MicroRNA Testing: The Latest in Testicular Cancer Markers

[Jose Silva]
...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...

[Jose Silva]
...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.

[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.