[00:19:20.50] In surgey we can move the ovaries around. They're normally down here by your hip bones. We basically disconnect them from one end of their blood supply, and move them up here -- under your rib cage -- so that if you need radiation, they're not down in the pelvic area where you get radiation. Sorry.
[00:19:45.95] And we talk realistically about vaginal malfunction, sexual function. Radiation causes a lot more damage, a lot more scarring in people for whom that's still a viable interest. Surgery is the preferred course of treatment if we can, if it's equally viable. If you look at sexual dysfunction after radiation therapy compared to surgery, fewer people resume sexual activity after radiation than after surgery. And that's primarily because the vagina is scarred more, it's not as stretchy, and it's just more uncomfortable.
[00:20:25.92] And as always, when we talk to people, if there is a choice we try to engage people in that choice -- to talk to them about what their options are and what their desires are. Radical hysterectomy. It's not the simple hysterectomy you think about with the uterus and the cervix coming out. We take not only the uterus and cervix, but we take a zone around it to get all of the cancer -- to make sure we have a good margin. We take the upper part of the vagina, and because of that it's a much bigger procedure. We can do it through an abdominal incision, we can do it laparoscopically -- where we make small incisions on the abdomen, look in with the scope and take it out -- or more commonly now, we're doing it with the robot-assisted surgery, which gives us a better view, and gives us less blood loss. It takes longer, but our lymph node sampling is better -- it's just for us, a better overall procedure.
[00:21:21.46] This is the picture -- this happens to have an ovary on it -- this is the uterus, ovary, and tube. This is the cervix and the cancer here -- it's a relatively small cancer. This is the rim of vagina -- remember we take the upper vagina. This is the tissue around the cervix that we take. So just like if you had a mole on your skin, you wouldn't take the spot, you'd take a zone around it to make sure you got everything.
[00:21:42.56] Radiation therapy. The goal is to treat the whole area that's at risk for -- not only where the cancer's located, but where it could spread to. So typically the whole pelvis is treated. You're treated to the outside of you body for four to six weeks usually, and then you're treated to the cervix through the vagina. We're finding across the state, sometimes, that people don't always get the cervical treatment. They get the outside because it's easy -- you can lay on a table, they can deliver the x-ray, and it's pretty straightforward. It takes -- you have to put a little stent into the cervix, the radiation therapist has to introduce a tube into the cervix with a ring on it, to be able to treat the cervix. That happens typically every other day, for three to five times. That's harder to do -- it's harder for the patient, it's harder for the therapist. You can see, though, if you don't do it the 4 year survival drops not quite in half, but pretty much. So it has to be done, and it's important to get.
[00:22:40.71] In 1999 five studies showed that radiation, given with a low weekly dose of chemotherapy, improved survival. So since then we've always been giving chemotherapy with the radiation. The chemotherapy, that's the least -- if anyone's received it, you probably wouldn't agree, but it's the least annoying, the easiest to tolerate -- is Cisplatin. So that's what we give weekly with the radiation.
[00:23:07.75] There are certain characteristics of the cancer that if you've had a hysterectomy make it more likely to come back, and make us more likely to recommend radiation. When I started this in the 1980s, we gave radiation to a lot of people. The radiation side effects are annoying, we prefer to try to avoid them if we can. And we really tailored it down to just a few risk factors that really deserve further treatment. We've also found that radiation alone doesn't make you live longer, you have to get chemotherapy with that radiation.
[00:23:38.43] So sometimes we see patients who have had a regular hysterectomy -- and oh, oops, there was a cancer in it. And it turns out that if that cancer is small that you might not need any further treatment -- that even though you didn't have a radical hysterectomy, you've been treated. Or, that you need radiation therapy just to the top of the vagina. If the cancer's bigger, then sometimes we go back and take out that tissue from around where the cervix used to be -- or more commonly, we offer radiation. And if the cancer's even bigger and some of it was left behind -- definitely radiation with chemotherapy.
[00:24:13.48] Survival's good. As long as there's not cancer left behind, the survival's the same as if you started out knowing you had cervical cancer with a standard treatment. The problem is, is that more women get radiation that might have avoided it in the first place. So it's important to -- if somebody presents the bleeding -- to make sure you've worked them up appropriately, and you've not missed the cancer before surgery.
[00:24:37.59] It is the most common cancer in pregnancy -- that still doesn't make it very common. It's more likely to be diagnosed early. Women are getting exams, they're presenting with the abnormal bleeding, they're more likely to show up for evaluation. There's no difference in survival, stage per stage, when you're pregnant or not pregnant.
[00:24:56.27] Symptoms of recurrence. Persistent pain, especially in the pelvis or the back. Vaginal bleeding. Swelling of one or both or your legs -- from pressure on the lymph supply. Blockage at the ureters -- the tubes that carry the urine from the kidneys to the bladder.
[00:25:14.60] Treatment is determined, as you can imagine, by where it recurred, what your previous treatment was, what your desires are, and what your overall state of health is. And, obviously, sometimes provider preference enters into it, but also patient preference should enter into it as well.
[00:25:33.18] Treatment options. If you just had surgery, it's usually radiation therapy and chemotherapy. It can be chemotherapy alone if you've already had radiation. It can be what's called a pelvic exenteration -- it's reserved for recurrences at the top of the vagina, so you remove the vagina, you remove the bladder, you remove the rectum, you remove most of the tissue between your hip bones from front to back. And it's a big procedure. You end up with ostemies for both stool and urine. It's not to be taken lightly, but the survival is 61% in well-selected patients -- which is much higher than any of these other treatment options for recurrence. So if it's an option, it's well worth thinking about.
[00:26:15.43] Clinical trials. Vaccines have been talked about, but there are none available. For treatment now -- prevention yes -- not treatment. And palliative care.
[00:26:26.96] Chemotherapy. The response rates are relatively low -- 10% to 50% -- and they're short duration, usually four to six months. So if you're a candidate for a surgery, it's usually a better choice. Cisplatin and Taxol, or paclitaxel, are the drugs of choice currently for recurrent cervix cancer. Some of you will recognize that as a common theme throughout the different disease types as well.
[00:26:52.71] Pelvic exenteration, I already talked about. Realistically, you may go home from the hospital in 10 days, but it takes a good six months to recover from the surgery, and it's really life-changing as you can imagine -- having that extensive disease removed.
[00:27:10.26] The more treatments you have, the more side affects you have from them. And we talked about radiation causing more vaginal changes -- more sexual dysfunction -- so if surgery's an option, we try to provide that. The bigger the area that gets treated, the more side effects you're going to have. It turns out that the higher the dose of radiation, the more side effects -- but it actually turns out that survival is better. So want to make sure you get appropriate delivery.
