Hints for Personalised Medicine in Genitourinary Cancers

Current and future treatment outlook

Maria De Santis from the Kaiser Franz Josef Hospital, Vienna, Austria discusses the importance of genetics in genitourinary cancers and the plethora of novel targeted therapies.

ESMO: How important is personalised medicine in treating genitourinary cancers?

Maria De Santis: Unfortunately, unlike in other tumour entities, we do not have biomarkers available to lead us in one direction or another. We recently got a hint for personalised medicine from bladder cancer research from a trial in a second-line setting of bladder cancer using the mTOR inhibitor, everolimus. And this study was actually negative – two responses in 45 patients. The investigators made a genomic sequencing and found two mutations: TSE1 (tissue-specific extinguisher 1) and NF2 (neurofibromatosis 2) in the responding patients. This finding gives us an explanation as to why those two patients responded to the mTOR inhibitor and the others did not.

Further research was carried out and bladder cancer patients were sequenced; the investigators from the Memorial Sloan-Kettering Cancer Center looked at actionable genomic alterations in those patients. Interestingly, they found actionable genomic alterations in 61 per cent of bladder cancer patients.

ESMO: How important are genetics in terms of renal cell and prostate cancers?

Maria De Santis: Cancer genetics is important and in my opinion will become more so. For prostate cancer, for example, genetics may become more significant in the very early setting as well as the late setting of the disease. With more and more prostate-specific antigen (PSA) testing, we find an increasing number of tumours, and also more benign or more indolent tumours. These patients are treated sometimes in a very aggressive way, subsequently we have a lot of unnecessary comorbidity around treatment in indolent cancers. What we would like to do is to discriminate those with indolent cancers and genetics might help us here. A recent study, hinted that BRCA1/2 mutations may indicate more aggressive tumours and might lead to more aggressive treatment compared to the patients without these mutations.

ESMO: Where we are now in treating genitourinary cancers?

Maria De Santis: We've made a lot of progress. We have many new agents for renal cell carcinoma in particular, and for prostate cancer. In renal cell carcinoma, we have targeted agents and in prostate cancer, drugs targeting the androgen receptor and androgen biosynthesis inhibitors. However what we do not have access to are biomarkers that can lead us to a more personalised use of these new drugs.

ESMO: How does the future look in terms of the treatment of genitourinary cancers?

Maria De Santis: In my opinion, we will have to refine the use of the new drugs we currently have access to, especially for renal cell cancer and prostate cancer. We have to find out how to better use these drugs and which patient groups can benefit the most. We have to identify drug combination that can provide a benefit in terms of delaying resistance for example. And we have to learn how to better manage the side effects of these drugs. This is the immediate future.

The more distant future, will lead us to a more personalised approach, based on the genetic changes that we find when sequence patients. And it will be easier when we know where to look, when we know what the key drivers are and which genetic alterations and mutations might not be important.

ESMO: What do patients with genitourinary cancers need to know about targeted treatments?

Maria De Santis: Firstly, I think that patients with genitourinary cancers should know that there are targeted treatments to help them with their cancers – renal cell cancer or prostate cancer for example, but especially renal cancer.

Furthermore, they should know that targeted therapies are not the same as chemotherapy. So, they do also have side effects but side effects profile differently than with chemotherapy. In my opinion, it is very important for patients to be informed on side effects and how to manage them especially. Because when you are informed, it is easier to manage and it is easier to stay on the drug despite some side effects.

And this is key, I think for a successful treatment with targeted therapies especially in renal cell cancer. The patient should stay on the drug as long as possible with the least possible side effects. What we don't want to do is to put off patients from an active treatment, if there are side effects that might be manageable. When you know what might happen, it's easier to handle.

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