GU Cancers 2018 | Using biomarkers to identify bladder cancer patients for neoadjuvant therapy

Talking about neo-adjuvant chemotherapy is part of the guidelines for any patient with muscle invasive bladder cancer who’s eligible for chemotherapy. And it’s not used as widely as it should be and there are reasons for that, and I think one of the the big steps forward is going to be to use biomarkers to guide which patients will benefit the most and will really improve care.

So my talk was mostly about different biomarkers and how close they are to clinical implementation and how good they have been in the initial studies. Right now they’re all under development so they’re not actually used in clinical practice and they need further validation but there are three main types of markers right now that look very promising. The first one I talked about are molecular subtypes of bladder cancer, so different groups have used different methods to classify bladder cancer based on RNA expression, so gene expression, and in general we have luminal and basal tumors which is terminology we know from breast cancer. And it looks like the basal tumors do particularly well with chemo, so they have the biggest benefit. So we could imagine prioritizing those patients for chemo and maybe not treating the other subtypes with chemotherapy, so that’s one idea. There’s something called the Coxon model which is also based on RNA expression where you can actually, for the individual patients RNA expression is matched to a database of RNA expression and you can predict how well that patient is going to respond to whatever the drug is. And that’s something I actually tested in a clinical trial through swabs which were in the cooperative groups and that’ll really give us some prospective validation as to whether that works or not. And then the third one, which I think might actually be the closest to clinical implementation, is using individual gene alterations, so mutations especially in DNA repair genes, and so if patients have a mutation in one of these genes they do very well with chemotherapy, so they’re some of the early studies show near 100 percent medium term survival.

So for any one of these markers you can imagine the marker positive patients getting chemo and the marker negative patients going straight on to surgery with possibility of neo adjuvant treatment if needed, so it’ll really make treatment a little bit more precise and hopefully avoid some of the toxicity of chemotherapy in patients who don’t really need itm and also avoid the delay in surgery in those patients who are unlikely to benefit from it.