Bladder Preservation Strategy: An Underutilized Potential Cure for Muscle Invasive Bladder Cancer - Xavier Maldonado

December 28, 2022

Alicia Morgans and Xavier Maldonado discuss the topic of bladder preservation in the treatment of muscle invasive bladder cancer. Dr. Maldonado shares the data presented at ASTRO, highlighting that bladder preservation, while suitable for very specific patients, has comparable metastasis-free survival rates to cystectomy. He mentions that prognostic factors such as tumor size, absence of multiple tumors, and only mild hydronephrosis influence treatment selection. Dr. Maldonado also suggests that older patients could fare better with bladder preservation. Moreover, he emphasizes the potential of biological markers such as MRE11 to predict patients' response to three-modality treatments, even though the utilization of such markers in clinical practice remains early-stage. The conversation underlines the importance of bladder preservation as a viable, yet underused, curative treatment for muscle invasive bladder cancer.

Biographies:

Xavier Maldonado, MD, PhD, Clinical Head, HU Vall d’Hebron, Radiation Oncology, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


Read the Full Video Transcript

Alicia Morgans: Hi, I'm so excited to be at SOGUG 2022, where I have the opportunity to speak with Dr. Xavier Maldonado, who is joining us from Barcelona. Thank you so much for being here.

Xavier Maldonado: Thank you for the invitation.

Alicia Morgans: Wonderful. Well, I'm really excited to talk with you about bladder preservation and the use of this strategy to try to cure patients of muscle invasive bladder cancer while allowing them to maintain their bladder, which is certainly what everyone wants, if this is possible.

So, I know there have been some recent updates and that we continue to think about prognostic factors and the outcomes for patients. I wonder if you can share your thoughts, set the stage by even giving us that latest data that was presented recently at ASTRO.

Xavier Maldonado: We are always thinking with the urologists and our medical oncologists, what is the best treatment for these patients, if bladder preservation treatments are really equivalent in terms of survival or metastasis-free survival, on other endpoints. We have new information, as you have mentioned, of ASTRO, is there is a pool of analysis of three hospitals, Mount Sinai, Boston, Massachusetts, and Southern University of California with Princess Margaret that confirm that this is a good strategy in very selected patients.

Patients with a maximum seven centimeters of tumor, more extension without either nephrosis or very mild nephrosis, and not multiple tumors. The metastasis-free survival is very similar from cystectomy and from the three modal treatment there is no impact in terms of other issues and there is a slight benefit of three modal treatment in terms of survival, but it was a secondary endpoint.

Alicia Morgans: So this is so important. Patient selection for bladder preservation is something that we certainly do in clinical practice. To your point, we have in most practices really actually generally at least in mine, excluded patients with hydronephrosis, patients who have multifocal tumors or patients who have very large tumors, as we are just unsure that we will be able to really eradicate the disease in those settings.

And we always want that maximal TURBT to try to reduce the disease burden even as we start the treatment. What I think is so interesting, and we don't have the answers for this yet, is that there are some clinical trials that are currently ongoing through the NRG in the US that allow patients with hydronephrosis for example, and I think it will be very interesting for us to see in that prospective trial if the effectiveness of our treatments are able to overcome what is generally, and again, consistently a poor prognostic sign.

Xavier Maldonado: You're right. I think that there are some very bad prognostic factors like bilateral hydronephrosis. Only lateral hydronephrosis is not so bad, so bad prognostic factor. It in terms of bladder preservation can be a concern because you have to focus your radiation on the trigone, just when the ureter enters in the bladder. So you can do that in this place of toxicity, but if there is a mild unilateral hydronephrosis or for instance, if the patient has an uneasy component but very focused, in my opinion this is not a cause for reject treatment for these patients.

For instance, in terms of age of these patients, we sometimes think that elder patients cannot be submitted to these treatments, and the different experiences shows the opposite of that.

Alicia Morgans: Absolutely, and I think when we at least consider cystectomy versus bladder preservation, older patients I think may actually fare better with bladder preservation if we are interested in trying to cure the cancer?

Xavier Maldonado: Yes. We have the recent experience of a British clinical trial, the BC2001 that has published the quality of the quality of the PROMs of these patients, and we see that in the first six months, there is an impact in the quality of life, but after that, the quality of life is exactly the same as before to being treated. With a slight percentage of patients, that has an impact in terms of toxicity. But there is not a reason for not thinking in this treatment if we think in terms of PROMs.

Alicia Morgans: Absolutely. I do think that patients also appreciate maintaining their bladder rather than adapting to a bag. In many cases, that can be very challenging for patients, especially older patients who may need assistance in some of their activities and other functions during the day.

Xavier Maldonado: I agree. I agree. And we have the confirmation that the patients that we have to rescue with surgery have the same overall survival as the ones who are cystectomy upfront. So we are not losing any opportunity in terms of survival, so it's the same. And this is consistently reproduced in literature and this is also checked in these presentations held at ASTRO this year.

Alicia Morgans: Wonderful. So any other bits of advice or pieces of information that you wanted to share so that folks who are considering this approach for treatment for their muscle invasive bladder cancer patients may learn?

Xavier Maldonado: We want to know more about markers, about biological markers. The most developed is MRE11, which is involved in DNA reparation, and there is also presented this year a full analysis of several RTOG clinical trials that speaks about the predictive value of this.

It can be checked by immunohistochemical. I think it's too early for incorporate this in the clinical practice, but it's a point that maybe we can follow with other several biomarkers that are on development, no markers linked to hypoxia, markers linked to infiltrative T-cells and think that they can show us which patient is going to have benefit of these three modality treatments.

Alicia Morgans: Well, I think that's so exciting and as we really try to ensure our patients have access to this treatment which is curative for these patients, we hope and expect it will be so important to have those biomarkers to help us make that decision with a little more clarity.

So I sincerely appreciate you sharing your expertise and especially because I think this is an underutilized approach to treating muscle invasive bladder cancer, I sincerely appreciate you bringing it to the forefront of our conversation so that we can continue to try to help our patients have the best outcomes from the cancer, but also live the best lives that they can too, other than that. So thank you for your time and for your expertise.

Xavier Maldonado: Thank you very much for this very interesting interview.