Dr. Kevin Kelly, Diagnosing and Treating Testicular
Cancer
January 31, 2010
Welcome to Yale Cancer Center Answers with Drs. Ed Chu and Francine Foss, I am Bruce Barber. Dr. Chu is Deputy Director and Chief of Medical Oncology at Yale Cancer Center and Dr. Foss is a Professor of Medical Oncology and Dermatology, specializing in the treatment of lymphomas. If you would like to join the conversation, you can contact the doctors directly. The address is canceranswers@yale.edu and the phone number is 1888-234-4YCC. This evening, Francine welcomes Dr. Kevin Kelly. Dr. Kelly is the Co-director of the Yale Cancer Center Prostate and Urologic Cancers Program and an Associate Professor of Medical Oncology at Yale School of Medicine.
Foss
Could you tell us what the different types of testicular cancer are
that are diagnosed?
Kelly
There can be several types of testicular cancer. There can be
germ cell tumors, which we will talk about in a minute, but there
can also be other tumors such as metastatic disease that actually
goes to the testicle, you can have a lymphoma in the testicle, or
from other structures within the testicles a tumor can arise.
Typically, when we talk about testicular cancers, the most common
type is what we call a germ cell tumor, and a germ cell tumor can
be broken down into two categories. One is what we call a
seminoma, and the other one is called non-seminoma germ cell
tumor.
Foss
Can you tell us a little bit about how frequently we see these
types of testicular cancers and what age group they occur in?
Kelly
If you look at the germ cell tumors, they are typically the most
common tumor that we see, that is usually between age 15 and 35.
There are around 8000 cases per year of germ cell tumors. The
other tumors that are not germ cell tumors can be found in the
older population and they are actually fairly rare tumors.
Foss
Say a young gentleman comes in with a testicular mass, and this
happened in my clinic the other day in fact, can you tell us how
commonly that would actually turn out to be a tumor as opposed to
something else?
Kelly
Again, as you know, when patients have a testicular mass, they
always should be checked out because germ cell tumors are curable
tumors. But again, finding masses within testicles is fairly common
and they need to be worked up appropriately. Workup would
include a good physical exam by the physician and an ultrasound in
a timely manner.
Foss
How often do you actually see young men coming in with these masses
that they don't know really what it is?
Kelly
As a primary physician, they typically will see around 10 of those
a year, but there are a lot
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of things in the groin and the scrotum that can actually feel like
masses. There can be hernias down there, sometimes you can
get a bruise or hematoma in the testicle, but what we get concerned
about with a testicular mass is if there is pain, if there is
growth in there and it doesn't go away. Those are the things
that any young person should really be concerned about.
Foss
For the average young person who may discover a mass there, first
stop would be say the primary care doctor?
Kelly
That is correct, the primary care doctor should take a look at it
and evaluate it.
Foss
And the next step, if the primary care doctor is worried, would be
to get an ultrasound?
Kelly
Yes, an ultrasound of the testes to evaluate whether it's a solid,
or what we call a fluid filled mass.
Foss
And then what's the next step, say if it is something that's
suspicious, what would happen next?
Kelly
Then he should be evaluated by a urologist who actually specializes
in testicular cancer to evaluate it further. If there is
something suspicious, if there is a solid mass in the testes, then
further workup, which includes what we call an orchiectomy, or
removal of the testicle, needs to be performed. This needs to
be done in a special way by bringing it up through the groin
instead of going through what we call the scrotal sac.
Foss
Is there ever a role to just stick a needle in one of these masses,
or does it always end up being a surgical procedure?
Kelly
If it is a solid mass, there is no role for doing a needle aspirate
right through the scrotum. There should be more of a surgical
procedure at that point. They do biopsy the testicles by
doing a small surgery to bring it up through the inguinal region
and biopsy it that way.
Foss
Can you talk about some epidemiologic factors associated with
testicular cancer, is there any connection with sexually
transmitted diseases?
