Tomorrow I’ll be presenting a poster on the topic of circulating tumour DNA in testicular cancer patients, more so to look at the detection of residual disease or recurrence. As we know, testicular cancer is a cancer predominantly of younger men. The traditional serum tumour markers alpha-fetoprotein, LDH, beta-HCG, they’re quite variable between patients and even between stages, so they’re not the most reliable tumour markers that we can depend on. We also use CAT scan imaging alongside with the serum tumour markers to look at things like residual disease recurrence, but I’d say altogether we have room for improvement with these kinds of modalities, so that’s kind of where the liquid biomarker ctDNA comes in. The goal of this study was to see how ctDNA measures up in comparison to CAT scan imaging, traditional serum tumour markers.
In our study we conducted a retrospective analysis at our institution, UCI, with patients from 2020 to 2025 that had any ctDNA level collected. Some patients only had one test done, some patients had over five tests done, and they had any histology of testicular cancer. We looked at 41 patients, we had a total of 153 ctDNA samples. There were about half seminomas, half non-seminomas in our patient population, we had all stages of testicular cancer, and we found that regardless of histology and regardless of stage, ctDNA was a superior test to traditional serum tumour markers and imaging findings. We actually calculated a sensitivity and specificity of 100 percent.
I want to note we had eight instances out of our 153 samples of ctDNA data points where there was discordance, and by discordance I mean either that the ctDNA was positive and the imaging was negative or the ctDNA was negative and something was being picked up on imaging. In the instances where ctDNA was positive and the imaging was negative, these were all followed up with serial short interval imaging, and in all of the cases where that imaging was completed there was disease that then showed up. So ctDNA was detecting recurrence ahead of CAT scan imaging. We had several cases where the ctDNA was negative but something was picked up on imaging, and that was, depending on what the concern was, followed up by surgery, and pathology was actually negative in all of our cases. So that was a very, very interesting finding from our study.
What is the clinical impact of these results?
As I mentioned, testicular cancer is a cancer predominantly of younger men, and there’s a two-fold clinical significance. One is, in terms of imaging, CAT scan is delivering radiation to young patients that could be at risk for secondary malignancies related to radiation in the long term, so if we have a better test, higher sensitivity, specificity, that even our imaging – which before pathology that’s kind of the gold standard – if we can avoid as much radiation by doing a simple blood test that’s a better test, that would be really beneficial for our patients. That’s one thing.
Also of course peace of mind for our patients, and then there’s some confusion with the serum tumour markers because you get false positives and there’s just a lot of variability as I also mentioned, so having a more dependable test would be really helpful for the clinicians as well.
What are the limitations of the ctDNA test in this setting?
Right now, I would say a limitation of our study, not necessarily the ctDNA itself, was just the heterogeneous nature of the study since ctDNA’s not guideline-based right now in the testicular cancer space. So we don’t have set intervals in which we’re collecting ctDNA, nor have we established what those intervals would be, so I think that’s kind of a general limitation of the evidence we have so far.
You can get false positives with ctDNA, I didn’t have any in our study, but it is possible. Usually with those cases we do a little more digging to get to the bottom of it, but I suspect that the rate of those false positives compared to the rate of false positives with the traditional serum tumour markers would be much lower.
It was a limitation in our study but I could see potentially, if it’s not guideline-based yet, costs could be a potential limiting factor of patients not at larger centres able to get the tests, having it done there. I think there’s still a lot we don’t know about ctDNA, how it measures up to, for example, miRNA, which is also being studied and has some good evidence in the testicular cancer sphere. So I’d love to see more studies on both these biomarkers and even comparing them together so we can see are there subsets of patients that one test is actually better than the other?
