publication date: May. 18, 2018
Conversation with The Cancer Letter
Fox Chase’s Rubin: Don’t morcellate and you won’t have to worry about cutting up missed cancers
Chief of the Division of Gynecologic Oncology, professor in the Department of Surgical Oncology, and the Paul Grotzinger and Wilbur Raab Chair in Surgical Oncology at Fox Chase Cancer Center
What’s your overall impression of the numbers and issues addressed by this study published in Obstetrics & Gynecology?
Obviously, it’s sort of tangentially related to the morcellation issue, obviously comes out of the morcellation issue, but I don’t think it sheds a tremendous amount of light on it, because the morcellation issue has primarily been related to the presence of an undetected leiomyosarcoma in patients having surgery for fibroids.
There’s not much you can get out of the Desai paper on that aspect of it. They only had, I think, five patients undergoing myomectomy who had cancer. We don’t know what kind of cancers they were, they might not even have been sarcomas, so it’s too small a dataset for that little piece of it.
In terms of the big picture, I would say there’s nothing in here that surprises me. What it says is when gynecologists are doing a hysterectomy for a presumed benign disease, they’re correct 98 percent of the time, and that’s not a bad record.
If you think about why gynecologists may be incorrect, I think there are a number of good explanations for it. You can’t get these things directly out of the paper because all we know from the inclusion criteria for this study was they were coded as having hysterectomy for benign conditions. If you ask yourself what benign conditions do women often have hysterectomy for it, I think you can begin to understand their results.
For example, abnormal bleeding is a very common cause for hysterectomy and gynecologists would typically evaluate women for the presence of, say, endometrial malignancy, which would be a common cause of abnormal bleeding by doing either office endometrial biopsy or dilation and curettage before the hysterectomy. Those things are pretty accurate, but not perfectly accurate, so I think they would account for some of the women who have what’s called corpus uteri cancer in this series.
Additionally, there could be—and the authors of the study mention this in their discussion—there could be women who are having surgery for precursor lesions of cancer, like complex and atypical hyperplasia of the endometrium. If it’s a precursor lesion, they would likely be coded as benign hysterectomy in the system, but we know that with that preoperative diagnosis, there’s about a 40 percent chance of having a uterine cancer, so they would account for some of the uterine cancers.
In terms of cervical cancer, Pap tests aren’t perfect. Some people have a normal Pap test yet have cervical cancers, so that accounts for some of it. Some of it could be women who go for hysterectomy without having a current Pap test, and that’s a mistake, unquestionably. And some of it could be women, again, who have precursor lesions like cervical dysplasia as their preoperative diagnosis. They go into this benign hysterectomy bucket, and they end up having cervical cancer in the final specimen. That is an issue, although it didn’t happen very commonly in this series.
In terms of ovarian cancer, that’s something that’s very difficult to diagnose early. There’s no effective screening for it so there probably are women in here who had, say, a mass, or a cyst on the ovary and the preoperative imaging and tumor markers looked benign. They’re in the benign hysterectomy bucket, but they had an undetected ovarian cancer, so I think they account for some of it.
In terms of the bigger picture for these women who had undetected cancer, hysterectomy is likely to be part of their treatment anyway, so if you say “Were they harmed?” I think in most cases, the answer is, “No.” There may have been a few women with cervical cancer, if they had an invasive cervical cancer a simple hysterectomy, which these were, is not the correct operation.
It also depends on the type of hysterectomy, right, whether it’s total abdominal hysterectomy, or whether it involved morcellation?
Yes, right, so that could be a little area of harm. I think, overall, 2 percent or so had cancer undetected. I think a lot of it could be explained by the things I mentioned and in most cases the hysterectomy was okay for the treatment anyway.
Are the stakes different for patients and how gynecologists preoperatively evaluate them, now that we have these numbers?
