Who is this trial for?
This trial was for adults with bladder cancer that had grown into the muscle of the bladder wall, who were able to receive cisplatin chemotherapy and were planned for surgery to remove the bladder.
People in the trial had:
- Muscle-invasive bladder cancer (MIBC) that had grown into the bladder muscle but had not spread to distant organs (stage T2–T4a, N0–1, M0).
- Cisplatin eligibility — good enough kidney function and general health to receive cisplatin, the strongest form of bladder-cancer chemotherapy.
- A plan for radical cystectomy (surgical removal of the bladder).
What kind of trial is this?
This trial tested whether adding immunotherapy to standard care could help treat bladder cancer around the time of surgery — both before the bladder is removed and after.
Background: why researchers asked this question
For muscle-invasive bladder cancer, the standard approach for cisplatin-eligible patients is chemotherapy before surgery (cisplatin-based, given to shrink the cancer and kill cells that may have spread) followed by removal of the bladder. It is effective, but not enough: roughly half of patients still have their cancer come back within three years.
Immunotherapy — drugs that help the immune system recognize and attack cancer — had already improved outcomes in advanced bladder cancer and, in the adjuvant (after-surgery) setting, had shown benefit on its own. Researchers asked a straightforward question: if you add immunotherapy to the chemotherapy before surgery, and continue it after surgery, do patients do better than with chemotherapy and surgery alone?
The immunotherapy tested was durvalumab, which blocks a protein called PD-L1 that tumors use to switch off immune cells. The idea of giving it before surgery is that the tumor is still in place to act as a target — teaching the immune system what to look for, so it can hunt down stray cancer cells afterward.
The trial: what was tested and how
NIAGARA enrolled 1,063 people with cisplatin-eligible muscle-invasive bladder cancer across 22 countries. They were randomly assigned to one of two groups:
- Durvalumab group (533 people): durvalumab plus gemcitabine–cisplatin chemotherapy for four cycles before surgery, then radical cystectomy, then durvalumab alone for eight cycles afterward.
- Comparison group (530 people): the same gemcitabine–cisplatin chemotherapy before surgery and the same operation — but no immunotherapy.
The two main measures were event-free survival (EFS) — how long people lived without their cancer coming back, becoming impossible to remove, or leading to death — and pathological complete response (pCR), meaning no live cancer was found in the removed bladder. Overall survival (how long people lived) was the key secondary measure.
Results: what they found
Adding durvalumab before and after surgery improved both the chance of staying cancer-free and overall survival — and, importantly, did so without a meaningful increase in serious side effects.
Durvalumab + chemo vs chemo alone — at 2 years
More people stayed alive and cancer-free at 2 years — a 32% lower risk of the cancer returning or of dying (HR 0.68).
More people were alive at 2 years with durvalumab added — a 25% lower risk of dying (HR 0.75).
More people had no live cancer found in the removed bladder. (This particular difference did not cross the study’s very strict statistical bar, but the survival gains above did.)
Crucially, the extra treatment was well tolerated. Serious (grade 3 or 4) treatment-related side effects were almost identical between the groups — 40.6% with durvalumab versus 40.9% with chemotherapy alone — and the same proportion of people were able to go on to have their surgery. In other words, durvalumab added benefit without adding much toxicity.
Why give immunotherapy before surgery, not just after?
When the tumor is still in the body, it acts as a “training sample” for the immune system. Giving immunotherapy before surgery lets immune cells learn to recognize the cancer while there is plenty of it to see. After the bladder is removed, those primed immune cells can patrol the body and destroy any stray cancer cells that surgery and chemotherapy left behind — which is what drives down the chance of the cancer returning.
The bottom line
For people with muscle-invasive bladder cancer who can receive cisplatin, adding durvalumab immunotherapy to chemotherapy before surgery — and continuing it afterward — improved both event-free survival and overall survival compared with chemotherapy and surgery alone, with almost no increase in serious side effects. This has established perioperative durvalumab as a new option for this large group of patients.
What this could mean for you
- This is for cisplatin-eligible patients. If you cannot receive cisplatin, a different approach (see EV-303) may apply — discuss which fits your situation.
- Treatment spans the whole surgery journey. The benefit came from giving immunotherapy both before and after the operation, not just one or the other.
- Added benefit, similar tolerability. Adding durvalumab did not meaningfully raise the rate of serious side effects — an unusually favorable trade-off.
Questions & comments
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