A combination of immunotherapy and targeted cancer treatment given before and after surgery may reduce the risk of recurrence and improve survival in patients with muscle‑invasive bladder cancer who cannot tolerate conventional chemotherapy. The findings come from a new study from Karolinska Institutet, published in The New England Journal of Medicine.
Muscle‑invasive bladder cancer is a serious disease with a high risk of recurrence. To lower the risk of recurrence, patients are often given cisplatin‑based chemotherapy before surgery, but around half of patients cannot receive this treatment, commonly due to impaired kidney function. In the phase 3 study, all participants underwent standard surgery, in which the bladder is removed. One of the groups also received a new combination treatment with the immunotherapy pembrolizumab and the targeted drug enfortumab vedotin before and after surgery.
Large differences between the groups
The results show that 75 per cent of participants treated with the combination therapy were alive without recurrence two years after enrolment, compared with 39 per cent in the control group. When the researchers looked at overall survival, a larger proportion of patients in the treatment group were also alive after two years. In addition, no tumour cells were found in the removed bladder tissue in 57 per cent of patients in the treatment group, compared with 9 per cent in the control group. In total, 344 participants from 27 countries took part in the study.
"These are very promising results for patients with few treatment options available before surgery. It is also reassuring that the treatment does not appear to affect the ability to proceed with surgery, which can otherwise be a concern when treatment is given beforehand," says Anders Ullén , professor of oncology at the Department of Oncology‑Pathology at Karolinska Institutet and the study's last author.
Side effects occurred in both groups
All patients who received the combination treatment experienced some form of side effect. Common side effects included itching and hair loss, and the most frequent serious side effect in both groups was urinary tract infection. Serious complications also occurred among those who underwent surgery alone, which the researchers note reflects the fact that many patients in this group are older and have other underlying health conditions.
"It is always important to balance the benefits of treatment against the risk of side effects. At the same time, the results indicate that the treatment may offer clinically meaningful improvements, reduce the risk of recurrence and improve survival for many patients. We hope that the findings can help inform future treatment practice," says Anders Ullén.
The study was conducted at more than 240 cancer clinics, in collaboration with researchers in Europe, Asia and North America. It was funded by Merck Sharp and Dohme together with Astellas Pharma and Seagen. Potential conflicts of interest are reported in the study.
Publication
Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer.
Vulsteke C, Adra N, Danchaivijitr P, Sabadash M, Rodriguez-Vida A, Zhang Z, Atduev V, Göger YE, Rausch S, Kang SH, Loriot Y, Bedke J, Galsky MD, O'Donnell PH, von Amsberg G, Alimohamed N, Sulimka G, Gupta S, Paramonov V, Nakane K, Mihm M, Meng C, Huang CD, Ramamurthy C, Homet Moreno B, Ullén A, The New England Journal of Medicine 18 Feb 2026, DOI:10.1056/NEJMoa2511674
