Surgical outcomes after neoadjuvant avelumab with or without chemotherapy for Muscle-Invasive bladder cancer: a Post-Hoc analysis of the aura trial (Oncodistinct-004).

PURPOSE: Neoadjuvant chemo-immunotherapy is emerging as promising strategy in muscle-invasive bladder cancer (MIBC), yet its perioperative safety remains understudied. This post-hoc analysis of the AURA phase-II trial assesses surgical outcomes following neoadjuvant avelumab with or without chemotherapy.

METHODS

We analyzed 88 patients with localized MIBC from the phase 2 multicenter AURA trial (NCT03674424) who underwent radical cystectomy after receiving either avelumab monotherapy (n = 22) or chemo-immunotherapy (n = 66). Surgical complications were classified using Clavien-Dindo criteria. A LASSO regression was used to identify predictors of overall complications, followed by multivariable and mixed-effects models.

RESULTS

No increased intra-operative surgical complexity was noted. The overall complication rate was 52%. Major complications occurred significantly more often in the chemo-immunotherapy group compared to monotherapy (21.2% vs. 15.4%, p = 0.03), despite more favorable patient profiles. Neobladder diversion and open surgery were both associated with higher complication rates (81% vs. ileal conduit 40%, p = 0.001; 61% vs. robotic surgery 53%, p = 0.04, respectively). Uretero-enteric stricture occurred in 7.6% of patients, with no significant difference between groups. The predictive model demonstrated high accuracy (AUC 0.851) and identified key risk factors for major complications: neobladder reconstruction (OR 10.9[2.4-48.4], p = 0.002), older age, longer operative time, and low preoperative hemoglobin. Limitations include the non-randomized treatment allocation and small sample size in the monotherapy group, which may limit generalizability.

CONCLUSION

Radical cystectomy after neoadjuvant immunotherapy+/-chemotherapy is feasible, safe, and is not associated with increased intra-operative surgical complexity. Neoadjuvant chemo-immunotherapy prior to cystectomy was associated with increased risk of major surgical complications compared to immunotherapy alone.