publication date: Nov. 21, 2014

Demetri: Morcellation Worsens Outcomes In Patients with Undiagnosed Cancers

 

 

As an oncologist who treats sarcoma, George Demetri has seen the adverse consequences of power morcellation, the surgical technique widely used to perform laparoscopic hysterectomies and remove putative fibroids.

In a small minority of cases, these fibroids instead represent unsuspected malignancies—including rare and aggressive leiomyosarcomas—which were impossible to detect prior to the morcellation procedure.

In those cases, power morcellators end up spreading the disease and, according to recent data, worsen patient outcomes.

Some proponents of the procedure have said that patients with sarcomas would have a poor prognosis with or without morcellation. Demetri, director of the Center for Sarcoma and Bone Oncology at Dana-Farber Cancer Institute and a professor of medicine at Harvard Medical School, disagrees.

“There’s a nihilism that I want to counteract in those who might say, ‘Well, these patients have a sarcoma, they’re destined to do badly anyway.’” Demetri said to The Cancer Letter.

“That’s an unfair assessment. That is a negative assessment of people who may do well. I have several patients who have had a uterine leiomyosarcoma that was treated optimally, and who are alive and well for 14 years.

“I think nihilism is not warranted, and that, to me, is the most important thing a sarcoma medical oncologist can add. I think we need to look out for the best interests of our patients.”

Demetri discussed this cross-disciplinary controversy in a conversation with Matthew Bin Han Ong, a reporter with The Cancer Letter.

Like repeated lightning strikes, two tragic events placed Harvard-affiliated institutions in the center of this controversy.

• Power morcellation performed at Brigham & Women’s Hospital was a part of the diagnostic step that was associated with the upstaged leiomyosarcoma of Erica Kaitz, who died Dec. 7, 2013. Kaitz, of Boston, had been active in raising money for research at Dana-Farber Cancer Institute.

• The morcellation procedure also upstaged the undetected tumor of former Beth Israel Deaconess Medical Center anesthesiologist Amy Reed (The Cancer Letter, July 4, 2014).

The debate over morcellation is especially divisive at Harvard, because gynecology-based investigators at Brigham and Women’s Hospital are conducting a clinical study aimed at gauging whether power morcellation performed in a containment bag might be able to limit the spread of cells (The Cancer Letter, July 4, 2014).

Critics say that power morcellation in routine gynecological surgery is not worth the risk, and alternative surgical procedures should be performed instead. Erica’s widower, Richard Kaitz, as well as Amy Reed and her husband, Hooman Noorchashm, formerly a cardiothoracic surgeon at Brigham, have been urging the Harvard institutions to abandon power morcellation altogether.

Demetri and his team had treated Erica Kaitz.

The Kaitzes were prominent donors to Dana-Farber. They started riding in the Pan-Mass Challenge charity biking event in 1993. It is the largest athletic fundraiser in the U.S., and raised $41 million for research at Dana-Farber this year.

Demetri oversees leiomyosarcoma research funded in part through the Erica Kaitz LMS NOW Research Fund at Dana-Farber. This fund raised about $2.9 million in 2012 and 2013. This year, Erica’s Entourage, a team riding with the Pan-Mass Challenge, raised over $1 million for the Erica’s Entourage Sarcoma Epigenomic Research Project at Dana-Farber and Harvard Medical School.

 

Matthew Ong: How do you know Richard Kaitz?

George Demetri: Erica, Rick’s wife, was a patient in our program, and Rick has given me permission to speak publicly about this. Our team knew her well.

Rick and I have biked together in Dana-Farber’s signature fundraising bike ride event. Our clinical director, Dr. Suzanne George, has led research and publications on this—so we know a good deal about power morcellation. However, I know that we’re on the medical oncology side of this equation—we see the patients after a diagnosis of sarcoma has been made—and the morcellation debate concerns arise before any such patients would be referred to us.

My expertise is in the disease biology and management of patients with a sarcoma diagnosis. Once the diagnosis has been made, there is no debate: if a patient has a diagnosed malignancy, morcellation is contraindicated.

I think we’ve missed the fundamental issue: there’s no reproducible, reliable, dependable way to know if a patient has a malignancy, so I don’t know how a doctor would know not to use this.

That’s where we are—but I am the first to say that I am not a surgeon—I am on the other side of the “therapy system” in this matter, after diagnosis.

