BackTable / Urology / Podcast / Transcript #3

Podcast Transcript: Management of Testicular Cancer

with Dr. Aditya Bagrodia and Dr. Jose Silva

Dr. Jose Silva talks with Urologist Dr. Aditya Bagrodia from UT Southwestern Medical Center about the medical and surgical management of testicular cancer. You can read the full transcript below and listen to this episode here on BackTable.com.

Table of Contents

(1) Initial Work-Up of a Testicular Mass

(2) Microlithiasis and Other Non-Cancerous Ultrasound Findings

(3) Imaging Beyond Initial Ultrasound: Timing and Indications

(4) Counseling Patients on Infertility and Hypogonadism

(5) Testicular Prosthesis

(6) Orchiectomy: Technique, Landmarks, and Avoiding Seeding

(7) Post-Operative Management, Surveillance, and Long-Term Care

(8) Indications for Partial Orchiectomy

(9) Burned-Out Testis Tumors and Management of Metastatic Disease

(10) Micro-RNAs as a Complement to Tumor Markers

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Management of Testicular Cancer with Dr. Aditya Bagrodia and Dr. Jose Silva on the BackTable Urology Podcast)
Ep 3 Management of Testicular Cancer with Dr. Aditya Bagrodia and Dr. Jose Silva
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[Jose Silva]
Hello, everyone, and welcome back to BackTable podcast. I'm your source of all things Urology. You can find all previous episodes of our podcast on iTunes, Spotify, and backtable.com. This is your host, Dr. Jose Silva. As your host this week, I'm very excited to introduce our guest today. We have Dr. Aditya Bagrodia from UT Southwestern Department of Urology. He's a urology oncologist. Welcome back, Aditya.

[Aditya Bagrodia]
Thanks for having me, Oche.

[Jose Silva]
You know, we had last time where we talked about bladder cancer. Today we're going to talk about testicular cancer. Where are you at now? In the office?

[Aditya Bagrodia]
Back in the office. Two small kids. For peace and quiet, this is going to be the best option.

[Jose Silva]
Have you had to do any work or anything there? Or just doing the podcast?

[Aditya Bagrodia]
Just podcast. A little bit of here and there. Nothing too intense.

(1) Initial Work-Up of a Testicular Mass

[Jose Silva]
Okay. So let's get into it. So today we're going to talk about testicular cancer. Aditya, I know that this is a topic that is very dear to you. We'll talk about that a little bit further.

So let's just start with a basic patient. He goes to your office. He's feeling a testicular mass. What's the next step?

[Aditya Bagrodia]
Yeah. I think obviously starting out with a comprehensive history and physical, understanding risk factors, history of undescended testicle, family history of testis cancer. Any issues or problems with fertility coming into this - Are they single? In a relationship? Any previous children? - is going to be mandatory.

And let's say this is going to be a generally unremarkable young man somewhere between the ages of 18 and 38. On exam, notable only for a testicular mass. Per guidelines - AUA guidelines, EAU guidelines, FCCA guidelines - the first next step is going to be to obtain a scrotal ultrasound as well as serum tumor markers.

(2) Microlithiasis and Other Non-Cancerous Ultrasound Findings

[Jose Silva]
Okay. So you do the ultrasound. You have the tumor markers. Let's talk about different pathologies that you can see in the ultrasound that are not cancer. Everybody asks about microlithiasis, calcification in the testicles. What would you do with these patients? And what's your next step? What do you counsel them on?

[Aditya Bagrodia]
Yeah. Yeah. I would say that microlithiasis is something that's oftentimes a source of concern for patients, for radiologists, and certainly for treating providers as well. And, the first thing you want to do is get an assessment of any risk factors.

So if the patient has any evidence of a personal history of testis cancer, history of cryptorchidism, family history of testis cancer, or issues with fertility then you have to kind of take the microlithiasis a little bit more seriously. On the opposite end of the spectrum, if they're just identified incidentally, no further follow-up is required, and the patient can be reassured. And there's a direct statement in the AUA guidelines along these lines.

Now, if they do have any of the risk factors, you're going to want to follow them. So of course the first thing's going to be self-exams, and then there's never been a study outlining whether six month ultrasounds for the first year followed by annually would be the best way to go. That's personally what I do. It's a conservative strategy, so that's, again, monthly self-exam.

[Jose Silva]
You do yearly?

[Aditya Bagrodia]
Mm-hmm (affirmative).

[Jose Silva]
Yearly ultrasound? Okay. So that's for only people with risk factors? Or everybody?

[Aditya Bagrodia]
That's going to be patients with risk factors. If they don't have risk factors, they're pretty much not at an increased risk of developing a cancer.

[Jose Silva]
I know when I was in residency there were two big... I had both of them, they practice differently... pediatric urologists, sorry. They did residency, fellowship, in different parts of the States. One of them did yearly ultrasound for pediatric patients. The other one just was good with the self examination. And so for pediatric population, would you do something different?

