Podcast Transcript: Management of Testicular Cancer

[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.