BackTable / Urology / Article
MicroRNA Testing: The Latest in Testicular Cancer Markers
Avery Wolfe • May 19, 2021 • 37 hits
Along with scrotal ultrasound, drawing testicular cancer markers is the first step in working up a testicular mass. Following testicular cancer tumor marker levels after orchiectomy is also critical in evaluating response to treatment and monitoring for residual or recurrent disease. However, traditional testicular cancer blood markers are not elevated in all testis cancers. The latest testicular cancer research is in microRNA testing, as microRNA biomarkers have been identified as uniquely sensitive and specific testicular cancer markers.
We’ve provided the highlight reel in this article, but you can listen to the full podcast below.
The BackTable Urology Brief
• The first step in working up a testicular mass is scrotal ultrasound and testicular cancer markers (AFP, LDH, beta-hCG).
• Baseline testicular cancer tumor marker levels should be established before orchiectomy, and testicular cancer blood markers should be followed out to their nadir levels postoperatively.
• Traditional testicular cancer markers are not elevated in all testis cancers. For example, beta-hCG is elevated in only 10-15% of seminomas.
• MicroRNA biomarkers are elevated in roughly 90% of all testis cancers, and microRNA testing may also be especially useful in identifying residual disease once available.
Table of Contents
(1) Traditional Testicular Cancer Markers: Initial Workup Of A Testicular Mass
(2) Using Testicular Cancer Markers Post-Operatively
(3) MicroRNA Biomarkers: A Complement to Traditional Testicular Cancer Markers
Traditional Testicular Cancer Markers: Initial Workup Of A Testicular Mass
Checking testicular cancer markers is one of the first steps in working up a testicular mass. These testicular cancer blood markers must be drawn before orchiectomy to establish a baseline for postoperative surveillance. Dr. Bagrodia also reviews his approach to marker-negative testicular masses, explaining his personal indications for proceeding with more advanced imaging versus regular ultrasound surveillance.
...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?
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...
...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?
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.
So you are doing the tumor markers at the same time as the ultrasound?
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.
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?
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.
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Using Testicular Cancer Markers Post-Operatively
As a urologic oncologist, Dr. Bagrodia discusses how he uses testicular cancer tumor marker levels to manage patients postoperatively. He explains the importance of following testicular cancer blood markers all the way to their nadir levels to avoid prematurely diagnosing metastatic disease, as well as his approach to navigating the anxiety so many of these young patients feel after orchiectomy.
...So then you will see [the patient] two weeks [after orchiectomy] 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?
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, Oche, first thing would be to have them 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...
MicroRNA Biomarkers: A Complement to Traditional Testicular Cancer Markers
Dr. Bagrodia addresses the shortcomings of traditional testicular cancer markers (namely that they are not elevated in all testis cancers) and highlights his latest testicular cancer research on microRNA biomarkers. These unique microRNA biomarkers are elevated in nearly 90% of testis cancer patients, so microRNA testing could revolutionize diagnosing equivocal tumors and identifying residual disease once commercially available.
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.
Mm-hmm (affirmative). Will this be another tumor marker? Do you see eventually not doing tumor markers and only doing this?
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.
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?
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.”
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.
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
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
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