A Global View on Metastatic Urothelial Carcinoma

Expert perspective on the current treatment paradigm of metastatic urothelial carcinoma across different regions of the world.


Ignacio Durán, MD, PhD: What’s the typical patient that we might see in a bladder cancer clinic? We’re talking typically about a man. Bladder cancer is about 3 times more frequent in men than in women. We’re talking about a person who’s probably in his early 70s. The median age at diagnosis in the United States is 72 or 73 years old. Normally, it’s going to be somebody with comorbidities. Bladder cancer has smoking as the main risk factor. Smoking is responsible for about 50% of bladder cancer cases in men and 25% of bladder cancer cases in women. This is the typical patient profile we see in the clinic.

These patients may present with a variety of symptoms. Hematuria is a classic symptom of bladder cancer, but this also applies to localized bladder cancer. When we talk about a metastatic patient, the symptoms may be very diverse and will depend on the location of the metastasis. We see patients who present with weight loss, loss of appetite, and pain in different regions. That could be 1 presentation, but other times they present with actual hematuria and some other symptoms. From a clinical perspective, it’s wide in terms of the clinical vignette for a patient with metastatic bladder cancer.

In terms of the treatment landscape of metastatic urothelial carcinoma, the first question we need to ask when we have a patient in the clinic is whether the patient can receive the best treatment, which is cisplatin. We have to divide our patients into what we call cisplatin eligible or ineligible. We do that by using the [Matthew] Galsky criteria. It’s very easy to do. The Galsky criteria have to do with how your system works in relation to organs that have more relevance when processing cisplatin, and how your body works in relation to those organs or systems that will receive the toxicity of cisplatin.

There are 5 Galsky criteria. The first 1 is creatinine clearance. If you have a patient with a creatinine clearance below 60 mL/min, then your patient would not be eligible for cisplatin. The second thing you need to have in a good shape when you receive cisplatin is your heart. If you have heart failure and you’re New York Heart Association class III or higher, that would be another Galsky criterion. Your heart isn’t good enough to deal with the hydration required to receive cisplatin. Then we have 2 other systems that need to be perfect: 1 is your neurological system. If you have any neuropathy that is grade 2 or higher, you cannot receive cisplatin. Or if your hearing system has an impairment of grade 2 or higher, you also cannot receive cisplatin. The last of the 5 Galsky criteria is ECOG performance status of 2 or higher. If your patient has any of these 5 items, they won’t be eligible to receive cisplatin.

The first question in your clinic is to divide your patients into cisplatin eligible or cisplatin ineligible. Once you’ve done that, you’re going to treat patients with either gemcitabine-cisplatin or gemcitabine-carboplatin depending on if they’re cisplatin eligible or ineligible. Once your patient has completed 4 to 6 cycles, if there’s benefit—benefit can be complete response, partial response, or stable disease—then the right way to go is to put your patients in a maintenance strategy with avelumab, a checkpoint inhibitor immunotherapy, until progression. If your patient doesn’t benefit on first-line chemotherapy, then you have to start thinking about second lines that we can extend later on and other questions.

There’s also an important question as to whether bladder cancer might differ in different regions. One thing that there’s no doubt about is that bladder cancer incidence changes across the world. We have areas that are zones of high incidence and other regions where the numbers are much lower. That’s probably influenced by the main risk factor, smoking. For instance, some countries in Europe—Greece, Belgium, Germany, Italy, and Spain—are probably the top countries in terms of bladder cancer incidence. A lot of that has to do with smoking history.

Other than the pure numbers in terms of incidence of bladder cancer, some varieties of this cancer may differ in their presentation depending on the geographical region. This is the case for a rare form of bladder cancer called squamous cell bladder cancer, which is more typical in Egypt. This is related to an infectious disease due to schistosoma. Schistosoma is very common in Egypt. That chronic infection in the bladder may increase the incidence of this type of bladder cancer. Those are the major differences across the world.

Transcript edited for clarity.

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