Well, I think the morcellation controversy, and the publicity surrounding it over the last four years, has really changed the practice in gynecology. I think there’s much less morcellation being done. I personally have never done it and I’m happy to say that. And, I think what little bit of it is being done is mostly being done in containment bags. So, I don’t think there’s any national data on this—it’s not like every time somebody does a morcellation they have to report it to somebody. We don’t know for certain.
My impression from talking to people nationally—I’ve been an examiner for the oral board exam in general obstetrics and gynecology for many years, so each year I examine around 30 candidates in OBGYN, and they present a case list of a year’s worth of cases, and morcellation has almost totally disappeared from the case list in the last three or four years. As I say, there’s no hard data source you could go to, but I think morcellation is a small fraction of what it used to be.
I think for the reasons I cited, I don’t necessarily think it’s a problem. If you’re talking about endometrial cancer, you know the common corpus cancers, certainly gynecologists are trained to be vigilant, they’re trained to do endometrial biopsy before hysterectomy for abnormal bleeding. They’re sort of already on board with looking out for that cancer. For cervical cancers, we have excellent Pap screening uptake in this country. I think there are relatively few patients having hysterectomies without having had a recent pap. I don’t see that as an issue.
The ovarian cancers are pretty much undetectable, so you’ll find one of these every now and then. Another question I had, how does this compare to, say, people doing surgery on other organs for presumed benign disease? If you looked a series of appendectomies, how often do you find cancer in the appendix, or a series of gallbladder operations for presumed benign disease. How often to you find a cancer there? I wouldn’t be surprised if it’s in the same range.
What are the exact clinical scenarios in which undetected cancer could be upstaged if you miss them?
Upstaging would only be done by morcellation—manual or power. This paper did not address that at all. It would just be morcellation. This paper did have a small number of myomectomies. It’s possible if you took a fibroid out in chunks, and it was malignant that you could upstage it that way. It’s similar to morcellation, basically. But there’s so few of them. I guess about 10 percent of these cases were myomectomy, and I think there are five cancers in the myomectomy patients as I recall.
The same would apply to the removal of ovaries, right? Besides morcellation, there is no other way of surgical dissemination of ovarian cancer.
That’s correct, basically. You’re right to think of it as two separate issues. One is the prevalence of undiagnosed cancer, and the second is, are these cancers being spread by an inappropriate surgical procedure?
There’s nothing in this Desai paper to address that specifically. Whether it’s open or laparoscopic or whatever would not spread cancer in the absence of morcellation.
There was no morcellation in any of these cases. So, it obviously relates to the morcellation issue. Now, if you’re thinking about chopping up the uterus, you ought to know that there’s tiny risk of a malignant fibroid and a small risk of cancer of the lining of the uterus also. As I say, I think Drs. Noorchashm and Reed have really changed the standard of practice for that, to their credit.
Have you come across manual morcellation in your review of the case lists?
Yes, there are occasional cases of manual morcellation. It’s more commonly done during vaginal hysterectomy to help deliver a large uterus through the vagina. I know of one case myself where there was a sarcoma. It’s unfortunate and probably shouldn’t happen. As you know, there’s no good way to diagnose leiomyosarcoma ahead of time. The best thing, I think, is to avoid morcellation or morcellate in a containment bag.
I don’t like morcellation. Even if you could look into your crystal ball and say these fibroids are benign absolutely, I wouldn’t do power morcellation. It sprays all that benign tissue around the abdominal cavity. Benign tissue can implant there and grow and cause problems too. I just think power morcellation is a bad idea.
The CDC is interested in convening a panel of experts to look at whether gynecologists need to be more rigorous in evaluating patients in the preoperative setting. Do you think such action is warranted, based on what you know now?
I think it ought to be looked at, for sure. You ought to be sure a fibroid is benign before you morcellate. It seems to make sense, but the devil is in the details. Very few fibroids are malignant; you know the estimates as well as I do. Maybe the high-end estimate is one in 500, and the low end is one in a few thousand. So, it doesn’t happen that often.