[Aditya Bagrodia]
Generally no. Of course the anxiety sometimes is a little bit higher among children and parents of children. And in the absence of high quality data, I think you also do need to synthesize that patient anxiety. Our job, certainly, is to explain to them that this is not an independent risk factor for developing a cancer, and to make them comfortable with that, but if you sense that the patient or the family may need a little bit more reassurance in addition to our counseling, I do think getting an ultrasound at six months or one year just to help them understand that there's nothing to worry about, I see very little downside for that.

(3) Imaging Beyond Initial Ultrasound: Timing and Indications

[Jose Silva]
Okay. So let's go back to our patient. So we have this patient. The ultrasound suggests that there's a mass, a solid mass in the testicle, and you do the tumor markers. Let's say the tumor markers are negative, or it really doesn't matter. Would you do, then, an x-ray or a CT scan of the abdomen and the chest?

[Aditya Bagrodia]
So ideally I would like to get my imaging prior to any surgical intervention just because you're going to have inflammation. You're going to have recovery, and sometimes you can have some nonspecific nodes afterwards. But that being said, oftentimes insurance companies won't pay for a CT scan in the absence of an actual cancer diagnosis.

So I'll order it, and this is my personal practice pattern. For my baseline I always get a CT scan - chest, abdomen, and pelvis. You want to know are there any non-specific, small pulmonary nodules. You want to really have an idea of the comprehensive setup before you embark on whatever strategy, whether that's surveillance or any type of additional treatment. So I will order it. Certainly if their tumor markers are elevated, and it's fairly pathognomonic. It's not that hard with insurance, sometimes it can be a bit of a contentious issue.

[Jose Silva]
So you are doing the tumor markers at the same time as the ultrasound?

[Aditya Bagrodia]
Yeah. So the tumor markers need to happen pre-orchiectomy. That's pretty much a guideline directed statement. You want to have a baseline. Again, for instance, if you have somebody that's got an AFP elevation, and then their path comes back pure seminoma, and you never got that information, that can impact your management.

[Jose Silva]
Yeah. I have had patients that they're already asleep in the OR, and I have checked... Maybe they did the LDH, or they didn't...something's missing so I’ll have to talk to the anesthetist, "Hey. Could you please draw some blood? Because I need that information." So maybe doing that, how you're doing it - do it at the same time as the ultrasound - the patient will make sure that they have the lab by the time the surgery happens and we don't have to run into that problem.

So, and is there a place for the MRI on the testicle for diagnosing difficult masses? Or some masses that the radiologist might mention that they're not completely solid? Are you using MRIs?

[Aditya Bagrodia]
Yeah. So first off, if you have an equivocal lesion - marker negative, small, hypervascular, hypoechoic - you're not sold that it's a cancer. The first thing I would do is just repeat imaging in six to eight weeks. The likelihood of you going from a localized stage to a metastatic stage is extremely low. And this is a common theme in the AUA guidelines as well as the EAU guidelines. It's better to get it right and take your time than to jump into it and either overtreat or mistreat.

So the first thing I'm going to do for an equivocal mass is actually repeat imaging in six to eight weeks. If that still looks equivocal, either you can continue on a surveillance program or if there's something that's evolving, changing, that's got you a little bit worried, that may be a role for something a little bit more advanced like an MRI or a contrast-enhanced ultrasound. But these are going to be very much reader-dependent, institution experience dependent, and I wouldn't use it as your initial modality.

[Jose Silva]
Okay. So for example, where I work we don't have the contrast-enhanced ultrasound. But the MRI, I definitely have done it a couple of times for those small masses. I haven't made any decisions based on the MRI. I usually, just like you do, I just follow the patient with ultrasound. If it becomes a little bit bigger, or painful, or something then I'll see if I can do a partial or whatever.

(4) Counseling Patients on Infertility and Hypogonadism

[Jose Silva]
So let's say you already tell patient, "Hey. We're doing a dual orchiectomy." Is there something else they're doing in terms of sperm retrieval prior to the surgery? Any other labs? Like testosterone labs? Things like that?

[Aditya Bagrodia]
Yeah. So excellent points. A couple of things. Starting out with the way I kind of counsel patients is say, "Hey, listen. The testes do two things. They make testosterone and they make sperm."

In terms of pre-orchiectomy testosterone levels, those are generally similar in men with testis cancer as healthy controls. Post-orchiectomy you will see hypogonadism in about 10% to 20% of patients. Now, whether that translates into clinical hypogonadism is patient-specific, but I definitely talk to them. In Texas that's actually a mandatory part of the consent.

The other aspect of this is, of course, sperm production. Now, you see some fertility or infertility with a baseline risk of oligospermia in about half of men presenting with testes cancer, and about 10% to 30% of men would have experienced infertility issues coming into it. Fortunately, post-orchiectomy paternity rates are about 90%, so generally they'll kind of even out.

