All these studies start, all of us as clinicians have some questions that basically are patients' questions because I learned from my supervisor that we used to listen to patients and sometimes you feel that you are not good enough or at least you cannot provide what they need. One of the questions that I have as a clinician is can I help these patients better? Can I do something better for them? In testicular cancer I have some questions, they are different questions but one of them is can we predict when these patients get chemotherapy, after the chemotherapy they have some residual disease that's spread in different parts of the body but we don't know which disease they have. In some cases they have only necrosis, fibrosis and we still take these patients for the OR room and we do a very invasive surgery.

So I had a case with a patient, 20 years old, and he was asking me, 'Why do you want me to do this surgery? Why do you want to do this surgery if you are not sure what I have?' So basically that was the question for this research - can we predict which type of histology that we have in these patients that get chemotherapy and after we can be sure what is the best treatment for them? That was the question that basically… or our hypothesis that basically we had to start this study.
Testicular cancer, since many years ago we don't have very good clinical markers either for diagnostic, either for prognostic. But recently, since 2006, there were new studies that found that microRNA, serum microRNA, so liquid biopsies that we can use, they are diagnostic for testicular germ cell tumours and they can detect seminoma, non-seminoma which is very important and they are very sensitive and at the same time they are very specific.

At the same time there were new studies that verified that we can use these microRNAs not only as a diagnostic tool but also as a prognostic tool because we can use them to follow up the treatment. Like patients on chemotherapy we can monitor treatment because these microRNAs decrease during treatment. Some other studies found that patients with relapse also have these elevated values of these different marker RNAs that we can just use, taking the serum from the patients. So my question was can we use these microRNAs to predict this disease that we have in these patients that we identify by CT scans after chemotherapy. So we have a new way to improve our approach, our clinical approach, and see if these patients really need to have the surgery. Basically if these patients have viable disease it makes sense to do the surgery. I was expecting to have higher values of these microRNAs in patients with viable disease instead of the other ones with necrosis and fibrosis that I was expecting to find very low levels or absent levels of these microRNAs.
Basically our hypothesis was correct so we found that patients with viable disease, for sure the patients that need to be treated, they have higher values of microRNAs which was interesting for us from the beginning because we didn't know exactly what we were expecting. So our hypothesis was correct. At the same time after we tried to evaluate in our clinical cohort if we had any chance, because we do this surgery in patients with residual lesions measuring more than 1cm. So our idea was to follow patients with a negative marker, like this microRNA with very low levels, and eventually admit that these patients could be followed instead of just going for surgery. What we found was that for the patients with negative marker and lesions with less than 3cm, so measuring more than 1cm, 3cm, we could follow these patients because we didn't have any patient with viable disease with a positive marker. So, all the patients with a negative marker were different, they had a different histology than viable disease. That means basically that we can use this marker to follow patients and when the marker is negative eventually we can increase the follow-up of these patients and follow patients with larger residual masses. Of course this is just a preliminary study but the results are very promising.

So what's your take home message for a doctor?

That's a challenging thing to say because we still have to prove it with different studies, different cohorts, more patients. One of the things that we have in microRNA is we have to have a standard way, a standardised assay, that we can use in different hospitals to make sure the results are reliable and we can repeat the results in different places. So we still have to do that. The results are just promising, I wouldn't say that we can change our way of following patients but at least we have something more that we didn't have before and for that reason I have faith that we can change a little bit the paradigm and we can give more to these patients and provide better care, for sure.