Additionally, patients often have multiple fibroids. Do you biopsy all of these? It’s not that easy to do. The uterus is a mobile organ. If you try to shove a core needle biopsy into it, it tends to sort of push out of the way. It’s also a very vascular organ. It has major blood supply coming in on both sides, at the top and bottom, and the fibroids may be growing close to the blood vessels.
I think if somebody asked the interventional radiologist, “Would you be happy sticking needles into this uterus?” they would be quite wary to do so, potentially. And finally, leiomyosarcoma is not an easy diagnosis for the pathologist to make. They’ve got to do things like count the number of mitoses and 10 high power fields and quantify atypia, look for tumor necrosis and I don’t know that they’d be able to do that accurately on a core needle biopsy.
I think you’d have to overcome all those problems before you could say that women with fibroids ought to have a biopsy before they’re morcellated. Which, as I say, sounds like a good idea. I think the better idea is don’t morcellate the damn thing. That would solve the problem.
Would preoperative workup of breast, esophageal, and prostate masses be appropriate to use as comparable examples?
I think some of the areas you have mentioned are a lot easier to biopsy. The breast is pretty easy to biopsy. Sometimes hard to tell what area to biopsy, but they do need a localization of mammographic abnormalities and that works pretty well.
Esophagus is easy to biopsy. You put a scope in, if you see something abnormal, you take a biopsy. Prostate is not easy to localize the abnormal area and that’s why they tend to do multiple biopsies. They do 12 or 15 template biopsies of the prostate hoping to hit the abnormal area. There’s a lot of inaccuracy there and a lot of patients having unpleasant, uncomfortable and morbid biopsies for a very low yield.
I think, if you try to biopsy a woman with a dozen fibroids, you’re probably going to have bigger problems than biopsying a prostate even. I think there’s a significant risk you’re going to make patients bleed and get complications out of this. But, as I say, you sort of have to ask the interventional radiologist. They’re the ones who would be putting these big needles in there and trying to get tissue.
So, you’re saying the biology is different, and biopsies are not as effective for fibroids?
I think it’s a question, first of all, of the likelihood of being malignant. If I told you your PSA is slightly elevated, you have somewhere between a one-in-500 and a one-in-2,000 chance right now of having cancer in your prostate. Would you like me to stick a big needle in there 12 times? What would you say? Forget about it, right? You would say forget about it.
So that’s sort of the issue with women with fibroids. It might be even more morbid than prostate biopsy. Plus, at least, if you stick a needle in a prostate cancer, the pathologist can identify the cancer and grade the cancer and all those kind of things. If you stick a needle in a leiomyosarcoma, you give the pathologist one tiny, little core. I think some of these biopsies might come out indeterminate anyway. Suspicious, but can’t be sure.
You’d have to talk to the pathologist. When they write a pathology report, leiomyosarcoma, they’ll quantify the number of mitoses per 10 high power fields. I don’t think you can get 10 high power fields to look at on a core needle biopsy. It’s not too likely. I think it would be hard for them to biopsy.
And again, you’re talking about doing all this so you don’t morcellate a sarcoma. My solution would be, don’t morcellate it.
Meaning, taking tissue out en bloc would be the answer?
Yes, remove it all.
This is an afterthought, but would there be a risk for overdiagnosing or even overtreatment?
I don’t think the risk is overdiagnosis. I think the risk would be the risks on the biopsy itself and women where the likelihood of cancer is extremely low. I think there’d be some risk of underdiagnosis. You could stick a needle in a sarcoma and maybe miss the sarcoma part of it an underdiagnose it.
Depending on the accuracy of it, you could make things worse. Gynecologists could say, “I biopsied this mass and they said it was a benign fibroid, so I’m going to feel free to morcellate it.”
Nobody really knows the accuracy of this kind of biopsy for leiomyosarcoma. I think not morcellating is a good idea.
Hopefully, if the CDC convenes this panel, they will be able to address all these concern and come up with some reasonable recommendations.
I haven’t been contacted, but I have heard it is in the works.