Practically, I think it's important that you examine the contralateral testicle. You ask about any issues or problems with fertility. And if they're worried about it, if their contralateral testicle isn't normal, if they've got any type of syndromic type of features, then I would have a very low threshold to perform pre-orchiectomy semen analysis and cryopreservation. A baseline testosterone, less inclined to obtain that just because I think it can be a source of anxiety in the absence of clinical hypogonadism, but certainly afterwards it's going to be something that I am counseling them about.

(5) Testicular Prosthesis

[Jose Silva]
Okay. Sounds good. So in terms of the procedure, are you counseling them on testicular implants prior to the procedure? Do you offer them? I use Coloplast. I usually do it at the time of the surgery. Do you do it afterwards? What is a good timing to offer it, and if we're going to offer it, then do it?

[Aditya Bagrodia]
Excellent point. As someone who sees patients that largely have had their orchiectomy, one of the things that we run across most frequently is that they were never offered a prosthesis. So, placement of a prosthesis is associated with better self-image, body image, profiles. There have been multiple studies to show that, and many of the feelings of loss, of uneasiness, and of shame can be mitigated by placing a prosthesis. And, unequivocally, it's going to be easier to place it at the time of orchiectomy. This myth of placing it at a different time is really just that...it's an old wives' tale.

So I also use a Coloplast. The majority of patients are going to use a large. It is something that oftentimes needs to be pre-arranged. Generally the prosthesis are not kept on the shelf at many hospitals, so you do want to know who your rep is and have them come in. Practically, that may not always be possible, but if you're not thinking about it at that initial consultation, you're going to miss the window. You're going to miss the opportunity.

[Jose Silva]
Yeah. I found that usually the patients that are saying, "Yes," to the implants are younger patients in their 20's, single patients, and they still want to have that feeling of both testicles. Patients already married with kids, they probably don't care. They will say, "Don't worry about it. I don't care." Is that the same reaction to you in Texas?

[Aditya Bagrodia]
Yeah. I would say generally it's kind of the same. And as you know, we can really impact that decision as well, and everybody's a little bit different, and if it's never offered and they don't know about it, they're not going to have an opinion. Typically, it is the young, single guys that are more interested in it and the older, married folks are less interested.

(6) Orchiectomy: Technique, Landmarks, and Avoiding Seeding

[Jose Silva]
Okay. So we have the patient. We're going for surgery. Definitely inguinal incision versus a scrotal incision. Can you go through the process? My first case that I did after residency, two years afterwards, I was a little lost. I mean, I forgot the anatomy. I really don't know where I was. I had to do a big incision to find the spermatic cord. What's your process? Can you talk about the landmarks? How you would go about this surgery?

[Aditya Bagrodia]
Yeah. Yeah. Absolutely. So certainly I would say while orchiectomy is not necessarily the most complex surgery that we do, it can get disorienting and it can be tricky. Obese patients, previous hernia repairs, previous undescended testicle repairs. These can all make it rather difficult.

If there's anything even remotely complex, if they're a little big, I'll put them in a slightly flexed position just to kind of open up the ring. Then once they're under anesthesia, before prepping, I will actually palpate the ring - the external ring, which is always deeper than anticipated just lateral to the pubic tubercle - and I'll mark it, at that point, even prior to prepping. I like doing this before prepping just because doing that physical exam ostensibly could seed something.

Then I'll generally try to make my incision, essentially with the inferior, medial most part of the incision just at the level of the ring. You want to come through the skin, come through the subcutaneous fat, clearly identify Scarpa's - and it's mandatory in a virgin case as well as a re-operative case that you really see the external oblique fascia and you have it properly cleared off. You can't compromise on that. And you can get lost, and if you get lost, there's some high-dollar real estate including the femoral artery and vein which are not too far below.

Then, once I've got my obliques well cleared off, I'll actually gently tug on the testicle, really see my cord sliding, just at the level of the ring, And then I'll open the ring with a right angle in a retrograde fashion, identify the ilioinguinal nerve, dissect it off. Then I personally will take two DeBakeys and tease the cord off the shelving edges of the external oblique fascia. I grab it with the Babcock, digitally come around it, put a quarter inch Penrose around it, which is, again, preferable and not mandatory. In theory you're preventing any retrograde tumor seeding when you actually ultimately deliver the testicle. And I would say in a re-operative case, a very tricky case, I don't think it's heresy to actually deliver the testicle, take down your gubernacular tract attachments, and then dissect your cord off retrograde. Regardless, after that, you take your cremasteric fibers down, and I really do try to get this to the level of the internal ring where I can actually see my peritoneal reflection.

[Jose Silva]
Hey, Aditya. Let me ask you a question. So is there any study that if you don't do the high ligation - or early vascular control, sorry - is there going to be seeding? Or is it just theoretical? Potential? I always do it because that's how I was taught to, but is there data like if you don't do it you’re going to have seeding?

[Aditya Bagrodia]
It's theoretical. And I don't want to minimize this important aspect of it. At the end of the day your risk of having in-transit cord metastases is about 5%. So to see a meaningful difference in a study you're going to have to have thousands of patients that received either high ligation or they didn't. But if you're lost, in my opinion delivering the testicle, finding your cord, tracing it back, and then securing it is probably better than digging around and getting into trouble.

