Metastatic Urothelial Carcinoma: Optimizing Use of Frontline Maintenance Therapy

Shared insight on the use of maintenance therapy in metastatic urothelial carcinoma with regard to PD-L1 testing and patient education.


Ignacio Durán, MD, PhD: When we discuss what to do to patients in my clinic, and when we gather with other specialists, we tend to do things when they are going to clearly determine our treatment choices. Nowadays, the determination of PD-L1 does not clearly determine what to do with my patients. We do not test for PD-L1 on a regular basis in my clinic. Some other groups do it. In my country [Spain], that could somehow direct you to treat a very small percentage of patients with I/O [immuno-oncology] in first line, but it’s not the case in my practice. I do not do this regularly.

Discussing starting maintenance treatment in patients with metastatic bladder cancer is something clinicians should be very clear about. When you try to wear the shoes of a patient who has received 4 to 6 cycles of chemotherapy, they’re probably tired of coming to the hospital and have accumulated some toxicities. When the patient comes for reassessment and has a CT scan, and the CT scan shows very good results, the patient probably wants to move on and say, “This is it. Now I’m treatment-free for a while.” At that point, you have to convince your patient that maintenance is probably the way to go.

How do you deal with that? How do you convince your patient that that’s probably the best option, rather than waiting for a relapse? There are a number of arguments. One is that bladder cancer, even though it’s a tumor that’s highly responsive to chemotherapy, is also going to relapse quickly in most patients. When the tumor comes back, patients might deteriorate quickly and might not be in a good condition to receive further treatment. They may lose that second-line option. That’s 1 reason for moving forward with treatment and going with maintenance.

Second, we believe in biology. The maintenance principle is based on some rationale. It’s not only a matter of sequencing things. It’s also believing that chemotherapy has some effect on overcoming tumor resistance by different mechanisms. We know that chemotherapy may induce what we call immunogenic cell death. It’s going to kill cancer cells, and it’s going to turn those cancer cells in a much better target for our immune system. Chemotherapy also causes depletion of immunosuppressive cell types, causing some breaks of the immune system. It also increases the presentation of tumor antigens and also triggered what we call T-cell infiltration, attracting T cells to the tumor. There’s biology behind the strategy of sequencing chemotherapy and immunotherapy.

The third argument that I use with my patients is that immunotherapy is not chemotherapy. Any maintenance treatment needs to be a treatment that has a very good balance in terms of safety. Once you get through the first doses, patients feel much more comfortable when they see that adverse effects are, in most of the cases, anecdotal. There’s a small percentage of patients that will have immune-related adverse events. But most patients are going to do very well with this treatment approach. Those are my arguments to justify maintenance.

Transcript edited for clarity.

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