MO: Do you think power morcellation should continue to be an option? If I’m not mistaken, the FDA Obstetrics and Gynecology Devices Advisory Committee had previously highlighted that there isn’t a surefire way of detecting these uterine malignancies pre-surgery.

GD: Imaging studies with CTs or MRIs show masses, but “masses” aren’t a diagnosis, so I’ll leave it at that.

Here’s the issue for our surgical colleagues:

What is a cogent, understandable argument for why morcellation is needed, and in which patients, given the risks of this procedure, in context with the risks of alternatives? That’s it.

The arguments are, of course, as we’ve all read and as we’ve all heard is, “Well, it’s easier to recover from this [morcellation] surgery, there may be frail patients who could not tolerate alternatives etc.”

If that is the case, I would like to think that the gynecological community can define and decide which patients are appropriate for this procedure that they view as medically necessary. That community needs to state this in no uncertain terms to patients, to themselves, to other physicians, to the FDA, and then that’s the way medical practice moves forward.

It’s no different than any other issue in medicine—or surgeries, for that matter.

Again, I want to emphasize that I am not a surgeon, and I have great respect for my surgical colleagues. I think very few surgeons talk to me about my drug development, and I don’t want to be on the other side of the fence talking about their surgery, since I respect their expertise.

MO: What would you say to a patient who may come to you and ask for your advice as to whether she should have her hysterectomy or myomectomy done via power morcellation?

GD: I doubt I would recommend it. But, again, maybe there are other details which would drive decisions in a specific case. Maybe there’s some issue that makes alternatives to a morcellation procedure more uniquely dangerous to some specific patient. Any decision in medicine and surgery is all about the details—and risks are inherent in any such decision as well.

Talk to the gynecologists. Even within that community, as I understand it, there are radical divisions of opinion. It’s their specialty. I can only talk about the people I’ve seen who have had the disease diagnosed.

There’s a nihilism that I want to counteract in those who might say, “Well, these patients have a sarcoma, they’re destined to do badly anyway.” That’s something that I can speak to.

That’s an unfair assessment. That is a negative assessment of people who may do well. I have several patients who have had a uterine leiomyosarcoma that was treated optimally, and who are alive and well enough for 14 years.

A subset of these patients are fine, God bless them. So I think not all of these patients do badly. I think nihilism is not warranted, and that, to me, is the most important thing a sarcoma medical oncologist can add. I think we need to look out for the best interests of our patients.

If there is a rational, understandable argument for why the risk-benefit would tilt in certain patients, let’s define who those patients are. Let’s explain the risk to our patients, as we do with everything else in medicine, and move forward as a community.

I don’t want to throw incendiary opinions or my bias as to what I might do, because none of us ever know what we would do if it were our wife, or our sister, or our daughter, until we’re in that position, and until we’re faced with real facts.

But that’s down to the fact that we have facts. And now, I think the data are quite remarkably consistent. The last few years of publications—now several different independent publications—are honing in on what I would consider to be a believable truth.

There is a certain number of patients who had a previously undiagnosed sarcoma or endometrial cancer or whatever, that underwent morcellation. That’s a fact.

So then the argument is, “How do you identify who they are?” Are there some patients for whom that procedure still represents—for whatever reason—a more favorable risk-benefit than any alternative procedure?

I know there are open procedures; there are other ways of doing things. I can’t comment on those, since that is the expertise of the gynecologic surgery community, and it is their responsibility to be held to that light of scientific inquiry, where patients and regulatory authorities can help them come to a wise decision. That’s probably the most responsible thing any of us can say.

I’m not going to shirk from saying it’s terrible when we get one of these patients who had morcellation. And then, the question is, “Well, gee whiz, did she understand the risks prior to the procedure? Would she have possibly died from an open procedure? And so, although it was an undiagnosed disease, it may be less difficult if she doesn’t look back with any regret?”

That’s what I’d like to hear. And that’s a rational, dispassionate discussion that serves the best interests of patients, and I think that should be our focus.

MO: If a patient has an undetected sarcoma or leiomyosarcoma, and it’s disseminated by a power morcellator, how fast does it propagate throughout the peritoneal cavity?

GD: I think it varies for different people. The biology of any individual’s sarcoma varies from one to another, and the argument is always that none of this is controlled data.

