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Cervical Cancer: Staging and Minimally Invasive Surgery

Panelists: Bradley Monk, MD, FACOG, FACS, St. Joseph's Hospital and Medical Center; Michael J. Birrer, MD, PhD, O'Neal Comprehensive Cancer Center; Jubilee Brown, MD, Levine Cancer Institute; Thomas Herzog, MD, UC College of Medicine; Krishnansu S. Tewari, MD, University of California, Irvine
Published: Thursday, Aug 29, 2019



Transcript:

Bradley Monk, MD, FACOG, FACS: Let’s transition now to cervical cancer. Cervical cancer obviously is the most common malignancy worldwide. We’re fortunate in the West and in an industrialized world to have screening and vaccination. But the incidence is not falling. It’s surprisingly very stable. And so we continue to be very passionate about treating cervical cancer. Last year the staging was changed. Krish, tell me why and how this staging for cervical cancer has changed.

Krishnansu S. Tewari, MD: Yes. Just to follow on what you said about ovary cancer, 2018 was a really interesting year for cervical cancer. Although not only in the screening and prevention area where we have new data showing that HPV [human papillomavirus] DNA testing may make Papanicolaou tests obsolete. But we also had a 2-dose vaccination program approved by the FDA.

Thomas Herzog, MD: And additional data just came out showing 1 dose may almost do it.

Krishnansu S. Tewari, MD: That’s exactly right.

Thomas Herzog, MD: In the young population.

Krishnansu S. Tewari, MD: In the young patients. But as far as the staging goes, for long-time patients with early-stage disease who end with advanced disease, the status of the lymph node has a very important prognostic aspect in determining who suffers from early death from recurrence. And so in the 2018 revision, lymph node status has finally been incorporated into the staging, and it can be lymph node status based on pathology or radiology.

The second thing is the T1b2 classification of tumors and T1b1 before it was a tumor diameter under 4 cm versus larger than 4 cm, now that category has been split into 3 groups: 2 cm, 2 cm to 4 cm, and then beyond 4 cm. I think this is going to give more granularity to allow oncologists treating these patients to really be able to tailor the therapeutic challenge in the early-staged patients. The patients with lesions larger than 4 cm all need to be treated with chemoradiation. I think that’s very clear.

Bradley Monk, MD, FACOG, FACS: Let’s talk about that. If they all need to be treated with chemotherapy and radiation, maybe there’s an opportunity for neoadjuvant chemotherapy in those T1b2, now T1b3, lesions over 4 cm. The idea would be to give them neoadjuvant chemotherapy, make it a small cancer, and then do a radical hysterectomy. There’s an abstract here presented that showed that neoadjuvant chemotherapy did not include outcomes. To your point, today, still, greater than 4 cm should be chemotherapy and radiation.

I’m very honored here to be with Jubilee Brown from North Carolina. She is president now, or come to be?

Jubilee Brown, MD: Vice president.

Bradley Monk, MD, FACOG, FACS: Vice president of the AAGL, the American Association of Gynecologic Laparoscopists. Thank you.

Jubilee Brown, MD: Thank you.

Bradley Monk, MD, FACOG, FACS: Most or much of our surgery is minimally invasive. We had a trial that showed that minimally invasive surgery—that is, minimally invasive radical hysterectomy, removal of the soft tissue from the upper vagina and lymph nodes, radical hysterectomy—should not be performed with this minimally invasive technique. And you’re the chair of the society. Maybe you should come back to our society. I know you’re already part of our society.

Jubilee Brown, MD: I would never give that up.

Bradley Monk, MD, FACOG, FACS: Has your practice changed with this LAG3 trial, which showed in a randomized fashion that minimally invasive radical hysterectomy cervical cancer patients do worse?

Jubilee Brown, MD: Nothing like putting me on the spot, Brad.

Thomas Herzog, MD: This is a deposition, by the way.

Jubilee Brown, MD: Right, exactly. I think you know it’s interesting. It certainly has changed counseling. I think it is true, the best trial that we have in this space. This was a randomized prospective international trial.