[Jose Silva]
Yeah.

[Aditya Bagrodia]
So once I'm at the level of the ring, I'll personally put an 0-silk down right at the level of the ring. This is going to be kind of a security stitch, and in addition if they do ultimately have a non-seminoma tumor requiring RPLND - whether that's chemo-naïve or post-chemo - you've got a landmark to make sure that you’ve completely excised the cord.

Then I separate the cord into two hemi-cords. Usually that's the vas and connective tissue surrounding it, and then the vessels in the other half. I'll put a 2-0 silk and then a 2-0 suture on each side to make sure it’s completely clamped, send the specimen off. I put a Raytec in underneath when I'm cutting the specimen just to make sure if there are any tumor cells within the cord that I'm not spilling.

Check for hemostasis one more time. Many times the patients will have a direct abdominal wall hernia - you can use some ETHIBOND sutures just to a Bassini-type repair while you're there. Fascia close with 2-0 vicryl, subcutaneous tissue with 3-0 vicryl, and then after that I'll tend to do monocryl with scrotal support. Typically Tylenol and ibuprofen would be perfectly fine for pain control.

[Jose Silva]
If you were going to do the implant, would you do it then at that stage that everything is over? Then you would bring the scrotum inside, and then just pull through?

[Aditya Bagrodia]
Yeah. So I actually would put the implant in prior to closing my external oblique fascia just to give myself a little bit of extra room. So once I've gone the orchiectomy, changed gloves, irrigate the field with antibiotic solution, prepare your prosthesis. If you're not familiar with it, it's certainly much, much easier than preparing, say, an IPP for instance, but generally your reps could come in and it's not too challenging.

What I will do is kind of try to preserve the neck going into the scrotum. I place my prosthesis in there, and then I will take an -0 Vicryl and a CT needle and try to close that neck, and the tab stays up. I don't suture it down into the dependent-most area of the testicle. That's just the way I've done it. I think there's some various different approaches here, obviously, but essentially you're going to get the prosthesis down in there. You're going to close that neck. I'll vigorously check to make sure it's not going to migrate cranially into the pre-pubertal space, and then that's pretty much the prosthesis placement.

[Jose Silva]
So I usually put in the most dependent part of the scrotum. Any reason why?

[Aditya Bagrodia]
Yeah. I just feel like the chances of it eroding through become a little higher if you tack it down.

[Jose Silva]
Okay.

[Aditya Bagrodia]
And I'll have the patients manually manipulate it down as part of their post-op.

[Jose Silva]
Have you seen extrusion?

[Aditya Bagrodia]
Fortunately not. I mean, certainly if a patient's going to be receiving chemotherapy, having a surgical complication is a catastrophe. So whether that's bleeding, whether that's an infection, etc. So I definitely take it pretty seriously, and if that was to delay their care, that would be pretty unacceptable.

(7) Post-Operative Management, Surveillance, and Long-Term Care

[Jose Silva]
Okay. So then you will see him two weeks afterwards just to see how it is, discuss the pathology. So for me, after this point, two weeks after and we discuss the pathology, then for me my next step will be to send them to the oncologist for further treatment in terms of whether he wants chemo, radiation, or RPLND. Whatever they decide, I'll leave that to the oncologist. But in your case, you're a urology-oncologist, so what's your next step for you?

[Aditya Bagrodia]
Yeah. So first thing is when they're leaving, oftentimes it's been a pretty fast moving train. Ultrasound, markers, primary care, urologist, orchiectomy, and then it's...bam, everything stops. You're at home. You're recovering. There's no new information coming, and you're kind of freaking out that you have cancer, and you're 22 years old.

So the first thing I'll do is I'll tell the patient, say, "Hey. This is normal. This is expected. You're going to have a lot of anxiety." and I'll try to actually see if they want to be set up with cancer center support services, whether that's support groups, etc., because I think that's massively important, and I think that's something that we really should kind of stand upfront in.

So then at their post-operative visits you've got the path, and of course you want your post-orchiectomy tumor markers. One of the most common things that I see done inappropriately is that you haven't followed the markers out to their nadir levels. And you've got Stage I patients, their AFP is still a little bit elevated, and they get diagnosed as having metastatic disease.

But going back to your question, first thing would be to have you comprehensively staged, CT scan chest, abdomen, and pelvis, as well as their post-orchiectomy nadir tumor markers. I literally had a guy who started out with an AFP at 48,000. It took three months for him to get down back to normal, but he never had a metastases. I could nearly guarantee you that if this patient was seen at the outside, when he came back two weeks later and his AFP was 10,000, they would have said, "Hey. You've got metastatic disease. Time to pickle you with some chemo." So you've got to follow the tumor markers out, and at this point they're staged, and maybe starting out with Stage I seminomas. So they have no evidence of metastases. We review every one of these cases in a multidisciplinary tumor board. We review the pathology, we review the imaging, And if they're a Stage I, nearly certainly I would say, "Let's keep an eye on you with a surveillance program."