Kelly
No there is not. There is no association from estrogens,
testicular trauma, HIV, or vasectomy. There is no
correlation. The major correlation is to something called
Klinefelter syndrome, and also undescended testicles can
predisposes patients to testicular cancer.
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Foss
In the setting of an undescended testicle, how much does a man
have to worry about that and is there any screening that needs to
be done?
Kelly
Anybody who has an undescended testicle needs to be evaluated and
followed very closely. Typically, when they are found to have
a descended testicle, it is brought down early in their life.
But sometimes this is not done and these patients need to be
watched very carefully.
Foss
Should all men be doing self exams?
Kelly
Absolutely, we teach women that breast exams are important, and
testicular exams are also important. If there is any abnormality,
they should go to their primary doctor.
Foss
At what age should a man start doing the testicular self exam?
Kelly
What we know is that the most common germ cells come between the
age 18 and 35, so when you start puberty, or a little afterwards,
you should start doing testicular exams.
Foss
Kevin, from a public health point of view, how often are primary
care physicians and pediatricians keyed into this issue, and do
they in fact instruct young man on how to do this?
Kelly
Unfortunately not. I think this is something that we have to
do better with and educate our colleagues in primary care that we
should be teaching young adults how to do testicular exams and the
importance of doing health maintenance.
Foss
Let's talk a little bit about a patient now that has a diagnosis,
so they have undergone a surgical procedure for a mass and they
have a diagnosis of testicular cancer. First of all, you
talked about a couple of different types. Could you go
through a little bit with us what those types are and what the next
steps would be?
Kelly
Yes, there are two main types of germ cell tumors, one is called
the seminoma and one is called the non-seminomatous
germ cell tumor. Again, these are different
types of tumors and they actually have a different growth rate and
also respond differently to different therapies. So, it is
very important when you actually have a diagnosis of germ cell
tumor to understand if you have a seminoma or non-seminomatous germ
cell tumor. In addition, what is very important in germ cell
tumors is looking at what we call tumor markers. These are
very characteristic for germ cell tumors and there are three main
ones we look at. One is what we call the beta HCG, the other
one is alpha-fetoprotein, and the last is LDH. Further
workup, when you are diagnosed with a germ cell tumor, would be a
CAT scan done of the chest,
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abdomen and pelvis, and with the blood markers and CT scans, you can show the extent of the cancer.
Foss
Would these blood tests be done prior to the original biopsy, or
are they only done after the diagnosis?
Kelly
Typically we try to get them before the orchiectomy, removal of the
testicle, and then subsequently, after we have removed the
testicle, we will repeat those blood tests.
Foss
So those blood tests are very good markers of whether or not there
is metastases left behind, can you talk a little bit about how
those markers change?
Kelly
We know that if the markers are very high, they are what we call
prognostic, or predict how severe the cancer is, and actually, it
helps us divide the patient's into what we call good risk,
intermediate risk, or poor risk tumors. And based on the risk
classification of this, a patient's treatment can be
determined.
Foss
Are these markers available to the average practicing oncologist in
their office, or do you have to come to a center to get these
markers drawn?
Kelly
No, these are common blood tests, it can be drawn almost
anywhere.
Foss
With respect to other blood tests, do you commonly see changes in
say kidney function, liver function, or blood counts when patients
present with testicular cancer?
Kelly
Typically not, perhaps in somebody who has very advanced stage of
one of these cancers, you may see some abnormalities, but typically
patient's can present with very large masses. They have some
pain or discomfort but typically their other organ functions are
intact.
Foss
Kevin, you talked about a CAT scan as being the diagnostic test
that you do, we use PET scans a lot for other kinds of
cancers. Can you talk about whether PET scanning has a role
here?
Kelly
PET scanning has a significant role in staging. We do use it
after treatment in what we call the seminomas to help us to
differentiate if there is any residual tumor remaining, but that's
still very controversial.
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Foss
With respect to metastases, do they pretty much go to all different
organs or are there patterns of metastases that you look for?