[00:27:37.44] Just some brief side effects of radiation. For any of you who've had it acutely, you may get diarrhea and fatigue. Some bowel and bladder irritation. Down the line, two or three years later, some people get bleeding from the bladder and the bowel. You can get scarring in the vagina. And as I noted, after two doses if you're not already menopausal, you typically are.
[00:28:04.10] Second cancers can develop on average 30 years later. This is not as important for somebody who's later in years. But for youngsters, teenagers, or people before menopause -- that's the real risk and people have to be surveilled for that.
[00:28:25.54] Radical hysterectomy. The most annoying side effect that we talk to you about before we have you agree to the surgery, is a slow bladder -- a lazy bladder. About 4% of people will have to catheterize themselves for the rest of their life to urinate after a radical hysterectomy. And that's because when we take that tissue around the cervix, we take the nerves that go to the bladder. Most people -- by the time six weeks after surgery has come and gone, and they've recovered from surgery -- don't have that problem. But it's real, so we tell people about it. I think, realistically, anyone who's had a radical hysterectomy will tell you that it's different to urinate. It's not quite normal -- they can do it, but it's not quite normal. A shorter vagina -- because you take the top of the vagina. Menopausal symptoms if the ovaries are removed. And then things that go with that -- vaginal dryness and sexual dysfunction. At the time of radical hysterectomy, we do not have to take out the ovaries. People think hysterectomy, ovaries are out -- that's not the case. The cancer spreads to the ovaries 1% to 2% of the time, so if you don't want to be menopausal -- you're a young woman, you've got lots of years of bone health, heart health, joint health -- we try to leave the ovaries. And that's possible about 80% of the time.
[00:29:44.31] Our goal is to make life as normal as possible after treatment for cervical cancer. I think over the years, certainly in my practice, we've tailored things more to try to make that possible. I think realistically you can improve quality of life after treatment for cervical cancer if you give people some idea of what to expect -- and you ask about issues, and you attempt to offer counseling. And offer hormone therapy if menopausal symptoms or vaginal systems are paramount. Dilators to make the vagina longer. And just making recommendations for more pleasant intercourse.
[00:30:24.57] We can use hormone replacement therapy after cervical cancer. It does not increase the risk of recurrence. Whether we use estrogen and progesterone, or whether we use estrogen alone, depends on whether there's a uterus present.
[00:30:39.12] After treatment is completed, you should be seen regularly. Usually we see people often in the first two years, because the recurrence risk is highest then. Typically people are asked questions. There's an exam -- pelvic exam as well as a Pap smear. x-rays and scans are ordered based on symptoms, and sometimes for other clinical reasons. Blood work is typically filed if you've received chemotherapy, to make sure all the organ systems are working. And you can expect long term management of side effects.
[00:31:14.35] Currently, we don't have any trials for cervical, vulvar, or vaginal cancers at the U. We'll be opening one associated with the gynecology oncology group that's using Avastin -- which is an anti-angiogensis drug -- with Taxol and Cisplatin -- the standard of care. We also haven't done it at St. Joe's, but we have the potential to open the same trial there.
[00:31:43.07] Do you guys want to ask questions after each one, or go through them all in the interest of time -- since we can run over on questions, I think, but we can't run over on the talk. What do you think? [INAUDIBLE] OK. Did you guys get little pieces of paper to write? OK.
[00:32:00.33] Ovary cancer. Fairly typical. This one is the uterus -- has lots of cancer on it. These are tiny ovaries, but they're filled with cancer. This is another example -- a very large ovary filled with cancer. So cancer doesn't have to be big. It's the second most common gynecologic cancer. It's 3% of new cancers in women. About 1% of women will develop ovary cancer in their lifetime. Symptoms are vague, so it's not often found until late stages. It most commonly occurs in women who are menopausal -- ages 50 to 75. And you can see here, roughly in 2009 the American Cancer Sociey estimated roughly 22,000 cases with 15,000 deaths. White women have the highest incidence, Hispanic women are second, followed by Asian-Pacific Islanders and black women. In 2006 -- found that white women were more likely to die of ovary cancer, but black women were next, followed by Hispanic, and again American Indian.
[00:33:11.35] There are several types of ovary cancer. Epithelial is the most common type that you think about, when you think about ovary cancer that gets all the press. It makes up 85% to 90% of ovary cancers. It's thought to come from the surface cells of the ovary. Peaks at age 63. There are both invasive and borderline types that I'll talk about. Germ cell tumors typically occur in youngsters. They come from cells in the ovary that develop into eggs, and they're less common. And then sex cord-stromal tumors. Granulosa cell is probably the most common -- perhaps somebody's had or heard of it. They occur in the connective tissues, or the body of the uterus, not where the eggs are being formed. And many occur at a young age as well.
[00:33:53.25] Causes are not well defined. People have theorized that if you make a lot of eggs -- because chickens get ovary cancer -- if you make a lot of eggs, you're more likely to get ovary cancer. Obviously a genetic predisposition, but that only accounts for 8% to 10% of ovary cancers. Talc exposure. Talc used to have asbestos in it. We're not sure if it was the asbestos, but there's a relationship between using talcum powder and having had ovary cancer. Germ cell and sex cord stromal tumors, nobody has any theories.
[00:34:26.15] Risk factors. Positive family history of breast, ovary, endometrial, and colorectal cancers all increase your risk of each other. A personal history of breast cancer increases your risk of ovary cancer. Mutations in BRCA 1 and 2 genes increase your risk. Obesity, not having children, late first pregnancy, early menses, late menopause, talc.
[00:34:52.26] Hormone replacement therapy studies are all over the board about that -- whether or not it increases the risk or not. White race has a higher predisposition. Increasing age. Living in North America and northern Europe -- something about the latitude. No prior breast feeding. Using Clomid for greater than 12 cycles -- not the other infertility drugs, but Clomid. Not having any kids. And oral contraceptive use is protective -- it cuts your risk in half.
[00:35:21.20] Genetic susceptibility accounts for 8% to 10% of ovary cancers. BRCA 1 and BRCA 2 are the most common that you hear about. With BRCA 1 the risk of ovary cancer is 20% to 40%, and it's less for BRCA 2. HNPCC, or hereditary nonpolyposis colon cancer, is usually -- Lynch syndrome, perhaps you've heard of that -- is usually associated with endometrial cancer, but if you have that mutation about 12% of women get ovary cancer as well.
[00:35:54.24] You can reduce your risk. Premenopausal women who have BRCA 1 or 2 mutations and have their ovaries removed, not only reduce their risk of ovary cancer, but also of breast cancer.
[00:36:10.21] If you have a positive family history -- say if you've got one first degree relative -- your risk goes from 1% to 4-5% for ovary cancer. If you have two or more members, it goes to 7%. If you got two or more first degree relatives, it goes to 25-50%. Women with a strong history should be offered genetic counseling. People can ask for it, but it's really our job to offer it.
