As a testicular cancer survivor, I’m always curious about what comes next in my life. I mean this in less of a metaphorical manner and more of “What is my follow-up protocol going to be for the next few years?” Currently, I get full-body CT scans once a year and my blood checked at various intervals. Sadly, with that amount of radiation hitting me, I have not developed any superpowers yet.
In late March, I came across a research study called “Serum Levels of MicroRNA-371a-3p (M371 Test) as a New Biomarker of Testicular Germ Cell Tumors: Results of a Prospective Multicentric Study.” While that mouthful of a title meant nothing to me, I reached out to Dr. Aditya Bagrodia to help me decipher the findings.
Dr. Bagrodia is an assistant professor in the Department of Urology at UT Southwestern Medical Center, where he also serves as the Dedman Family Scholar in Clinical Care. His clinical and research focus centers on patients with testicular cancer, primarily in biomarker profiles and molecular signatures of urologic tumors as predictors of clinical outcomes.
Between his specialty and principal authorship or co-authorship of more than 100 articles in peer-reviewed publications, I felt he was the top dog to help me understand this study and share the findings in layman’s terms.
What’s unique about testicular cancer tumors?
Before delving into the research, we must first have a cursory understanding of the biology of testicular cancer tumors. They are very special—and not just because they affect such a “special” part of our bodies.
About half of them secrete chemicals (known as serum tumor markers AFP, HCG, and LDH) that can be measured in the blood, which is not typical of most other cancerous tumors. If one or more of these tumor marker levels are elevated, it essentially confirms a testicular cancer diagnosis. This is especially true if the levels continue to rise once the testicle is removed through an orchiectomy.
However, having a normal level of these tumor markers does not rule out testicular cancer, as one type of testicular cancer (seminoma) only shows elevated markers in 15 percent of cases. The other category (nonseminoma) secretes tumor markers about 60 percent of the time. In my own case of being diagnosed with nonseminoma testicular cancer, my tumor markers were always in the normal range.
What are the major findings of this study?
However, there are new data to support that altered MiRNAs, which are small molecules of RNA that regulate which genes are expressed in the body, can also be used as a more accurate measure than the aforementioned tumor markers. Specifically, 85 percent of seminoma and 95 percent of nonseminoma tumors secrete altered MiRNA (known as MiRNA 371). This study aimed to prove if this was a viable option for continued tracking.
The study compared roughly 600 testicular cancer patients to 250 non-cancery males. In the former group, if the patients had elevated MiRNA 371, the chance of having testicular cancer was 97 percent. If the MiRNA 371 test was not found to be elevated, there was a 83 percent chance that no cancer was present.
In addition to other findings, such as MiRNA levels significantly dropping after orchiectomy, it was determined that this testing could be a more accurate measure than any of the currently used tumor markers.
What does it all mean for testicular cancer patients survivors?
The first thing to note is that this study is just the first step. This process hasn’t been through regulatory processes to make it a test that can be used for clinical decision-making, so it can only be used for research purposes instead of helping decide a course of treatment for a testicular cancer patient. However, there are a number of theoretical applications for the future.
First, if a testicular mass is discovered through a self-exam, and a mass is found present on an ultrasound, the current next step is to measure the AFP, LDH, and HCG levels. By adding in testing for MiRNA 371, doctors could have the probability of testicular cancer being present versus another issue. This could prevent an unnecessary surgery and help keep the Uniballers a more exclusive club.
Secondly, if testicular cancer is confirmed, MiRNA 371 levels can help decide the course of treatment. For example, if levels are shown to be diminishing after orchiectomy, a patient may not need to undergo chemotherapy. Conversely, if levels continue to rise but nothing is showing up in other screenings, they could have chemotherapy as a preventative measure.
Third, testing for MiRNA 371 can also help to identify how well chemotherapy is treating the testicular cancer. As someone who had to wait until weeks after my treatment to see if the hell I put my body through was effective or not, this is a huge benefit in my mind.
Finally, this testing can help eliminate the need for more invasive follow-up scans, such as lab draws and CT scans. This helps cut down on costs and exposure to radiation. Until the CT machines are significantly cheaper and give me the superpowers I’ve craved for years, I am entirely OK with this.
What are the next steps?
While this pertains only to testicular cancer patients and survivors right now, in the future it may be something that can be evaluated for the average male.
The next steps is to validate these findings by conducting larger studies, which are already well underway. The collection and processing of blood samples also needs to be standardized, so it is not dependent on any one particular lab. Once these items are complete, this testing can be offered as a viable option for ongoing treatment and follow up.
One important thing to note is that teratoma, a rarer type of testicular cancer that often occurs after chemotherapy, cannot be reliably detected by miRNA 371.
Dr. Bagrodia summarized his hopes for the future by saying:
“Ideally, the test would be compared to the standard of care (i.e. classic serum tumor markers and imaging) with respect to performance characteristics.
Finally, the ultimate goal would be randomized trials based on miRNA 371 to establish new treatment guidelines and better, more personalized care for patients with testicular cancer!”
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