Bladder Cancer · Medical · Perioperative · Evidence cut-off 26 Oct 2026

VOLGA

In cisplatin-ineligible muscle-invasive bladder cancer, does perioperative durvalumab plus enfortumab vedotin improve outcomes over cystectomy-based control?

One underlying study; aliases and follow-up reports consolidated. Primary discipline: Medical.

Population and eligibility

695 patients with muscle-invasive bladder cancer considered for radical cystectomy and unable/unwilling to receive cisplatin-based neoadjuvant chemotherapy.

Cisplatin-ineligible or cisplatin-declining perioperative population; distinct from cisplatin-eligible NIAGARA.

Sample size

695 across three arms randomised/evaluable as reported.

Intervention

Three cycles neoadjuvant enfortumab vedotin plus perioperative durvalumab; a separate experimental arm also added tremelimumab.

Comparator

Radical cystectomy-based control with protocol-specified adjuvant options.

Endpoints and results

EFS and OS; pathological response, safety and treatment delivery also evaluated.

Durvalumab+enfortumab vedotin: 24-month EFS 63.5% vs 45.1%; HR 0.51 (95% CI 0.38–0.67; p<0.001).
24-month OS 78.4% vs 69.4%; HR 0.58 (95% CI 0.40–0.83; p=0.003).
Triplet arm 24-month EFS 60.1% vs 45.1%; HR 0.61 (95% CI 0.47–0.80; p<0.001); OS benefit not established at this interim analysis.
Grade ≥3 AEs of any cause 71.1% doublet, 79.5% triplet, 50.2% control.

Absolute Effect and outcome visualisation

24-month EFS

% event-free at 24 months · 24 months. Bars show source-reported fixed-time percentages.

Durvalumab + EV

63.5%

Triplet

60.1%

Control

45.1%

Interpretation: Doublet vs control absolute EFS difference 18.4 points; approximate landmark NNT 6 at 24 months. The triplet is a separate comparison and should not be directly ranked against the doublet without a prespecified test.

Toxicity, discontinuation and quality of life

Trial-specific harms: Grade ≥3 AEs of any cause >50% in all arms and highest with the triplet; consider skin, neuropathy, metabolic and immune toxicities.

Treatment burden/discontinuation: Neoadjuvant systemic therapy can affect dose delivery and surgery timing; full completion and delay data need detailed review.

Quality of life: No numerical QoL effect asserted without the full PRO analysis.

Subgroups, maturity and limitations

Subgroups: Keep each experimental-arm comparison separate; no direct superiority claim between doublet and triplet.

Maturity: NEJM primary report published 24 Oct 2026; follow-up continues.

Limitations: Newly published study; source-level detailed safety and subgroup tables should be reviewed in ongoing freshness audit.

Clinical interpretation

VOLGA reports improved EFS and OS for perioperative durvalumab plus enfortumab vedotin vs control in cisplatin-ineligible MIBC; triplet OS benefit is not established and toxicity is substantial.

Use current regional guidelines, patient fitness, biomarkers, competing risks, alternatives and regulatory status before clinical application. Clinical freshness review and browser-rendered QA remain pending.

Primary sources and registry

Registry: NCT04960709

The Absolute Effect · Updated 26 October 2026 · Never derive NNT from median survival.