Bradley Monk, MD, FACOG, FACS: The New England Journal of Medicine.

Jubilee Brown, MD: The New England Journal of Medicine published it. It randomized patients with early cervical cancer into laparoscopy, not robotic, versus open abdominal radical hysterectomy. And did show at 4-year disease-free survival was worse, and overall survival [OS] worse, in the minimally invasive cohorts.

I will say there were, however, some substantial flaws in that study, and those have been detailed elsewhere but really from statistical standpoint to pathology, to full data being available, it leads to some questions on, can we generalize this to all our patients. I think, however, it is important to move forward with this and to hopefully answer that question.

The staging that Krish outlined may be helpful, and it may be that we can use minimally invasive surgery for the new T1b2, basically up to 4 cm. Or maybe just T1b1, less than 2 cm. And I think further studies will look at that.

Bradley Monk, MD, FACOG, FACS: But I have to make decisions now. I get it, and I counsel the patient. But my patients generally say, “Look, Monk, tell me what to do, and then I’ll waive it.” I have to make a recommendation to my patients. What’s the recommendation for cervical cancer that’s that big?

Jubilee Brown, MD: It’s a matter of a lot of debate. My personal opinion, based on looking at all these data and also looking at our own single-institution data, is that I counsel the patient appropriately. I share with them all the lack of information, and I think that minimally invasive surgery is still appropriate for those small cancers.

Bradley Monk, MD, FACOG, FACS: What do you think, Krish?

Krishnansu S. Tewari, MD: I completely agree with her. You know, the couple of points I want to make about that trial, though, is the study wasn’t focused on robotics, but the fallout has all been on robotics. There was also an FDA alert about not performing robotic surgery for cervical cancers and breast cancer. And I think there’s a disconnect because I would submit and agree that doing a radical hysterectomy with a laparoscope is probably challenging for many of us, including ourselves. But robotic is different, and it almost approximates an open operation. And so I agree with Jubilee. It needs to be studied further.

Bradley Monk, MD, FACOG, FACS: Tom, you’re a surgeon, what do you think?

Thomas Herzog, MD: Well, I’ll take the dissenting view here. I’m not one to ignore the phase III New England Journal of Medicine paper and evidence. There was also a companion piece that was published that showed almost the same affect looking at the SEER [Surveillance, Epidemiology, and End Results] database, and I’m not a huge fan.

Jubilee Brown, MD: Oh, but that’s a database study.

Thomas Herzog, MD: I understand, and I’m not a big fan of that. But it shows exactly the same thing in a phase III prospective study. It showed that there wasn’t something unique about that population when you look at a United States population. And it showed the same thing. At this point I’m counseling the patients, and most of them are opting to be open. They go home in 2 days. They’re young patients, they’re healthy, they go home in a couple of days after an open procedure.

Bradley Monk, MD, FACOG, FACS: I did an open radical last week, and she went home the next day.

Thomas Herzog, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: I was on call. I wasn’t that happy about it, but my partner said, “Send her home.”

Thomas Herzog, MD: They usually go home in 2 days.

Jubilee Brown, MD: But I think we have to be careful about really how we counsel our patients. And it’s our responsibility to make sure that we give the best treatment to patients.

Bradley Monk, MD, FACOG, FACS: But they don’t know.

Jubilee Brown, MD: We need to make sure we don’t espouse a trial that has type 1 error. Maybe it does.

Bradley Monk, MD, FACOG, FACS: I’m not advocating against counseling. But I think we owe them a guide, a road map, and whether they choose to take it or not is their choice. Right? So I’m going to take a more moderate approach. I think a minimally invasive radical for substantial cancer, which could even be 1 cm to 2 cm, probably should be open. But for a small tumor that you can barely see, it probably doesn’t matter. And that patient, quite frankly, doesn’t need a radical anyway.

That’s the point, right? If you need a real radical, probably make an incision, and if you don’t need a real radical, then laparoscopy.

Jubilee Brown, MD: I think we need to study it further. I don’t think we’re there yet.