[00:36:36.37] There is really no viable screening test for ovary cancer at this time. You hear about CA 125, you hear about transvaginal ultrasound -- they're expensive, they're not sensitive or specific enough, they're not proven to pick up early cancer. And unfortunately, it's not the late ovary cancer that you're worried about -- you'd like to pick it up early.
[00:37:01.40] Other risk reductions. Taking your ovaries out prophylactically -- meaning before you have developed cancer. That's typically used for BRCA 1 and BRCA 2 patients. Tubal ligation cuts your risk in half. Hysterectomy reduces your risk. Oral contraceptive use, particularly for five to 10 years, reduces your risk. And that reduction seems to last for a good 30 years, so long after people would typically discontinue oral contraceptives. And having more than three pregnancies is protective, but I'm not sure that people would decide just to conceive just to protect themselves against ovary cancer. But nonetheless, it's been noted.
[00:37:41.56] Symptoms. They're about as vague as you can get. Bloating, discomfort, bowel complaints, some sort of pelvic or abdominal pain, urinary complaints without really having a bladder infection, difficulty eating, unexplained weight loss, frequent urination, new constipation, new fatigue, indigestion. All very common symptoms that often send people down a path looking for other more common diseases -- like irritable bowel, for example.
[00:38:16.25] The evaluation. You should expect a physical exam, including a pelvic exam. There may be a transvaginal ultrasound involved. There may be an abdominal or pelvic CT involved. And part of that depends on presentation and complaints. PET scans -- we use those fairly frequently, they're now approved for both the initial diagnosis of ovary cancer and the follow up. Chest x-ray to look for disease in the chest. Tumor markers that are appropriate for age. Look at blood work for other organ systems -- kidneys, liver. And if there's some primary bowel complaint, or we're worried about the colon, we might ask for a colonoscopy. If the stomach issues are prime, we might ask for an upper endoscopy.
[00:39:04.51] Diagnosis. Just like for cervix -- have to have a biopsy, have to to have some tissue. It's not how it looks on the scan. It's not the numbers -- you need tissue.
[00:39:17.17] Tumor markers are blood tests that can be drawn to follow up cancers, typically. They're not usually diagnostic. Common ones that you've probably heard about. CA 125 -- most frequently thought of with ovary cancer, but it turns out that pancreas cancer is the second most common for which it's elevated. CA 19-9 -- the reverse is true. More often elevated for pancreas cancer, but ovary is the second most common. HE4 and OVA1 -- I'll talk about briefly, those are newer tests approved by the FDA. Problem with CA 125 -- it's elevated in about 80% to 85% of advanced cancers, but only in about 30% to 50% of early cancers. That's why it's not a screening test. And in premenopausal women, endometriosis makes it high, pregnancy makes it high, being on your menses -- if you have it drawn then -- makes it high. So it's not a screening test.
[00:40:12.51] And as I said, the FDA recently approved two new tests, HE 4 and OVA 1. Again, they're not screening tests. HE 4, or human epididymis protein 4, has one use -- it's for monitoring progressive disease in people who have known cancer. It's particularly useful in women who might not have the CA 125 as a marker. There's also a recent paper that showed that it might be useful in differentiating in premenopausal women, whether or not the cyst on the ovary might be endometriosis, or might be cancer. OVA 1 is a blood test that sort of vaguely takes five different assays, and they use this algorithm and they come out with an answer. We're all a little bit nervous about this, because the company owns the algorithm and there's not a lot of explanation about how it all interacts. But it's a test that is being sold, and has been approved by the FDA, for determining whether or not somebody has a high enough suspicion with regards to their pelvic mass -- as to whether or not they should be referred to a gynecologic oncologist for care, or whether they should see a regular gynecologist.
[00:41:29.44] Germ cell and sex-cord stromal tumors have unique markers that we follow during treatment as well.
[00:41:37.57] Pappilary serous is the most common type of epithelial ovary cancer. It's uncommon below the age of 40. It's what you usually hear about. Most present at advanced stages.
[00:41:47.69] There's a subtype called low malignant potential, or borderline ovary cancers. Those are also epithelial, but they're very different. They usually present at an early stage. They now are usually treated with surgery both primarily and if they recur. Their recurrence rate is quite low. And occasionally they have aggressive features and we treat them with chemotherapy -- but for the most part it's surgical.
[00:42:12.38] And this is just an example of a big borderline cancer -- my hand next to it.
[00:42:21.71] Germ cell cancers -- 3% to 5%. They're almost always one-sided, unilateral. And most of them, again, present at Stage I -- meaning confined to the ovary. Tend to be very treatable. Again, occurring mostly in youngsters.
[00:42:35.26] Sex-cord stromal tumors. Again, occurring at earlier ages. The most common is the granulosa cell tumor that you most likely hear about. 5% to 6% of ovary cancers. Again, they're usually one-sided -- usually confined to the ovary. And again, typically treatable.
[00:42:50.90] Overall, treatment for ovary cancer is usually surgical, followed by chemotherapy. Sometimes the cancer's too advanced. We look at CT scans. We do an exam. We think that we can't achieve the goal of surgery -- which is to remove all the visible disease -- so we have radiologists do a biopsy, often under ultrasound guidance or CT scan guidance, of a mass or fluid to try to determine what cell type. Sometimes we don't really realize this until we've gotten to the operating room and already made an incision, and we just take the biopsy ourselves. Other times we do laparoscopy to determine it. And in that case, usually we give chemotherapy first, with the goal being to shrink the cancer, and ultimately to try to perform surgery.
[00:43:38.77] Surgical treatment most commonly is an incision on your belly that usually goes from the pubic bone to well above the belly button. Remove the uterus if it's still present -- both tubes and ovaries. The omentum, which is a fat pad that hangs down off your stomach and your colon -- it often collects tumor. Lymph nodes sit in the pelvic area, along with your hip bones here and along the aorta. Lumps and bumps that we see, we remove -- nodules. We take biopsies if we don't see anything -- to let the microscope look and make sure there's no cancer there. And, again, sometimes we have to modify things based on patient desires, age, and overall health.
[00:44:20.91] So the example of the omentum that I was talking about. It's attached to the colon and hanging down. It's pretty typically filled with cancer.
[00:44:29.95] We have some devices that we use to try to remove the disease. The goal of surgery being to get rid of everything visible. This is a leep. You think of it more commonly being used on the cervix to take off abnormal cells, but we sometimes use it to scrape abnormal cells off the lining of the body. We have this ultrasound machine -- it's handheld -- it breaks up tumor cells, washes them away, and sucks them out as well.
