Hi, I'm Dr. Roni Nitecki Wilke, and I'm an assistant
professor at the department of Gynecologic Oncology and
Reproductive Medicine at MD Anderson Cancer Center.
Today I am joined by my colleague, Dr. Amir Jazaeri,
who's a professor of Gynecologic Oncology and Reproductive
Medicine at MD Anderson Cancer Center.
And this is the Cancerwise Podcast.
Hi, Dr. Jazaeri.
Hi, Roni. It's great to be here with you.
Thank you for joining me.
We are going to discuss personalizing ovarian cancer
treatment and what that means, all the way from
individualizing care for women with ovarian cancer, who are
getting treatment to what it means to individualized
treatment for patients who are at risk of getting ovarian
cancer.
That sounds great. There's been a lot that's been happening
in this area.
Let's talk about personalizing ovarian cancer treatment
first. So, the first thing I'd like to ask you is
what is minimal residual disease?
What has interested you in this concept and how
have you applied it to ovarian cancer care?
Yeah. Thank you for that question.
So, when I think back that the, we're
using the same treatments in ovarian cancer now then,
that, that haven't changed since I was a medical student,
that, that's troubling.
And so, as you know, the problem with ovarian cancer
isn't the initial treatments.
The surgery and the chemotherapy works pretty well.
But the problem is that many women who
appear to be in remission, in fact, have residual
disease that until now have been difficult
to detect.
And that's where we sort of refer
to as minimal residual disease or MRD.
And as you know, a few years ago we started
to offer these women a minimally
invasive outpatient procedure called second-look
laparoscopy.
And what we found was really amazing, that
at the time of surgery, we can detect residual
cancer in 25 to 65%
of women who otherwise would have a normal CT
scan and a normal CA-125 tumor marker.
So, you mean that women can have a completely normal
scan and have a normal tumor marker, and still
have disease that can be seen at the time of surgery?
Unfortunately, the answer is yes for a large proportion
of women.
I'm sure that some of our listeners would also be surprised
to hear this. And do you think that this may be the reason
why ovarian cancer can, and for most
women, does recur?
Absolutely. And of course, when we use terms like
recurrence or the cancer is back,
I think that makes sense on some level.
But the truth is that the cancer never leaves the body.
So, it's this residual disease that over time
stays, grows, and eventually shows itself
in the form of clinically detectable disease.
Only then patients are restarted on chemotherapy
and after they become resistant to those treatments
do we think about investigational treatments or clinical
trials. And I think one of the ways we are
trying to push the field forward is to say
if women have minimal residual disease, and if we
know that that's associated with a worse outcome,
why not offer patients these investigational
treatments at this point, rather than wait
until the cancer becomes bigger
and more difficult to treat?
So, it sounds like minimal residual disease
could be an opportunity for patients, or at least the
knowledge that the minimal residual disease exists,
could be an opportunity to initiate treatment earlier
than patients would get otherwise.
You know, I find it always interesting to have
this discussion with patients.
When you tell women that
even though you're giving them good news with a CT
scan that's normal and a CA-125 that's normal,
that there may be still residual disease, most
of the patients that I talk to are interested in knowing.
You know, I think in the past we have kind
of turned a blind eye to this, or at
least I would always hope that my patients
are in that 10 or 15% of patients
that might be cured.
But the reality is that, of course, most patients
are not. And to offer them something
better than just hope that may not be
based on reality.
I think that's something that patients really relate to
and quite frankly, demand.
Yeah, I would agree with that entirely.
So, what happens when you take
a patient to the operating room and you discover
MRD, or minimal residual disease?
What do you offer the patient at that point?
That's a great question.
First of all, it may sound counterintuitive, but
sometimes during the surgery, many times during the
surgery, we're not even sure if there is minimal residual
disease present or not.
During the second-look laparoscopy, we often try
to biopsy areas that look different.
For example, there may be scar tissue from the initial
surgery, but even if not, we try to
cover areas with biopsies that are favorite
hiding places for ovarian cancer.
Because we can only biopsy so many areas, we also
put in sterile saline into the abdominal cavity,
and we aspirate the saline.
That saline touches all the surfaces and collect
cells that may exfoliate or fall
off of surfaces into the fluid.
That fluid is then collected along with all the biopsies,
and everything is sent to the pathology lab.
It often isn't until we get the final pathology
report that even I know if there has been
minimal residual disease or not.
And of course, then we share this information with the
patients and together we come up with the next best step.
For some patients that have minimal residual disease,
we have clinical trials that might be the right treatment
option. This is the use of immunotherapy
to intervene at a time where we think
residual cancer cells that might be present might be
relatively chemo-resistant, since they've lasted
through six or seven cycles of chemotherapy.
For other patients who are negative or otherwise
might have PARP inhibitors as an option, we still
don't have any evidence that PARP inhibitors don't
work if you have minimal residual disease.