Kelly
There are patterns that we look for. For seminoma, both germ
cell tumors, they have a tendency to go to the lymph nodes in the
back of the abdomen and they also spread to the lung, but in rare
cases, it can go to bone, liver, or the brain.
Foss
When a patient presents with metastases, which I take is a common
finding for these patients, what is your approach at that point? Do
you need to go in and biopsy those metastases? Do you assume that
you know that they are testicular cancer, and how does that change
your treatment?
Kelly
In rare cases we wouldn't go in and re-biopsy if we find the
diagnosis on the removal of the testicle, plus the blood markers
are also good indication of the activity of distant disease.
At this juncture, we would evaluate what stage they are and
typically that is broken down into three stages; stage 1, 2, and 3,
depending if he has localized disease of the testicle. Stage
2 would be disease in the back of the abdomen, and 3 is anything
that has spread beyond the lymph nodes in the back of the
abdomen. We combine that with the blood markers and we can
actually classify those patient's into the three risk categories;
good risk, intermediate risk, or poor risk. Subsequently, it
also depends on their cell type. We know that seminomas,
almost all of those, are good risk. It is typically the
non-seminomatous germ cell tumors that have the intermediate or
poor risk features, and based on that we can actually determine
whether radiotherapy, surgery, or chemotherapy followed by surgery
is most appropriate for the patient.
Foss
At what point do you get the radiation therapist involved in the
management of these patients?
Kelly
Typically the seminomas are the ones that are radiosensitive and
those are the patients that will receive radiation therapy
typically as adjuvant therapy in the back of the abdomen. If
you have very small tumors or lymph nodes in the back of the
abdomen, then radiation therapy may also be appropriate for that
patient, but typically radiotherapy is not used in the management
of non-seminomatous germ cell tumors.
Foss
Thank you Kevin, we are going to take a break now. We are talking
with Dr. Kevin Kelly on the management of testicular cancer.
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Foss
Welcome back to Yale Cancer Center Answers. This is Dr.
Francine Foss and I am here with Dr. Kevin Kelly, Co-director of
the Yale Cancer Center Prostate and Urologic Cancers Program.
Tonight we are talking about testicular cancer. Kevin, you told us
a lot about the two different types of testicular cancer and how
you diagnose patients and about the different prognostic groups,
and I am wondering, how many of these patients actually present in
the good prognostic group as opposed to the more advanced
disease?
Kelly
The majority actually are good prognosis, but the important thing
about germ cell tumors is that an early diagnosis and treatment is
directly related to the cure rate. So the earlier we find
these patients, the quicker we work them up and diagnose them, the
better off they are. We have to remember this is a germ cell tumor,
this is the one tumor that we can actually cure. Over 90% of
patients we can actually cure with the appropriate diagnosis and
treatment of these patients.
Foss
That's terrific news Kevin. I remember a long time ago now, when I
was actually at the National Cancer Institute, and we were doing a
lot of aggressive therapy for these types of patients and at that
time we learned that the drug cisplatin really had a tremendous
role in this disease. In fact, we still use that drug today, but
can you step us through the treatment for patients with advanced
testicular cancer and what happens after they complete their
therapy?
Kelly
Typically patients who don't have surgery or radiation therapy
upfront, do get chemotherapy, and there are two main chemotherapies
that we use. One is, as you described, based on cisplatin,
which is a very potent chemotherapy. The other drug is called
etoposide. Then again, there are some patients that it is
appropriate to use another drug called bleomycin. Depending on what
risk category they are we will either use two drugs or three
drugs. As these patients get to around 12 weeks of
chemotherapy, that is when we usually reevaluate to
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see if there is any residual cancer remaining. If there is, then there is a very strong role for surgery to resect any residual amount of tumor tissue left behind.
Foss
Would the surgery typically be done in different parts of the body?
Are there specific areas, say like the lungs, which you target for
the surgical excision?