[00:44:58.71] Given that there's a fair amount involved in the surgery, the NIH recommended that women with a high chance essentially of having an ovary cancer, should have the opportunity to have that surgery performed by a gynecologic oncologist. And this is part of the reason -- 46% of women with ovary cancer are not staged appropriately. Meaning they haven't had the right surgery to look for where the disease is -- to determine treatment, to determine prognosis. Gynecologic oncologists get it right most often -- not 100% of the time. OB/GYNs get it right half of the time. And general surgeons -- who do a lot of the surgery in the community -- get it right about one third of the time.
[00:45:40.83] Surgery has two goals -- staging and getting the disease out. The more disease you get out, the less you leave behind, the better people do.
[00:45:49.67] If you take an ovary cancer that's confined to the ovary, like this one, that looks like you could take out an ovary -- you don't see anything else in abdomen, the lymph nodes look normal-sized, the fat pad looks normal, don't see any lumps and bumps. 30% of those people will have microscopic disease if you do enough biopsies and remove lymph nodes. That's why it's not sufficient to just take the uterus tubes and ovaries out.
[00:46:10.65] Stage. Again, like most stages. 1 is confined to the organ. 2 has spread a little bit away from the organ, but still in the pelvis. 3 has spread to the fat pad and the lymph nodes. And 4 to the liver, the lungs, outside the abdomen.
[00:46:28.36] With run of the mill ovary cancer, epithelial type, most people present with Stage 3 and 4.
[00:46:35.57] Survival. Very good for Stage 1, but we don't catch that very often. Much less for Stage 3 and 4.
[00:46:46.02] If you look at people who we've been able to take all the cancer out, get them to no visible disease at the time of surgery, 75% of those women will be alive a year after diagnosis. Many of them will have revisited chemotherapy, however. 46% are still alive at five years, and most of those women have seen multiple cycles of chemotherapy.
[00:47:11.12] Definitive therapy, as I've said, is staging and debulking. Chemotherapy is always recommended -- it's not always accepted, but it's always recommended. If you have Stage 1 disease, then usually you can get away with three cycles of chemotherapy -- or often you can. All other stages -- 2, 3, and 4 -- you get six cycles of chemotherapy.
[00:47:31.69] Borderline cancers. Surgery, debulking -- usually don't need chemotherapy. Fertility sparing treatment is appropriate, these occur in slightly younger women. It's OK to leave the other ovary -- the recurrence risk is higher but the survival doesn't change. It just means they're more likely to need another surgery. It's also an age group that the interest is in having more children. Fertility is an issue. It's acceptable to use fertility drugs in this group.
[00:47:59.84] Germ cell cancers and sex-cord stromal tumors. Again, staging. It's also appropriate to use fertility sparing surgery, because these are often younger women. We do use chemotherapy, increasingly so. I'm on the NCCN ovary panel, and there's a couple of medical oncologists on the panel who treat kids -- and mostly kids get this disease. And we used to give everybody three to six cycles of chemotherapy -- that was pretty toxic, but kids tolerate chemotherapy well. They really have moved to -- if you can take all the disease out at the time of surgery -- to using chemotherapy less and less for this disease, and waiting to see if it comes back.
[00:48:41.92] Again, fertility sparing I've alluded to. It's acceptable to leave the other ovary, to leave the uterus if there's no disease on them. You, however, do have to remove lymph nodes, omentum, do the biopsies, and prove that the cancer hasn't spread. Otherwise, you've not done the woman a favor.
[00:49:01.74] Chemotherapy. I'm going to talk about the way it's given. We used to give it all intravenously -- through an IV. We now, for more advanced disease, also give it intraperitoneally, which means into the abdomen. There's a little port that sits on the rib cage here under the skin, and the catheter tip runs into the abdomen. The nurses, in infusion, hook up a needle there and give chemotherapy directly into the abdomen. Recent studies have shown that if you can get the cancer out to less than one centimeter, that intraperitoneally chemotherapy in combination with IV chemotherapy is the most appropriate, and leads to the best outcomes.
[00:49:41.82] You can imagine that if you're putting chemotherapy directly into the belly -- you're distending the belly, it's uncomfortable, there's more nausea associated with that drug combination -- that quality of life might not be as good. And it's not, but at one year after treatment it's the same as somebody who received just the intravenous. The key is right here. People who get a combination live 16 months longer, and have six months longer before the disease comes back. So if you can debulk people -- getting all the disease out -- if it's appropriate to offer them that -- the disease is Stage 3, confined to the abdomen -- then we should offer it. Now, people don't always accept it because of the side effects . It's arduous, you get treated on day one with intravenous, you get treated on day two with intraperitoneal, you get treated again on day eight with intraperitoneal. It's a lot of work compared to coming in once every three weeks for intravenous chemotherapy. So it's much harder for the patient receiving it, and it's harder for the people delivering it.
[00:50:48.79] Some of the things that we do to people. We create early menopause, or we make menopausal symptoms worse. If you've already gone through menopause, you still have your ovaries and we take them out -- many women notice their hot flashes are worse. I think there's a change -- the ovary was still making a little bit of hormone. We cause scar tissue. We cause adhesions -- sometimes those lead to bowel obstructions. Most of the time they don't lead do it -- but it happens. Chemotherapy side effects. The acute ones, everything you think of -- hair loss, nausea, fatigue, effects on your blood counts, anemia. More chronic changes -- neuropathy, or numbness and tingling in your fingers and toes, which can be permanent. We occasionally use radiation -- you know about the side effects of that from the cervical talk. And it's psychosocial. It's depressing, we cause a lot of anxiety -- we definitely change people's lives.
[00:51:43.99] You can use hormone replacement therapy again after the treatment for ovary cancer. We usually use it only if people are having symptoms that aren't treatable by any other method, or if their quality of life is just poor. If you're going through chemotherapy you've gone through this life-changing surgery -- emphasis is on quality of life. There's mixed data regarding whether or not it enhances progression of disease. And so really it concentrates on quality of life.
[00:52:15.16] A lot of our patients use complementary techniques during chemotherapy. They usually use it before, during, or after. Some of the common reasons are control of nausea and vomiting. Things like acupuncture, acupressure, sea band stimulation basically of the anti-nausea point, mindfulness stress reduction, guided imagery, ginger for control of nausea. Relief of treatment associated symptoms, like menopause and control of neuropathy. All common reasons to use complementary medicine.