Thomas Herzog, MD: Well, we do, I agree. I’m happy to study it further. But in the face of that, you can’t.

Jubilee Brown, MD: Right, I agree.

Transcript Edited for Clarity

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Transcript:

Bradley Monk, MD, FACOG, FACS: Let’s transition now to cervical cancer. Cervical cancer obviously is the most common malignancy worldwide. We’re fortunate in the West and in an industrialized world to have screening and vaccination. But the incidence is not falling. It’s surprisingly very stable. And so we continue to be very passionate about treating cervical cancer. Last year the staging was changed. Krish, tell me why and how this staging for cervical cancer has changed.

Krishnansu S. Tewari, MD: Yes. Just to follow on what you said about ovary cancer, 2018 was a really interesting year for cervical cancer. Although not only in the screening and prevention area where we have new data showing that HPV [human papillomavirus] DNA testing may make Papanicolaou tests obsolete. But we also had a 2-dose vaccination program approved by the FDA.

Thomas Herzog, MD: And additional data just came out showing 1 dose may almost do it.

Krishnansu S. Tewari, MD: That’s exactly right.

Thomas Herzog, MD: In the young population.

Krishnansu S. Tewari, MD: In the young patients. But as far as the staging goes, for long-time patients with early-stage disease who end with advanced disease, the status of the lymph node has a very important prognostic aspect in determining who suffers from early death from recurrence. And so in the 2018 revision, lymph node status has finally been incorporated into the staging, and it can be lymph node status based on pathology or radiology.

The second thing is the T1b2 classification of tumors and T1b1 before it was a tumor diameter under 4 cm versus larger than 4 cm, now that category has been split into 3 groups: 2 cm, 2 cm to 4 cm, and then beyond 4 cm. I think this is going to give more granularity to allow oncologists treating these patients to really be able to tailor the therapeutic challenge in the early-staged patients. The patients with lesions larger than 4 cm all need to be treated with chemoradiation. I think that’s very clear.

Bradley Monk, MD, FACOG, FACS: Let’s talk about that. If they all need to be treated with chemotherapy and radiation, maybe there’s an opportunity for neoadjuvant chemotherapy in those T1b2, now T1b3, lesions over 4 cm. The idea would be to give them neoadjuvant chemotherapy, make it a small cancer, and then do a radical hysterectomy. There’s an abstract here presented that showed that neoadjuvant chemotherapy did not include outcomes. To your point, today, still, greater than 4 cm should be chemotherapy and radiation.

I’m very honored here to be with Jubilee Brown from North Carolina. She is president now, or come to be?

Jubilee Brown, MD: Vice president.

Bradley Monk, MD, FACOG, FACS: Vice president of the AAGL, the American Association of Gynecologic Laparoscopists. Thank you.

Jubilee Brown, MD: Thank you.

Bradley Monk, MD, FACOG, FACS: Most or much of our surgery is minimally invasive. We had a trial that showed that minimally invasive surgery—that is, minimally invasive radical hysterectomy, removal of the soft tissue from the upper vagina and lymph nodes, radical hysterectomy—should not be performed with this minimally invasive technique. And you’re the chair of the society. Maybe you should come back to our society. I know you’re already part of our society.

Jubilee Brown, MD: I would never give that up.

Bradley Monk, MD, FACOG, FACS: Has your practice changed with this LAG3 trial, which showed in a randomized fashion that minimally invasive radical hysterectomy cervical cancer patients do worse?

Jubilee Brown, MD: Nothing like putting me on the spot, Brad.

Thomas Herzog, MD: This is a deposition, by the way.

Jubilee Brown, MD: Right, exactly. I think you know it’s interesting. It certainly has changed counseling. I think it is true, the best trial that we have in this space. This was a randomized prospective international trial.

Bradley Monk, MD, FACOG, FACS: The New England Journal of Medicine.

Jubilee Brown, MD: The New England Journal of Medicine published it. It randomized patients with early cervical cancer into laparoscopy, not robotic, versus open abdominal radical hysterectomy. And did show at 4-year disease-free survival was worse, and overall survival [OS] worse, in the minimally invasive cohorts.