[Jose Silva]
So Aditya, everybody goes through the tumor board for you guys?

[Aditya Bagrodia]
Every patient. Every patient.

[Jose Silva]
Okay. Every patient with a cancer at your institution, everybody goes for a tumor board.

[Aditya Bagrodia]
So every testis cancer patient goes to a tumor board. A garden variety prostate cancer patient or a bladder cancer patient, not necessarily, but anything even remotely complex we have tumor boards almost every week. I kind of arrange the germ cell tumor board, and we have medical oncologists, radiation oncologists, pathologists, radiologists, every time. And there's a lot of good data that expert care, multidisciplinary care, high-volume care, is directly associated with outcomes especially in testis cancer.

[Jose Silva]
That's awesome, and definitely it reassures the patient that they are having the best option in terms of the treatment, so that's good.

[Aditya Bagrodia]
So kind of maybe just walking through it, so a Stage I seminoma, I kind of run through, again, "Hey. You've got one testicle. The testicles make sperm, and they make testosterone. Here's the signs and symptoms that we'll be continually monitoring for." I really try to emphasize to them that if they don't have a primary care physician it's mandatory that they have one. The downstream side effects of hypogonadism include depression, low self-esteem, loss of libido, and even kind of more medical things like osteoporosis, lipid metabolism, insulin resistance, sarcopenia down the way, so I really try to take this opportunity to get them plugged in.

Then I don't do any kind of risk-adapted management of seminoma patients - whether that's size, whether that's really testis invasion. Unless they are absolutely pushing for some type of adjuvant treatment, which would be either carboplatin or radiotherapy, I'm going to push them for surveillance. The risk of relapse is 10% to 12%. I'll tell them that about 90% of these take place in the first two years, and after that they're generally home free.I also want to mention self-exams once monthly. Set a reminder. But for Stage I seminoma, that's pretty much going to be it.

[Jose Silva]
Yeah. So usually at my institution they do one dose or one session of the carboplatin instead of the observation. I think that's the way to go with what they're choosing. Patients that have contraindication for chemotherapy or radiation, they will go to observation. And they're doing good, but definitely it's good to hear from your perspective what you would recommend. That's why we're talking about this. So let's continue with the other stages.

[Aditya Bagrodia]
Yeah. So I'm just going to take a minute to address that, and you mentioned that your general role in testis cancer management is to kind of do the orchiectomy, get the ultrasound, get the markers, and then get your oncologist involved. Of course carboplatin is a guideline-directed option, but in the vast majority of patients they're going to be over-treated, and they're going to be exposed to the risks, which are not zero. If they relapse, they have different relapse types of behavior, and I would say at most major US centers (that's going to be Memorial Sloan Kettering where I trained, Indiana, etc.) observation is going to be the option. So I would encourage you to touch base with your oncologist and revisit this.

[Jose Silva]
Definitely.

[Aditya Bagrodia]
So Stage II seminomas, this is kind of an evolving area. So just Stage II germ cell tumors, broadly speaking, if somebody comes in with an equivocal node - let's say one centimeter at the short axis, a solitary node...you don't necessarily want to jump in. We know from surgical series that if you go in and do an RPLND, 20% to 30% of those patients are actually going to be pathological N0. So again, going back to this notion of being slow, being deliberate, and making sure we're not over-treating. And usually what I mean explicitly by that is I'll usually repeat imaging in six to eight weeks, and I would always repeat a CT scan of the chest to make sure they don't have any metastases as well as the abdomen, and pelvis, and their tumor markers.

But a Stage II seminoma, if they're low-volume, and that's going to be one node less than three centimeters, really all options are on the table. And that's going to be radiotherapy or good, risk-directed chemotherapy with either BEP x3 or EP x4, and I would say that there's been resurgent interest in primary RPLND in this setting as well. There's two large studies, one out of Germany and one in the US - our institution was the fourth highest enrolling site for basically RPLND for low-volume seminoma. Early results are excellent, and you can potentially mitigate some of the side effects associated with chemotherapy or radiotherapy.

With that being said, the standard-of-care options still are going to be radiotherapy or chemotherapy. If they've got bulky disease, 2C, multifocal disease, you're pretty much going to be best off going with chemotherapy. And if it's limited, radiation would be an option. The most important thing is that all options are available at your institution and presented to the patient.

[Jose Silva]
For patients that have teratoma in their pathology, would that change your approach? Would you be more inclined to do an RPLND on those patients? Or it really doesn't matter? You will do a chemotherapy trial and see how it goes?

[Aditya Bagrodia]
Yeah. Yeah. So excellent question. So moving on into non-seminoma landscape... If they're a stage 1A - so no lymphovascular invasion - nearly all those patients I would advise that they go on to a surveillance program, and that's going to be standard markers, imaging, chest x-rays. One caveat. If they do have a malignant, transformed element in the orchiectomy specimen - so any type of secondary malignant transformation - then I would at least talk to them about upfront RPLND per AUA guidelines.