So, for many of those patients, the treatment
options that currently are existing are the best we have.
But even then, we are trying to really identify
what might be the Achilles heel of this MRD
so that we can come up with more effective treatments for
patients.
That's really exciting that patients have
these opportunities at MD Anderson to
take part in a clinical trial so early in their disease
course.
Of course, you're no stranger to individualization
of treatment, and I've heard about the wonderful work that
you're doing in trying to prevent ovarian cancer.
I think our audience would love to know that we are
actually succeeding in ovarian cancer prevention.
So, why don't you tell us about how
incidence of ovarian cancer is changing over time?
Yeah, absolutely. That is a great question, Dr. Jazaeri.
Thank you for the invitation to speak about this.
I really think that one of the most important things
about ovarian cancer prevention is to talk about
who really prevention matters
for, and I would argue that it probably matters for
everyone, for every person that has
ovaries and fallopian tubes.
But I think it matters particularly for patients who we
know have a genetic predisposition
to develop ovarian cancer.
In fact, what we now call ovarian cancer, we really think
starts in the fallopian tube.
And that knowledge over the past few decades has really
opened doors for alternative treatment strategies.
Now you may ask, why do we need alternative treatment
strategies? So, for any patient with
a BRCA1 or a BRCA2 mutation,
there is a recommendation to undergo a risk-reducing
surgery. During the surgery, the surgeon would
remove both the fallopian tubes and the ovaries
in women who are quite young.
So, for patients who are BRCA1 carrier,
the recommended age to have the surgery is between
age 35 and 40, and for BRCA2
carriers it is between 40 and 45.
So, for most of these patients, they will
still be premenopausal, meaning their ovaries
are still working, making estrogen and progesterone
that impacts their entire bodies.
And while this strategy that is the
recommendation and is the standard of care, has
been shown to decrease both the risk of
ovarian cancer and the risk of death in these patients,
it comes at a cost.
And I think going through menopause early is a big cost,
both in terms of, sort of, short-term
symptoms, but also there are some more
long-term impacts that patients can see.
Yeah. Why don't you share with our audience what some of
the long-term health results of early menopause
or surgical menopause are?
Yeah. So, certainly, you know, when we
talk about the long-term impacts, we think of things like
bone loss, which I think is very important for patients
who are expected to live for a longer time.
We're preventing cancer and then we put them at risk for
osteopenia and osteoporosis.
We've also shown in studies that removing ovaries
too early is tied to an increased risk
of cardiovascular death.
Now, that risk may be small, but it's certainly been seen
in modeling studies in the literature.
There's also some data, I would say,
not quite as clear cut that shows an increased risk,
potentially with some cognitive disorders like Alzheimer's.
So, you know, the story is not 100% clear.
But we know that removing ovaries very early
does have long lasting impacts.
So what are we doing at MD Anderson to try to address this
issue of we want to prevent cancer, but we
don't want patients to go through early menopause?
So going back to this idea that
we think that the majority of these cancers probably start
in the fallopian tube opens up an opportunity
to offer an alternative strategy.
But essentially the idea is, if we think
that the origin of these cancers is in the
fallopian tubes, what if we removed fallopian tubes
first and allowed patients to have more time
with their ovaries? So, we would be removing the agent
that we think is responsible for cancer development
but preserve the ovaries and prevent
women from going into early menopause.
And the study that we currently have open is the TUBA-WISP
II trial.
And what it allows is for women to
keep their ovaries for an extra five years
beyond what the guidelines recommend.
So, for a woman with a BRCA1 mutation,
she could have her fallopian tubes removed by the
age of 40, but then she can hold on to her
ovaries until age 45.
For a woman with BRCA2, she could hold on
to her ovaries until age 50.
And this allows a lot of women to
get what we hope is ovarian
cancer prevention, but not at the expense of going
into menopause so early in their lives.
You know, some of our audience may have
heard the term opportunistic salpingectomy.
What is that? And, and how do you think that might
impact rates of ovarian cancer?
Yeah. Thank you for that question.
That's an excellent question.
I would like to differentiate the strategy
that we're talking about in TUBA-WISP II
from opportunistic salpingectomy.
So, opportunistic salpingectomy means that when
a woman is getting surgery for
any indication, whether it's a C-section or
a hysterectomy or a procedure that has nothing to
do with a Gyn organ, there is an opportunity
to remove the fallopian tubes.
If a woman is getting, for example, a hernia repair
and the surgeon is able to see the fallopian tubes,
removing them at that time would be an opportunistic
salpingectomy.
This is a strategy that has been employed
in increasing rates since 2010, and
it's very popular in women that are getting gynecologic
surgery. But we hope that that also expands to women who
are getting any surgery, because once the fallopian
tubes are no longer needed for spontaneous pregnancy,
they really have no function.
