Abstract
The PURE-01 trial evaluated three cycles of pembrolizumab 200 mg followed by radical cystectomy (RC) in patients with cT2-3b N0 M0 muscle-invasive bladder cancer (MIBC) ineligible for or refusing cisplatin. A total of 155 patients were treated. We report survival outcomes after median follow-up of >60 mo and associations with pathological response rates and biomarker levels. In the intention-to-treat population, the 5-yr event-free survival rate was 68% and the 5-yr overall survival (OS) rate was 77%. In the RC cohort, the 5-yr recurrence-free survival (RFS) rate was 77%. Pathological response categories were significantly associated with survival, with a 5-yr OS rate of ∼90% in the group achieving a complete or major response (p < 0.001). The 5-yr cumulative risk of recurrence was 19%, with three of 31 relapses occurring beyond 5 yr after RC. Eight patients refused RC and underwent transurethral resection; seven remain alive and disease-free. Transcriptome-wide profiling of pretreatment tissue was available for 102 patients. Stratification by genomic subtyping classifier showed that the claudin-low subtype (n = 14) had the highest 5-yr RFS rate, with a 5-yr OS rate of 93%. At long-term follow-up, PURE-01 demonstrates sustained survival outcomes and confirms the prognostic relevance of pathological response and molecular subtypes. These results support further investigation of single-agent immunotherapy as a potential de-escalation strategy in selected patients.