Kelly
Very typically what we will do is an abdominal surgery where we
remove all the lymph nodes in the back of the abdomen and if there
is any residual cancer in the lungs, we will go and resect those
out of the lungs also.
Foss
And after that surgical excision do you give more therapy?
Kelly
In rare occasions we would give additional therapy, but in most
cases if we have given appropriate chemotherapy upfront, and we can
do an adequate surgical procedure, then patients will not need any
further therapy.
Foss
The way we give this chemotherapy now, can you talk a little bit
about the toxicities and the complications, because I know a drug
like cisplatin can have a lot of neurologic toxicity?
Kelly
Yes, it can. We have come a long way over the last 20 years
in terms of how we actually give chemotherapy. When I started
treating these patients I actually had to treat them all as
inpatients for days and weeks, but now all these treatments are
done as outpatient. We have better medications to protect
from any nausea or vomiting. We know that if we give adequate
hydration and are very active upfront, patients can do very well
with the chemotherapy, and most of my patients who are going
through the therapy right now are still working at least part-time
or full-time with it, or going to school.
Foss
Kevin, we hate to use the word cure because we are never sure with
our patients, but after a patient goes through the chemotherapy and
surgical excision, and everything is taken out, what do you tell
them?
Kelly
We know that the probability of these patients, from many long-term
studies we have found over the years, is that patients that have no
tumor after the resection, the blood markers remain negative, and
if they pass three to five years, the majority of those patients
will not recur. But it is important to remember that we can't
always predict who is going to be cured and not cured, while the
majority are, we still have to monitor patients very closely
afterwards not only for recurrence of the disease, but these are
young patients and they can have complications from the
chemotherapy and we have to monitor them for many years
afterwards.
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Foss
I would like to talk a little bit more about that in a minute, but
I just want to touch on the role of stem cell transplant.
There still are some patients with testicular cancer that go on to
get high dose therapy and a stem cell transplant. Can you
talk about that a little?
Kelly
Yes, upfront chemotherapy or salvage chemotherapy can cure the
majority of the patients, but there are small fractions of patients
where the frontline chemotherapy does not work. Subsequently,
we give very high doses of chemotherapy with peripheral stem cell
rescue, these are cells that help to support the high dose
chemotherapy and with that there are patients that can still be
cured with high dose chemotherapy.
Foss
The stem cell transplant that we are talking about involves getting
peripheral blood stem cells as opposed to bone marrow cells?
Kelly
That is correct Francine.
Foss
And it is pretty similar to what we do for the hematologic
malignancies.
Kelly
We took a chapter from your book.
Foss
Thank you. So, I guess the question is, how often do you
actually do that? What percentages of patients actually go to a
stem cell transplant?
Kelly
A small fraction overall, I would estimate around 10% to 20%.
Foss
You didn't mention any new drugs, and I know there are a lot of
targeted therapies and antibodies out there now for other kinds of
cancers. Are there any drugs like that that are applicable to the
treatment of testicular cancer?
Kelly
As you know, this is one of the cancers that we have done well in
trying to treat and cure. So, there hasn't been a huge
initiative to look at new drugs because the drugs we have work so
well; however, there are some new drugs, some of the targeted
therapies, in patients who are really refractory, that we are
trying, but since it's a rare tumor is very hard to do these
clinical trials.
Foss
Also I understand it can be somewhat heterogenous in terms of the
different cell types within some of these testicular cancers.
Kelly
That is correct. When it becomes more advanced and refractory
to other therapies these are very difficult tumors to treat.
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Foss
Another point is that in the case of brain metastasis, that is a
situation where you often times do well by excising those.
Kelly
You can excise them, or even use radiation therapy even if it is
non-seminoma, but typically even chemotherapy in this situation
will cross the blood-brain barrier and also treat the brain
metastases.
Foss
A patient who presents with brain metastases doesn't necessarily
have a dismal prognosis?
Kelly
We have had some very famous people who have gone on and done very
well with brain metastases.
Foss
You touched on the issue of complications of therapy and I would
like to just get back to that right now, could you elaborate a
little bit about that?