And in areas where there
is more and more of this opportunistic salpingectomy,
we are starting to see hints of a decrease
in the incidence of ovarian cancer.
So, my gut feeling is that this strategy works on a
population level.
There needs to be years more of data for
us to know for sure.
The reason I want to make a distinction between this
strategy, which I think is a really important one for our
audience to know, and the strategy that we're employing
in TUBA-WISP II is that for
women at a population level, risk of ovarian
cancer, opportunistic salpingectomy
is an incredible opportunity.
For women who have a predisposing mutation,
their risk of ovarian cancer is so high,
and we already have a strategy that we know
works. We have to be able to compare
this alternative strategy of removing fallopian tubes first
to the standard of care, to make sure that
it is as efficacious, meaning that it works as well,
before we can recommend it to everyone.
I think another question that comes up, you touched upon
mutations in BRCA1 and BRCA2
genes. Are there genetic mutations that would
put women at elevated risk for breast
or ovarian cancer?
Yes, there certainly are.
And thank you for mentioning that.
Mutations in RAD51C and D, BRIP1, PALB2,
they're, just to name a few, there are others, but that
whole group that I just mentioned, they are also eligible
to participate in the TUBA-WISP II trial.
Those mutations, I think there's less known about them
than with BRCA1 and BRCA2,
but it is an important group to consider and thank you for
mentioning that. They are also eligible for this trial.
And can you mention the huge role that our genetic
counselors play in in genetic testing
and helping patients understand their results?
Our genetic counselors play an enormous role, and they
are an incredible resource to a lot of patients
at this institution.
In our department, every patient that is diagnosed
with a new ovarian cancer is referred
to our genetic counselor for testing.
And also, anybody that has seen anywhere in the hospital
that has a family history that indicates that
their family may have an increased risk
of having one of these hereditary genetic cancer syndromes
are referred to our genetic counselors as well.
They spend time with our patients talking to them about
their family history, figuring out exactly
what their risk is before testing, recommending
testing if it's appropriate, and then going through the
results with our patients after they have completed testing
to make sure that the patients understand exactly what they
are and are not at risk for, and what are the things that
they can do to either screen for cancer
or prevent cancer?
I think another area of research
for risk reduction is in the area of cascade
testing, and I believe Dr. Rauh Hain has
interest.
Can you briefly tell our audience about some of that?
Cascade genetic testing is incredibly important.
Basically, in lieu of population
level genetic testing, which is not something that
we're doing right now. It's not something that is
recommended. It's not something that we have the sort of
public health infrastructure for.
And by that you mean testing everybody.
Everybody.
The best way to figure out if you have
one of these mutations is to look at your
family. And if there is a person in your family
that has one of these mutations, any first
degree relative has a 50% chance
of carrying that same mutation.
And so, cascade genetic testing, what it does is it focuses
on that family unit to increase testing
amongst a population of people that have a higher risk
of having a positive genetic test.
And the importance of that is, the more people that we find
that have these mutations, the more cancers we can prevent.
And that is, that is why I'm so passionate
about this work, because once
cancer develops, we do everything that we can.
But wouldn't it be amazing if we could prevent it from ever
happening? So, patients do not have to go through all
of the difficult treatment and surgery that we ask of them
to do when they're diagnosed with an advanced malignancy.
Yeah. Well, that sounds like a lot of good news so
that patients don't ever have to deal with ovarian
cancer.
Yes. I'm hoping we'll know more and more with the years to
come and develop more and more strategies to figure
out who's at risk and how to best care for them.
Dr. Jazaeri, I wanted to ask you, for our younger
patients that are diagnosed with early-stage
disease, do we have any options for fertility sparing
if that is something that they desire?
That is a great question.
You know, with the recognition that many young
patients deal with cancer
and that that cancer treatment can impact their fertility,
ASCO, which is the American Society for Clinical Oncology,
has put out guidelines several years ago that
recommends evaluation of young
and reproductive age men and women
for possibility of infertility
before initiation of cancer therapy.
I think we're very lucky at MD Anderson to
have colleagues in our Oncofertility
department who see actually patients not just with
gynecologic cancers, but across the entire
institution to counsel them on
ways to retain their fertility while
undergoing effective cancer treatment.
And of course, these are Dr. Terri Woodard
and Dr. Laurie McKenzie in our Oncofertility
department.
You know, I think many of our audience may not know,
but cancers such as cervical cancer, ovarian
cancer, certain types of uterine
cancer may be successfully
treated without loss of
fertility or with preservation of opportunities
for future assisted reproductive technologies.
Yeah, the, they're an incredible, incredible
service to our patients. And I'm so happy that we're able
to collaborate with them so closely.
Well, thank you so much for joining me for this
enlightening conversation.
I had a great time.
This has been very fun.
And thank you for tuning in today.
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