[00:52:59.03] I think I would encourage you to feel free to discuss it with your oncologist. Many people don't -- many oncologists are resistant -- but it's so commonly used that we find that people are sort of reluctant to tell us about it. So talk about it, ask about it. There's a website that we can actually go to, put out by Memorial Sloan Kettering, which is a cancer institute in New York. It gives us some guidelines if there's information on what's appropriate, what's not appropriate to use with drugs. There's also some rationale for combining natural products in traditional chemotherapy -- there's a fair amount of lab research on that. You can sometimes diminish effects on normal tissue, so that you can give higher doses -- some of you in the audience know about glutamine, which we give for people who are getting Taxol to help reduce the neuropathy. Again, a natural product -- we can give more chemotherapy, and hopefully get a better response. You can potentially make the chemotherapy more active by combining it with natural drugs. Some of the antioxidants have been shown to do this, with chemotherapy drugs like ARA-C and VP-16. And it turns out that somebody did a study with green tea powder, and found that you could get mitomycin C and Adriamycin -- which are two chemotherapy drugs -- into cancer cells better in conjunction with the green tea power. So it's all interesting. It's not clear that what you take by mouth actually gets to the cancer, and is as functional as it is in the test tube -- but for the most part, most of these products are safe.
[00:54:28.62] Recurrence after initial treatment. The longer the cancer takes to come back, the better off you are. If it's been a very long time, and for us that's more than a year, we would consider repeat surgical debulking -- meaning repeat removal of the tumor if we can. And usually we would use the same chemotherapy drugs. If it's been less than six months since you finished your original treatment, then it's difficult to get the cancer to go away. It's considered chemotherapy resistant. It's not clear that there are any drugs that are going to work great, and we certainly would consider clinical trials for those patients. But often we use a long list of drugs that we have available, and try to fit them to people's lifestyles and fit them to their tumor.
[00:55:17.56] If more than six months has passed since you got chemotherapy and a recurrence occurs, you have about the same chance of responding to the initial drug.
[00:55:28.56] And if you've had many treatments -- you're tired of treatment, your body's tired of treatment, there are no other treatment options, clinical trials aren't an option -- then palliative treatment is appropriate. And that's primarily concentrating on treatments to relieve symptoms. So sometimes we do surgery if people have a bowel blockage, to relieve that -- to make people feel better. People sometimes accumulate fluid on their abdomen -- we can drain that, and make people feel better. Sometimes that as people get fluid around their lungs, we can drain that and make people feel better.
[00:56:05.75] Surveillance after completion of treatment. You're all done with chemotherapy, you will see us regularly -- typically more often in the first two years. Again, because things are most likely to recur during that time. Usually every three months for a year, every four months for another year. You can expect an exam. You can expect to be asked about how you're doing. You can expect a Pap smear once a year. And a tumor marker check usually at every visit. We do scans -- PET scans, CT scans -- as indicated. They're not necessarily routine.
[00:56:41.49] One comment about CA 125 here. It will often rise about four to six months before we can pick up disease on exam, and before you can pick it up on CT scans or PET scans. So that's one of the reasons why we monitor it. As you may know -- I think it even made the Wall Street Journal -- there was recently an article that suggested that it doesn't matter to survival if you check the CA 125 regularly, and if it goes up before people have symptoms. So there's been a move or a push to have us check CA 125 less often, and only check them if people have symptoms and surveillance. I don't think any of us have managed to convert to that behavior, but the evidence is out there.
[00:57:33.35] And then endometrial cancer is the last one. You can see it here. This is the uterus, it's been cut open. There's a tube. Probably an ovary over there. There's a cancer, it looks fairly typical.
[00:57:46.60] There are two types. One that comes from the lining of the uterus, called endometrial. One that comes from the body or the muscle of the uterus, called sarcomas. Endometrial is the most common.
[00:58:00.38] It's also our most common cancer. It's the fourth leading cancer in women. It's the seventh cause of death from cancer. And you can see it is more common -- 42,000 cases in 2009, estimated by the American Cancer Society, and about 7,800 deaths.
[00:58:17.45] Average age is 60. Again, postmenopausal. 25% occur in premenopausal women. 5% of women less than 40. If you have an endometroid -- name sounds very similar -- ovarian cancer, 15% to 20% of those women will also have an endometrial cancer. Endometrial cancer's more common in white women, but just like for cervix cancer -- black women typically do worse stage for stage. Most people with this cancer present at an early stage. Most people just need surgery for treatment.
[00:58:54.58] Risk factors. Hereditary nonpolyposis -- colon cancer. I mentioned for ovary cancer that there was a 12% of ovary cancer if you have that gene mutation. There's about a 20% risk of endometrial cancer. This is the one group for which screening is recommended. Annual endometrial biopsy beginning at the age of 35. And often if people are having their colon removed because they have a very high risk colon cancer, they have a hysterectomy at the same time.
[00:59:25.70] Endometrial cancer, there are two types. One is thought to be estrogen-related, either because you're making too much estrogen in your fatty tissue, or because you were taking only estrogen pills after menopause for menopausal symptoms. It has a precursor lesion -- it's well differentiated, well behaved, typically slow growing, typically confined to the uterus. And surgery is the mainstay of treatment. The other type has no excessive estrogen -- it tends to occur in slightly older women, it tends to be higher grade, it tends to be poorly differentiated, it's more aggressive and more likely to spread outside the uterus. Risk factors for endometrial cancer -- obesity, diabetes, hypertension, not having any children, late menopause, personal history of getting a breast, endometrial, colon, or ovary cancer. Tobacco use cuts your risk in half, but it increases your risk of lung cancer -- so I'm not goint to recommend it.
[01:00:21.47] [LAUGHTER]
[01:00:24.59] Unopposed estrogen for greater than 10 years. It was fairly common. Women on estrogen and progesterone had periods. Period are inconvenient after menopause, so the progesterone was dropped and people took just estrogen.
[01:00:39.01] The precursor lesion is hyperplasia, or atypical hyperplaysia. Say you show up with bleeding after menopause, somebody does a biopsy, and you have atypical hyperplasia. At that moment in time, you have a 30% chance of having a coexistent endometrial cancer that wasn't picked up on biopsy. If you don't have one then, 20 to 30 years from then you're just as likely to get one. So it's considered the precursor, just like CIN or CIS is a precursor lesion in cervix. Oral contraceptives cut your risk in half, and tamoxifen increases your risk -- but as you know it decreases your risk of recurrent breast cancer, and improves survival in breast cancer. So that's a discussion you need to have with your medical oncologist. Other drugs like tamoxifen -- Evista, aromatase-inhibitors -- don't increase the risk.
[01:01:32.48] There's no routine role for screening, unless you have Lynch Syndrome -- or HNPCC.
[01:01:40.27] It's probably not preventable. There's and ongoing GOG study, 210, that's basically asked everybody in the country who was willing to join on the study, to contribute a small piece of their tumor. It's stored in a tissue bank. Somebody, sometime is going to do genetic studies on that, molecular studies, hormone studies, and try to determine is there some way to look -- since it's such a common cancer -- in the bloodstream. Is there a simple marker that we can determine a way to prevent this.
