Drug combination helps more people with bladder cancer live longer

An estimated 78 in every 100 people receiving the drug combination were alive two years after joining the VOLGA trial, compared with 69 in every 100 in the comparison group who were offered surgery without the trial medicines. The findings could expand treatment options for people unable to receive cisplatin chemotherapy, potentially providing an option to receive less drug treatment after surgery than some other approaches.

The trial involved people whose cancer had grown into the bladder’s muscle wall. It tested two medicines: durvalumab, which helps the immune system respond to cancer, and enfortumab vedotin, which uses an antibody to deliver a cell-killing drug.

Professor Thomas Powles, Professor of Genitourinary Oncology at Barts Cancer Institute, Queen Mary University of London, coordinated the international trial. Professor Powles is also Chair of Barts Cancer Centre at Barts Health NHS Trust.

The findings were published in the New England Journal of Medicine and announced at ESMO 2026. The study was sponsored by AstraZeneca.

Why are more treatment options needed?

Cancer that has grown into the bladder’s muscle wall is called muscle-invasive bladder cancer. If it has not spread to distant organs, surgery or radiotherapy can be used to remove or destroy the cancer, potentially preventing it from returning.

Removing the bladder is one treatment option. But even after surgery, cancer can return if microscopic cancer cells remain elsewhere in the body. Chemotherapy containing cisplatin can improve survival when given before surgery. However, kidney problems, hearing loss or other health conditions can make it unsuitable for some people.

Recent trials have expanded the options for people with bladder cancer. For people who can receive cisplatin, adding durvalumab to chemotherapy before surgery, then continuing durvalumab afterwards, improves survival. NICE, which assesses treatments for NHS use, recommends this approach.

Another combination, pembrolizumab and enfortumab vedotin, has also improved survival in trials, including among people unable to receive cisplatin. In the KEYNOTE-905 trial involving these patients, both medicines were given before and after surgery. Enfortumab was given for nine treatment cycles: three before surgery and six afterwards.

VOLGA tested a different approach: giving just three cycles of enfortumab, all before surgery, with durvalumab before and afterwards. Researchers wanted to see whether this could improve survival while avoiding the need to give enfortumab during recovery from major surgery.

What did the treatment involve?

The trial involved 695 people across 25 countries who could not receive cisplatin or had chosen not to have it. They were assigned by chance to three groups.

One group was offered durvalumab and enfortumab before surgery, followed by durvalumab afterwards. A second was offered the same medicines plus another immunotherapy, tremelimumab. The comparison group was offered surgery without these trial medicines, but could receive other approved medicines afterwards.

What were the benefits and risks?

The survival improvement with durvalumab and enfortumab – 78 versus 69 people in every 100 alive at two years – was statistically significant. The combination also improved ‘event-free survival’, which measured how long people lived without their cancer progressing or returning. It also counted not undergoing planned bladder-removal surgery while cancer remained as an event, whether this was because of worsening health or a decision not to proceed. At two years, an estimated 64 in every 100 were alive without a recorded event, compared with 45 in every 100 in the comparison group.

The tremelimumab combination improved event-free survival, but did not show a statistically significant overall survival benefit at this analysis.

The survival benefit came with additional risks compared with surgery without the trial medicines. Health problems classified as severe or worse occurred in about 71 in every 100 receiving durvalumab and enfortumab, compared with 50 in every 100 in the comparison group. These included problems from any cause, not all of which were caused by the medicines. One death was considered treatment-related in the durvalumab–enfortumab group, and five in the group also receiving tremelimumab.

What happens next?

Researchers will continue following participants to understand how long the survival benefit lasts and assess longer-term effects of treatment.

VOLGA showed that durvalumab with enfortumab helped people live longer than those offered surgery without the trial medicines. However, it did not compare this combination directly with pembrolizumab and enfortumab, which improved survival in the recent KEYNOTE-905 trial. Therefore, the findings cannot tell doctors which approach offers the best balance of survival and side-effects for patients. Further trials could answer this question and establish who needs enfortumab after surgery and who could safely have less treatment.

Before the VOLGA combination can become a routine NHS option, it requires regulatory approval, which will consider the benefits and risks.

VOLGA adds to recent progress in bladder cancer treatment, providing evidence for another option for people who cannot receive cisplatin chemotherapy. This growing range of approaches gives researchers more opportunities to find treatments that help people live longer while limiting side effects and the demands of treatment.

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