If they're a stage IB, this is an area where all options of observation, one cycle of BEP, chemotherapy, or RPLND are going to be on the table, and again, I think it's most important that we can comprehensively run through the patients’ risks and benefits of each approach. And I really will try not to impart a bias on these patients. I try to present it to them, “Ultimately the risk of relapse is about 50%. If we go on surveillance, we save you any treatment but if you recur largely you may require chemotherapy.” However, some of those patients would be candidates for RPLND.I do have them see a medical oncologist as well if they're considering adjuvant treatment, just between BEP, chemotherapy.

Now if they've got like a 90% teratoma, I probably wouldn't push for adjuvant BEP chemotherapy, but I certainly wouldn’t push for surgery as well. If they ultimately decide that they want to go on surveillance, let's just say, and they pop up a little node, and they're primary landing zone marker negative, in that case nearly certainly I would say, "Hey. Let's move onto surgery here. Chemotherapy is not going to be a great option because there's a real risk that we may end up double-treating with chemotherapy and surgery." So it's nuanced. It's going to be looking at that orchiectomy pathology. It's going to be reviewing that CT scan yourself, and also with a multi-disciplinary specialist. If it's cystic, if it's in the landing zone, etc., these are all valuable bits of information.

And with that, I would also say that it's absolutely critical to look at your own scans. The number of times that people come in on testis cancer surveillance with positive nodes, very obvious that are read as “ Unremarkable, no adenopathies” is actually shocking.

[Jose Silva]
Yeah. Like you said, sometimes those one centimeter nodes are usually read “unremarkable,” but they weren't there before, so definitely have the patient have all those imaging studies that are given to the radiologist to make the best decision.

[Aditya Bagrodia]
Yeah. And for a Stage II patient, what I will do is...Let's just say they had... Either they were diagnosed at Stage II, or they developed a metastasis on surveillance. What I'll typically do if they're electing surgery is schedule the surgery six to eight weeks out, repeat the imaging right before that. And if they have lots of metastasis, obviously surgery was never going to help them. If the node is involuted, which can happen, again, in non-trivial percentages of the case, you could safely avoid it. And then if things have remained basically stable, you've kind of filtered out the patient that you're likely going to help with surgery.

(8) Indications for Partial Orchiectomy

[Jose Silva]
Okay. So let's talk about other situations. Partial orchiectomies - is there a role? I mean, in Europe they're doing that for some cases. Are you doing some partial orchiectomies at your place?

[Aditya Bagrodia]
Yeah. Yeah. So testis-sparing surgery does get a lot of attention, and per the AUA guidelines, if you've got a normal contralateral testicle, a radical inguinal orchiectomy should be performed. Now, of course, you're going to have patients - we see these not infrequently with bilateral tumors, or they've got a solitary testicle - and these are cases where absolutely you want to not just get it right but get it perfect.

So for starters, it's mandatory, in my opinion, to get a semen analysis and a baseline testosterone. If they're azoospermic, and they're hypogonadal, you're not really doing them any favors by doing a partial orchiectomy. Take it one step further. If they're azoospermic and hypogonadal, that's the case where you want to have your infertility specialist there to actually do a sperm extraction at the time of orchiectomy, and we've done that before.

Now let's say they've got some androgen production, and they've got some evidence of spermatogenesis. So of course you want to cryo-preserve. Then you really want to talk to the patient about what they prioritize here? Do they prioritize androgen production and fertility preservation? Or do they prioritize oncologic control? So, you have that conversation at the front, and you run through the various scenarios.

All right. So let's just say that they do want to consider a partial orchiectomy. So this is going to be important that the tumor is less than about two centimeters. If it's on one of the poles or superficial under the capsule, that makes it a lot easier. And then you want to make sure that your GU pathologist is on standby, not just any ‘Tom, Dick, and Harry’.So what I will do is, just like we initially talked about, deliver the testicle, make sure that the field is squared off. If you're concerned at all about being able to find the tumor, it's also not a bad idea to have your ultra-stenographer on deck. I'll make a tunicle incision and, using loops, resect the mass, send it for frozen, and also take biopsies, and close up the testicle at that point. And then I'll put it on ice at that time as well.

So you really want to make sure that they don't have any germ cell neoplasia in situ, which can be a difficult intraoperative diagnosis, and then you also want to confirm that it's a testis cancer. So let's just say that it's a testis cancer with no GCNIS. Then you go ahead and proceed with your orchiopexy, your scrotal support, and so forth. Many times germ cell neoplasia in situ is difficult to diagnose from intraoperative sections. But if you've got negative margins and an absence of germ cell neoplasia in situ, then you just go on a surveillance program. Self-exams. I will typically get an ultrasound at three months, at six months, and then annually thereafter. That's not necessarily guideline-directed care.


If they do have germ cell neoplasia in situ, their risk of developing an invasive tumor is going to be right around 50%, So you can either give them adjuvant radiotherapy to mitigate that risk down to about 1% to 2%, or you can observe them, allow them to be... They have to know, "Hey. There's a real chance of developing a tumor," and if they're, for instance, trying to have a kid naturally, now would be the window to try to do it.