[01:02:12.40] Symptoms. Any kind of bleeding after menopause. It could be a spot, it could be discharge, it can be just a little bit of discoloration on a pad. It's not normal, it should be evaluated. Most bleeding isn't cancer, but almost all cancers -- 80% to 90% -- are associated with abnormal bleeding If the uterus gets big and the blood's not coming out, you might have pelvic pain or pressure, and the uterus might be enlarged.
[01:02:38.94] Evaluation. You can expect a speculum exam. You can expect, typically, a Pap smear if you haven't had a recent one. You can expect a pelvic exam. And you can expect what's called an endometrial biopsy. For anyone who's had it, it's a tube about this long -- a couple millimeters wide. It goes up through the cervix and it sucks cells out of the lining of the uterus. It's about 30 seconds of pretty intense menstrual-like cramping -- but we've used it to replace the DNC, so people don't have to go the operating room to have a formal DNC. If you still have bleeding, if the endometrial biopsy didn't give an answer or a diagnosis -- you still have to go for a DNC.
[01:03:18.51] Common types are endometroid. High risk types are papillary serous and clear cell, as well as carcinosarcoma.
[01:03:27.91] Grade. One of the things you'll hear -- people often come in and say, I'm Grade 1. And it's not where it is, it's how it looks under the microscope to the pathologist. It does to some degree dictate behavior, so Grade 1 is typically well behaved -- confined to the uterus, slow growing. Grade 3 is typically more aggressive -- poorly behaved, and tends to spread to lymph nodes and beyond the uterus.
[01:03:52.30] Stage, on the other hand, describes where it has spread to -- and that's determined at the time of surgery. The staging system was revised this past year, so I have to learn my third staging system. In theory they changed it to associate stage where the cancer is, to align it with prognosis. But all of our treatments are based on the old staging system, so we're in a little bit of confusion right now. Stage 1 -- again, confined to the uterus. Stage 2 -- spread to the cervix, which we don't consider part of the uterus. Stage 3 -- spread to the ovaries, spread to lymph nodes. Stage 4 -- bladder, bowel, and beyond.
[01:04:36.61] Again, 5 year survival is quite good for early stage disease -- Stage 1. And Stage 4 -- much lower. And then the high-risk types -- uterine papillary serous, clear cell, carcinosarcomas -- each one of those stages is much, much lower within each stage.
[01:04:57.86] Again, pre-op evaluation. Exam. Blood work. Blood work to look to see what other organ systems are doing, how they're functioning. CA 125 -- you think of it for ovary cancer, but for endometrial cancer it's useful in predicting whether or not disease is outside the uterus. So if it's elevated and you have endometrial cancer, about 80% of the time there's disease in the lymph nodes, or somewhere outside the uterus. What it means for the oncologist is at the time of surgery they're obligated to, not only take the uterus tubes and ovaries out as well as the cervix, but also make sure they get lymph nodes in the pelvic area, in the para-aortic area, a little piece of the fat pad -- that omentun -- and search well for disease. Chest x-ray and then scans are used selectively.
[01:05:46.03] Surgery again, very similar to what you heard for ovary. Uterus, tubes, ovaries, cervix. Sometimes lymph nodes in the pelvic area, as well as along the aorta -- the main blood vessel in your body. And for high-risk types, the omentum, or that fat pad that hangs down off the bowel.
[01:06:03.46] Surgical treatment for endometrial cancer is done for treatment, as well as staging.
[01:06:12.24] And it turns out -- we used to think that ovary cancer was the only cancer that we took care of that it mattered whether or not you got all the disease out. But it turns that if you have endometrial cancer and it's spread beyond the uterus, that if you can take out all the big lymph nodes, if you can take out any bulky -- or lumps and bumps that you see in there -- that the prognosis is better. So over the years we've moved to doing that, as well as for ovary cancer. There was a paper recently, in 2009, that looked at whether or not we could safely leave ovaries in premenopausal women. So not very many women younger than 50 get this cancer, but there are a number that do. And menopause is a real issue. It's uncommon if you have a Grade 1 cancer that doesn't go very deeply into the wall of the uterus, for it to spread to the ovaries -- about 1% to 3%. So it's acceptable if somebody's willing to take the small risk of spread to the ovaries, to leave the ovaries so people can avoid menopausal symptoms.
[01:07:16.33] Sometimes people don't want surgery. Sometimes we can't offer surgery for medical reasons. Some of these situations. Young women. Say they're in their teens -- that's the most common example for us -- who have an endometrial cancer who still want to have kids. You can treat them with progestins, but you have to do a DNC every three to four months to determine that it's working. It's not as effective as surgery, but it's the only thing that allows you to your uterus and potentially have a child. Sometimes we see women who are not very healthy -- they can't withstand surgery. We offer them progestins, or just radiation. If it's Grade 1 or Grade 2 cancer -- confined to the uterus -- radiation works just as well. It saves them from the risk of anesthesia and surgery. We run into people who don't want surgery. We offer them radiation.
[01:08:06.84] You can turn the camera off then. [INAUDIBLE]
[01:08:11.17] If a woman doesn't want surgery, we'll offer them progesterone or radiation. If a woman doesn't want surgery or radiation, we can offer them progestins. I saw a lady today, who I've been seeing since 2007, who won't have anything. She gets transfused -- not quite weekly -- but she bleeds a lot. She gets blood regularly, she gets iron infusions. But she has been disinclined to have surgery. And that's a prerogative.
[01:08:42.77] Sometimes the cancer has spread to the cervix, and we don't think we can take it out surgically without leaving some of it behind -- which is considered a no-no for us. So in that case we radiate people -- again, shrink the cancer. And then about four weeks after the radiation's finished, come back and do a hysterectomy. It turns out that treatment course works better, because you're then able to get all the disease out.
[01:09:08.56] Radiation, for anyone who's had it, usually starts four to six weeks after hysterectomy -- after you're well healed. It's usually given to the outside of the body. And then for endometrial cancer, sometimes to the top of the vagina with what we call a cylinder -- it looks like the world's largest tampon.
[01:09:34.79] There are times when we do surgery and we don't know there's an endometrial cancer. We went in for an ovary mass, it was benign. Somebody wanted a hysterectomy, we took the uterus out, and we find a cancer. Sometimes we look in the uterus, and it doesn't look like the cancer has invaded into the wall, so we don't remove lymph nodes. Sometimes the patient has trouble during surgery, and we just sort of need to make the surgery as fast as possible. And sometimes it's just not done because the person doing the surgery wasn't aware they should do it. In that case, usually, if the cancer goes deep into the wall of the uterus -- is a high-risk type cancer -- we offer radiation therapy to improve survival.
[01:10:17.07] Chemotherapies that are used for endometrial cancer. Adriamycin and Cisplatin are the most common. Taxol and carboplatin is also used. And then for high-risk cancers, we use things called ifosfamide.
