Posterior reversible encephalopathy syndrome during enfortumab vedotin therapy: a case report

Cancer treatment has entered a new era where medicines are designed to act like guided missiles, seeking out specific markers on cancer cells while leaving healthy tissue largely untouched. One such class of drugs, known as antibody-drug conjugates, works by attaching a powerful poison to a targeting molecule that delivers it directly to the tumor. Enfortumab vedotin is a prime example of this approach, used to treat advanced urothelial carcinoma, a type of bladder cancer. While these drugs are highly effective at shrinking tumors, they are not without risk. The most common side effects involve the nerves in the hands and feet, causing a tingling or numb sensation. However, the brain is a complex organ, and when powerful medications enter the bloodstream, they can sometimes cause unexpected reactions there as well. Understanding how these treatments affect the central nervous system is critical, because symptoms like sudden vision changes or confusion can be mistaken for the cancer spreading, leading to delays in the correct treatment.

A team of researchers at Kameda Medical Center in Japan recently documented a rare and serious reaction in a patient receiving enfortumab vedotin. The patient was a man in his fifties who had been treated for bladder cancer. After initial surgery and a different type of immunotherapy failed to stop the cancer from spreading to his liver, doctors switched him to enfortumab vedotin. The drug was administered according to a standard schedule, but just one day after his second dose, the situation changed dramatically. The man suddenly became confused and lost his ability to see clearly in both eyes. He did not have a headache, nor did he experience seizures, which are common signs of other neurological emergencies. Instead, his consciousness was altered, and his vision was impaired, prompting an immediate visit to the hospital.

When doctors examined the patient, they found that his blood pressure had risen significantly compared to his baseline, and his kidney function was already compromised, likely due to the loss of one kidney during his initial cancer surgery and the stress of the disease. To understand what was happening inside his brain, the medical team performed a magnetic resonance imaging scan. The images revealed bright, swollen areas in the back part of the brain, specifically in the regions responsible for vision. These findings pointed to a condition called posterior reversible encephalopathy syndrome. This is a state where the blood vessels in the brain leak fluid into the surrounding tissue, causing swelling that disrupts normal function. The location of the swelling explained why the patient's primary symptoms were visual disturbances and confusion.

The medical team made a crucial decision to stop the cancer treatment immediately. They did not assume the symptoms were caused by the cancer spreading to the brain, a common fear in such cases. Instead, they treated the condition as a reaction to the medication. The patient was managed conservatively, meaning he was given supportive care to let his body recover while his blood pressure was monitored and controlled. The result was rapid and encouraging. Within a short time, the patient's confusion cleared, and his vision returned to normal. A follow-up scan confirmed that the swelling in his brain had completely disappeared, leaving no permanent damage. This outcome proved that the condition was indeed reversible, provided it was recognized and treated quickly.

The researchers believe that a combination of factors likely triggered this event. The patient already had high blood pressure and reduced kidney function, both of which are known risk factors for this type of brain swelling. The medication itself, which contains a potent toxin designed to kill cancer cells, may have placed additional stress on the body's ability to filter and process the drug. Because the patient's liver was also affected by metastatic cancer, the drug might have stayed in his system longer than usual, increasing the chance of toxicity. While the study cannot prove with absolute certainty that the drug alone caused the syndrome, the timing of the symptoms appearing right after the dose, combined with the rapid recovery after stopping the drug, strongly suggests a link.

This case serves as an important reminder for medical professionals and patients alike. While enfortumab vedotin is a powerful tool against bladder cancer, it can occasionally cause severe reactions in the brain that mimic other serious conditions. If a patient on this therapy suddenly experiences vision loss or confusion, doctors must consider this specific syndrome as a possibility. Early detection through brain imaging and the immediate cessation of the drug can prevent permanent injury. By sharing this story, the authors hope to ensure that this rare side effect is recognized sooner, allowing patients to receive the right care and recover fully from an otherwise frightening complication.