Kelly
There are a lot of complications in young men that can occur with
the treatment of germ cell tumors. The first to start off is
you remove one of the testicles, so they can have difficulty with
fertility. Even just having germ cell tumor decreases the motility
of the sperm and sperm count. Subsequently, we may have other
therapies which actually influence the sperm count such as
radiation therapy or chemotherapy. Before any patient ever
goes through any therapy with germ cell tumors, we always recommend
sperm banking. This allows them to have a family in the
future. Other things that can happen is when these patients
go through surgery a lot of times the nerves that help have
appropriate erections and erectile functions are disrupted and they
may get what we call retrograde ejaculation. Thus, that may
also decrease the ability to have children in the future. So
that's one of the areas. Subsequently, patients who actually
have chemotherapy are at increase risk for leukemia. They can
have problems with cardiac disease, lung problems, or peripheral
vascular disease. These all are monitored for a prolonged
period of time after therapy.
Foss
And how do you go about monitoring those?
Kelly
This is where we typically refer them back to the primary physician
and we talk to the primary physician and tell them to look out for
certain symptoms and signs. This includes doing the regular
health maintenance workup, make sure of no cardiac disease, doing
chest x-rays, looking and making sure they do a CBC on a yearly
basis just to monitor any long-term toxicity from the
chemotherapy.
Foss
You talked about the sperm banking, I just wanted to clarify that
for folks who don't know much about that. The sperm is banked
and is kept forever?
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Kelly
Well it is cryo-preserved and is kept forever as long as you pay
the bill, I guess.
Foss
Another question I had is touching on the psychosocial issues
associated with say losing a testicle for a young man. Can
you talk a little bit about that, I am sure that there are folks
that work with you such as social workers that help with these
patients.
Kelly
Yes, that is an issue, and a lot of times we do prosthesis within
the scrotal sac so it appears to be normal. There are some
circumstances where you know just the change in an appearance while
they are getting chemotherapy does affect this young population,
especially if they are in school, and we just have to support them
thought this time and really encourage him that things will get
better. We do have support groups here run by social workers, but
we also have a very strong network of other germ cell tumor
patients that work with our patients to assure them that they can
have normal life after the treatment.
Foss
Kevin, what happens if a patient recurs?
Kelly
It's devastating but there is still a chance that we can cure these
patients, but we still need some better drugs for those patients
who recur at this juncture.
Foss
Are there national trials looking at new therapies for these
patients?
Kelly
There are some, but again, it's a very rare tumor and it's very
difficult to do these trials.
Foss
What do you see that's new on the forefront in the management or
diagnosis of testicular cancer?
Kelly
I think that one of things is to better understand why young
individuals develop germ cell tumors. What's interesting is
there is an increasing trend of diagnosis, or there are increased
trends of the number of germ cell tumor cases that are rising
throughout the world. We actually have epidemiologic studies
ongoing to understand why this is occurring. Most likely it
is probably related to some of the environmental factors which are
influencing the development of germ cell tumors. I think a
better understanding about some environmental factors is important
and why there is an increase in trend for the development of germ
cell tumors is critical at this juncture.
Foss
And one thing we didn't touch on Kevin, is whether or not there is
a racial predilection for germ cell tumors?
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Kelly
It is typically found in whites over African-Americans, but
African-Americans still can develop germ cell tumors.
Foss
Well thank you Kevin, this was really a terrific discussion on a
disease that fortunately is one of the ones that we can cure
nowadays, and that's the good news here. You have been
listening to Yale Cancer Center Answers and I would like to thank
my guest Dr. Kevin Kelly for joining me tonight. From Yale
Cancer Center this is Dr. Francine Foss wishing you a safe and
healthy week.
If you have any questions or would like to share your comments, you can go to yalecancercenter.org, where you can also subscribe to our podcast and find written transcripts of past programs. I am Bruce Barber and you are listening to the WNPR Health Forum from Connecticut Public Radio.