Eight months after receiving approval from the U.S. Food and Drug Administration (FDA), a new treatment for metastatic bladder cancer has received a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).
This positive opinion will now be reviewed by the European Commission (EC), which has the authority to approve medications for all EU member states, as well as Iceland, Liechtenstein and Norway. The treatment is expected to be approved across the European Union, with the additional bureaucratic process likely to take about one to two months.
The treatment combines the drugs Enfortumab Vedotin (Padcev) and Keytruda (pembrolizumab) for first-line treatment of advanced bladder cancer. It is the first and only therapy that offers an effective alternative to chemotherapy, which has been the standard treatment for patients with metastatic or inoperable bladder cancer.
The positive opinion is based on a clinical trial that showed patients receiving this drug combination doubled their survival time compared to those treated with chemotherapy. In March, the European Society for Medical Oncology (ESMO) and the American Cancer Society (NCCN) updated their guidelines, recommending this combination as the first-line treatment for patients with metastatic bladder cancer.
Dr. Michal Sarfaty, an expert in clinical oncology and head of the Uro-oncology Unit at Sheba Medical Center, explained that "the combination of immunotherapy—a biological treatment that works on the immune system—with targeted chemotherapy that specifically attacks tumor cells has been researched for some time. About two years ago, we saw impressive preliminary results, something unprecedented, with very high response rates to the treatment. In October, a study comparing this new combination to standard chemotherapy, which had been the recommended treatment until then, showed remarkable results.
"For many years, the first-line treatment for metastatic bladder cancer was chemotherapy," Dr. Sarfaty added. "This is a very aggressive disease, similar to metastatic pancreatic or lung cancer. What we saw in the study was that the new combination therapy doubled the duration of response and overall survival time. Notably, 29% of patients achieved a complete response, meaning a total disappearance of metastases on imaging—a remarkable outcome we had not seen before."
Dr. Sarfaty also mentioned that an analysis of the study showed that all subgroups of patients benefited from the new combination compared to chemotherapy, regardless of age, sex, metastasis location, PDL-1 levels in the tumor, or other parameters. "In the past, when a patient with metastatic bladder cancer came to me, I would decide on treatment based on various clinical and pathological indicators. Now, it’s clear that all patients will benefit more from this combination than from any other treatment we previously offered—this is truly a revolution in treatment."
Dr. Michal SarfatyShe emphasized, "I don’t use the word 'cure,' but that is certainly our goal. With such high response rates, some patients may indeed achieve long-term survival and live a long time without the disease.
"Bladder cancer not only affects a person’s physical functioning throughout their illness but also significantly impacts their quality of life and mental well-being, often exacerbated by late diagnosis and the symptoms associated with both the disease and its treatment," Dr. Sarfaty explained. "The study found that patients who experienced moderate to severe pain at diagnosis saw a significant improvement in quality of life with the new combination therapy compared to those treated with chemotherapy."
Regarding access to the treatment in Israel, Dr. Sarfaty noted that "since the treatment is approved by the FDA and soon in Europe, anyone with private insurance can receive it. However, it is very important to us that it be included in the next health care basket (Israel's universal health care option) so that everyone can access it."
Bladder cancer is the ninth most common cancer worldwide and the fifth most common in Israel. Europe has the highest rate of new bladder cancer cases globally, with over 165,000 people diagnosed with the disease in the European Union (EU) each year. Moreover, the disease claims more than 50,000 lives annually. According to the Israel Cancer Association, approximately 1,800 cases of bladder cancer are diagnosed annually in Israel, some of which are already invasive with metastases. Treatment for these patients aims to slow cancer spread, delay its growth, shrink the tumor and extend survival time.
Most bladder cancers (about 90%) start in the urothelial cells and are known as Transitional Cell Carcinoma (TCC) or Urothelial Cell Carcinoma (UCC). Depending on the depth of tumor invasion into the bladder wall, tumors are classified into two groups: non-invasive tumors, where the tumor is confined to the mucosa or submucosa, and invasive tumors, where the tumor has penetrated the bladder muscle and has the potential to spread to nearby lymph nodes or organs outside the urinary tract. If the disease spreads, it is called "metastatic bladder cancer" or "advanced bladder cancer." Typically, metastatic bladder cancer spreads to the bones, lungs and liver, but it can also spread to other organs.
The Health Ministry recently approved a groundbreaking urine test based on the identification of biomarkers (bio-markers) on DNA extracted from cells in the sample. These markers indicate an increased risk of a cancerous tumor, even one that may not be visible on imaging or invasive diagnostic tests.
The new test, called Bladder EpiCheck, allows for early diagnosis with a simple urine test in individuals with suspicious symptoms and for detecting recurrence in those who have already recovered but are at high risk of relapse. The test is represented in Israel by Medical Link, has been approved by the U.S. Food and Drug Administration (FDA) for detecting disease recurrence, and is included in the guidelines of the European Association of Urology (EAU). It also carries the CE mark for European conformity.
According to the Israel Cancer Association, the disease is more common in men than in women, and its prevalence increases after age 60. The following factors may increase the risk of developing bladder cancer:
Smoking: Smoking tobacco products is responsible for about half of bladder cancer cases. Smokers are 4-7 times more likely to develop the disease compared to non-smokers. The chemicals in cigarette smoke enter the bloodstream and reach the bladder after being processed by the kidneys, where they irritate the cells lining the bladder. This irritation can disrupt cell division, leading to malignancy.
Occupational exposure to chemicals: Another major risk factor is exposure to certain chemicals in the workplace. These substances are found in iodine, rubber, gas, plastic and paint factories, as well as other chemical industries. The effects of these substances are not immediate, and the damage may manifest 25 years after exposure.
Repeated urinary tract infections: Repeated urinary tract infections and untreated bladder stones can lead to a rarer form of bladder cancer called squamous cell carcinoma. People with spinal cord injuries who have a permanent catheter (catheter) are at higher risk for urinary tract infections and, consequently, bladder cancer.
Family history: The risk of bladder cancer is slightly higher in close relatives of those who have had the disease, likely due to similar risk factors, such as smoking. Rarely, a hereditary gene may cause bladder cancer, including Cowden Syndrome—a rare condition involving a mutation in the PTEN gene, which normally helps regulate cell growth. This mutation slightly increases the risk of developing cancers, including bladder cancer. Lynch Syndrome, primarily associated with colon and uterine cancer, can also increase the risk of bladder cancer.
Symptoms of bladder cancer:
Blood in the urine (hematuria): The most common symptom of bladder cancer is the sudden or intermittent appearance of blood in the urine, usually without pain. Sometimes the blood is not visible and is only detected microscopically. If you notice blood in your urine, seek medical attention immediately. The amount of bleeding does not indicate the severity of the disease.
Urination problems: Another symptom is urinary problems, such as burning during urination, frequent urination, especially at night, or difficulty emptying the bladder. These symptoms do not necessarily indicate bladder cancer and are often caused by other conditions, such as benign prostatic hyperplasia or bladder stones. However, if one or more of these symptoms appear, it is crucial to consult a doctor for further evaluation. If symptoms persist after treatment, additional tests may be required.
Pain in the lower back or abdomen: Pain is a less common symptom but may sometimes occur.
Symptoms of advanced bladder cancer that has spread to other organs include difficulty urinating, lower back pain on one side, loss of appetite and weight loss, weakness and fatigue, swelling in the feet and bone pain. Many of these symptoms can be caused by conditions other than bladder cancer, but it is important to seek medical evaluation.