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GU Cancers 2021 | RETAIN BLADDER: a risk-adapted approach to muscle invasive bladder cancer

Daniel Geynisman, MD, Fox Chase Cancer Center, Philadelphia, PA, describes the interim analysis of the ongoing Phase II RETAIN BLADDER study, which aims to evaluate a risk-adapted approach to the treatment of muscle invasive bladder cancer (MIBC). In this study, tumors from 71 patients with MIBC were sequenced for mutations, with the aim of identifying a specific subset of patients that could be spared cystectomy or chemoradiation following standard of care neoadjuvant chemotherapy, in order to improve quality of life while preserving oncologic outcomes in these patients. This interview took place during the 2021 Genitourinary Cancers Symposium.

Transcript (edited for clarity)

RETAIN is a Phase II trial for patients with muscle invasive bladder cancer, clinically T2 to T3. And the whole point, the whole idea, is to see if some of them can be spared a cystectomy or local aggressive treatments, such as chemoradiation to their bladder. The standard of care for muscle invasive bladder cancer is neoadjuvant chemotherapy followed by cystectomy or chemoradiation. We know that some patients at the time of their cystectomy, after they’ve had chemotherapy, will have no more disease...

RETAIN is a Phase II trial for patients with muscle invasive bladder cancer, clinically T2 to T3. And the whole point, the whole idea, is to see if some of them can be spared a cystectomy or local aggressive treatments, such as chemoradiation to their bladder. The standard of care for muscle invasive bladder cancer is neoadjuvant chemotherapy followed by cystectomy or chemoradiation. We know that some patients at the time of their cystectomy, after they’ve had chemotherapy, will have no more disease. They will be what we call ypT0. And the question then comes up, can those patients be spared a cystectomy? A cystectomy is a huge quality of life detriment, and any patient would like to avoid it if possible, but obviously the oncologic outcomes have to be preserved. And so, the question is, is there a way ahead of time to be able to select appropriately patients who can avoid the surgery, who can avoid chemoradiation?

What we did is we selected these patients by giving them neoadjuvant chemotherapy, sequencing their pre-chemotherapy tumors, and look for certain mutations, one of four, that have previously been shown to correlate with excellent oncologic outcomes and correlate with really good response to chemotherapy. And those happened to be RCC2, FANCC, RB1, and ATM. And if they had one of those four mutations, we then looked again in their bladder after their chemotherapy, and if they had no disease and there were no disease on imaging, they were allowed to go on to active surveillance. The rest of the patients were treated as standard of care as you would normally. And these results that we presented was for all of the 71 patients on trial, and in particular focusing on the subset, the 26 patients who went on to active surveillance, what we showed is that there are two sorts of important key findings.

One is a good proportion of them, actually over 50% did end up having a recurrence of their disease. However, the vast majority the recurrence was non-muscle invasive bladder cancer, and they have been able to be treated with intravesical therapy for most of them, and still have been able to be spared a cystectomy. Their overall survival is excellent at this point with a median follow-up of approximately 20 months. There have been two deaths, but as we pointed out during the presentation, deaths are bound, unfortunately, to occur no matter what in this population. And the question is, if you can sort of keep that percentage as you would expect for the overall group, for patients with muscle invasive bladder cancer, and yet still preserved bladder and a proportion of them, does that make sense? Is that a quality of life when? So to speak, and we believe that it is.

And so the primary endpoint is two year metastasis-free survival, which we’re comparing to our baseline, and our historical controls. And that has not been reached yet for all patients so that’s why these are the interim results. But so far, it seems certainly intriguing. There are two other trials that are attempting very similar approaches, an Alliance trial and the Hoosier trial. Those are ongoing, and we need to see what those results are, we need to see what our final results are. And then we can put all of this together and figure out what are the really right biomarkers to move forward in this type of a paradigm, where we’re again trying to spare patients a cystectomy. I would also point out that at this point, certainly this is not a standard of care. This should only be done on clinical trial. And those were the key findings.

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