There is one example of a patient who had morcellation and is rendered free of disease, but within three weeks, has massive, bulky disease in multiple places. Well, do I think it’s because the morcellator spread things around, and during the healing process, growth factors were released and that accelerated the process?

In my heart of hearts, probably yes. Can I prove it? Absolutely not.

And the argument would be, “Well, you don’t know what would’ve happened to her had she just had an open procedure. Maybe all of this would’ve happened anyway.”

And to be rigorous, you have to say, “Yes, that is possible.” But that’s why you do studies and when you look at all the studies where there are people who had undiagnosed leiomyosarcomas and got sarcoma-type open procedures vs. those who were undiagnosed and had a “surprise” diagnosis with morcellation.

The ones who had morcellation did worse. Their disease came back faster.

So I think the data are quite consistent in multiple independent, retrospective analyses—again, retrospective, not controlled.

But, you know, at some point, you have to use common sense, and I’m comfortable with the data saying, “It does worsen outcomes.”

That’s a key point. It worsens outcomes. That’s a qualitative statement—how much worse vs. how much would whatever outcome would have been worse with an alternative surgical procedure.

I don’t know: Were all of those women adequately informed? Did they really understand? Were the numbers quoted as correctly as we now know them, I think, to be?

These are the questions. And I think, also, I don’t want doctors to be graded or judged based on current information that really wasn’t available even five years ago. Our whole view of the epidemiology of the undiagnosed leiomyosarcomas is very different now because we have independent sources from Korea, from the recent Columbia University study, as well as from studies at Harvard. (See Cited Articles below.)

These papers were published in the last three to four years. So I think it’s not fair to say, “Well, doctors seven years ago should’ve known that.” How could they have known that? They didn’t know that.

But now that we know that, can we move on and start talking from data? And I think that’s the discussion to have.

MO: Have you heard of the registry study that Brigham is conducting?

GD: Believe it or not, that goes through a separate IRB. That’s through the Partners IRB, not our cancer center IRB.

I’m not a device developer. I actually don’t really know how the device researchers design their clinical studies.

I’m a fan of regulatory science. I’m not a negative person, so I would have to say that our gynecology colleagues at the Brigham and Women’s Hospital hopefully have a good rationale for what they’re doing. I think that the patients who would conceivably be study participants in this—it would be an interesting consent process. It would be interesting to know what doctors tell patients in such a consent process.

As we all know, a consent form is a form; consenting patients to a clinical investigation is a process. I’ve served on our IRB for about 24 years and I love it, and I take informed consent extremely seriously.

There are so many interesting elements to this that—what can I say—this is a different kind of research from what I do. This is surgery, and I would have to say, on some level, it would be interesting to have the FDA speak for themselves.

It’s a very difficult situation; isn’t it? And again, I think this is where I do trust our regulators to look out for the safety of our patients.

I have to trust them, and that’s where, if there is a cogent argument about why this is such an important procedure and tool for this group of doctors and some specifiable type of patients, I would like to understand that. And I think the public would want to understand that—in words that we can all understand.

MO: Did I miss anything that you’d like to address?

GD: I would like to see this come to some conclusion. I would have everybody be able to move on with some peace around this. It’s painful for all of us to watch.

 

 

Cited Articles:

1) Wright JD, Tergas AI, Burke WM, Cui RR, Ananth CV, Chen L, Hershman DL. Uterine pathology in women undergoing minimally invasive hysterectomy using morcellation. JAMA. 2014 Sep 24;312(12):1253-5. doi: 10.1001/jama.2014.9005.

2) Park JY, Park SK, Kim DY, Kim JH, Kim YM, Kim YT, Nam JH. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol. 2011 Aug;122(2):255-9. doi: 10.1016/j.ygyno.2011.04.021. Epub 2011 May 12.

3) George S, Barysauskas C, Serrano C, Oduyebo T, Rauh-Hain JA, Del Carmen MG, Demetri GD, Muto MG. Retrospective cohort study evaluating the impact of intraperitoneal morcellation on outcomes of localized uterine leiomyosarcoma. Cancer. 2014 Oct 15;120(20):3154-8. doi: 10.1002/cncr.28844. Epub 2014 Jun 12.

4) Seidman MA, Oduyebo T, Muto MG, Crum CP, Nucci MR, Quade BJ. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms. PLoS One. 2012;7(11):e50058. doi: 10.1371/journal.pone.0050058. Epub 2012 Nov 26.

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