[01:10:36.85] Surveillance. You can expect a regular visit with a gynecologist or an oncologist. Typically again, frequently during the first two years when recurrence risks are highest. And then less frequently. And after five years, once a year. As long as you can crawl in for your Pap smear, you get a Pap smear after five years. Physical and pelvic exams. We do a Pap smear at the top of the vagina, because it turns out that that's where the recurrence risk is highest. We also follow CA 125 if it was high before surgery, or if you were treated for a high-risk type of cancer. And we only do scans if they're indicated, and blood work if you've had prior chemotherapy or radiation.
[01:11:20.67] Symptoms of recurrence. Obviously, pretty much [? none of it ?] depend on where the recurrence is, but vaginal bleeding -- since the top of the vagina is one of the most common spots. Pain. Coughing up blood if it's spread to the lung. Headache. Neurologic symptoms -- if it's spread to the head. Ascites -- which is fluid collecting on the abdomen. Or sometimes fluid will collect around the base of the lung as well -- called a pleural effusion. The treatment is determined by where it is, what previous treatment you've had, what your desires are, and how healthy you are. It's quite frankly, with endometrial cancer, tough to treat recurrences. The exception being if it recurs at the top of the vagina -- that's fairly responsive to radiation treatment. And you can see 5 year survivals are as high as 53%.
[01:12:14.55] Progestins. 15% to 24% response rate, that lasts about four months. Again, there are pills you can take, they're fairly innocuous, but the response rate isn't very high. Clinical trials for people who need chemotherapy is an option that we recommend. Chemotherapy response rates are about 35%, they last about six months. So again, we haven't found the ideal chemotherapy.
[01:12:46.66] Surgery we occasionally use for recurrence if it's isolated -- one spot in the lung, one spot in the liver, top of the vagina. Sometimes we are able to remove it.
[01:12:58.82] Side effects of treatments. You've heard about the side effects of chemotherapy, radiation. The more you combine, the more the side effects.
[01:13:10.48] Sarcomas are the other cancer, they come from the muscle of the uterus. They make up 1% to 4% of uterine cancers. They're typically treated with hysterectomy -- removal of the uterus, and cervix, and tubes and ovaries. They're less likely to spread to lymph nodes, they're more likely to spread through the blood stream to liver and lungs. So those are areas that we do radiologic tests on, to see if anything's spread. They're usually more aggressive than the run of the mill endometrial cancer. Radiation doesn't increase survival afterwards, but it does keep them from coming back in the pelvic area -- so it's often offered. We do use chemotherapy for some of them, and for others we use hormones.
[01:13:57.03] The GOG is a nationwide cooperative group that's united to treat women's cancers, and pre-cancers to some degree. We participate with it at the university, as does St. Joe's. Depending on just time mostly, sometimes we have more trials open at St. Joe's than we do at the U, and vice versa. If a trial is at the university, we try to bring people from St. Joe's over there, and the opposite is true as well -- in an effort to just sort of maximize people's exposure to trials.
[01:14:33.90] These slides show some of the trials that are available for ovary and endometrial cancer. 212 is designed to see if we can improve on outcomes after finishing chemotherapy. So you've had your debulking surgery, you've had your initial six to eight cycles of chemotherapy, your disease is gone, it's not on x-ray, it's not on blood test, it's not on exam. You have a 50-50 chance of it coming back. There's a trial that's looking at giving 12 additional doses of chemotherapy intravenously once a month, to see if you can improve survival. It works for lymphomas and leukemias, it's not so clear it works for ovary. But the trial is being done. And it's with Taxol, two different forms of it -- and paclitaxel and ziotax. And then, as for any properly done trial, there's a placebo arm -- meaning one group of patients isn't getting any treatment, because they have to be used as the comparison group. St. Joe's also has a Phase II study of Taxol and carboplatin, with or without an antiangiogenesis drug for ovary cancer.
[01:15:52.54] And for endometrial cancer, St. Joe's has a trial open with radiation with or without chemotherapy, for cancer of the endometrium. Recall this is the standard of care for cervix. And it's being looked at since, I think, about the third trial they've done -- not they at St. Joe's, but they with the radiation group -- looking at this issue. This is the molecular staging study of endometrial cancer that I mentioned. Just collecting tissue so that people can look to see -- can we understand this better, can we detect it, and potentially can we prevent it. St. Joe's also has a Phase II evaluation of the AZD6244 in the treatment of recurrent or persistent endometrial cancer. And that's a drug that interferes with growth factor.
[01:16:41.72] University of Michigan. We participated in the GOG trial -- this, again, collecting all gynecologic specimens. And again, they're being stored for people to ask specific questions. And then Ron Buckanovich, who's a medical oncologist in our division, who runs some Phase I trials -- meaning that we don't know if they're active against ovary cancer. We know they have some activity against cancers in general, and we're looking to see what dose is most appropriate. He has a Phase I study of an antiangiogenesis drug in people with relapsed ovarian or peritoneal cancer. And then otherwise, at the University of Michigan we have the other GOG trials open that we have at St. Joe's.
[01:17:28.34] And that's it. Questions? Anything I can --
[01:17:32.71] [APPLAUSE]
[01:17:34.49] Almost made it, but not quite.
[01:17:36.17] SPEAKER 1: So if you have a moment to write down your questions, we can pass the microphone around for questions. Complete the second part of your survey. And if you're interested in the focus group, make sure that you sign up on the way out. So again, does anyone have questions they want to bring [INAUDIBLE] DR. JOHNSTON: I don't mind questions that are called out, but I think that because -- I have to repeat them. OK. If I stop spitting into it with my braces [INAUDIBLE]
[01:18:16.14] [READING QUESTION]
[01:18:16.59] What did you say about the risk of taking estrogens and progesterone in ovary cancer? We used to just give it. Quality of life on chemotherapy wasn't great -- women were menopausal, hot flashes. It was routine to give everyone who had a hysterectomy estrogen, and we gave it. And then studies started coming out that said, well you know maybe estrogen increases your risk of ovary cancer. So once you had ovary cancer, maybe it made it worse to actually give it. And it turns out that we use tamoxifen, which is an antiestrogen, to treat some ovary cancers. So people started to be a little bit hesitant about giving out estrogen. And people have actually attempted to do studies. And there are some theoretical reasons why actually giving estrogen might actually reduce the recurrence of ovary cancer. And there are other studies that say, well the women that took estrogen didn't do as well. So when you have a cancer that has such a poor prognosis, you need a lot of women to be able to answer this question. So I don't think the question's been answered satisfactorily, and so most of us have, quite frankly, just stepped back a little bit -- like we have with women in general with menopause -- and said, evaluate the symptoms, evaluate the treatment options, and just try to make people feel as good as they can. For most ovary cancers, the risk of taking it probably is very low compared to the risk of the disease itself. Does that answer the question? SPEAKER 2: So what about women who've never had [INAUDIBLE] but still had the treatment for a number of years. Does that increase the risk of getting it?