I will say there were, however, some substantial flaws in that study, and those have been detailed elsewhere but really from statistical standpoint to pathology, to full data being available, it leads to some questions on, can we generalize this to all our patients. I think, however, it is important to move forward with this and to hopefully answer that question.

The staging that Krish outlined may be helpful, and it may be that we can use minimally invasive surgery for the new T1b2, basically up to 4 cm. Or maybe just T1b1, less than 2 cm. And I think further studies will look at that.

Bradley Monk, MD, FACOG, FACS: But I have to make decisions now. I get it, and I counsel the patient. But my patients generally say, “Look, Monk, tell me what to do, and then I’ll waive it.” I have to make a recommendation to my patients. What’s the recommendation for cervical cancer that’s that big?

Jubilee Brown, MD: It’s a matter of a lot of debate. My personal opinion, based on looking at all these data and also looking at our own single-institution data, is that I counsel the patient appropriately. I share with them all the lack of information, and I think that minimally invasive surgery is still appropriate for those small cancers.

Bradley Monk, MD, FACOG, FACS: What do you think, Krish?

Krishnansu S. Tewari, MD: I completely agree with her. You know, the couple of points I want to make about that trial, though, is the study wasn’t focused on robotics, but the fallout has all been on robotics. There was also an FDA alert about not performing robotic surgery for cervical cancers and breast cancer. And I think there’s a disconnect because I would submit and agree that doing a radical hysterectomy with a laparoscope is probably challenging for many of us, including ourselves. But robotic is different, and it almost approximates an open operation. And so I agree with Jubilee. It needs to be studied further.

Bradley Monk, MD, FACOG, FACS: Tom, you’re a surgeon, what do you think?

Thomas Herzog, MD: Well, I’ll take the dissenting view here. I’m not one to ignore the phase III New England Journal of Medicine paper and evidence. There was also a companion piece that was published that showed almost the same affect looking at the SEER [Surveillance, Epidemiology, and End Results] database, and I’m not a huge fan.

Jubilee Brown, MD: Oh, but that’s a database study.

Thomas Herzog, MD: I understand, and I’m not a big fan of that. But it shows exactly the same thing in a phase III prospective study. It showed that there wasn’t something unique about that population when you look at a United States population. And it showed the same thing. At this point I’m counseling the patients, and most of them are opting to be open. They go home in 2 days. They’re young patients, they’re healthy, they go home in a couple of days after an open procedure.

Bradley Monk, MD, FACOG, FACS: I did an open radical last week, and she went home the next day.

Thomas Herzog, MD: Yeah.

Bradley Monk, MD, FACOG, FACS: I was on call. I wasn’t that happy about it, but my partner said, “Send her home.”

Thomas Herzog, MD: They usually go home in 2 days.

Jubilee Brown, MD: But I think we have to be careful about really how we counsel our patients. And it’s our responsibility to make sure that we give the best treatment to patients.

Bradley Monk, MD, FACOG, FACS: But they don’t know.

Jubilee Brown, MD: We need to make sure we don’t espouse a trial that has type 1 error. Maybe it does.

Bradley Monk, MD, FACOG, FACS: I’m not advocating against counseling. But I think we owe them a guide, a road map, and whether they choose to take it or not is their choice. Right? So I’m going to take a more moderate approach. I think a minimally invasive radical for substantial cancer, which could even be 1 cm to 2 cm, probably should be open. But for a small tumor that you can barely see, it probably doesn’t matter. And that patient, quite frankly, doesn’t need a radical anyway.

That’s the point, right? If you need a real radical, probably make an incision, and if you don’t need a real radical, then laparoscopy.

Jubilee Brown, MD: I think we need to study it further. I don’t think we’re there yet.

Thomas Herzog, MD: Well, we do, I agree. I’m happy to study it further. But in the face of that, you can’t.

Jubilee Brown, MD: Right, I agree.

Transcript Edited for Clarity
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