I was invited to give the keynote lecture on testicular cancer and the topic of the talk is the management of marker negative stage IIa testes cancer. That is a very specialised situation which we face in the treatment of testicular cancer. As you probably know, testicular cancer has an extremely good prognosis and more than 90% of patients, even with metastatic disease, are eventually cured of their disease. Marker negative stage IIa represents a particular problem. Stage IIa means these patients have enlarged lymph nodes in the retroperitoneum of somewhere between 0-2cm, not larger, that is what we call IIa. Marker negative means that the tumour markers are negative. The tumour markers help us greatly in testes cancer because if the patients with small lymph nodes have positive tumour markers we know they have disease. If it's marker negative then we do know from old surgical series that up to 40% of these patients actually don't have tumour in those lymph nodes, they are benign or enlarged lymph nodes or lymph nodes enlarged for other reasons. That's where the challenge comes because you do not want to treat a patient unless they absolutely need it. The challenge here, for that stage, is really in the end to correctly identify those patients who are in need of treatment and those patients who are not.
So far we are trying to do that by simply using clinical means. There is no imaging method, not CT scan, not PET scan, not MRI, which can reliably tell us whether a patient has or does not have germ cell tumour. So for the majority of these patients if we encounter these lymph nodes we would watch them and see whether they actually grow or not or, if that's not possible or if we are in doubt or if the lymph nodes remain stable, in certain situations we advise the patients to undergo surgery to clarify the situation.

There are some potential developments on the horizon which may actually help us to improve that situation. There is a lot of research going on right now in something called microRNA. These are non-coding RNAs which regulate oncogenes and suppressor genes and the tumours actually shed that genetic material into the blood and we can isolate them and measure them. It appears that a certain microRNA, microRNA 371, is really specific for germ cell tumours and it behaves as an ideal biomarker should behave. It is measurable when the patient has tumour, it disappears rapidly if the patient is free of tumour. We are currently trying to develop that method because if that really holds what it promises right now then in the future if we have a patient like that we could simply draw a vial of blood, analyse it and say yes, you do or you don't have tumour and that would, of course, greatly help us.

The reason why we try to avoid over-treatment in patients is because we know whatever we do can have long-term complications. For chemotherapy and radiation the most scary consequences of treatment are the development of secondary malignancies or increased cardiovascular risk, all things which we know now can twenty, thirty years after successful treatment of a testes cancer impair the life expectancy of a patient.
If you have a marker negative stage IIa the safe thing right now, unless you are absolutely sure that this is tumour, if there is unequivocally evidence that this is tumour, and that's what I do, I watch these patients, I tell them come back in eight weeks, we repeat a CT scan. If the lymph nodes get bigger then we treat you, if they stay the same then we probably continue to watch you. If they regress then we continue to watch you.

Anything else to add on this topic?

For this particular stage I don't think so. The treatment itself follows the regular guidelines for treatment - it's either chemotherapy or surgery for non-seminoma and chemotherapy or radiation for seminoma. In this particular circumstance where these patients have lymph nodes less than 2cm I actually, particularly for non-seminoma, I prefer often a surgical approach because it has the least long-term toxicity and yields excellent outcomes if, and this is something that I would like to emphasise, if the surgery is done in an expert centre. This is something which we need to be aware of. There have been good data suggesting that if these types of surgeries are done in community centres which do not have the experience or not enough experience that the outcomes in terms of relapse rate, as well as complication rate, goes up. So these patients should be seen in an expert centre and operated by an expert surgeon.

What about overtreatment?

When we talk about suboptimal treatment, which includes overtreatment or undertreatment, we now have data that the treating centre actually plays a major role in the outcome of these patients. We now have data from different groups, including the French group, the German group, which indicate that there is up to 40-50% of patients who are treated outside of expert centres that the treatment is suboptimal. Suboptimal could be that they don't get enough chemotherapy, they get too much chemotherapy, the wrong or missing indication for surgery and that has been shown. Why is that important? Because all that can impact outcome. There is data from various groups around the world now. So one of the challenges for the treatment of testes cancer in general for the future, and I think that is currently probably the low-hanging fruit in terms of how can we improve the outcomes in testes cancer, is that we improve the quality of care on a broad basis and across different geographies.

In modern times like this where you have easy access, where you can upload pathology reports, imaging, and digitalise them so that anybody in the world can see them, all these new technologies give us the opportunity to actually do that without having every patient be seen at an expert centre because that is not always possible. But if you have the appropriate infrastructure you can contact an expert centre and ask for advice or just for a discussion of a treatment plan.