[01:19:57.79] DR. JOHNSTON: It's debated. Birth control pills, which contain both estrogen and progesterone, cut your risk in half. But it's a different estrogen in progestoral. And the problem with the Women's Health study that looked at estrogen and progesterone versus estrogen alone, estrogen and progesterone increased the risk of breast cancer -- which is the more common cancer in women. And estrogen alone did not -- they sort of forgot to advertise that part of it -- but it did not. But what they both did was they increased the risk of heart disease, particularly in women who have heart disease, and they increased the risk of stroke. So besides the ovary cancer, there's a lot of other issues that come into it. And if you have ovary cancer, you're at an increased risk for breast cancer. So some people don't want to add the estrogen if they're not super symptomatic -- to start increasing risk -- particularly if they've done well from the point of view their ovary cancer.
[01:20:54.53] [READING QUESTION]
[01:20:54.83] In what percentage of patients is the primary cancer source unable to be diagnosed, and how does this affect treatment and cure? There's not an absolute number, but it's common enough to have a diagnosis of cancer of unknown primary, and to have a standard of care for that. There are drugs -- and they change over time, in the years I've been doing this they've changed multiple times -- but there's a regimen that mostly medical oncologists, sometimes [? G1 ?] oncologists, end up giving. It turns out that the drugs that are always used contain at least two of the drugs that are active against ovary cancer. Because sometimes ovary cancer is a great mimic, sometimes we can't actually figure out -- the ovary's are normal sized, and yet it came from the ovary. So I can't give you an absolute percent. And it doesn't affect treatment and cure, because there's a standard set of drugs for that.
[01:21:58.24] [READING QUESTION]
[01:21:58.73] Please further describe the ovary cancer symptom of pelvic pain. It's vague, it's nonspecific -- I can't impress upon you how nonspecific complaints about ovary cancer are. I went to a CDC funded expert panel on ovary cancer and symptoms, and whether we could recommend screening or whether we could come up with a consensus on -- if you have this symptom you should get this work up. And basically, out of all that came a short little paper saying if people have symptoms don't just do a GI evaluation, think a little bit beyond that. If the GI evaluation -- meaning your colon, your stomach, your small intestine are all normal -- think beyond that, just don't say irritable bowel. For some people, it's just some pressure. And a lot of people it's what they notice in retrospect -- oh yeah, I had that. And then what I see is when people come back -- we've been following, and they've been treated -- and they say my pain is back. In retrospect, they remember they had the pain, but they may not have noticed it -- because, you know, you have aches and pains, a little pressure on your bladder, a little bit of bowel pressure, feel a little bit fuller than you usually are. And that's just life. So there's no set place in the body where it happens, there's no set change. Not a very satisfying answer, I know.
[01:23:26.36] Hyperplasia is overgrowth of the lining of something. Basically, it's usually in reaction to some sort of stimulus in the uterus -- it's in reaction estrogen. The lining is normally very thin in a postmenopausal woman because they're not cycling anymore, there aren't very many hormones from the ovary. But if there's estrogen, that lining gets thicker and thicker -- you can see that on ultrasound. And there are different types of hyperplasia. Some are associated with only a 1% chance of having an endometrial cancer, and some are associated with the 30% chance. But it just means, basically, overgrowth.
[01:24:15.86] [READING QUESTION]
[01:24:16.11] In patients with a family history of ovary cancer, is genetic testing recommend? Typically, if there are a couple of first degree relatives, we do end up recommending genetic counseling. Increasingly more people are accepting of that. Initially there were concerns about insurance, job loss, healthcare, costs. But I think people are more interested now in finding out. And if you've already got ovary cancer it's not really helping you per se, but it may help your children, it may your siblings -- and sometimes in retrospect, it helps your parents. So we do end up recommending it. We also screen people. So people who are BRCA 1 and BRCA 2 positive, we screen them with ultrasounds and CA 125's. Even though I showed you information that said that they're not very sensitive at picking up ovary cancer, it's the best we've got. So since they're at higher risk, that group gets screened.
[01:25:20.61] [READING QUESTION]
[01:25:20.97] Is HPV vaccine covered by most insurance? I would say yes. And kids -- uninsured children are covered by the Vaccine for Children Program. So up to the age of 18, I believe. Right? OK.
[01:25:40.70] [READING QUESTION]
[01:25:41.00] Is endometrial cancer connected to endometriosis? No. People who have endometriosis are at slightly higher risk for ovary cancer. But endometriosis is so common, and that slight increased risk is low. But it's not related to endometrial cancer -- even though it is the lining of the uterus simplistically growing outside of the uterus. The way they're related is that both are stimulated by estrogen. A big difference is endometriosis is usually in premenopausal women, and endometrial cancer is usually in postmenopausal women. But they're not related, even though the words are similar.
[01:26:25.78] [READING QUESTION]
[01:26:26.00] How many types of HPV testing in a typical screening? They just check for the high-risk types. There are specific tests out now that can test for just 16, but nobody's really recommending that right now as a treatment course.
[01:26:42.71] [READING QUESTION]
[01:26:43.29] Please review possible screening for ovarian cancer. So again, the only people for whom screening is really indicated are those with a strong genetic risk of ovary cancer. And that's because the modalities of ultrasound and CA 125, even if they're done regularly, just aren't very good at picking up early ovary cancer. And you end up doing a lot of surgeries for lesions, masses, cysts that are benign, without actually picking up the cancer. Or, in most of the series -- so there are a couple big series, one in England and one from Kentucky. They have 22,000 people, roughly, in each one. They weren't picking up early ovary cancers. People were -- their CA 125's started to bump, or they had something new on their ultrasound. The cancers were more often advanced when they went to surgery, even though they'd been followed regularly. It's hard. It's sort of dismaying, because you know you can do a mammogram for breast cancer, but until we can really somehow get to the ovary and see it and see what's going on inside of it -- it doesn't get big before it gets bad, it does something before it gets big. And a lot of ovary cancer is in small ovaries. So you're not necessarily going to pick up a small ovary on an ultrasound.
[01:28:08.61] SPEAKER 3:
[01:28:09.11] I have a question. When does a first degree [UNINTELLIGIBLE]
[01:28:15.60] DR. JOHNSTON: Your sister or your mom? Guess we could throw boys in there too.
[01:28:23.86] SPEAKER 1: Are there any other questions? Thank you very much, Dr. [INAUDIBLE]
[01:28:28.22] DR. JOHNSTON: Sure, thank you for coming.
[01:28:30.19] [APPLAUSE]
[01:28:34.08] [MUSIC PLAYING]

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May 13, 2010 at the Downtown Library: Multi-Purpose Room

Length: 1:29:00

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