Outcomes of patients with muscle-invasive bladder cancer who declined radical cystectomy in perioperative therapy trials conducted at San Raffaele Comprehensive Cancer Center
Menée à partir des données de plusieurs essais de phase II incluant 279 patients atteints d’un cancer de la vessie infiltrant le muscle, cette étude évalue, en fonction du taux de réponse clinique complète après traitement néoadjuvant, la survie des patients ayant subi une cystectomie radicale par rapport à ceux ayant refusé cette chirurgie et bénéficié, à la place, d'une seconde résection transurétrale de vessie puis évalue l'intérêt d'ajouter une immunothérapie
Background: Although trimodality therapy is an established bladder-preserving option, the optimal management of patients with muscle-invasive bladder cancer (MIBC) declining radical cystectomy (RC) after neoadjuvant therapy is undefined.
Patients and methods: This was a post-hoc analysis of prospectively collected data from multiple single-arm phase 2 trials (PURE-01, SURE-01/02, NureCombo) conducted at a single center. Patients had cT2-4N0M0 MIBC with pure or predominant (≥50%) urothelial carcinoma. Patients who declined RC underwent repeated transurethral resection of the bladder tumor (reTURBT), with adjuvant or maintenance therapy continued per protocol. Outcomes of interest were event-free survival (EFS), metastasis-free survival (MFS), and overall survival (OS). Subgroup analyses used Cox proportional hazards models evaluating the association between surgery type and EFS/OS within clinically relevant strata: age, variant histology, cT-stage, and perioperative versus neoadjuvant-only approach.
Results: 279 patients were analyzed, 213 (76.4%) undergoing RC, 54 reTURBT (19.3%) and 12 (4.3%) no surgery, enrolled between 02/17 and 07/25. In the reTURBT group 41(76%) had a cT2 stage, 30 (56%) received adjuvant immune-checkpoint inhibitors (ICI). The median follow-up of this cohort was 25 months (interquartile range: 17-32). While the outcomes of ypT0Nx (reTURBT) vs ypT0N0 (RC) patients were similar, those with non-ypT0Nx at reTURBT had a significantly shorter EFS and OS vs non-ypT0N0 (p<0.001). reTURBT was associated with worse EFS vs RC in most strata, with a statistical significance observed in patients with baseline cT3–4 stage (age-adjusted HR: 2.34, 95% confidence intervals [CI]: 1.05–5.22). No significant differences were observed in other subgroups nor for OS in any subgroup, including the use of adjuvant ICI.
Conclusions: Patients with MIBC achieving a clinical complete response had similar systemic tumor control regardless of surgery type. Patients with non ypT0 response refusing RC warrants evaluation of novel sequential therapies or standard chemo-radiotherapy. The benefit of adjuvant ICI compared to exclusive neoadjuvant approach remains uncertain.
ESMO Open , article en libre accès, 2026