But the bottom line is, yes, you want to be familiar with this option. Doing a radical orchiectomy on a solitary tumor or doing bilateral orchiectomies is not a trivial decision. It's obviously an easier decision, but again, having the kind of clinical chops and the multi-disciplinary team to make those decisions is important.

[Jose Silva]
I mean, and also partial orchiectomy is not easy, And you can have complications, you can have bleeding afterwards, and you can have other problems that might end up causing maybe more problems to the patient, so definitely have that conversation with them, But you're trying to preserve function with the partial orchiectomy.

[Aditya Bagrodia]
Absolutely. Absolutely.

[Aditya Bagrodia]
Yeah. Because even cryopreservation and assisted reproductive technology techniques, they're not cheap. These are young men.

[Jose Silva]
Yeah.

[Aditya Bagrodia]
And even if you cryo-preserve, if they ultimately end up requiring something pretty intensive, that can be $8,000 to $10,000 dollars. We take care of patients at our safety-net hospital, in addition to our tertiary care center, and they're not going to go and spend $30,000 for IUI, etc.

[Jose Silva]
Yeah. Some patients can't even pay for the preservation.

[Aditya Bagrodia]
Mm-hmm (affirmative). Yep.

(9) Burned-Out Testis Tumors and Management of Metastatic Disease

[Jose Silva]
Let alone doing the other stuff. So I had a patient, I don't remember when it was, but….incidental finding, they call us, the radiologist says that on the ultrasound, he has a burned-out tumor. I did a full workup to see, make sure there wasn't anything else. Eventually I did an orchiectomy just to be safe. It came out like atrophy, didn't mention anything of cancer. Do you see these kind of patients?

[Aditya Bagrodia]
Yeah. So that's tricky. So you've got them worked up comprehensively with CT scan chest, abdomen, and pelvis. You've got their tumor markers, and let's say everything is stone-cold normal. But you're gonna be pretty sure, pretty confident, in your radiologist that this is in fact a burned-out, regressed tumor, which of course can happen. And whether that's the tumor outgrowing its blood supply, or whether that's some type of immune response, is not entirely clear.

But, going back to it about 80- 90% of people are going to have germ cell neoplasia in situ along with any tumor. So if you're stone-cold convinced that this is a tumor and not some other imaging artifact - some resolved orchitis, small infarct, some dilated rete testis - you could do an orchiectomy, and that would be a very, very conservative thing to do, or you could go on a less intensive intervention such as starting out with serial ultrasounds, serial self-exams, and then generally spacing those apart. And again, explaining the idea that the patient might have germ cell neoplasia in situ that ultimately develops into an invasive tumor. It's a very oncologically safe thing to do if you're stone-cold sold, but when that testis comes back as no GCIS or anything - good news is no cancer, bad news is it took your testicle being removed.

[Jose Silva]
Yeah. I think this patient was in his 60's, so he didn't care.

[Aditya Bagrodia]
Sure.

[Jose Silva]
So it was easy. Definitely a 20-year-old with the same findings, more difficult. Without kids, more difficult. So if I have a patient like that, would you say safer or better for the patient doing a serial ultrasound?

[Aditya Bagrodia]
I would.

[Jose Silva]
Okay.

[Aditya Bagrodia]
I would. I mean, this is a case, also, where you could consider a biopsy. Not done very commonly in the United States at all. I mean in Europe it's something that's a little bit more frequent. I personally think that's still overkill. I would start out with self-exams and imaging, and just kind of start spacing those out over time.

[Jose Silva]
Good. So Aditya, I know that you're doing a lot of research on testicular cancer, and we'll talk about that in a little bit. Anything else you want to add? I mean, anything else important? I think we've covered everything, but if there's something else that you want to mention about testicular cancer.

[Aditya Bagrodia]
Yeah. For the sake of completeness, if the patients do have metastatic disease, it's important that they get appropriately staged, they receive an ICG/GCG risk stratification, and direct communication with a medical oncologist. And certainly at our institution I think really dotting your i's, crossing your t's.

There's more and more data that ports are associated with development of thromboembolic events. A lot of these patients are receiving oral anticoagulation at the onset of diagnosis. Getting them safely through chemotherapy, assessing them properly afterwards, and then if they require post-chemo RPLND, that of course falls squarely back in our wheelhouse.

So it just highlights, again, you want to have your patients managed by physicians that see this type of disease day in and day out. Dying of testis cancer really shouldn't happen, but equally as important we don't want to harm these young cancer survivors for the rest of their lives with our decisions that we make if they're not just perfectly fine. And much of my research is actually focused on trying to really make sure we treat patients when they need to be treated and safely avoid treatment when that can be done.

