The drug pembrolizumab (trade name: Keytruda) has been approved in Germany since August 2017 for the treatment of advanced urothelial carcinoma.

The word “urothelial” comes from the medical term for the type of membrane tissue lining the urinary tract (urothelium). The urinary tract includes the renal pelvis, the ureter, the urinary bladder and the upper part of the urethra. In more than 90 out of 100 people with a urothelial carcinoma, it develops in the bladder (bladder cancer).

The early signs usually include painless bleeding of the mucous membranes lining the bladder, which turns the urine a brownish color. People may also feel like they have to urinate more often. The symptoms of advanced urothelial carcinoma and bladder cancer may include pain in the abdomen or kidneys, enlarged lymph nodes, or bone pain. It is more common in men than in women.

Pembrolizumab is used to treat advanced urothelial carcinoma and bladder cancer that can no longer be surgically removed or that has already spread to other parts of the body (metastasis). The drug can be used in first-line treatment as well as after chemotherapy. The drug is an option for first-line treatment only in people whose tumor has high levels of the protein PD-L1. This protein weakens the body's immune response against the tumor cells. Pembrolizumab blocks the effect of the PD-L1 protein, increasing the ability of the immune system to fight the cancer cells.


Pembrolizumab comes in the form of a powder that is dissolved in a liquid and then given through an infusion (an IV drip), entering the bloodstream directly through a vein. The infusion is given every three weeks and lasts about 30 minutes each time. This treatment is stopped if severe side effects occur or if the cancer continues to progress.

Other treatments

For patients with urothelial carcinoma or bladder cancer who can’t have cisplatin-based first-line treatment and whose tumor has high levels of the protein PD-L1, the standard treatment is chemotherapy that has been individually tailored by a doctor.

For patients whose cancer returns within 6 months of treatment with platinum-based chemotherapy (early relapse), the drug vinflunine is an option. If the cancer comes back more than 6 months after the chemotherapy (late relapse), another course of cisplatin-based chemotherapy can be considered.


In 2019, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) wanted to take another look into whether pembrolizumab has any advantages or disadvantages compared with the current standard treatments for people with advanced urothelial carcinoma or bladder cancer.

In 2019, the manufacturer didn't provide relevant data concerning first-line treatment.

In the studies provided by the manufacturer for the first assessment in 2017, only the data of patients who had already had platinum-based chemotherapy were suitable for the analysis. Treatment with pembrolizumab was compared to standard treatment with the drug vinflunine: 82 people had treatment with pembrolizumab and 90 had treatment with vinflunine. The study lasted about 2 years and 3 months. In almost all of the patients, the cancer had already spread to other parts of the body (metastasis). The following results were found for this group of people:

What are the advantages of pembrolizumab?

  • Life expectancy: The study suggests that pembrolizumab has an advantage here: While half of the participants who were given pembrolizumab had passed away after about 11 months, this had already happened after 7 to 8 months in people who had the standard treatment.
  • The study also suggests that pembrolizumab has advantages in terms of symptoms such as nausea, vomiting, loss of appetite and constipation. For instance, it took longer for nausea or vomiting to occur or get worse in people who had treatment with pembrolizumab: While it took about 7 months for this to happen in half of the people in the pembrolizumab group, it only took 2 to 3 months for it to happen in half of those in the standard treatment group.
  • Serious side effects: The study suggests that pembrolizumab has an advantage here, too: The amount of time it took for serious side effects to occur in half of the participants was about 6 months in the pembrolizumab group, and only about 1 month in the standard treatment group.

What are the disadvantages of pembrolizumab?

  • No disadvantages were found compared with the standard treatment.

No difference

  • There was no difference between the treatment groups in terms of the following:
    • Pain
    • Exhaustion
    • Sleep problems
    • Diarrhea
    • Overall health and health-related quality of life
    • Treatment stopped due to side effects: In each group, 9 to 15 out of 100 people stopped the treatment because of side effects.

What remains unanswered?

  • Immune-mediated severe side effects: The manufacturer didn't provide usable data about advantages or disadvantages of the new treatment compared to the standard treatment. Immune-mediated side effects are medical conditions in which someone’s immune system attacks their own body.

More information

This information summarizes the main results of reviews produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The reviews were commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of the reviews and the hearings received, the G-BA passed a resolution on the added benefit of pembrolizumab (Keytruda): 2017 and 2019.