(10) Micro-RNAs as a Complement to Tumor Markers

[Aditya Bagrodia]
And I'll maybe highlight one area that we've done quite a bit of work on, and these pertain to microRNAs. So thus far, as we all know, tumor markers are good but they're not perfect. Say, for instance, in seminomas HCG will only be elevated in about 10% to 15% of the time. Over the last decade, there has been a body of work that showed that a series of microRNAs were uniquely present in testis tissue, and one step further they can actually be measured in the blood. And suffice to say in the pre-orchiectomy setting, regardless of seminoma versus non-seminoma, regardless of a mediastinal tumor or a retroperitoneal tumor, regardless of a pediatric testis cancer or adult, ovarian germ cell tumor or male, these microRNAs are elevated in about 90% of patients.

So we have recently published our work in the Journal of Urology showing that the performance characteristics of these microRNAs drawn immediately prior to surgery, including in patients with solitary testis masses, bilateral tumors, and even post-chemotherapy orchiectomy patients, correctly identified about 95% of patients that were likely to have residual cancer. So in the diagnostic area, this is going to be a game changer.

We published another study where we checked the serum microRNA immediately prior to chemotherapy-naïve RPLND. These are going to be Stage I and Stage II patients, and suffice to say the specificity and sensitivity were about 90%. So now instead of just a coin flip, "Hey, listen, you're in Stage 1B. There's a 50% chance," we're really kind of individualizing care.

[Jose Silva]
Mm-hmm (affirmative). Will this be another tumor marker? Do you see eventually not doing tumor markers and only doing this?

[Aditya Bagrodia]
I think it'll be complementary. I think, say, again, you have a patient with a pure seminoma on orchiectomy but their AFP was 800. The microRNA is not going to give you that histology-specific information, but I do see it being a tumor marker. There's two large studies - we have both of those open here, and we're in the process of opening up a study for patients with Stage I disease and dictate adjuvant treatment based on microRNA status. But in terms of diagnosis, staging, monitoring, monitoring response to chemotherapy, and even surveillance, this is poised to be a game changer.

[Jose Silva]
And for patients like when we talk about a small testicular mass that's equivocal, that we're not sure whether it's an actual mass prior to doing a biopsy? or the patient that I told you about, the burned-out tumor? Would this have a place in those patients?

[Aditya Bagrodia]
Nearly certainly, and I can't tell you how many times in our tumor board - the microRNAs are not commercially available to make clinical decisions - this exact thing comes up. “Man, it would be nice to have a microRNA at this time.”

[Jose Silva]
Okay. Okay. Well, yeah. That sounds interesting. Like you're saying, game changer. Definitely more tools for us to make better decisions. Better safety for the patient. And like you mentioned, sometimes the decision that we make either might cure them from cancer, but we cripple them in other aspects of their lives. So definitely those tools that you're working on are going to be great for us.

[Aditya Bagrodia]
Yeah. Yeah. So thank you, and I would just add - most, if not all, people that treat any reasonable amount of testis cancers are more than happy to field questions, informal consults, formal consults. Certainly with telehealth that's been something that's exploded, and myself, I get a lot of emails from colleagues, from people in the community, and would be more than happy to help offer my two cents, or present any cases in our tumor boards, so I would be happy to provide contact information for that as well.

[Jose Silva]
No, no. That's great. That's great. It's good to hear from you guys, have your perspective, so we don't lose ours.

[Aditya Bagrodia]
Yeah. Yeah. And I mean, I think just sticking to the guidelines 101.

[Jose Silva]
Yeah. Exactly.

[Aditya Bagrodia]
Getting your markers. Getting your ultrasound. Talking about sperm banking. Talking about androgen deficiency. Getting them plugged in with a PCP. Talking about a prosthesis. This is squarely in our wheelhouse, and as it gets complex and nuanced it gets trickier, but this kind of stuff we can absolutely do it.

[Jose Silva]
And like you mentioned, the AUA does a great job just putting out the guidelines, so it's already there. It's a matter of just following the prescription and the step-by-by, and you will do no harm.

[Aditya Bagrodia]
There you go. Yeah. Just, again, leave it with these are young guys. Testis cancer is actually responsible for the most life-years lost of any non-pediatric cancers, so we kind of... Many people think of these as, "Oh, yeah. They're curable. No big deal. It's testis cancer," but as you mentioned, the opportunity to help these patients is profound, and the opportunity to hurt them in the same breath with non-guideline directed care is also pretty real.

[Jose Silva]
Well, thank you, Aditya. Enjoy the weekend, and we'll speak again soon. Take care.

[Aditya Bagrodia]
Awesome. Awesome. Happy New Year's. Thank you again for having me.

[Jose Silva]
Happy New Year. Bye-bye.

Podcast Contributors

Dr. Aditya Bagrodia discusses Management of Testicular Cancer on the BackTable 3 Podcast

Dr. Aditya Bagrodia

Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.

Dr. Jose Silva discusses Management of Testicular Cancer on the BackTable 3 Podcast

Dr. Jose Silva

Dr. Jose Silva is a board certified urologist practicing in Central Florida.

Cite This Podcast

BackTable, LLC (Producer). (2021, April 17). Ep. 3 – Management of Testicular Cancer [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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